Chiral phosphoramidimidates and derivatives thereof

Abstract

The present invention relates to chiral phosphoramidimidates, their salts and metal complexes as well as derivatives thereof and their use as catalysts.

Claims

1. A chiral phosphoramidimidate having the general formula (I): ##STR00089## or a tautomeric and/or ionic form thereof, wherein: X represents O, S, Se or NR.sup.N, Z.sup.1 to Z.sup.4 are, independently from each other, the same or different and represent O, S, Se or NR.sup.N, n stands for 0 or 1, W is selected from hydrogen, halogen, a metal selected from Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ru, Rh, Pd, Ag, W, Re, Os, Ir, Pt, Au, Al, Pb, La, Sm, Eu, Yb, or U, or a cationic organic group, or a substituted silicon —SiR.sup.IR.sup.IIR.sup.III, wherein R.sup.I, R.sup.II and R.sup.III are the same or different and each stands for hydrogen, halogen, C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbon or a partially arene-hydrogenated form thereof, aryl-(C.sub.1-C.sub.6)-alkyl, or heteroaryl-(C.sub.1-C.sub.6)-alkyl, each said aliphatic hydrocarbon, heterocycloalkyl, aromatic hydrocarbon or partially arene-hydrogenated form thereof, arylalkyl, or heteroaryl-alkyl optionally being substituted on a hydrocarbyl portion thereof by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons or partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, heteroaryl-(C.sub.1-C.sub.6)-alkyl, or heterosubstituents, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are, independently from each other, the same or different and are each an aliphatic, heteroaliphatic, aromatic or heteroaromatic hydrocarbon group, each optionally being further substituted by one or more heterosubstituents, or aliphatic, heteroaliphatic, aromatic or heteroaromatic hydrocarbon groups, whereby R.sup.1 may form a ring system with any one of R.sup.2, R.sup.3 or R.sup.4 and the other two of R.sup.2, R.sup.3 or R.sup.4 may form a ring system with each other; and R.sup.N is an electron withdrawing group, being the same or different on each N and being selected from: i. -alkyl, —CO-alkyl, —(CO)—O-alkyl, sulfinyl alkyl, sulfonyl alkyl, or —(P═O)-dialkyl, wherein alkyl is a C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon having at least one halogen substituent on the alkyl residue; ii. aryl, —CO-aryl, —(CO)—O-aryl, sulfinyl aryl, sulfonyl aryl, or —(P═O)-diaryl, wherein aryl is a C.sub.6 to C.sub.18 aromatic hydrocarbon, optionally having at least one halogen substituent on the aryl residue; iii. heteroaryl, —CO-heteroaryl, —(CO)—O-heteroaryl, sulfinyl heteroaryl, sulfonyl heteroaryl, or —(P═O)-di-heteroaryl, wherein heteroaryl is a C.sub.2 to C.sub.20 aromatic hydrocarbon having one or more heteroatoms, and wherein the heteroaryl optionally has at least one halogen substituent on the heteroaryl residue; or in the case that X represents NR.sup.N, one R.sup.N may be bridging the two P═N— units to form a ring represented by formula: ##STR00090## wherein R.sup.N1 represents —(SO)—, —(SO.sub.2)— or —(NR.sup.N2)— wherein R.sup.N2 is an electron withdrawing group being selected from -alkyl, —CO-alkyl, or —(CO)—O-alkyl, wherein alkyl is a C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon having at least one halogen substituent on the alkyl residue.

2. A chiral phosphoramidimidate according to claim 1, wherein in formula (I), Z.sup.1 to Z.sup.4 independently represent O, S or NR.sup.N, n is 1, and X, R.sup.1 to R.sup.4, R.sup.N as well as W are as defined in claim 1, as represented by formula (II): ##STR00091##

3. A chiral phosphoramidimidate according to claim 1, wherein at least one moiety ##STR00092## forms a five to ten-membered ring structure, whereby R.sup.1 and R.sup.2 together are forming a ring system with Z.sup.1 and Z.sup.2 and/or whereby R.sup.3 and R.sup.4 together are forming a ring system with Z.sup.3 and Z.sup.4, wherein R.sup.1 to R.sup.4, Z.sup.1 to Z.sup.4, n, R.sup.N, and X are as defined in claim 1.

4. A chiral phosphoramidimidate according to claim 1, which has the formula (IIIa): ##STR00093## wherein R.sup.1 to R.sup.4 and W are as defined in claim 1, and wherein R.sup.N1 represents —(SO)—, —(SO.sub.2)— or —(NR.sup.N2)— wherein R.sup.N2 is an electron withdrawing group being selected from -alkyl, —CO-alkyl, or —(CO)—O-alkyl, wherein alkyl is a C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon having at least one halogen substituent on the alkyl residue.

5. A chiral phosphoramidimidate according to claim 1, wherein, in formula (I), Z.sup.1 to Z.sup.4 represent O, and R.sup.1 to R.sup.4, X as well as W are as defined in claim 1, and n=1, said phosphoramidimidate having the formula (IIIb): ##STR00094## wherein R.sup.N is an electron withdrawing group as defined in claim 1.

