Process for synthesizing highly optically active 1,3-disubstituted allenes

Abstract

The present invention relates to a process for efficiently synthesizing highly optically active 1,3-disubstituted allenes, i.e., a one-step process for preparing highly optically active 1,3-disubstituted allenes by using a functionalized terminal alkyne, an aldehyde and a chiral ,-diphenyl prolinol as reactants under the catalysis of a divalent copper salt. The operation of the process is simple, and the raw materials and reagents are readily available. The process has a broad-spectrum of substrates and a good compatibility for a wide variety of functional groups such as glycosidic units, primary alcohols, secondary alcohols, tertiary alcohols, amides, malonates, etc., and does not require the protection for the functional groups. The obtained axially chiral allene has a moderate to high yield and a good diastereoselectivity or enantioselectivity.

Claims

1. A process for synthesizing optically active 1,3-disubstituted allenes, in a heated reaction comprising a functionalized terminal alkyne, an aldehyde and a chiral secondary amine as reactants, a divalent copper salt as a catalyst and an organic solvent, thereby producing a variety of functionalized axially chiral 1,3-disubstituted allenes; wherein the process consists of: adding in sequence to a reaction under nitrogen atmosphere: a divalent copper salt, a chiral secondary amine, a terminal alkyne, an aldehyde and an organic solvent; subjecting the reaction to anhydrous and anaerobic treatment by heating for 12-24 h in an oil bath; returning the reaction to room temperature, diluting the reaction with the organic solvent, washing the reaction with dilute hydrochloric acid, separating the organic phase, extracting the aqueous phase with the organic solvent, washing with saturated brine, drying with anhydrous sodium sulfate, filtering, concentrating and subjecting reaction products to column chromatography, so as to obtain the axially chiral allene; wherein the reaction has a following reaction equation: ##STR00038## wherein R.sup.1 comprises functional groups selected from glycosidic units, primary alcohols, secondary alcohols, tertiary alcohols, amides, malonates, alkyl group or aryl group, and R.sup.2 is an alkyl group or an aryl group.

2. The process for synthesizing optically active 1,3-disubstituted allenes of claim 1, wherein the catalyst is copper bromide, copper chloride, copper acetate, copper sulfate or copper triflate.

3. The process for synthesizing optically active 1,3-disubstituted allenes of claim 1, wherein the chiral secondary amine is selected from the group consisting of (S)-3a and enantiomers thereof: ##STR00039##

4. The process for synthesizing optically active 1,3-disubstituted allenes of claim 1, wherein the organic solvent is 1,4-dioxane, toluene, benzene, chlorobenzene, p-xylene, o-xylene, m-xylene, or mesitylene.

5. The process for synthesizing optically active 1,3-disubstituted allenes of claim 3, wherein the organic solvent is 1,4-dioxane, toluene, benzene, chlorobenzene, p-xylene, o-xylene, m-xylene, or mesitylene.

Description

PREFERRED EMBODIMENTS OF THE INVENTION

(1) The following examples are given for further illustrating the specific solutions of the present invention.

EXAMPLE 1

(2) ##STR00003##

(3) Wherein equiv refers to equivalent; de refers to diastereomeric excess; cc refers to enantiomeric excess.

(4) To a flame-dried Schlenk tube were added CuBr.sub.2 (44.9 mg, 0.2 mmol), 1a (387.0 mg, 1.0 mmol), (S)-3a (304.5 mg, 1.2 mmol), and 2a (180.1 mg, 1.4 mmol)/dioxane (3.0 mL) sequentially under nitrogen atmosphere. The Schlenk tube was then equipped with a condenser and the outlet connected to the vacuum line with a nitrogen flow was closed. The reaction was complete after being stirred at 130 C. for 16 h as monitored by TLC (eluent: petroleum ether/ethyl acetate=3/1). Then the resulting mixture was diluted with ethyl acetate (30 mL), and washed with an aqueous solution of hydrochloric acid (v/v=10%). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layer was washed with brine and dried over anhydrous Na.sub.2SO.sub.4. After filtration and evaporation, the residue was purified by chromatography (eluent: petroleum ether/ethyl acetate=3/1) on silica gel to afford (R.sub.a)-4aa (246.5 mg, 49%) as a liquid: 98% de (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH=95/5, 0.3 mL/min, =214 nm, t.sub.R(major)=24.9 min, t.sub.R(minor)=26.8 min); [].sub.D.sup.20=32.2 (c=1.07, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.28-4.95 (m, 5 H), 4.64 (d, J=7.8 Hz, 1 H), 4.35-4.24 (m, 2 H), 4.18-4.07 (m, 2 H), 3.74-3.63 (m, 1 H), 2.09 (s, 3 H, Me), 2.05 (s, 3 H, Me), 2.03 (s, 3 H, Me), 2.01 (s, 3 H, Me), 2.12-1.94 (m, 2 H, CH.sub.2), 1.48-1.20 (m, 10 H, CH.sub.25), 0.89 (t, J=6.9 Hz, 3 H, Me); .sup.13C NMR (75 Hz, CDCl.sub.3) 205.4, 170.5, 170.2, 169.3, 169.2, 98.8, 92.1, 87.2, 72.8, 71.6, 71.0, 68.2, 67.8, 61.7, 31.7, 28.98, 28.95, 28.9, 28.3, 22.5, 20.6, 20.52, 20.45, 20.4, 13.9; IR (neat) (cm.sup.1) 2928, 2856, 1963, 1757, 1435, 1370, 1226, 1165, 1041; MS (ESI, m/z) 521 (M+Na.sup.+), 516 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.25H.sub.38O.sub.10 (%): C, 60.23; H, 7.68; Found: C, 60.21; H, 7.37.

EXAMPLE 2

(5) ##STR00004##

(6) Following the procedure of Example 1. The reaction of CuBr.sub.2 (89.3 mg, 0.4 mmol), 1a (772.5 mg, 2.0 mmol), (R)-3a (607.6 mg, 2.4 mmol), and 2a (360.6 mg, 2.8 mmol) in dioxane (6.0 mL) afforded (S.sub.a)-4aa (508.2 mg, 51%) (eluent: petroleum ether/ethyl acetate=3/1) as a liquid: 98% de (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH=95/5, 0.4 mL/min, =214 nm, t.sub.R(minor)=35.5 min, t.sub.R(major)=36.5 min); [].sub.D.sup.20=+36.8 (c=0.975, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.28-4.95 (m, 5 H), 4.64 (d, J=7.8 Hz, 1 H), 4.34-4.25 (m, 2 H), 4.18-4.07 (m, 2 H), 3.75-3.66 (m, 1 H), 2.08 (s, 3 H, Me), 2.04 (s, 3 H, Me), 2.03 (s, 3 H, Me), 2.00 (s, 3 H, Me), 2.12-1.95 (m, 2 H, CH.sub.2), 1.48-1.18 (m, 10 H, CH.sub.25), 0.88 (t, J=6.6 Hz, 3 H, Me); .sup.13C NMR (75 Hz, CDCl.sub.3) 205.1, 170.3, 169.9, 169.1, 169.0, 98.7, 92.0, 87.1, 72.6, 71.5, 70.9, 68.1, 67.5, 61.6, 31.5, 28.8, 28.7, 28.1, 22.3, 20.39, 20.35, 20.3, 13.8; IR (neat) (cm.sup.1) 2929, 2857, 1962, 1759, 1435, 1367, 1227, 1166, 1040; MS (ESI, m/z) 516 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.25H.sub.38O.sub.10 (%): C, 60.23; H, 7.68; Found: C, 60.61; H, 7.71.

EXAMPLE 3

(7) ##STR00005##

(8) Following the procedure of Example 1. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 1a (388.1 mg, 1.0 mmol), (S)-3a (303.3 mg, 1.2 mmol), and 2b (168.8 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ab (273.0 mg, 55%) (eluent: petroleum ether/ethyl acetate=2.5/1) as a liquid: 97% de (HPLC conditions: Chiralcel IA-H column, hexane/i-PrOH=95/5, 1.0 mL/min, =214 nm, t.sub.R(major)=16.4 min, t.sub.R(minor)=23.0 min); [].sub.D.sup.20=30.4 (c=1.405, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.39-7.19 (m, 5 H, ArH), 5.50-5.37 (m, 1 H), 5.22-5.11 (m, 2 H), 5.06 (t, J=9.6 Hz, 1 H), 4.95 (t, J=8.9 Hz, 1 H), 4.35 (d, J=7.8 Hz, 1 H), 4.32-4.19 (m, 2 H), 4.13-4.02 (m, 2 H), 3.55-3.29 (m, 3 H), 2.07 (s, 3 H, Me), 2.029 (s, 3 H, Me), 2.026 (s, 3 H, Me), 2.00 (s, 3 H, Me); .sup.13C NMR (75 Hz, CDCl.sub.3) 205.7, 170.4, 170.0, 169.15, 169.06, 139.2, 128.34, 128.28, 126.3, 98.2, 91.5, 88.0, 72.5, 71.3, 70.8, 68.0, 67.0, 61.5, 34.7, 20.5, 20.42, 20.35; IR (neat) (cm.sup.1) 3063, 3028, 2945, 2884, 1964, 1756, 1602, 1495, 1450, 1433, 1370, 1226, 1165, 1041; MS (ESI, m/z) 529 (M+K.sup.+), 513 (M+Na.sup.+), 508 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.25H.sub.30O.sub.10 (%): C, 61.22; H, 6.16; Found: C, 61.32; H, 6.03.

