MARKOVNIKOV-SELECTIVE PALLADIUM CATALYST FOR CARBONYLATION OF ALKYNES WITH HETEROARENES

Abstract

Markovnikov-selective palladium catalyst for carbonylation of alkynes with heteroarenes.

Claims

1. Compound having the structure (1): ##STR00022##

2. Use of a compound according to claim 1, for catalysing a carbonylation reaction.

3. A process comprising the following process steps: a) initially charging an alkyne, b) adding a compound according to claim 1 and a substance including Pd, c) feeding in N-methylpyrrole and CO, d) heating the reaction mixture, with conversion of the alkyne to the product.

Description

[0017] The invention is illustrated in detail hereinafter by working examples.

[0018] Ligand Synthesis

##STR00002##

##STR00003##

Synthesis of N,N-dipyrrolylmethane

[0019] Pyrrole (9.00 ml, 130 mmol) was added to a stirred suspension of powdered potassium hydroxide (24 g, 0.43 mol, 3.31 equiv.) in DMSO (100 ml) at room temperature. After 1 h, the mixture was heated to 40 C. and DCM (6.32 ml, 98.6 mmol, 0.76 equiv.) was added slowly. The solution was heated at 40 C. for a further 4 h. Once cool, ether (100 ml) and water (100 ml) were added and the layers separated. The aqueous layer was extracted with ether three times, the combined organic extracts were washed with water three times, then brine, and dried with MgSO.sub.4 and the solvent removed under reduced pressure to afford a pale yellow solid. Recrystallisation from chloroform gave 1,2-di(pyrrol-1-yl)methane in 72% yield.

Synthesis of N, N-diimidazolmethane

Analogues to N,N-dipyrrolylmethane

[0020] Synthesis of (1) and (2):

[0021] In a three nacked 100 ml round bottom flask, N, N-dipyrrolylmethane (5 mmol) was dissolved in 15 ml of freshly distilled Et.sub.2O under argon. TMEDA (15 mmol) was added followed by n-BuLi (10.5 mmol, 1.6 M in hexane) at room temperature. The reaction mixture was stirring for 1 h at room temperature, a yellow suspension was obtained. Then the yellow suspension was slowly added via syringe to a solution of CIPR.sub.2 (10 mmol in 15 ml Et.sub.2O, R=Ph or Cy). The mixture was further stirring for 1 h, then degassed water (10 ml) was added and the mixture was stirred to get a clear solution. The aqueous layer was extracted with Et.sub.2O (215 ml) and the combined organic layers were washed with degassed water (10 ml). The solution was dried over Na.sub.2SO.sub.4 and concentrated to get a yellow viscous liquid which was recrystallized from ethanol. For yield and characterizations please see below.

[0022] Characterizations:

##STR00004##

[0023] 1.0 g, 39% yield (5 mmol scale, 97% purity), white solid.

[0024] .sup.1H NMR (300 MHz, CD.sub.2Cl.sub.2) 7.23-7.18 (m, 20H), 6.85-6.83 (m, 2H), 6.17 (t, J=2.8 Hz, 2H), 6.00 (dd, J=3.6, 2.8 Hz, 2H), 5.83 (dd, J=3.6, 1.6 Hz, 2H);

[0025] .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2) 137.1, 133.7, 129.1, 128.9, 127.8, 125.7, 119.8, 110.5, 58.1

[0026] .sup.31P NMR (122 MHz, CD.sub.2Cl.sub.2) 33.0.

[0027] HRMS (ESI) [C.sub.33H.sub.52N.sub.2P.sub.2+H].sup.+ calculated mass 539.36785, measured mass 539.36811.

##STR00005##

[0028] 0.54 g, 20% yield (5 mmol scale, 95% purity), off white solid.

[0029] .sup.1H NMR (300 MHz, d.sup.8-Toluene) 7.18-7.15 (m, 2H), 6.53-6.51 (m, 2H), 6.40-6.38 (m, 2H), 6.31-6.29 (m, 2H), 1.86-1.56 (m, 24H), 1.25-1.06 (m, 20H);

[0030] .sup.13C NMR (75 MHz, d.sup.8-Toluene) 126.1, 124.3, 1161, 109.6, 57.0, 34.2, 30.4, 29.1, 27.

[0031] .sup.31P NMR (122 MHz, d.sup.8-Toluene) 31.0.

[0032] HRMS (ESI) [C.sub.33H.sub.52N.sub.2P.sub.2+H].sup.+ calculated mass 539.36785, measured mass 539.36811.

[0033] Synthesis of (3):

##STR00006##

[0034] analogues to (1) and (2)

[0035] Catalyst Experiments

##STR00007##

[0036] Catalyst Results

[0037] The results of the catalyst experiments are summarized in Tables 1;

TABLE-US-00001 TABLE 1 p Pd(acac).sub.2 Yield Ligand (bar) T ( C.) t (h) (mol) (%) 1* 40 70 12 2 88 2 40 70 12 2 0 3 40 70 12 2 0 *inventive compound alkyne = 1-octyne

[0038] Reaction conditions: (Ia) (1.0 mmol), (IIa) (0.5 mmol), Pd(acac).sub.2 (2.0 mol %), Ligand (4.0 mol %), p-TsOH (10.0 mol %), CO (40 bar), Toluene (1.0 mL), 70 C., 12 h.

[0039] Further results of carbonylation experiments with different alkynes (I) are summarized in Table 2:

TABLE-US-00002 TABLE 2 [00008] [00009] [00010] [00011] [00012] [00013] [00014] [00015] [00016] [00017] [00018] [00019] [00020] [00021]

[0040] Reaction condition: alkyne (I) (1.0 mmol), N-methylpyrrole (II) (0.5 mmol), Pd(acac).sub.2 (1.0 mol %), (1) (2.0 mol %), p-TsOH (5.0 mol %), CO (40 bar), Toluene (1.0 mL), 70 C., 12 h.

[0041] In each case, the yield of isolated compound (III) is given, and the number in the parenthesis indicates the (III/III) ratio determined by GC analysis.

[0042] [a] Reaction at 90 C.

[0043] [b] Reaction at 100 C. for 20 h,

[0044] [c] Reaction at 90 C. for 20 h.

[0045] It was shown on the basis of the experiments described above that the stated problem has been solved by the inventive compounds.