6. A chiral phosphoramidimidate according to claim 1, wherein (R.sup.1, R.sup.2, Z.sup.1.sub.n and Z.sup.2.sub.n) and (R.sup.3, R.sup.4, Z.sup.3.sub.n and Z.sup.4.sub.n), respectively are as defined in claim 1 and each form a ring structure which may be the same or different and is derived from a bridged, optionally dimeric, aromatic structure selected from biphenyl optionally substituted, BINOL, TADDOL, VAPOL, SPINOL, 1,1′-binaphthalene, 1,1′-bianthracene, 1,1-biphenanthrene, or a partially arene-hydrogenated form of said aromatic ring structures including 8H-BINOL, each of said ring systems optionally being substituted by one or more substituents which may be the same or different on each position and are each selected from hydrogen, heterosubstituents, C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbon or a partially arene-hydrogenated form thereof, aryl-(C.sub.1-C.sub.6)-alkyl, or heteroaryl-(C.sub.1-C.sub.6)-alkyl each said aliphatic hydrocarbon, heterocycloalkyl, aromatic hydrocarbon or partially arene-hydrogenated form thereof, arylalkyl, or heteroaryl-alkyl optionally being substituted by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons and partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, heteroaryl-(C.sub.1-C.sub.6)-alkyl, or a heterosubstituent, wherein n, R.sup.N, X and W are as defined in claim 1, or a tautomeric and/or ionic form thereof, wherein the ring structure formed by (R.sup.1, R.sup.2, Z.sup.1 and Z.sup.2) and (R.sup.3, R.sup.4, Z.sup.3 and Z.sup.4) may be the same or different and is chiral.

7. A chiral phosphoramidimidate according to claim 6, wherein the compound of formula (I) has the formula (IV): ##STR00095## wherein in said formula (IV), the substituent R may be same or different on each position and is each selected from hydrogen, heterosubstituents, C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons and partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, or heteroaryl-(C.sub.1-C.sub.6)-alkyl, and each said aliphatic hydrocarbon, heterocycloalkyl, aromatic hydrocarbon or partially arene-hydrogenated form thereof, arylalkyl, or heteroaryl-alkyl optionally being substituted by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons and partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, heteroaryl-(C.sub.1-C.sub.6)-alkyl, or a heterosubstituent, and R.sup.N, X and W are as defined in claim 1, or a tautomeric and/or ionic form thereof.

8. A chiral phosphoramidimidate according to claim 1, wherein at least one of said ring structures optionally formed by (R.sup.1, R.sup.2, Z.sup.1 and Z.sup.2) and (R.sup.3, R.sup.4, Z.sup.3 and Z.sup.4) respectively is chiral.

9. A chiral phosphoramidimidate according to claim 1, wherein the ring structures optionally formed by (R.sup.1, R.sup.2, Z.sup.1 and Z.sup.2) and (R.sup.3, R.sup.4, Z.sup.3 and Z.sup.4), respectively, are identical.

10. A chiral phosphoramidimidate according to claim 1, which has the following formula (IVa): ##STR00096## wherein the substituent R may be the same or different on each position and is each selected from hydrogen, heterosubstituents, C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons and partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, or heteroaryl-(C.sub.1-C.sub.6)-alkyl, and each said aliphatic hydrocarbon, heterocycloalkyl, aromatic hydrocarbon or partially arene-hydrogenated form thereof, arylalkyl, or heteroaryl-alkyl optionally being substituted by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons and partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, heteroaryl-(C.sub.1-C.sub.6)-alkyl, or a heterosubstituent, R.sup.N, X and W have the meaning as defined in claim 1, or a tautomeric and/or ionic form thereof.

11. A chiral phosphoramidimidate according to claim 1, which has the following formula (IVb): ##STR00097## wherein the substituent R may be the same or different on each position and each is selected from hydrogen, heterosubstituents, C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons and partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, or heteroaryl-(C.sub.1-C.sub.6)-alkyl, and each said aliphatic hydrocarbon, heterocycloalkyl, aromatic hydrocarbon or partially arene-hydrogenated form thereof, arylalkyl, or heteroaryl-alkyl optionally being substituted by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons and partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, heteroaryl-(C.sub.1-C.sub.6)-alkyl, or a heterosubstituent; X represents O, S, Se or NR.sup.N, and W is as defined in claim 1; or a tautomeric and/or ionic form thereof.

12. A chiral phosphoramidimidate according to claim 1, wherein W is hydrogen.

13. Method of using a chiral phosphoramidimidate of the formula (I) as defined in claim 1 wherein W is H as a chiral Brønsted acid catalyst in organic synthesis.

14. Method of using a chiral phosphoramidimidate of the formula (I) as defined in claim 1 wherein W is a metal or the phosphoramidimidate of formula (I) is anionic as a chiral anion in phase-transfer catalysis, or as chiral anion for organic salts, metal salts or metal complexes as catalysts.

15. Method of using a chiral phosphoramidimidate of the formula (I) as defined in claim 1 as a chiral catalyst in a synthetic reaction in organic synthesis, wherein the synthetic reaction is selected from aldol reactions, vinylogous aldol reactions, Mukaiyama aldol reactions, vinylogous Mukaiyama aldol reactions, Mukaiyama-Michael reactions, Michael additions, Mannich reactions, TMSCN additions onto aldehydes, TMSCN additions onto ketones, TMSCN additions onto imines, esterifications, etherifications, pinacol rearrangements, acetalizations, transacetalization, spiroacetalization, cycloadditions, hydroaminations, hydroalkoxylation, hydrations, haloalkoxylation, haloamination, olefin activations in general including ene-reactions and Prins reactions, Friedel-Crafts reactions, epoxide openings, Ritter reactions, nucleophilic substitutions of alcohols, asymmetric ring openings, asymmetric reductions, transfer hydrogenations, alkyne additions, imine additions, Strecker reactions, allylations, propargylations, reductions, epoxidations, olefin metathesis, isomerizations, Diels-Alder reactions, hetero-Diels-Alder reactions, aminalizations, iminium catalysis and enamine catalysis.