EXAMPLE 4

(9) ##STR00006##

(10) Following the procedure of Example 1. The reaction of CuBr.sub.2 (44.7 mg, 0.2 mmol), 1a (386.1 mg, 1.0 mmol), (S)-3a (303.5 mg, 1.2 mmol), and 2c (187.6 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ac (253.4 mg, 50%) (eluent: petroleum ether/ethyl acetate=2.5/1) as a liquid: 99% de (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=90/10, 1.0 mL/min, =214 nm, t.sub.R(major)=13.1 min, t.sub.R(minor)=19.3 min); [].sub.D.sup.20=37.7 (c=1.32, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.34-7.15 (m, 5 H), 5.31-4.95 (m, 5 H, ArH), 4.57 (d, J=8.1 Hz, 1 H), 4.32-4.18 (m, 2 H), 4.16-4.01 (m, 2 H), 3.70-3.61 (m, 1 H), 2.74 (t, J=7.7 Hz, 2 H), 2.40-2.28 (m, 2 H), 2.07 (s, 3 H, Me), 2.03 (s, 3 H, Me), 2.02 (s, 3 H, Me), 2.00 (s, 3 H, Me); .sup.13C NMR (75 Hz, CDCl.sub.3) 205.3, 170.5, 170.2, 169.3, 169.2, 141.2, 128.4, 128.2, 125.9, 99.2, 91.5, 87.9, 72.8, 71.7, 71.2, 68.3, 67.7, 61.8, 35.1, 30.0, 20.59, 20.56, 20.49, 20.47; IR (neat) (cm.sup.1) 3063, 3024, 2942, 2861, 1964, 1757, 1603, 1496, 1453, 1432, 1369, 1225, 1165, 1041; MS (ESI, m/z) 527 (M+Na.sup.+), 522 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.26H.sub.32O.sub.10 (%): C, 61.90; H, 6.39; Found: C, 61.41; H, 6.25. HRMS calcd. for C.sub.26H.sub.36NO.sub.10 (M+NH.sub.4.sup.+): 522.2334; Found: 522.2322.

EXAMPLE 5

(11) ##STR00007##

(12) Following the procedure of Example 1. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1a (385.4 mg, 1.0 mmol), (S)-3a (304.1 mg, 1.2 mmol), and 2d (121.2 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ad (245.2 mg, 54%) (eluent: petroleum ether/ethyl acetate=3/1) as a solid: 97% de (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=95/5, 1.0 mL/min, =214 nm, t.sub.R(minor)=17.6 min, t.sub.R(major)=18.9 min); [].sub.D.sup.20=26.7 (c=1.00, CHCl.sub.3); m.p. 68-69 C. (DCM/n-hexane); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.28-4.95 (m, 5 H), 4.63 (d, J=8.1 Hz, 1 H), 4.36-4.21 (m, 2 H), 4.20-4.04 (m, 2 H), 3.73-3.61 (m, 1 H), 2.09 (s, 3 H, Me), 2.06 (s, 3 H, Me), 2.04 (s, 3 H, Me), 2.02 (s, 3 H, Me), 2.17-1.87 (m, 2 H, CH.sub.2), 1.76-1.59 (m, 1 H, CH), 0.94 (d, J=6.6 Hz, 6 H, Me2); .sup.13C NMR (75 Hz, CDCl.sub.3) 205.9, 170.5, 170.2, 169.23, 169.16, 98.8, 90.5, 86.5, 72.7, 71.6, 71.0, 68.1, 67.8, 61.7, 37.8, 28.1, 22.0, 21.9, 20.54, 20.51, 20.44, 20.42; IR (KBr) (cm.sup.1) 2957, 2871, 1964, 1757, 1434, 1369, 1226, 1165, 1041; MS (ESI, m/z) 479 (M+Na.sup.+), 474 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.22H.sub.32O.sub.10 (%): C, 57.88; H, 7.07; Found: C, 57.89; H, 7.08.

EXAMPLE 6

(13) ##STR00008##

(14) Following the procedure of Example 1. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1a (388.5 mg, 1.0 mmol), (5)-3a (305.5 mg, 1.2 mmol), and 2e (157.5 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ae (275.1 mg, 57%) (eluent: petroleum ether/ethyl acetate=3/1) as a solid: 99% de (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=95/5, 1.0 mL/min, =214 nm, t.sub.R(minor)=16.4 min, t.sub.R(major)=19.1 min); [].sub.D.sup.20=(c=0.92, CHCl.sub.3); m.p. 102-103 C. (DCM/n-hexane); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.27-4.96 (m, 5 H), 4.66 (d, J=8.1 Hz, 1 H), 4.36-4.22 (m, 2 H), 4.19-4.05 (m, 2 H), 3.72-3.63 (m, 1 H), 2.09 (s, 3 H, Me), 2.05 (s, 3 H, Me), 2.03 (s, 3 H, Me), 2.01 (s, 3 H, Me), 2.22-1.89 (m, 1 H, CH), 1.81-1.60 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.40-1.00 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.3, 170.4, 170.0, 169.2, 169.1, 98.7, 98.0, 88.1, 72.7, 71.5, 71.0, 68.1, 67.8, 61.6, 36.6, 32.8, 32.6, 25.8, 25.6, 20.5, 20.42, 20.36; IR (KBr) (cm.sup.1) 2925, 2851, 1965, 1741, 1447, 1412, 1380, 1287, 1260, 1227, 1171, 1115, 1094, 1058, 1036; MS (ESI, m/z) 505 (M+Na.sup.+), 500 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.24H.sub.34O.sub.10 (%): C, 59.74; H, 7.10; Found: C, 59.80; H, 7.04.

EXAMPLE 7

(15) ##STR00009##

(16) Following the procedure of Example 1. The reaction of CuBr.sub.2 (44.7 mg, 0.2 mmol), 1a (384.2 mg, 1.0 mmol), (S)-3a (305.5 mg, 1.2 mmol), and 2f (101.4 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4af (233.9 mg, 53%) (eluent: petroleum ether/ethyl acetate=2.5/1) as a liquid: 99% de (HPLC conditions: Chiralcel IA-H column, hexane/i-PrOH=95/5, 1.0 mL/min, =214 nm, t.sub.R(minor)=15.1 min, t.sub.R(major)=16.1 min); [].sub.D.sup.20=23.1 (c=1.08, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.30-5.14 (m, 3 H), 5.10 (t, J=9.6 Hz, 1 H), 5.01 (dd, J.sub.1=9.6 Hz, J.sub.2=8.1 Hz, 1 H), 4.66 (d, J=7.8 Hz, 1 H), 4.36-4.24 (m, 2 H), 4.17-4.07 (m, 2 H), 3.72-3.64 (m, 1 H), 2.40-2.24 (m, 1 H, CH), 2.09 (s, 3 H, Me), 2.05 (s, 3 H, Me), 2.03 (s, 3 H, Me), 2.01 (s, 3 H, Me), 1.03 (d, J=6.6 Hz, 6 H, Me2); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.0, 170.5, 170.2, 169.3, 169.2, 99.5, 98.7, 88.5, 72.8, 71.6, 71.1, 68.2, 67.9, 61.8, 27.5, 22.3, 22.2, 20.6, 20.51, 20.45, 20.4; IR (neat) (cm.sup.1) 2962, 2871, 1961, 1755, 1434, 1367, 1227, 1165, 1040; MS (ESI, m/z) 460 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.21H.sub.30O.sub.10 (%): C, 57.01; H, 6.83; Found: C, 57.05; H, 6.72.

