Process for the preparation of optically active ortho-substituted 4-aryl-dihydropyridines

A process for the preparation of an optically active 1,4-dihydropyridine wherein the chiral C atom in the 4 position carries an ortho substituted aryl radical of the formula ##STR21## in which R.sup.1 represents an aryl radical of the formula ##STR22## in which A, D and E are identical or different and denote hydrogen, halogen, cyano, trifluoromethyl or denote straight-chain or branched alkyl or alkenyl having in each case up to 6 carbon atoms, each of which is optionally substituted by aryl having 6 to 10 carbon atoms, by a 5- to 7-membered saturated to unsaturated heterocycle having up to 3 hetero atoms selected from the group consisting of S, N and O or by straight-chain or branched alkoxycarbonyl having up to 8 carbon atoms or carboxyl, or

• denote a group of the formula --NR.sup.6 R.sup.7, --OR.sup.8, --S(O).sub.2 R.sup.9, --SR.sup.10 or --P(O)(OR.sup.11)(OR.sup.12),
• in which
• R.sup.6, R.sup.7, R.sup.8 and R.sup.10 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms, benzyl, aryl having 6 to 10 carbon atoms or a 5- to 7-membered saturated or unsaturated heterocycle having up to 3 hetero atoms selected from the group consisting of S, N and O,
• a denotes a number 1 or 2,
• R.sup.9 denotes straight-chain or branched alkyl having up to 6 carbon atoms, benzyl, phenyl or tolyl,
• R.sup.11 and R.sup.12 are identical or different and denote hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms,
• L denotes a direct bond, a sulphur or oxygen atom or a radical of the formula --NH or SO.sub.2,
• T, depending on the definition of the substituent L, has one of the chemically meaningful meanings given above of A, D and/or E and is identical to or different from this, but in the cases L=bond or --SO.sub.2 does not represent hydrogen, or denotes a radical of the formula --CHF.sub.2,
• or
• D and E, in the directly adjacent case, or E and T, with inclusion of the aromatic double bond, in each case together form a 5- to 8-membered, partially unsaturated or unsaturated carbocycle or heterocycle having up to 3 hetero atoms selected from the group consisting of S, N and O, where the ring systems are optionally up to disubstituted identically or differently by halogen, hydroxyl, nitro, cyano, trifluoromethyl, by straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, by aryl having 6 to 10 carbon atoms or by a 5- to 6-membered aromatic heterocycle having up to 3 hetero atoms selected from the group consisting of S, N and O,
• R.sup.2 and R.sup.5 are identical or different and represent cyano, nitro, carboxyl or straight chain or branched alkoxycarbonyl having up to 6 carbon atoms which is optionally substituted by straight-chain or branched alkoxy or acyl having in each case up to 8 carbon atoms or by straight-chain or branched alkyl having up to 6 carbon atoms, which is optionally substituted by straight-chain or branched acyl having up to 4 carbon atoms, pyridyl, furanyl or by a group of the formula --NR.sup.13 R.sup.14,
• in which
• R.sup.13 and R.sup.14 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, aryl having 6 to 10 carbon atoms or benzyl, where the ring systems are optionally substituted by halogen,
• or
• alkoxycarbonyl is optionally substituted by a group of the formula --NR.sup.15 R.sup.16,
• in which
• R.sup.15 and R.sup.16 have the meaning cited above of R.sup.13 and R.sup.14 and are identical to or different from these,
• or
• R.sup.2 and/or R.sup.5 represent a radical of the formula --PO(OR.sup.17)(OR.sup.18), --SO.sub.2 R.sup.19 or --CO--NR.sup.20 R.sup.21,
• in which
• R.sup.17 and R.sup.18 have the meaning given above of R.sup.10 and R.sup.11 and are identical to or different from these,
• or
• R.sup.17 and R.sup.18 together form a radical of the formula ##STR23## R.sup.19 has the meaning given above of R.sup.9 and is identical to or different from this,
• R.sup.20 and R.sup.21 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms or phenyl,
• R.sup.3 and R.sup.4 are identical or different and represent amino, cyano or straight-chain or branched alkinyl or alkyl having in each case up to 4 carbon atoms, each of which is optionally substituted by hydroxyl or by a group of the formula --(O--CO).sub.b --NR.sup.22 R.sup.23,
• in which
• b denotes a number 0 or 1,
• R.sup.22 and R.sup.23 are identical or different and have the meaning given above of R.sup.6 and R.sup.7,
• or
• alkyl is optionally substituted by straight-chain or branched alkoxy having up to 6 carbon atoms which itself is optionally substituted by a group of the formula --NR.sup.24 R.sup.25,
• in which
• R.sup.24 and R.sup.25 have the meaning given above of R.sup.13 and R.sup.14 and are identical to or different from these,
• or
• R.sup.2 and R.sup.3, or R.sup.4 and R.sup.5, together form a radical of the formula ##STR24## in which X denotes an oxygen or sulphur atom or a group of the formula --NR.sup.26 or --(CH.sub.2).sub.c,
• in which
• R.sup.26 denotes hydrogen, phenyl or straight-chain or branched alkyl having up to 4 carbon atoms,
• c denotes a number 1, 2 or 3,
• and
• Y denotes a group of the formula CO--, SO.sub.2 -- or --SO,
• which comprises first converting by oxidation of the corresponding dihydropyridine which has a chiral C atom in the 4 position and is substituted by an ortho-substituted aryl or heteroaryl radical and which is present in the synperiplanar (sp) form of formula (Ia) or antiperiplanar (ap) form of formula (Ib) or its antipode ##STR25## in which R.sup.2, R.sup.3, R.sup.4, R.sup.5, L and T have the meaning given above
• and ##STR26## includes the ortho-substituted aromatic ring systems cited above under the substituent R.sup.1,
• into an atropisomeric pyridine of the formulae (IIa) or (IIb) ##STR27## in which R.sup.2, R.sup.3, R.sup.4, R.sup.5, L, T and ##STR28## have the meaning given above, and, in a second step, reducing the pyridines formed above back into the 1,4-dihydropyridine of formula (I), wherein either an inversion takes place to form the mirror-image isomer or a racemization takes place with partial retention to a differing extent.