16. A chiral phosphoramidimidate having the general formula (I): ##STR00098## or a tautomeric and/or ionic form thereof, wherein: X represents O, S, Se or NR.sup.N, Z.sup.1 to Z.sup.4 may be, independently from each other, the same or different and represent O, S, Se and NR.sup.N, n stands for 0 or 1, W is selected from hydrogen, halogen, a metal selected from Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ru, Rh, Pd, Ag, W, Re, Os, Ir, Pt, Au, Al, Pb, La, Sm, Eu, Yb, or U, or a cationic organic group, or a substituted silicon —SiR.sup.IR.sup.IIR.sup.III, wherein R.sup.I, R.sup.II and R.sup.III are the same or different and each stands for hydrogen, halogen, C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbon or a partially arene-hydrogenated form thereof, aryl-(C.sub.1-C.sub.6)-alkyl, or heteroaryl-(C.sub.1-C.sub.6)-alkyl, each said aliphatic hydrocarbon, heterocycloalkyl, aromatic hydrocarbon or partially arene-hydrogenated form thereof, arylalkyl, or heteroaryl-alkyl optionally being substituted on a hydrocarbyl portion thereof by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons or partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, heteroaryl-(C.sub.1-C.sub.6)-alkyl, or heterosubstituents, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be, independently from each other, the same or different and are each an aliphatic, heteroaliphatic, aromatic or heteroaromatic hydrocarbon group, each optionally being further substituted by one or more heterosubstituents, or aliphatic, heteroaliphatic, aromatic or heteroaromatic hydrocarbon groups, whereby R.sup.1 may form a ring system with any one of R.sup.2, R.sup.3 or R.sup.4 and the other two of R.sup.2, R.sup.3 or R.sup.4 may form a ring system with each other; and R.sup.N is an electron withdrawing group, being the same or different on each N and being selected from: i. -alkyl, —CO-alkyl, —(CO)—O-alkyl, sulfinyl alkyl, sulfonyl alkyl, or —(P═O)-dialkyl, wherein alkyl is a C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon having at least one halogen substituent on the alkyl residue; ii. aryl, —CO-aryl, —(CO)—O-aryl, sulfinyl aryl, sulfonyl aryl, or —(P═O)-diaryl, wherein aryl is a C.sub.6 to C.sub.18 aromatic hydrocarbon, optionally having at least one halogen substituent on the aryl residue; iii. heteroaryl, —CO-heteroaryl, —(CO)—O-heteroaryl, sulfinyl heteroaryl, sulfonyl heteroaryl, or —(P═O)-di-heteroaryl, wherein heteroaryl is a C.sub.2 to C.sub.20 aromatic hydrocarbon having one or more heteroatoms, and wherein the heteroaryl optionally has at least one halogen substituent on the heteroaryl residue; or in the case that X represents NR.sup.N, one R.sup.N may be bridging the two P═N— units to form a ring represented by formula: ##STR00099## wherein R.sup.N1 represents —(SO)—, —(SO.sub.2)— or —(NR.sup.N2)— wherein R.sup.N2 is an electron withdrawing group being selected from -alkyl, —CO-alkyl, or —(CO)—O-alkyl, wherein alkyl is a C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon having at least one halogen substituent on the alkyl residue.

17. A chiral phosphoramidimidate having the general formula (I): ##STR00100## or a tautomeric and/or ionic form thereof, wherein: X represents O, S, Se or NR.sup.N, Z.sup.1 to Z.sup.4 are, independently from each other, the same or different and represent O, S, Se or NR.sup.N, n stands for 0 or 1, W is selected from hydrogen, halogen, a metal selected from Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ru, Rh, Pd, Ag, W, Re, Os, Ir, Pt, Au, Al, Pb, La, Sm, Eu, Yb, or U, or a cationic organic group, or a substituted silicon —SiR.sup.IR.sup.IIR.sup.III, wherein R.sup.I, R.sup.II and R.sup.III are the same or different and each stands for hydrogen, halogen, C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbon or a partially arene-hydrogenated form thereof, aryl-(C.sub.1-C.sub.6)-alkyl, or heteroaryl-(C.sub.1-C.sub.6)-alkyl, each said aliphatic hydrocarbon, heterocycloalkyl, aromatic hydrocarbon or partially arene-hydrogenated form thereof, arylalkyl, or heteroaryl-alkyl optionally being substituted on a hydrocarbyl portion thereof by one or more groups selected from C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbons, optionally having one or more unsaturated bonds, C.sub.3-C.sub.8-heterocycloalkyl, C.sub.6 to C.sub.20 aromatic hydrocarbons or partially arene-hydrogenated forms thereof, aryl-(C.sub.1-C.sub.6)-alkyl, heteroaryl-(C.sub.1-C.sub.6)-alkyl, or heterosubstituents, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are, independently from each other, the same or different and are each an aliphatic, heteroaliphatic, aromatic or heteroaromatic hydrocarbon group, each optionally being further substituted by one or more heterosubstituents, or aliphatic, heteroaliphatic, aromatic or heteroaromatic hydrocarbon groups, whereby R.sup.1 may form a ring system with any one of R.sup.2, R.sup.3 or R.sup.4 and the other two of R.sup.2, R.sup.3 or R.sup.4 may form a ring system with each other; and R.sup.N is an electron withdrawing group, being the same or different on each N and being selected from: i. sulfinyl alkyl, or sulfonyl alkyl, wherein alkyl is a C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon having at least one halogen substituent on the alkyl residue; ii. sulfinyl aryl, or sulfonyl aryl, wherein aryl is a C.sub.6 to C.sub.18 aromatic hydrocarbon having at least one halogen substituent on the aryl residue; iii. sulfinyl heteroaryl, or sulfonyl heteroaryl, wherein heteroaryl is a C.sub.2 to C.sub.20 aromatic hydrocarbon having one or more heteroatoms, and wherein the heteroaryl has at least one halogen substituent on the heteroaryl residue; or in the case that X represents NR.sup.N, one R.sup.N may be bridging the two P═N— units to form a ring represented by formula: ##STR00101## wherein R.sup.N1 represents —(SO)—, —(SO.sub.2)— or —(NR.sup.N2)— wherein R.sup.N2 is an electron withdrawing group being selected from -alkyl, —CO-alkyl, or —(CO)—O-alkyl, wherein alkyl is a C.sub.1 to C.sub.20 straight chain, branched chain or cyclic aliphatic hydrocarbon having at least one halogen substituent on the alkyl residue.