EXAMPLE 8

(17) ##STR00010##

(18) Following the procedure of Example 1. The reaction of CuBr.sub.2 (89.7 mg, 0.4 mmol), 1a (386.8 mg, 1.0 mmol), (S)-3a (304.6 mg, 1.2 mmol), and 2g (196.8 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ag (277.3 mg, 54%) (eluent: petroleum ether/ethyl acetate=2/1) as a liquid: 99% de (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=95/5, 0.6 mL/min, =214 nm, t.sub.R(major)=57.1 min, t.sub.R(minor)=62.3 min); [].sub.D.sup.20=111.8 (c=1.04, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.34-7.27 (m, 2 H, ArH), 7.25-7.19 (m, 2 H, ArH), 6.23 (dt, J.sub.1=6.2 Hz, J.sub.2=2.3 Hz, 1 H, one proton of CHCCH), 5.65 (dd, J.sub.1=13.8 Hz, J.sub.2=6.3 Hz, 1 H, one proton of CHCCH), 5.22 (t, J=9.5 Hz, 1 H), 5.14-4.97 (m, 2 H), 4.65 (d, J=7.8 Hz, 1 H), 4.47-4.37 (m, 1 H), 4.29-4.18 (m, 2 H), 4.10 (dd, J.sub.1=12.3 Hz, J.sub.2=2.4 Hz, 1 H), 3.66-3.58 (m, 1 H), 2.03 (s, 3 H, Me), 2.02 (s, 3 H, Me), 2.00 (s, 3 H, Me), 1.99 (s, 3 H, Me); .sup.13C NMR (75 Hz, CDCl.sub.3) 206.4, 170.3, 169.9, 169.1, 169.0, 132.8, 132.0, 128.7, 127.9, 99.2, 94.9, 91.8, 72.7, 71.7, 71.1, 68.2, 66.6, 61.7, 20.4, 20.3; IR (neat) (cm.sup.1) 2956, 2925, 2869, 2849, 1953, 1755, 1492, 1456, 1429, 1376, 1224, 1039; MS (ESI, m/z) 535 (M(.sup.37Cl)+Na.sup.+), 533 (M(.sup.35Cl)+Na.sup.+), 530 (M(.sup.37Cl)+NH.sub.4.sup.+), 528 (M(.sup.35Cl)+NH.sub.4.sup.+); HRMS calcd. for C.sub.24H.sub.31.sup.35ClNO.sub.10 (M(.sup.35Cl)+NH.sub.4.sup.+): 528.1631; Found: 528.1614.

EXAMPLE 9

(19) ##STR00011##

(20) Following the procedure of Example 1. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1b (498.9 mg, 1.0 mmol), (S)-3a (304.1 mg, 1.2 mmol), and 2e (156.9 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R)-4be (297.4 mg, 50%) (eluent: petroleum ether/ethyl acetate=2.5/1) as a solid: 99% de (HPLC conditions: Chiralcel IA-H column, hexane/i-PrOH=80/20, 1.0 mL/min, =214 nm, t.sub.R(minor)=9.5 min, t.sub.R(major)=10.9 min); [].sub.D.sup.20=21.6 (c=0.97, CHCl.sub.3); m.p. 117-118 C. (EtOAc/n-hexane); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.78 (d, J=8.4 Hz, 2 H, ArH), 7.35 (d, J=8.1 Hz, 2 H, ArH), 5.27-5.08 (m, 3 H), 4.97-4.86 (m, 2 H), 4.58 (d, J=8.1 Hz, 1 H), 4.27-4.17 (m, 1 H), 4.16-3.97 (m, 3 H), 3.77-3.68 (m, 1 H), 2.45 (s, 3 H), 2.03 (s, 3 H, Me), 2.00 (s, 3 H, Me), 1.99 (s, 3 H, Me), 2.10-1.95 (m, 1 H, CH), 1.82-1.59 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.40-0.98 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.2, 170.1, 169.3, 169.1, 145.0, 132.2, 129.8, 127.9, 98.7, 98.2, 88.2, 72.4, 71.3, 70.8, 68.4, 67.9, 67.5, 36.6, 32.8, 32.7, 25.9, 25.7, 21.5, 20.47, 20.42, 20.39; IR (KBr) (cm.sup.1) 2926, 2852, 1962, 1758, 1598, 1449, 1369, 1245, 1218, 1178, 1040; MS (ESI, m/z) 612 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.29H.sub.38O.sub.11S (%): C, 58.57; H, 6.44; Found: C, 58.81; H, 6.38.

EXAMPLE 10

(21) ##STR00012##

(22) Following the procedure of Example 1. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 1c (472.5 mg, 1.0 mmol), (S)-3a (303.2 mg, 1.2 mmol), and 2e (158.1 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ce (256.2 mg, 45%) (eluent: petroleum ether/ethyl acetate=1.5/1) as a liquid: 99% de (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=95/5, 1.0 mL/min, =214 nm, t.sub.R(minor)=27.3 min, t.sub.R(major)=29.6 min); [].sub.D.sup.20=38.9 (c=1.35, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.89 (t, J=5.4 Hz, 1 H), 5.27-5.13 (m, 3 H), 5.02-4.85 (m, 2 H), 4.62 (d, J=8.1 Hz, 1 H), 4.34-4.24 (m, 1 H), 4.18-4.07 (m, 1 H), 3.61-3.40 (m, 3 H), 2.23-2.11 (m, 2 H), 2.06 (s, 3 H, Me), 2.05 (s, 3 H, Me), 2.00 (s, 3 H, Me), 2.10-1.95 (m, 1 H, CH), 1.82-1.54 (in, 7 H, CH.sub.23 and one proton of CH.sub.2), 1.39-1.00 (in, 1 3H, CH.sub.26 and one proton of CH.sub.2), 0.88 (t, J=6.6 Hz, 3 H, Me); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.3, 173.1, 170.1, 169.5, 169.2, 99.2, 98.3, 88.3, 72.7, 72.4, 71.1, 68.7, 68.4, 38.8, 36.7, 36.5, 32.9, 32.7, 31.5, 29.1, 28.9, 25.9, 25.7, 25.4, 22.5, 20.52, 20.47, 13.9; IR (neat) (cm.sup.1) 3312, 2926, 2853, 1961, 1760, 1651, 1538, 1447, 1373, 1248, 1220, 1165, 1050; MS (ESI, m/z) 604 (M+K.sup.+), 588 (M+Na.sup.+), 566 (M+H.sup.+); Anal. Calcd. for C.sub.30H.sub.47NO.sub.9 (%): C, 63.70; H, 8.37; N, 2.48; Found: C, 63.60; H, 8.39; N, 2.29.

EXAMPLE 11

(23) ##STR00013##

(24) Following the procedure of Example 1. The reaction of CuBr.sub.2 (67.0 mg, 0.3 mmol), 1d (457.3 mg, 1.0 mmol), (S)-3a (304.0 mg, 1.2 mmol), and 2e (157.3 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4de (255.0 mg, 46%) (eluent: petroleum ether/ethyl acetate=2.5/1) as a liquid: 98% de (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=80/20, 0.5 mL/min, =214 nm, t.sub.R(minor)=12.2 min, t.sub.R(major)=14.3 min); [].sub.D.sup.20=30.0 (c=1.375, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.26-5.12 (m, 3 H), 4.96 (dd, J.sub.1=9.8 Hz, J.sub.2=8.0 Hz, 1 H), 4.88 (t, J=9.5 Hz, 1 H), 4.52 (d, J=8.1 Hz, 1 H), 4.25 (ddd, J.sub.1=11.4 Hz, J.sub.2=6.3 Hz, J.sub.3=2.7 Hz, 1 H), 4.06 (ddd, J.sub.1=11.7 Hz, =7.5 Hz, J.sub.3=2.4 Hz, 1 H), 3.76 (s, 3 H, Me), 3.74 (s, 3 H, Me), 3.67 (dd, J.sub.1=9.6 Hz, J.sub.2=5.1 Hz, 1 H), 3.52 (td, J.sub.1=9.6 Hz, J.sub.1=2.9 Hz, 1 H, CH), 2.30-2.19 (m, 1 H), 2.13-1.94 (m, 11 H), 1.81-1.60 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.40-1.00 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.1, 170.1, 169.5, 169.2, 169.1, 169.0, 99.2, 98.1, 88.3, 72.6, 71.6, 71.1, 71.0, 68.1, 52.6, 52.5, 47.4, 36.6, 32.8, 32.7, 30.2, 25.9, 25.7, 20.52, 20.49, 20.4; IR (neat) (cm.sup.1) 2927, 2852, 1961, 1755, 1436, 1367, 1245, 1218, 1159, 1046; MS (ESI, m/z) 577 (M+Na.sup.+), 572 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.27H.sub.38O.sub.12 (%): C, 58.47; H, 6.91; Found: C, 58.04; H, 6.68. HRMS calcd. for C.sub.27H.sub.42N O.sub.12 (M+NH.sub.4.sup.+): 572.2702; Found: 572.2688.