18. Process for preparing a chiral phosphoramidimidate of the general formula (I) according to claim 1, said process comprising the steps of: (a) reacting a compound of the general formulae (V) with a compound of the formula (VI) in the presence of a basic compound in an organic solvent to yield a compound of the formula (VII) as follows: ##STR00102## (b) oxidizing compound (VII) to yield compound (VIII) as follows: ##STR00103## and (c) removing leaving group L.sup.3 from compound (VIII) to yield a compound of the general formula (I) as follows: ##STR00104## wherein in said formulae (V), (VI), (VII), (VIII) and (I): L.sup.1 is a electropositive leaving group and is selected from hydrogen, a metal selected from Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ru, Rh, Pd, Ag, W, Re, Os, Ir, Pt, Au, Al, Pb, La, Sm, Eu, Yb, or U, or a cationic organic group, or a substituted silicon —SiR.sup.IR.sup.IIR.sup.III, wherein R.sup.I, R.sup.II and R.sup.III may be same or different and are as defined in claim 1; L.sup.2 is an electronegative leaving group selected from halogen, alkoxy, aryloxy, heteroaryloxy, sulfonyl, or heteroaryl; L.sup.3 is a leaving group selected from hydrogen, halogen, alkyl, alkoxy, aryloxy, heteroaryloxy, aryl, or heteroaryl; and R.sup.1-4, Z.sup.1-4, X, R.sup.N, n, and W are as defined in claim 1.

19. Process for preparing a chiral phosphoramidimidate of the general formula (I) according to claim 1, said process comprising the step of: reacting a compound of the general formulae (IX) with a compound of the formula (X) in the presence of a basic compound in an organic solvent to yield a compound of the formula (I) as follows: ##STR00105## wherein in said formulae (IX), (X), and (I): L.sup.1 is an electropositive leaving group selected from hydrogen, a metal selected from Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ru, Rh, Pd, Ag, W, Re, Os, Ir, Pt, Au, Al, Pb, La, Sm, Eu, Yb, or U, or a cationic organic group, or a substituted silicon —SiR.sup.IR.sup.IIR.sup.III, wherein R.sup.I, R.sup.II and R.sup.III may be same or different and are as defined in claim 1; L.sup.2 is an electronegative leaving group selected from halogen, alkoxy, aryloxy, heteroaryloxy, sulfonyl or heteroaryl; and R.sup.1-4, Z.sup.1-4, X, R.sup.N, n, and W are as defined in claim 1.

20. Process for preparing a chiral phosphoramidimidate of the general formula (I) according to claim 1, said process comprising the step of: reacting a compound of the general formulae (XI) with a compound of the formula (XII) in an organic solvent to yield a compound of the formula (I) as follows: ##STR00106## wherein in said formulae (XI), (XII) and (I): L.sup.4 represents a leaving group selected from —N.sub.3 or —N(L.sup.1)(L.sup.2) and L.sup.1 and L.sup.2 are independently selected from an electropositive leaving group selected from hydrogen, a metal selected from Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ru, Rh, Pd, Ag, W, Re, Os, Ir, Pt, Au, Al, Pb, La, Sm, Eu, Yb, U or a cationic organic group, or a substituted silicon —SiR.sup.IR.sup.IIR.sup.III, wherein R.sup.I, R.sup.II and R.sup.III may be same or different and are as defined in claim 1 above; or an electronegative leaving group selected from halogen, alkoxy, aryloxy, heteroaryloxy, sulfonyl or heteroaryl; and R.sup.1-4, Z.sup.1-4, n, and W are as defined in claim 1.

Description

EXAMPLES

Example 1—(S)-3,3′-bis(2,4,6-triisopropylphenyl)-[1,1′-binaphthalene]-2,2′-dinaphthyl-N,N′-bis((trifluoro-methyl)sulfonyl)phosphoramidimidate ((+)-4

(1) ##STR00074##

(2) In a flame dried flask under Ar (S)-3,3′-bis(2,4,6-triisopropylphenyl)-[1,1′-binaphthalene]-2,2′-diol (0.10 g, 0.15 mmol, 1.0 equiv) was dissolved in freshly distilled pyridine (1.5 mL, 0.10 M), PCl.sub.5 (63 mg, 0.30 mmol, 2.0 equiv) was added, and heated to 85° C. for 5 h. The reaction mixture was cooled to RT, CF.sub.3SO.sub.2NH.sub.2 (0.27 g, 1.8 mmol, 12 equiv) and N,N-dimethylpyridin-4-amine (DMAP, 10 mg, 0.08 mmol, 0.5 equiv) were added, heated to 85° C. for 5 d, cooled to RT, and concentrated under reduced pressure. HCl (10 mL, 1.0 M) was added, extracted with CH.sub.2Cl.sub.2 (1×10 mL, 2×5 mL), washed with brine (10 mL), dried (Na.sub.2SO.sub.4), filtered, and concentrated under reduced pressure. Purification by CC (silica gel, MeOH/CH.sub.2Cl.sub.2 0:1 to 1:49), acidification in CH.sub.2Cl.sub.2 (10 mL) with HCl (2×10 mL, 6.0 M) followed by drying under reduced pressure with MePh (3×3 mL) afforded compound (+)-4 (0.10 g, 66%) as a brown solid.

Example 2—((Trifluoromethyl)sulfonyl)phosphorimidoyl trichloride (P(NTf)Cl.SUB.3

(3) ##STR00075##

(4) In a flame dried flask under Ar equipped with a magnetic stirring bar, which was connected to a cooling trap containing a 10 wt % NaOH(aq) solution and a vacuum pump, a mixture of TfNH.sub.2 (3.0 g, 20 mmol, 1.0 equiv) and PCl.sub.5 (5.5 g, 26 mmol, 1.3 equiv) was heated to 110° C. under Ar, until HCl evolution ceased. The liquid mixture was heated to 110° C. for 2 h at 300 mbar. The reaction was monitored by .sup.1H, .sup.19F, and .sup.31P NMR to ensure full consumption of TfNH.sub.2. Purification of the obtained slightly yellow clear liquid by fractional distillation (0.07 mbar, b.p.=60° C., oil bath=90° C.) afforded P(NTf)Cl.sub.3 (3.5 g, 61%) as a colorless clear oil.

Example 3—(S,S)—N-(2,6-diphenyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)-N-methyl-2,6-di-phenyldinaptho[2,1-d: 1′,2′-f][1,3,2]dioxa-phosphepin-4-amine (7dd

(5) ##STR00076##

(6) In a flame dried flask under Ar (S)-3,3′-diphenyl-[1,1′-binaphthalene]-2,2′-diol (0.32 g, 0.72 mmol, 2.0 equiv) was dissolved in MePh (2.4 mL, 0.30 M), (PCl.sub.2).sub.2NMe (84 mg, 0.36 mmol, 1.0 equiv), Et.sub.3N (0.44 g, 4.3 mmol, 12.0 equiv), then tetrazole (10 mg, 0.14 mmol, 0.4 equiv) in MeCN (0.32 mL, 0.50 M) was added, and stirred at RT for 24 h. The reaction mixture was diluted with MePh (2.4 mL), filtered, and concentrated under reduced pressure, which afforded crude compound 7dd as a colorless solid.

Example 4—(S,S)-4,4′-(methylazanediyl)bis(2,6-diphenyldinaphtho[2,1-d:1′,2′f][1,3,2] ((trifluoromethyl)-sulfonyl)phosphoramidimidate ((+)-7d

(7) ##STR00077##

(8) To an ice cold solution of NaN.sub.3 (1.2 g, 18 mmol, 50 equiv) in H.sub.2O (3.0 mL, 6.0 M) was added a solution of Tf.sub.2O (1.0 g, 3.6 mmol, 10 equiv) in CH.sub.2Cl.sub.2 (3.0 mL, 1.2 M), stirred at 0° C. for 2 h. H.sub.2O (0.5 mL) was added, the layers were separated and the aqueous layer was extracted with CH.sub.2Cl.sub.2 (2×1 mL). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered, and added to (S,S)—N-(2,6-diphenyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)-N-methyl-2,6-diphenyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine (7dd) (0.35 g, 0.36 mmol, 1.0 equiv) at 0° C. under Ar. The reaction mixture was stirred at 0° C. for 2 h, warmed to RT (remove cooling bath), stirred at RT for 28 h, and concentrated under reduced pressure. Purification by CC (silica gel, MTBE/hexanes 1:9 to 1:4) afforded compound (+)-7d (0.31 g, 68%) as a colorless solid.

Example 5—(S,S)-3,3′-diphenyl-[1,1′-binaphthalene]-2,2′-dinaphthyl-N′—P,P-dinaphthoxy-N-((trifluoro-methyl)sulfonyl)phosphorimidoyl-N-((trifluoromethyl)sulfonyl) phosphoramidimidate ((+)-5d

(9) ##STR00078##

(10) A mixture of (S,S)-4,4′-(methylazanediyl)bis(2,6-diphenyldinaphtho [2,1-d:1′,2′-f][1,3,2]((trifluoro-methyl)-sulfonyl)-phosphoramidimidate (7d) (0.13 g, 0.10 mmol, 1.0 equiv) and n-Bu.sub.4NI (TBAl, 0.56 g, 1.5 mmol, 15 equiv) in THF (2.0 mL, 0.05 M) was heated to 45° C. for 5 h. The reaction mixture was cooled to RT, diluted with MTBE (15 mL), washed with brine, NaHSO.sub.3, HCl (6.0 M), NaHCO.sub.3 (each 10 mL), dried (Na.sub.2SO.sub.4), filtered, and concentrated under reduced pressure. Purification by CC (silica gel, EtOAc/hexanes 3:7 to 2:3), acidification in CH.sub.2Cl.sub.2 (2 mL) with HCl (2 mL, 6.0 M), stirred at RT for 0.5 h, diluted with CH.sub.2Cl.sub.2 (8 mL) washed with HCl (2×10 mL, 6.0 M), followed by drying under reduced pressure with MePh (3×3 mL) afforded compound (+)-5d (0.10 g, 82%) as a colorless solid.