EXAMPLE 12

(25) ##STR00014##

(26) Following the procedure of Example 1. The reaction of CuBr.sub.2 (67.3 mg, 0.3 mmol), 1e (388.0 mg, 1.0 mmol), (S)-3a (303.7 mg, 1.2 mmol), and 2e (158.0 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ee (240.3 mg, 50%) (eluent: petroleum ether/ethyl acetate=3/1) as a liquid: 96% de (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=95/5, 1.0 mL/min, =214 nm, t.sub.R(major)=20.0 min, t.sub.R(minor)=23.5 min); [].sub.D.sup.20=26.7 (c=1.24, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.40 (d, J=3.0 Hz, 1 H), 5.27-5.13 (m, 3 H), 5.02 (dd, J.sub.1=10.4 Hz, J.sub.2=3.2 Hz, 1 H), 4.62 (d, J=8.1 Hz, 1 H), 4.37-4.27 (m, 1 H), 4.23-4.07 (m, 3 H), 3.89 (t, J=6.6 Hz, 1 H), 2.16 (s, 3 H, Me), 2.09 (s, 3 H, Me), 2.06 (s, 3 H, Me), 1.99 (s, 3 H, Me), 2.20-1.93 (m, 1 H, CH), 1.83-1.60 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.40-0.99 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.3, 170.12, 170.09, 170.0, 169.2, 99.2, 98.0, 88.2, 70.8, 70.4, 68.6, 67.8, 66.8, 61.1, 36.6, 32.8, 32.6, 25.8, 25.7, 20.5, 20.43, 20.36; IR (neat) (cm.sup.1) 2926, 2852, 1961, 1754, 1449, 1370, 1223, 1170, 1132, 1075, 1057; MS (ESI, m/z) 505 (M+Na.sup.+), 500 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.24H.sub.34O.sub.10 (%): C, 59.74; H, 7.10; Found: C, 59.77; H, 6.97.

EXAMPLE 13

(27) ##STR00015##

(28) Following the procedure of Example 1. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 1f (400.8 mg, 1.0 mmol), (S)-3a (304.6 mg, 1.2 mmol), and 2e (157.2 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4fe (230.3 mg, 46%) (eluent: petroleum ether/ethyl acetate=3/1) as a solid: 96% de (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH=95/5, 0.5 mL/min, =214 nm, t.sub.R(minor)=23.0 min, t.sub.R(major)=24.5 min); [].sub.D.sup.20=47.9 (c=1.24, CHCl.sub.3); m.p. 103-104 C. (EtOAc/n-hexane); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.27-5.14 (m, 3 H), 5.14-5.01 (m, 2 H), 4.58 (d, J=9.9 Hz, 1 H), 4.25 (dd, J.sub.1=12.5 Hz, J.sub.2=5.0 Hz, 1 H), 4.13 (dd, J.sub.1=12.2 Hz, J.sub.2=2.0 Hz, 1 H), 3.71-3.62 (m, 1 H), 3.35 (ddd, J.sub.1=13.8 Hz, J.sub.2=7.5 Hz, J.sub.3=2.3 Hz, 1 H), 3.24 (ddd, J.sub.1=13.8 Hz, J.sub.2=6.5 Hz, J.sub.3=3.0 Hz, 1 H), 2.08 (s, 3 H, Me), 2.07 (s, 3 H, Me), 2.03 (s, 3 H, Me), 2.02 (s, 3 H, Me), 2.12-1.94 (m, 1 H, CH), 1.82-1.60 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.40-1.00 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 203.7, 170.5, 170.0, 169.2, 98.5, 88.8, 82.7, 75.7, 73.8, 69.7, 68.1, 61.9, 37.2, 33.0, 32.9, 30.1, 25.9, 25.7, 20.6, 20.5, 20.4; IR (KBr) (cm.sup.1) 2926, 2852, 1953, 1756, 1448, 1371, 1225, 1040; MS (ESI, m/z) 516 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.24H.sub.34O.sub.9S (%): C, 57.81; H, 6.87; Found: C, 58.03; H 6.82.

EXAMPLE 14

(29) ##STR00016##

(30) Following the procedure of Example 1. The reaction of CuBr.sub.2 (44.7 mg, 0.2 mmol), 1g (402.0 mg, 1.0 mmol), (S)-3a (306.1 mg, 1.2 mmol), and 2e (157.2 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ge (183.2 mg, 37%) (eluent: petroleum ether/ethyl acetate=2.5/1) as a solid: 98% de (HPLC conditions: Chiralcel IC column, hexane/i-PrOH=96/4, 0.4 mL/min, =214 nm, t.sub.R(minor)=76.6 min, t.sub.R(major)=78.3 min); [].sub.D.sup.20=47.8 (c=1.38, CHCl.sub.3); m.p. 86-87 C. (DCM/n-hexane); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.21 (t, J=9.5 Hz, 1 H), 5.14-4.94 (m, 4 H), 4.53 (d, J=8.1 Hz, 1 H), 4.28 (dd, J.sub.1=12.3 Hz, J.sub.2=4.8 Hz, 1 H), 4.13 (dd, J.sub.1=12.3 Hz, J.sub.2=2.4 Hz, 1 H), 3.92 (dt, J.sub.1=9.6 Hz, J.sub.2=6.9 Hz, 1 H), 3.71 (ddd, J.sub.1=10.1 Hz, J.sub.2=4.8 Hz, J.sub.1=2.4 Hz, 1 H), 3.55 (dt, J.sub.1=9.6 Hz, J.sub.2=7.2 Hz, 1 H), 2.32-2.20 (m, 2 H, CH.sub.2), 2.09 (s, 3 H, Me), 2.05 (s, 3 H, Me), 2.03 (s, 3 H, Me), 2.01 (s, 3 H, Me), 2.13-1.88 (m, 1 H, CH), 1.80-1.58 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.37-0.97 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 203.2, 170.6, 170.2, 169.3, 169.2, 100.7, 97.4, 87.4, 72.7, 71.6, 71.1, 69.7, 68.2, 61.8, 36.9, 32.9, 32.8, 29.3, 26.0, 25.8, 20.6, 20.5, 20.4; IR (KBr) (cm.sup.1) 2926, 2852, 1959, 1757, 1448, 1369, 1225, 1170, 1040; MS (ESI, m/z) 514 (M+NH.sub.4.sup.+); Anal. Calcd. for C.sub.25H.sub.36O.sub.10 (%): C, 60.47; H, 7.31; Found: C, 60.54; H, 7.25.

EXAMPLE 15

(31) ##STR00017##

(32) Following the procedure of Example 1. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 1h (862.1 mg, 1.0 mmol), (S)-3a (304.4 mg, 1.2 mmol), and 2e (157.5 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R)-4he (456.7 mg, 48%) (eluent: petroleum ether/ethyl acetate=1.5/1) as a syrup: 98% de (HPLC conditions: (Supercritical Fluid Chromatography) Chiralcel IA column, CO.sub.2/i-PrOH=80/20, 1.5 mL/min, =214 nm, t.sub.R(minor)=8.3 min, t.sub.R(major)=14.2 min); [].sub.D.sup.20=13.8 (c=1.21, CHCl.sub.3); NMR (300 MHz, CDCl.sub.3) 7.98-7.88 (m, 4 H, ArH), 7.84-7.78 (m, 2 H, ArH), 7.55-7.45 (m, 2 H, ArH), 7.43-7.32 (m, 5 H, ArH), 7.28-7.20 (m, 2 H, ArH), 5.88 (t, J=9.6 Hz, 1 H), 5.51 (dd, J.sub.1=9.6 Hz, J.sub.2=8.1 Hz, 1 H), 5.41 (t, J=9.8 Hz, 1 H), 5.26-5.12 (m, 3 H), 5.11-4.98 (m, 2 H), 4.94 (d, J=7.8 Hz, 1 H), 4.65 (d, J=7.8 Hz, 1 H), 4.43-4.33 (m, 1 H), 4.29-4.12 (m, 2 H), 4.10-3.97 (m, 3 H), 3.78 (dd, J=18.8 Hz, J=11.3 Hz, 1 H), 3.74-3.65 (m, 1 H), 2.09 (s, 3 H, Me), 2.01 (s, 3 H, Me), 2.00 (s, 3 H, Me), 1.99 (s, 3 H, Me), 2.12-1.85 (m, 1 H, CH), 1.79-1.57 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.34-0.95 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.1, 170.3, 170.0, 169.2, 169.1, 165.5, 165.1, 164.8, 133.4. 133.02, 132.99, 129.6, 129.54, 129.47, 129.1, 128.5, 128.4, 128.3, 128.11, 128.05, 100.6, 99.2, 98.2, 88.2, 73.5, 72.8, 72.6, 71.6, 71.5, 70.9, 69.5, 68.2, 68.0, 67.7, 61.6, 36.5, 32.8, 32.5, 25.8, 25.7, 25.6, 20.5, 20.4, 20.3; IR (neat) (cm.sup.1) 3063, 2927, 2852, 1959, 1754, 1739, 1602, 1452, 1369, 1284, 1251, 1224, 1176, 1094, 1069, 1037; MS (MALDI, m/z) 995 (M+K.sup.+) 979 (M+Na.sup.+); Anal. Calcd. for C.sub.51H.sub.56O.sub.18 (%): C, 64.01; H, 5.90; Found: C, 64.00; H, 5.80.