Example 6—(S,S)-3,3′-diphenyl-[1,1′-binaphthalene]-2,2′-dinaphthyl-N′—P,P-dinaphthoxy-N-((trifluoro-methyl)sulfonyl)phosphorimidoyl-N-trifluoromethyl)sulfonyl)-phosphoramidimidate ((+)-5d

(11) ##STR00079##

(12) In a flame dried flask under Ar (S)-3,3′-diphenyl-[1,1′-binaphthalene]-2,2′-diol (2.02 g, 4.6 mmol, 2.0 equiv) was dissolved in MePh (15 mL, 0.30 M), P(NTf)Cl (1.37 g, 4.8 mmol, 2.1 equiv), then Et.sub.3N (2.8 g, 27.6 mmol, 12.0 equiv) was added, and stirred at RT for 15 min. NH.sub.3 (39 mg, 2.3 mmol, 1.0 equiv) in dioxane (6.6 mL, 0.35 M, titrated) was added, stirred at RT for 10 min, then heated to 100° C. for 3 d. The reaction mixture was cooled to RT, diluted with EtOAc (20 mL), washed with HCl (1.0 M) and brine (each 20 mL), dried (Na.sub.2SO.sub.4), filtered, and concentrated under reduced pressure. Purification by CC (silica gel, EtOAc/MePh 3:17), acidification in CH.sub.2Cl.sub.2 (2 mL) with HCl (2 mL, 6.0 M), stirred at RT for 0.5 h, diluted with CH.sub.2Cl.sub.2 (8 mL) washed with HCl (2×10 mL, 6.0 M), followed by drying under reduced pressure with MePh (3×3 mL) afforded compound (+)-5d (2.24 g, 78%) as a colorless solid.

Example 7—(R,R)—N-(2,6-di(naphthalene-2-yl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)-N-methyl-2,6-di(naphthalen-2-yl)dinaphtho[2,1-d: 1′,2′-f][1,3,2]dioxaphosphepin-4-amine (7bb

(13) ##STR00080##

(14) In a flame dried flask under Ar (R)-[2,2′:4′,1″:3″,2′″-quaternaphthalene]-2″,3′-diol (0.10 g, 0.18 mmol, 2.0 equiv) was dissolved in MePh (0.45 mL, 0.40 M), (PCl.sub.2).sub.2NMe (21 mg, 0.09 mmol, 1.0 equiv), then Et.sub.3N (45 mg, 0.45 mmol, 5.0 equiv) was added, and stirred at RT for 3 d. The reaction mixture was diluted with MePh (0.45 mL), filtered, and concentrated under reduced pressure, which afforded crude compound 7bb as a colorless solid.

Example 8—(R,R)-4,4′-(methylazanediyl)bis(2,6-di(naphthalen-2-yl)dinaphtho[2,1-d:1′,2′-f][1,3,2]((tri-fluoromethyl)sulfonyl)phosphoramidimidate ((−)-7b

(15) ##STR00081##

(16) To an ice cold solution of NaN.sub.3 (0.29 g, 4.5 mmol, 50 equiv) in H.sub.2O (0.75 mL, 6.0 M) was added a solution of Tf.sub.2O (0.25 g, 0.90 mmol, 10 equiv) in CH.sub.2Cl.sub.2 (0.75 mL, 1.2 M), stirred at 0° C. for 2 h. The layers were separated and the aqueous layer was extracted with CH.sub.2Cl.sub.2 (2×0.3 mL). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered, and added to (R,R)—N-(2,6-di(naphthalen-2-yl)dinaphtho[2,1-d:1′,2′-f][1,3,2]di-oxaphosphepin-4-yl)-N-methyl-2,6-di(naphthalen-2-yl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine (7bb) (0.10 g, 0.09 mmol, 1.0 equiv) at 0° C. under Ar. The reaction mixture was stirred at 0° C. for 3 h, warmed to RT (remove cooling bath), stirred at RT for 5 d, and concentrated under reduced pressure. Purification by CC (silica gel, MTBE/hexanes 3:7, then silica gel, MePh) afforded compound (−)-7b (0.61 g, 46%) as a colorless solid.

Example 9—(R,R)-[2,2′:4′,1″:3″,2′″-quaternaphthalene]-2″,3′-dinaphthoxy-N-((trifluoromethyl)sulfonyl)-phosphorimidoyl-N-((trifluoromethyl)sulfonyl)-phosphoramidimidate ((−)-5b

(17) ##STR00082##

(18) A mixture of (R,R)-4,4′-(methyl-azanediyl)bis(2,6-di(naphthalen-2-yl)dinaphtho[2,1-d: 1′,2′-f][1,3,2] ((trifluoromethyl)sulfonyl)phosphoramidimidate ((−)-7b) (0.30 g, 0.21 mmol, 1.0 equiv) and n-Bu.sub.4NI (TBAl, 1.2 g, 3.2 mmol, 15 equiv) in THF (4.2 mL, 0.05 M) was heated to 60° C. for 5.5 h. The reaction mixture was cooled to RT, diluted with MTBE (15 mL), filtered, washed with brine, Na.sub.2SO.sub.3, HCl (1.0 M, each 10 mL), dried (Na.sub.2SO.sub.4), filtered, and concentrated under reduced pressure. Purification by CC (silica gel, EtOAc/hexanes 1:3 to 3:7), acidification in CH.sub.2Cl.sub.2 (2 mL) with HCl (2 mL, 6.0 M), stirred at RT for 0.5 h, diluted with CH.sub.2Cl.sub.2 (8 mL) washed with HCl (2×10 mL, 6.0 M), followed by drying under reduced pressure with MePh (3×3 mL) afforded compound (−)-5b (0.18 g, 59%) as a colorless solid.

Example 10—(S,S)—N-(2,6-bis(3,5-dimethylphenyl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)-2,6-bis(3,5-dimethylphenyl)-N-methyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine (7cc

(19) ##STR00083##

(20) In a flame dried flask under Ar (S)-3,3′-bis(3,5-dimethylphenyl)-[1,1′-binaphthalene]-2,2′-diol (0.29 g, 0.60 mmol, 2.0 equiv) was dissolved in MePh (1.5 mL, 0.40 M), (PCl.sub.2).sub.2NMe (70 mg, 0.30 mmol, 1.0 equiv), then Et.sub.3N (0.15 g, 1.5 mmol, 5.0 equiv) was added, and stirred at RT for 25 h. The reaction mixture was diluted with MePh (1.5 mL), filtered, and concentrated under reduced pressure, which afforded crude compound 7cc as a colorless solid.

Example 11—(S,S)-4,4′-(methylazanediyl)bis(2,6-3,5-dimethylphenyl)dinaphtho[2,1-d:1′,2′-f][1,3,2]((trifluoro-methyl)sulfonyl)phosphoramidimidate ((+)-7c

(21) ##STR00084##

(22) To an ice cold solution of NaN.sub.3 (0.98 g, 15 mmol, 50 equiv) in H.sub.2O (2.5 mL, 6.0 M) was added a solution of Tf.sub.2O (0.85 g, 3.0 mmol, 10 equiv) in CH.sub.2Cl.sub.2 (2.5 mL, 1.2 M), stirred at 0° C. for 2 h. The layers were separated and the aqueous layer was extracted with CH.sub.2Cl.sub.2 (2×0.6 mL). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered, and added to (S,S)—N-(2,6-bis(3,5-dimethylphenyl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)-2,6-bis(3,5-imethylphenyl)-N-methyldinaphtho[2,1-d: 1′,2′-f][1,3,2]dioxaphosphepin-4-amine (7cc) (0.32 g, 0.30 mmol, 1.0 equiv) at 0° C. under Ar. The reaction mixture was stirred at 0° C. for 2 h, warmed to RT (remove cooling bath), stirred at RT for 13 h, and concentrated under reduced pressure. Purification by CC (silica gel, MePh/hexanes 7:3) and recrystallisation (CH.sub.2Cl.sub.2/pentane) afforded compound (+)-7c (0.19 g, 45%) as a colorless solid.

Example 12—(S,S)-3,3′-(2,6-bis(3,5-dimethylphenyl)-[1,1′-binaphthalene]-2,2′-dinaphthyl-N′—P,P-dinaphthoxy-N((trifluoromethyl)sulfonyl)phosphorimidoyl-N-((trifluoromethyl) sulfonyl)phosphor-amidimidate ((+)-5c

(23) ##STR00085##

(24) A mixture of (S,S)-4,4′-(methylazanediyl)bis(2,6-3,5-dimethylphenyl)dinaphtho[2,1-d: 1′,2′-f][1,3,2]((trifluoromethyl)sulfonyl)phosphoramidimidate ((+)-7c) (0.10 g, 0.07 mmol, 1.0 equiv) and n-Bu.sub.4NI (TBAl, 0.39 g, 1.1 mmol, 15 equiv) in THF (1.4 mL, 0.05 M) was heated to 45° C. for 2.5 h. The reaction mixture was cooled to RT, diluted with MTBE (10 mL), filtered, washed with brine, Na.sub.2SO.sub.3, HCl (1.0 M, each 10 mL), dried (Na.sub.2SO.sub.4), filtered, and concentrated under reduced pressure. Purification by CC (silica gel, EtOAc/hexanes 1:4), acidification in CH.sub.2Cl.sub.2 (2 mL) with HCl (2 mL, 6.0 M), stirred at RT for 0.5 h, diluted with CH.sub.2Cl.sub.2 (8 mL) washed with HCl (2×10 mL, 6.0 M), followed by drying under reduced pressure with MePh (3×3 mL) afforded compound (+)-5c (54 mg, 57%) as a colorless solid.

Example 13—(S)-4-azido-2,6-bis(2,4,6-triethylphenyl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepine 4-oxide

(25) ##STR00086##

(26) In a flame dried flask under Ar (S)-3,3′-bis(2,4,6-triethylphenyl)-[1,1′-binaphthalene]-2,2′-diol (0.61 g, 1.0 mmol, 1.0 equiv) was dissolved in freshly distilled pyridine (2.0 mL, 0.5 M), POCl.sub.3 (0.38 g, 2.5 mmol, 2.5 equiv) was added, and heated to 85′C for 14 h. The reaction mixture was cooled to RT and concentrated under reduced pressure. The residue was suspended in CH.sub.2Cl.sub.2 (10 mL), filtered (silica gel), washed with HCl (10 mL, 1.0 M), dried (MgSO.sub.4), filtered, and concentrated under reduced pressure. The crude mixture was dissolved in CH.sub.2Cl.sub.2 (3 mL), filtered (silica gel), and concentrated under reduced pressure. The colorless solid was dissolved in dry acetone and THF (each 0.7 mL, 0.70 M) under Ar, NaN.sub.3 (22 mg, 0.34 mmol, 2.0 equiv), then TBAF (13 mg, 0.05 mmol, 0.05 equiv) was added, and stirred at RT for 2 d. The reaction mixture was diluted with CH.sub.2Cl.sub.2 (5 mL), filtered (silica gel), and concentrated under reduced pressure. Purification by CC (silica gel, EtOAc/hexanes 1:19) afforded compound (0.55 g, 80%) as a colorless solid.

Example 14 (S)—N-2,6-bis(2,4,6-triethylphenyl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphenin-4-yl)-1,1,1-trifluoromethanesulfonamide

(27) ##STR00087##

(28) In a flame dried flask under Ar a mixture of CF.sub.3SO.sub.2NH.sub.2 (9 mg, 0.06 mmol, 1.2 equiv) in THF (0.15 mL, 0.40 M) was cooled to 0° C., a solution of n-BuLi (4 mg, 0.06 mmol, 1.2 equiv) in hexanes (24 μL, 2.5 M) was added and stirred at 0′C for 3 h. In a second flame dried flask under Ar to a solution of (S)-3,3′-bis(2,4,6-triethylphenyl)-[1,1′-binaphthalene]-2,2′-diol (30 mg, 0.05 mmol, 1.0 equiv) in MePh (0.25 mL, 0.20 M) was added PCI (7 mg, 0.06 mmol, 1.1 equiv), then Et.sub.3N (17 mg, 0.17 mmol, 3.4 equiv), and stirred at RT for 3 h. The MePh mixture was filtered, then added to the ice cold THF mixture, warmed to RT (remove cooling bath), and stirred at RT for 4 h. The reaction mixture was filtered and concentrated under reduced pressure, which afforded crude compound (14 mg, 36%) as a colorless solid.