EXAMPLE 16

(33) ##STR00018##

(34) Following the procedure of Example 1. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1i (861.1 mg, 1.0 mmol), (5)-3a (304.2 mg, 1.2 mmol), and 2e (157.2 mg, 1.4 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ie (492.2 mg, 51%) (eluent: petroleum ether/ethyl acetate=1.5/1) as a syrup: 98% de (HPLC conditions: (Supercritical Fluid Chromatography) Chiralcel IA column, CO.sub.2/i-PrOH=70/30, 1.5 mL/min, =214 nm, t.sub.R(minor)=4.5 min, t.sub.R(major)=6.1 min); [].sub.D.sup.20=13.5 (c=1.12, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.80-7.88 (m, 4 H, ArH), 7.85-7.78 (m, 2 H, ArH), 7.55-7.20 (m, 9 H, ArH), 5.88 (t, J=9.8 Hz, 1 H), 5.51 (dd, J.sub.1=9.8 Hz, J.sub.2=8.0 Hz, 1 H), 5.46-5.36 (m, 2 H), 5.26 (dd, J.sub.1=10.4 Hz, J.sub.2=8.0 Hz, 1 H), 5.20-5.12 (m, 2 H), 5.03 (dd, J.sub.1=10.4 Hz, J.sub.2=3.5 Hz, 1 H), 4.95 (d, J=7.8 Hz, 1 H), 4.62 (d, J=7.8 Hz, 1 H), 4.44-4.34 (m, 1 H), 4.25-3.97 (m, 5 H), 3.92 (t, J=6.5 Hz, 1 H), 3.79 (dd, J.sub.1=10.8 Hz, J.sub.2=7.5 Hz, 1 H), 2.110 (s, 3 H, Me), 2.107 (s, 3 H, Me), 2.01 (s, 3 H, Me), 1.98 (s, 3 H, Me), 2.18-1.85 (m, 1 H, CH), 1.79-1.57 (m, 5 H, CH.sub.22 and one proton of CH.sub.2), 1.34-0.95 (m, 5 H, CH.sub.22 and one proton of CH.sub.2); .sup.13C NMR (75 Hz, CDCl.sub.3) 204.1, 170.1, 170.0, 169.9, 169.2, 165.5, 165.1, 164.8, 133.4, 133.02, 132.98, 129.5, 129.4, 129.0, 128.5, 128.4, 128.3, 128.1, 128.0, 101.0, 99.2, 98.2, 88.2, 73.5, 72.8, 71.5, 70.7, 70.4, 69.5, 68.4, 68.2, 67.7, 66.8, 61.0, 36.4, 32.8, 32.5, 25.8, 25.7, 25.6, 20.6, 20.4, 20.33, 20.28; IR (neat) (cm.sup.1) 3066, 2927, 2852, 1959, 1740, 1602, 1451, 1370, 1281, 1255, 1218, 1177, 1090, 1069; MS (MALDI, m/z) 979 (M+Na.sup.+); Anal. Calcd. for C.sub.51H.sub.56O (%): C, 64.01; H, 5.90; Found: C, 64.04; H, 5.88.

EXAMPLE 17

(35) ##STR00019##

(36) To a flame-dried Schlenk tube with a polytetrafluoroethylene plug were added CuBr.sub.2 (44.7 mg, 0.2 mmol), (S)-3a (253.1 mg, 1.0 mmol), 1j (84.3 mg, 1.5 mmol)/dioxane (1.5 mL), and 2a (192.4 mg, 1.5 mmol)/dioxane (1.5 mL) sequentially under nitrogen atmosphere. The Schlenk tube was then sealed by screwing the polytetrafluoroethylene plug tightly with the outlet connected to the vacuum line with a nitrogen flow being closed. The reaction was complete after being stirred at 130 C. for 12 h as monitored by TLC (eluent: petroleum ether/ethyl acetate=10/1). Then the resulting mixture was diluted with ether (30 mL), and washed with an aqueous solution of hydrochloric acid (3 M, 20 mL). The organic layer was separated, and the aqueous layer was extracted with ether (20 mL). The combined organic layer was washed with brine and dried over anhydrous Na.sub.2SO.sub.4. After filtration and evaporation, the residue was purified by chromatography (eluent: petroleum ether/ethyl acetate=8/1) on silica gel to afford (R.sub.a)-4ja (86.8 mg, 52%) as a liquid: 95% ee (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH=98/2, 0.6 mL/min, =214 nm, t.sub.R(major)=10.9 min, t.sub.R(minor)=11.8 min); [].sub.D.sup.20=68.9 (c=1.01, CHCl.sub.3); (reported value: 97% ee; [].sub.D.sup.20=66.1 (c=1.03, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.37-5.24 (m, 2 H, CHCCH), 4.17-4.07 (m, 2 H, OCH.sub.2), 2.08-1.96 (m, 2 H, CH.sub.2), 1.57 (t, J=4.8 Hz, 1 H, OH), 1.48-1.20 (m, 10 H, CH.sub.25), 0.88 (t, J=6.8 Hz, 3 H, Me); .sup.13C NMR (75 MHz, CDCl.sub.3) 202.9, 94.0, 91.7, 60.8, 31.8, 29.08, 29.07, 29.0, 28.6, 22.6, 14.1; IR (neat) (cm.sup.1) 3336, 2956, 2926, 2855, 1963, 1465, 1376, 1013; MS (EI): m/z (%) 168 (M.sup.+, 0.04), 55 (100). (reference: J. Ye, W. Fan, S. Ma, Chem. Eur. J. 2013, 19, 716).

EXAMPLE 18

(37) ##STR00020##

(38) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 1j (84.6 mg, 1.5 mmol), (S)-3a (252.6 mg, 1.0 mmol), and 2h (150.2 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4jh (75.2 mg, 54%) (eluent: petroleum ether/ethyl acetate=8/1) as a liquid: 94% ee (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH=100/1, 0.5 mL/min, =214 nm, t.sub.R(major)=18.9 min, t.sub.R(minor)=20.0 min); [c].sub.D.sup.20=78.5 (c=1.11, CHCl.sub.3) (reported value: 98% ee; [].sub.D.sup.21=78.4 (c=1.03, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.36-5.23 (m, 2 H, CHCCH), 4.11 (dd, J.sub.1=5.6 Hz, J.sub.2=3.2 Hz, 2 H, OCH.sub.2), 2.08-1.96 (m, 2 H, CH.sub.2), 1.80 (s, 1 H, OH), 1.49-1.21 (m, 6 H, CH.sub.23), 0.89 (t, J=7.1 Hz, 3 H, Me); .sup.13C NMR (75 MHz, CDCl.sub.3) 203.0, 93.9, 91.6, 60.7, 31.2, 28.7, 28.6, 22.4, 14.0; IR (neat) (cm.sup.1) 3337, 2957, 2927, 2857, 1963, 1466; MS (EI): m/z (%) 122 ((MH.sub.2O).sup.+, 0.68), 55 (100). (reference: J. Ye, W. Fan, S. Ma, Chem. Eur. J. 2013, 19, 716).

EXAMPLE 19

(39) ##STR00021##

(40) Following the procedure of Example 17. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1j (84.2 mg, 1.5 mmol), (S)-3a (253.1 mg, 1.0 mmol), and 2c (201.4 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4jc (106.1 mg, 61%) (eluent: petroleum ether/ethyl acetate=8/1 to petroleum ether/ethyl acetate=5/1) as a liquid: 95% ee (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH=100/1, 1.0 mL/min, =214 nm, t.sub.R(major)=22.4 min, t.sub.R(minor)=24.4 min); [].sub.D.sup.20=38.0 (c=0.89, CHCl.sub.3) (reported value: 96% ee; [].sub.D.sup.2=38.7 (c=1.05, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.36-7.13 (m, 5 H, ArH), 5.35-5.21 (m, 2 H, CHCCH), 4.04-3.90 (m, 2 H, OCH.sub.2), 2.83-2.64 (m, 2 H, CH.sub.2), 2.46-2.24 (m, 2 H, CH.sub.2), 1.62 (s, 1 H, OH); .sup.13C NMR (75 MHz, CDCl.sub.3) 203.2, 141.4, 128.4, 128.2, 125.9, 92.9, 92.1, 60.4, 35.0, 29.9; IR (neat) (cm.sup.1) 3366, 3084, 3062, 3026, 2923, 2856, 1962, 1603, 1496, 1453, 1062, 1011; MS (EI) m/z (%): 174 (M.sup.+, 0.03), 156 ((MH.sub.2O).sup.+, 41.67), 91 (100). (reference: J. Ye, W. Fan, S. Ma, Chem. Eur. J. 2013, 19, 716).