Example 15 (S,S)-3,3′-bis(2,4,6-triethylphenyl)-[1,1′-binaphthalene]-2,2′-dinaphthyl-1,1,1-trifluoro-methanesulfonamide-amido-phosphoranylidene-phosphoamidate

(29) ##STR00088##

(30) In a flame dried flask under Ar to a crude mixture of (S)—N-2,6-bis(2,4,6-triethylphenyl)-dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-yl)-1,1,1-trifluoromethanesulfonamide (0.71 g, 0.90 mmol, 1.4 equiv, not isolated as described for analytical data) in MePh/THF (13 mL, 0.05 M) was added (S)-4-azido-2,6-bis(2,4,6-triethylphenyl)-dinaphtho[2,1-d: 1′,2′-f][1,3,2]dioxaphosphepine 4-oxide (0.45 g, 0.64 mmol, 1.0 equiv). The reaction mixture was stirred at 50° C. for 3 d, then heated to 100′C for 23 h, cooled to RT, diluted with MTBE (10 mL), filtered, washed with HCl (1.0 M), brine (each 10 mL), dried (Na.sub.2SO.sub.4), filtered, and concentrated under reduced pressure. Purification by CC (silica gel, EtOAc/hexanes 1:9 to 3:17), acidification in CH.sub.2Cl.sub.2 (2 mL) with HCl (2 mL, 6.0 M), stirred at RT for 0.5 h, diluted with CH.sub.2Cl.sub.2 (8 mL) washed with HCl (2×10 mL, 6.0 M), followed by drying under reduced pressure with MePh (3×3 mL) afforded compound (0.71 g, 76%) as a colorless solid.

(31) Catalytic Tests

(32) As referred to in Scheme 3, some catalytic reactions are generally explained as follows.

(33) General Catalytic Asymmetric Allylation of Aldehydes and Acetals with Allyltrimethylsilane:

(34) In a Schlenk tube under an Ar atmosphere the catalyst (1 to 5 mol %) and the aldehyde (0.03 mmol, 1.0 equiv) in the respective solvent (respective volume) was cooled to the respective temperature. After 20 min, allyltrimethylsilane (18 mg, 0.16 mmol, 5.2 equiv) was added dropwise to the stirred solution, and the sealed Schlenk tube was either placed in a pre-cooled cryostat (−57° C.) or in a Dewar filled with dry ice and some acetone (−78° C.). Upon consumption of all aldehyde/acetal monitored by TLC or GC analysis, aqueous HCl (0.2 mL, 1.0 M) was added to the stirred reaction mixture, which was then warmed to room temperature and stirred vigorously for 2 h (only for aldehydes). The mixture was diluted with Et.sub.2O (0.2 mL) and basified with saturated aqueous NaHCO.sub.3 (0.5 mL). The layers were separated and the aqueous layer was extracted with Et.sub.2O (3×0.5 mL). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered and concentrated under reduced pressure (>100 mbar). Purification by CC (silica gel) afforded the corresponding homoallylic alcohol or ether.

(35) General Catalytic Asymmetric Diels-Alder Reaction and Mukaiyama Additions:

(36) In a Schlenk tube under an Ar atmosphere the catalyst (1 mol %) and the ester (0.02 mmol, 1.0 equiv) in the respective solvent (respective volume) was cooled to the respective temperature. SKA (0.02 mmol, 0.05 or 1.0 equiv) was added (then the corresponding diene (0.2 mmol, 10.0 equiv)) to the stirred solution. Upon consumption of all ester monitored by TLC or GC analysis, aqueous HCl (0.1 mL, 1.0 M) was added to the stirred reaction mixture, which was then warmed to room temperature and stirred vigorously for 2 h. The mixture was diluted with Et.sub.2O (0.2 mL) and the layers were separated. The aqueous layer was extracted with Et.sub.2O (3×0.5 mL). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered and concentrated under reduced pressure. Purification by CC (silica gel) afforded the corresponding bicyclic ester or diester.

(37) General Catalytic Asymmetric Procedure for Oxa-Pictet-Spengler Reactions:

(38) A flask (2 mL, stirring bar) was charged with corresponding aromatic alcohol (0.02 mmol), catalyst (5 mol %), and activated molecular sieves (5 Å, 10 mg). The vial was flushed with argon and sealed. Dry solvent (0.1 mL) was added and adjusted to the respective temperature, then the aldehyde (0.05 mmol) was added. Upon consumption of all aldehyde/acetal monitored by TLC or GC analysis, the reaction mixture was basified with Et.sub.3N, filtered and concentrated under reduced pressure. Purification by CC (silica gel) afforded the corresponding ether.

(39) General Catalytic Asymmetric Procedure for Prins-Cyclization Reactions:

(40) Unless specified otherwise, aldehyde (0.12 mmol) and 3-methyl-3-buten-1-ol (0.10 mmol) were added to the mixture of catalyst (0.005 mmol, 5 mol %) and 50 mg 5 Å molecular sieves in anhydrous solvent (0.1 M). The vial was flushed with argon and sealed. Upon consumption of all aldehyde/acetal, the reaction mixture was basified with Et3N, filtered and concentrated under reduced pressure. Purification by CC (silica gel) afforded the corresponding ether.