EXAMPLE 20

(41) ##STR00022##

(42) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.6 mg, 0.2 mmol), 1j (84.5 mg, 1.5 mmol), (S)-3a (253.6 mg, 1.0 mmol), and 2d (129.5 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4jd (57.3 mg, 45%) (eluent: petroleum ether/ethyl acetate=8/1) as a liquid: 96% ee (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=200/1, 1.0 mL/min, =214 nm, t.sub.R(major)=18.7 min, t.sub.R(minor)=22.0 min); [].sub.D.sup.20=79.9 (c=0.955, CHCl.sub.3) (reported value: 98% ee; [].sub.D.sup.22=80.3 (c=1.01, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.35-5.19 (m, 2 H, CHCCH), 4.11 (dd, J.sub.1=5.9 Hz, J.sub.2=2.9 Hz, 2 H, OCH.sub.2), 1.97-1.89 (m, 2 H, CH.sub.2), 1.76-1.57 (m, 2 H, CH and OH), 0.93 (d, J=6.6 Hz, 6 H, Me2); .sup.13C NMR (75 MHz, CDCl.sub.3) 203.6, 92.3, 91.0, 60.8, 38.1, 28.4, 22.12, 22.10; IR (neat) (cm.sup.1) 3338, 2956, 2926, 2893, 2870, 1962, 1466, 1384, 1367, 1056, 1014; MS (EI) m/z (%): 126 (M.sup.+, 0.10), 108 ((MH.sub.2O).sup.+, 31.12), 55 (100). (reference: J. Ye, W. Fan, S. Ma, Chem. Eur J. 2013, 19, 716).

EXAMPLE 21

(43) ##STR00023##

(44) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.7 mg, 0.2 mmol), 1j (84.8 mg, 1.5 mmol), (5)-3a (252.2 mg, 1.0 mmol), and 2e (168.2 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4je (94.2 mg, 62%) (eluent: petroleum ether/ethyl acetate=8/1) as a liquid: 94% ee (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH=98/2, 0.6 mL/min, =214 nm, t.sub.R(major)=15.7 min, t.sub.R(minor)=18.6 min); [].sub.D.sup.20=98.1 (c=1.045, CHCl.sub.3) (reported value: 99% ee; [].sub.D.sup.22=100.3 (c=1.00, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.41-5.25 (m, 2 H, CHCCH), 4.10 (dd, J.sub.1=5.7 Hz, J.sub.2=3.0 Hz, 2 H, OCH.sub.2), 2.08-1.93 (m, 1 H, CH from Cy), 1.88-1.58 (m, 6 H, OH and five protons from Cy), 1.37-1.00 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 201.8, 99.9, 92.6, 60.8, 37.0, 33.0, 32.9, 26.0, 25.9; IR (neat) (cm.sup.1) 3331, 2924, 2851, 1961, 1448, 1412, 1011; MS (EI) m/z (%): 152 (M.sup.+, 0.38), 134 ((MH.sub.2O).sup.+, 6.78), 55 (100). (reference: J. Ye, W. Fan, S. Ma, Chem. Eur J. 2013, 19, 716).

EXAMPLE 22

(45) ##STR00024##

(46) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.7 mg, 0.2 mmol), 1k (126.8 mg, 1.5 mmol), (S)-3a (253.2 mg, 1.0 mmol), and 2e (168.6 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ke (89.3 mg, 50%) (eluent: petroleum ether/ethyl acetate=12/1) as a liquid: 97% ee (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=95/5, 0.6 mL/min, =214 nm, t.sub.R(major)=8.9 min, t.sub.R(minor)=10.2 min); [].sub.D.sup.20=99.2 (c=0.97, CHCl.sub.3) (reported value: 97% ee; [].sub.D.sup.20=99.5 (c=1.15, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.38-5.26 (m, 2 H, CHCCH), 2.07-1.92 (m, 1 H, CH from Cy), 1.84-1.59 (m, 6 H, OH and five protons from Cy), 1.34 (s, 6 H, Me2), 1.37-0.98 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 199.1, 102.1, 101.0, 69.5, 37.2, 33.02, 32.99, 30.0, 29.9, 26.03, 26.00; IR (neat) (cm.sup.1) 3358, 2974, 2925, 2851, 1960, 1448, 1373, 1361, 1228, 1149; MS (EI) m/z (%): 180 (M.sup.+, 0.29), 165 (MMe).sup.+, 3.81), 59 (100). (reference: J. Ye, S. Li, B. Chen, W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B. Wan, Y. Wang, X. Xie, Q. Yu, W. Yuan, S. Ma, Org. Lett. 2012, 14, 1346).

EXAMPLE 23

(47) ##STR00025##

(48) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 11 (186.8 mg, 1.5 mmol), (S)-3a (252.7 mg, 1.0 mmol), and 2e (168.2 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4le (115.6 mg, 53%) (eluent: petroleum ether/ethyl acetate=20/1) as a liquid: 98% ee (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=100/1, 0.5 mL/min, =214 nm, t.sub.R(major)=23.5 min, t.sub.R(minor)=26.2 min); [].sub.D.sup.20=106.6 (c=1.21, CHCl.sub.3) (reported value: 96% ee; [].sub.D.sup.20=108.6 (c=0.98, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.31 (d, J=4.2 Hz, 2 H, CHCCH), 2.08-1.90 (m, 1 H, CH from Cy), 1.87-1.40 (m, 15 H), 1.40-1.00 (m, 6 H); .sup.13C NMR (75 MHz, CDCl.sub.3) 199.9, 101.3, 100.8, 70.4, 38.4, 38.2, 37.2, 33.1, 33.0, 26.00, 25.97, 25.5, 22.4; IR (neat) (cm.sup.1) 3373, 2926, 2851, 1960, 1448, 1347, 1262, 1242, 1146, 1056, 1034; MS (EI) m/z (%): 220 (M.sup.+, 0.69), 99 (100). (reference: J. Ye, S. Li, B. Chen, W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B. Wan, Y. Wang, X. Xie, Q. Yu, W. Yuan, S. Ma, Org. Lett. 2012, 14, 1346).

EXAMPLE 24

(49) ##STR00026##

(50) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.7 mg, 0.2 mmol), (S)-1m (197.6 mg, 1.5 mmol), (S)-3a (252.7 mg, 1.0 mmol), and 2e (168.3 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (S,R.sub.a)-4me (152.0 mg, 67%) (eluent: petroleum ether/ethyl acetate=12/1) as a liquid: >99% de, >99% ee (major isomer) (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=98/2, 1.0 mL/min, =214 nm, t.sub.R(major)=19.4 min; [].sub.D.sup.20=69.7 (c=1.24, CHCl.sub.3) (reported value: 92% de, >99% ee; [].sub.D.sup.20=60.7 (c=1.02, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.42-7.21 (m, 5 H, ArH), 5.47-5.38 (m, 1 H, one proton from HCCCH), 5.38-5.30 (m, 1 H, one proton from HCCCH), 5.21 (d, J=5.4 Hz, 1 H, PhCH), 2.33 (s, 1 H, OH), 2.07-1.91 (m, 1 H, CH from Cy), 1.80-1.56 (m, 5 H, five protons from Cy), 1.35-0.96 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 201.2, 143.2, 128.3, 127.5, 126.0, 100.9, 96.9, 72.3, 37.1, 32.9, 26.0, 25.9; IR (neat) (cm.sup.1) 3365, 3063, 3029, 2924, 2850, 1960, 1599, 1489, 1449, 1015; MS (EI) m/z (%): 228 (M.sup.+, 2.53), 107 (100). (reference: J. Ye, S. Li, B. Chen, W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B. Wan, Y. Wang, X. Xie, Q. Yu, W. Yuan, S. Ma, Org. Lett. 2012, 14, 1346).

EXAMPLE 25

(51) ##STR00027##

(52) Following the procedure of Example 17. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), (R)-1m (198.5 mg, 1.5 mmol), (S)-3a (253.7 mg, 1.0 mmol), and 2e (168.1 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R,R.sub.a)-4me (133.3 mg, 58%) (eluent: petroleum ether/ethyl acetate=12/1) as a liquid: 98% de, >99% ee (major isomer) (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=98/2, 1.0 mL/min, =214 nm, t.sub.R(major)=11.1 min; [].sub.D.sup.20=52.6 (c=0.98, CHCl.sub.3) (reported value: 94% de, 97% ee; [].sub.D.sup.20=56.8 (c=0.98, CHCl.sub.3)); NMR (300 MHz, CDCl.sub.3) 7.40-7.29 (m, 4 H, ArH), 7.29-7.21 (m, 1 H, ArH), 5.47-5.38 (m, 1 H, one proton from HCCCH), 5.37-5.30 (m, 1 H, one proton from HCCCH), 5.18 (dd, J.sub.1=5.9 Hz, J.sub.2=2.6 Hz, 1 H. PhCH), 2.30 (s, 1 H, OH), 2.07-1.93 (m, 1 H, CH from Cy), 1.80-1.56 (m, 5 H, five protons from Cy), 1.36-0.98 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 200.9, 143.1, 128.3, 127.5, 126.1, 101.2, 97.0, 72.1, 37.1, 32.9, 26.0, 25.9; IR (neat) (cm.sup.1) 3373, 3063, 3029, 2924, 2850, 1961, 1599, 1493, 1449, 1014; MS (EI) m/z (%): 228 (M.sup.+, 2.17), 107 (100). (reference: J. Ye, S. Li, B. Chen, W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B. Wan, Y. Wang, X. Xie, Q. Yu, W. Yuan, S. Ma, Org. Lett. 2012, 14, 1346).

EXAMPLE 26

(53) ##STR00028##

(54) Following the procedure of Example 17. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), (S)-1m (198.2 mg, 1.5 mmol), (R)-3a (253.8 mg, 1.0 mmol), and 2e (167.9 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (S,S.sub.a)-4me (131.5 mg, 57%) (eluent: petroleum ether/ethyl acetate=12/1) as a liquid: 97% de, 99% ee (major isomer) (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=98/2, 1.0 mL/min, =214 nm, t.sub.R(minor)=11.7 min, t.sub.R(major)=16.1 min; [].sub.D.sup.20=+56.6 (c=1.34, CHCl.sub.3) (reported value: 89% de, >99% ee; [].sub.D.sup.20=+54.7 (c=1.17, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.41-7.21 (m, 5 H, ArH), 5.47-5.38 (m, 1 H, one proton from HCCCH), 5.37-5.30 (m, 1 H, one proton from HCCCH), 5.18 (dd, J.sub.1=5.7 Hz, J.sub.2=2.4 Hz, 1 H, PhCH), 2.33 (s, 1 H, OH), 2.08-1.93 (m, 1 H, CH from Cy), 1.80-1.56 (m, 5 H, five protons from Cy), 1.36-0.98 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 200.9, 143.1, 128.3, 127.5, 126.1, 101.2, 97.0, 72.1, 37.0, 32.9, 26.0, 25.9; IR (neat) (cm.sup.1) 3365, 3062, 3029, 2924, 2850, 1961, 1602, 1492, 1449, 1014; MS (EI) m/z (%): 228 (M.sup.+, 1.93), 107 (100). (reference: J. Ye, S. Li, B. Chen, W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B. Wan, Y. Wang, X. Xie, Q. Yu, W. Yuan, S. Ma, Org. Lett. 2012, 14, 1346).

EXAMPLE 27

(55) ##STR00029##

(56) Following the procedure of Example 17. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), (R)-1m (197.6 mg, 1.5 mmol), (R)-3a (254.0 mg, 1.0 mmol), and 2e (169.2 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R,S.sub.a)-4me (153.4 mg, 67%) (eluent: petroleum ether/ethyl acetate=12/1) as a liquid: 98% de, >99% ee (major isomer) (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=98/2, 1.0 mL/min, =214 nm, t.sub.R(major)=13.4 min; [].sub.D.sup.20=+73.0 (c=1.165, CHCl.sub.3) (reported value: 93% de, >99% ee; [].sub.D.sup.20=+60.8 (c=0.62, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.41-7.21 (m, 5 H, ArH), 5.47-5.38 (m, 1 H, one proton from HCCCH), 5.37-5.30 (m, 1 H, one proton from HCCCH), 5.19 (d, J=5.7 Hz, 1 H, PhCH), 2.40 (s, 1 H, OH), 2.07-1.91 (m, 1 H, CH from Cy), 1.80-1.56 (m, 5 H, five protons from Cy), 1.35-0.97 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 201.2, 143.2, 128.3, 127.5, 126.0, 100.8, 96.9, 72.3, 37.1, 32.87, 32.85, 26.0, 25.9; IR (neat) (cm.sup.1) 3358, 3062, 3029, 2924, 2850, 1961, 1602, 1493, 1449, 1015; MS (EI) m/z (%): 228 (M.sup.+, 2.23), 107 (100). (reference: J. Ye, S. Li, B. Chen, W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B. Wan, Y. Wang, X. Xie, Q. Yu, W. Yuan, S. Ma, Org. Lett. 2012, 14, 1346).

EXAMPLE 28

(57) ##STR00030##

(58) Following the procedure of Example 17. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1n (106.0 mg, 1.5 mmol), (S)-3a (252.6 mg, 1.0 mmol), and 2e (168.4 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4ne (83.5 mg, 50%) (eluent: petroleum ether/ethyl acetate=6/1) as a liquid: 96% ee (HPLC conditions: Chiralcel IC column, hexane/i-PrOH=100/1, 0.6 mL/min, =214 nm, t.sub.R(minor)=20.5 min, t.sub.R(major)=22.0 min); [].sub.D.sup.20=84.5 (c=1.095, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.18-5.07 (m, 2 H, CHCCH), 3.70 (t, J=6.3 Hz, 2 H, OCH.sub.2), 2.30-2.19 (m, 2 H, CH.sub.2), 2.05-1.89 (m, 1 H, CH from Cy), 1.89-1.57 (m, 6 H, OH and five protons from Cy), 1.37-0.98 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 203.4, 97.7, 88.0, 62.0, 37.1, 33.04, 33.02, 32.4, 26.1, 26.0; IR (neat) (cm.sup.1) 3340, 2924, 2851, 1961, 1448, 1049; MS (EI) m/z (%): 166 (M.sup.+, 6.05), 67 (100); HRMS calcd for C.sub.11H.sub.18O [M.sup.+]: 166.1358; Found: 166.1365.

EXAMPLE 29

(59) ##STR00031##

(60) Following the procedure of Example 17. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1o (313.4 mg, 1.5 mmol), (S)-3a (253.9 mg, 1.0 mmol), and 2e (167.8 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4oe (180.0 mg, 59%) (eluent: petroleum ether/ethyl acetate=5/1) as a liquid: 98% ee (HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH=95/5, 0.5 mL/min, =214 nm, t.sub.R(major)=34.1 min, t.sub.R(minor)=35.6 min); [].sub.D.sup.20=102.0 (c=1.05, CHCl.sub.3) (reported value: 99% ee; [].sub.D.sup.20=105.5 (c=1.07, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.80-7.72 (m, 2 H, ArH), 7.30 (d, J=7.8 Hz, 2 H, ArH), 5.21-5.12 (m, 1 H, one proton of CHCCH), 5.11-5.01 (m, 1 H, one proton of CHCCH), 4.85 (t, J=5.9 Hz, 1 H, NH), 3.60-3.50 (in, 2 H, NCH.sub.2), 2.42 (s, 3 H, CH.sub.3), 1.98-1.82 (m, 1 H, CH from Cy), 1.73-1.53 (m, 5 H, five protons from Cy), 1.32-0.89 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 202.3, 143.3, 137.0, 129.6, 127.0, 100.4, 88.4, 42.0, 36.7, 32.8, 32.7, 25.9, 25.8, 21.4; IR (neat) (cm.sup.1) 3284, 2924, 2850, 1962, 1598, 1495, 1418, 1329, 1161, 1094; MS (EI) m/z (%): 305 (M.sup.+, 1.14), 91 (100). (reference: J. Ye, W. Fan, S. Ma, Chem. Eur. J. 2013, 19, 716).

EXAMPLE 30

(61) ##STR00032##

(62) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 1p (238.4 mg, 1.5 mmol), (S)-3a (254.3 mg, 1.0 mmol), and 2d (129.9 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4pd (136.8 mg, 59%) (eluent: petroleum ether/ethyl acetate=5/1) as a liquid: 93% ee (HPLC conditions: Chiralcel AY-H column, hexane/i-PrOH=90/10, 1.0 mL/min, =214 nm, t.sub.R(major)=9.8 min, t.sub.R(minor)=11.2 min); [].sub.D.sup.20=92.5 (c=0.78, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.82-7.73 (m, 2 H, ArH), 7.51-7.35 (m, 3 H, ArH), 6.52 (bs, 1 H, NH), 5.30-5.19 (m, 2 H, CHCCH), 4.05-3.95 (m, 2 H, NCH.sub.2), 1.96-1.86 (m, 2 H, CH.sub.2), 1.73-1.55 (m, 1 H, CH), 0.894 (d, J=6.6 Hz, 3 H, Me), 0.891 (d, J=6.6 Hz, 3 H, Me); .sup.13C NMR (75 MHz, CDCl.sub.3) 203.8, 167.3, 134.5, 131.3, 128.4, 126.8, 92.9, 87.8, 38.5, 38.0, 28.3, 22.1, 22.0; IR (neat) (cm.sup.1) 3320, 3064, 2955, 2927, 2869, 1964, 1727, 1644, 1603, 1578, 1538, 1489, 1465, 1308, 1076; MS (EI) m/z (%): 229 (M.sup.+, 7.05), 105 (100); HRMS calcd for C.sub.15H.sub.19NO [M.sup.+]: 229.1467; Found: 229.1469.

EXAMPLE 31

(63) ##STR00033##

(64) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), 1q (232.8 mg, 1.5 mmol), (S)-3a (253.2 mg, 1.0 mmol), and 2i (150.6 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4qi (160.3 mg, 67%) (eluent: petroleum ether/ethyl acetate=50/1 to petroleum ether/ethyl acetate=20/1) as a liquid: 96% ee (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=100/0, 1.0 mL/min, =214 nm, t.sub.R(minor)=19.7 min, t.sub.R(major)=20.4 min); [].sub.D.sup.20=63.5 (c=1.055, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.22-5.12 (m, 1 H, one proton of CHCCH), 5.11-5.03 (m, 1 H, one proton of CHCCH), 4.71 (bs, 1 H, NH), 3.77-3.63 (m, 2 H, NCH.sub.2), 1.93-1.78 (m, 1 H, CH), 1.53-1.21 (m, 13 H, Me2 and CH.sub.22), 0.90 (t, J=7.4 Hz, 3 H, Me), 0.89 (t, J=7.4 Hz, 3 H, Me); .sup.13C NMR (75 MHz, CDCl.sub.3) 203.0, 155.6, 97.7, 89.0, 79.1, 42.7, 39.3, 28.3, 27.5, 27.2, 11.6, 11.4; IR (neat) (cm.sup.1) 3351, 2965, 2931, 2875, 1963, 1698, 1505, 1456, 1392, 1366, 1250, 1172, 1053; MS (EI) m/z (%): 239 (M.sup.+, 0.01), 183 ((M.sup.tBu+H).sup.+, 45.91), 57 (100); HRMS calcd for C.sub.14H.sub.25NO.sub.2 [M.sup.+]: 239.1885; Found: 239.1878.

EXAMPLE 32

(65) ##STR00034##

(66) Following the procedure of Example 17. The reaction of CuBr.sub.2 (45.0 mg, 0.2 mmol), 1r (255.7 mg, 1.5 mmol), (5)-3a (252.5 mg, 1.0 mmol), and 2d (129.6 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4rd (121.9 mg, 51%) (eluent: petroleum ether/ethyl acetate=20/1) as a liquid: 94% ee (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=100/1, 0.7 mL/min, =214 nm, t.sub.R(minor)=10.9 min, t.sub.R(major)=11.7 min); [].sub.D.sup.20=64.4 (c=0.87, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.15-5.04 (m, 2 H, CHCCH), 3.74 (s, 6 H, Me2), 3.51 (t, J=7.5 Hz, 1 H, CFI), 2.62-2.54 (m, 2 H, CH.sub.2), 1.90-1.82 (m, 2 H, CH.sub.2), 1.72-1.56 (m, 1 H, CH), 0.910 (d, J=6.6 Hz, 3 H, Me), 0.906 (d, J=6.6 Hz, 3 H, Me); .sup.13C NMR (75 MHz, CDCl.sub.3) 204.6, 169.3, 169.2, 91.3, 86.6, 52.4, 51.3, 38.2, 28.3, 28.0, 22.09, 22.06; IR (neat) (cm.sup.1) 2956, 2927, 2869, 1964, 1754, 1739, 1436, 1342, 1271, 1232, 1154, 1044; MS (EI) m/z (%): 240 (M.sup.+, 27.06), 97 (100); HRMS calcd for C.sub.13H.sub.20O.sub.4 [M.sup.+]: 240.1362; Found: 240.1362.

EXAMPLE 33

(67) ##STR00035##

(68) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.8 mg, 0.2 mmol), 1r (255.7 mg, 1.5 mmol), (5)-3a (252.8 mg, 1.0 mmol), and 2e (168.2 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4re (135.7 mg, 51%) (eluent: petroleum ether/ethyl acetate=15/1) as a liquid: 95% ee (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=100/1, 1.0 mL/min, =214 nm, t.sub.R(minor)=9.0 min, t.sub.R(major)=9.6 min); [].sub.D.sup.20=84.0 (c=1.045, CHCl.sub.3) (reported value: 99% ee; [].sub.D.sup.20=85.4 (c=1.05, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 5.20-5.08 (m, 2 H, CHCCH), 3.740 (s, 3 H, Me), 3.737 (s, 3 H, Me), 3.51 (t, J=7.5 Hz, 1 H, CH), 2.63-2.54 (m, 2 H, CH.sub.2), 2.00-1.85 (m, 1 H, CH from Cy), 1.78-1.57 (m, 5 H, five protons from Cy), 1.35-0.95 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 202.7, 169.33, 169.29, 98.9, 88.2, 52.4, 51.2, 37.1, 32.82, 32.78, 28.0, 26.0, 25.9; IR (neat) (cm.sup.1) 2926, 2851, 1959, 1757, 1738, 1617, 1436, 1343, 1233, 1155, 1035; MS (EI) m/z (%): 266 (M.sup.+, 6.72), 91 (100). (reference: J. Ye, W. Fan, S. Ma, Chem. Eur. J. 2013, 19, 716).

EXAMPLE 34

(69) ##STR00036##

(70) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.9 mg, 0.2 mmol), is (207.8 mg, 1.5 mmol), (S)-3a (253.4 mg, 1.0 mmol), and 2c (201.5 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4sc (119.3 mg, 47%) (eluent: petroleum ether) as a liquid: 90% ee (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=100/0, 0.3 mL/min, =214 nm, t.sub.R(minor)=17.9 min, t.sub.R(major)=19.7 min); [].sub.D.sup.20=50.0 (c=0.84, CHCl.sub.3); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.30-7.21 (m, 2 H, ArH), 7.21-7.12 (m, 3 H, ArH), 5.16-5.02 (m, 2 H, CHCCH), 2.72 (t, J=7.8 Hz, 2 H, CH.sub.2), 2.35-2.20 (m, 2 H, CH.sub.2), 1.99-1.87 (m, 2H, CH.sub.2), 1.42-1.18 (m, 12 H, CH.sub.26), 0.88 (t, J=6.8 Hz, 3H, Me); .sup.13C NMR (75 MHz, CDCl.sub.3) 204.0, 141.9, 128.5, 128.2, 125.8, 91.5, 90.2, 35.5, 31.9, 30.7, 29.4, 29.3, 29.2, 29.1, 28.9, 22.7, 14.1; IR (neat) (cm.sup.1) 3086, 3063, 3027, 2924, 2854, 1962, 1721, 1604, 1496, 1455, 1373, 1331, 1284, 1075, 1028; MS (EI) m/z (%): 256 (M.sup.+, 12.85), 91 (100); HRMS calcd for C.sub.19H.sub.28 [M.sup.+]: 256.2191, found: 256.2194.

EXAMPLE 35

(71) ##STR00037##

(72) Following the procedure of Example 17. The reaction of CuBr.sub.2 (44.8 mg, 0.2 mmol), 1t (153.2 mg, 1.5 mmol), (S)-3a (253.1 mg, 1.0 mmol), and 2e (168.4 mg, 1.5 mmol) in dioxane (3.0 mL) afforded (R.sub.a)-4te (90.1 mg, 46%) (eluent: petroleum ether) as a liquid: 96% ee (HPLC conditions: Chiralcel OD-H column, hexane/i-PrOH=100/0, 0.3 mL/min, =214 nm, t.sub.R(major)=20.1 min, t.sub.R(minor)=22.1 min); [].sub.D.sup.20=355.3 (c=1.01, CHCl.sub.3) (reported value: 99% ee; [].sub.D.sup.19=330.3 (c=0.94, CHCl.sub.3)) (The results we repeated the reaction in ref. 3: 99% ee; [].sub.D.sup.20=379.0 (c=1.125, CHCl.sub.3)); .sup.1H NMR (300 MHz, CDCl.sub.3) 7.32-7.23 (m, 4 H, ArH), 7.21-7.11 (m, 1 H, ArH), 6.15 (dd, J.sub.1=6.6 Hz, J.sub.2=3.0 Hz, 1 H, one proton from CHCCH), 5.56 (t, J=6.3 Hz, 1 H, one proton from CHCCH), 2.20-2.04 (m, 1 H, CH), 1.90-1.57 (m, 5 H, five protons from Cy), 1.38-1.09 (m, 5 H, five protons from Cy); .sup.13C NMR (75 MHz, CDCl.sub.3) 204.1, 135.2, 128.5, 126.6, 126.4, 101.0, 95.4, 37.6, 33.2, 33.1, 26.1, 26.0; IR (neat) (cm.sup.1) 3082, 3062, 3030, 2924, 2851, 1946, 1597, 1496, 1458, 1257, 1071, 1028; MS (EI) m/z (%): 198 (M.sup.+, 30.22), 130 (100). (reference: R. L, J. Ye, T. Cao, B. Chen, W. Fan, W. Lin, J. Liu, H. Luo, B. Miao, S. Ni, X. Tang, N. Wang, Y. Wang, X. Xie, Q. Yu, W. Yuan, W. Zhang, C. Zhu, S. Ma, Org. Lett. 2013, 15, 2254).

(73) Finally, it should be noted that the above mentioned is just only some specific examples of the present invention. Obviously, the present invention is not limited to the above examples, which can have many variations. All the modifications derived directly or envisaged by a person skilled in the art from the disclosure of the present invention shall fall within the scope of the present invention.