Diastereoselective synthesis of a highly functionalized cyclohexene embedded with a quaternary stereogenic centre by self Diels–Alder dimerization of a [3]dendralene attached to a (−)-menthol auxiliary

A novel route to a chiral functionalized [3]dendralene attached to a (−)-menthol auxiliary has been developed, which involves a dimethylsulfonium methylide mediated olefination of a substituted ethenylidene phosphonoacetate (−)-menthyl ester, followed by a Horner–Wordsworth–Emmons reaction with 4-bromobenzaldehyde. The chiral [3]dendralene was reactive enough to undergo intermolecular Diels–Alder cyclodimerization to give the highly substituted cyclohexene with very high regio- and diastereoselectivity.

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(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-bromoacetateC12H21BrO2[α]D24=-64.8 (c 4.08 MeOH)Source of chirality: (−)-MentholAbsolute stereochemistry: (1R,2S,5R)

(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(diethoxyphosphoryl)acetateC16H31O5P[α]D24=-52.25 (c 1.24, MeOH)Source of chirality: (−)-MentholAbsolute stereochemistry: (1R,2S,5R)

(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetateC16H25F6O5P[α]D24=-38.0 (c 2.32, MeOH)Source of chirality: (−)-MentholAbsolute stereochemistry: (1R,2S,5R)

(2E,4E)-(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]-5-phenylpenta-2,4-dienoateC25H31F6O5P[α]D23=-37.1 (c 1.26, MeOH)Source of chirality: (−)-MentholAbsolute stereochemistry: (2E,4E)-(1R,2S,5R)

(2Z,4E)-(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]-5-phenylpenta-2,4-dienoateC25H31F6O5P[α]D23=-43.5 (c 0.38, MeOH)Source of chirality: (−)-MentholAbsolute stereochemistry: (2Z,4E)-(1R,2S,5R)

(2Z,2′Z)-Bis[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl] 2,2′-[(1R,2R)-2-{(E)-styryl}-1,2,3,4-tetrahydro-(1,1′-biphenyl)-2,5-diyl]bis[3-(4-bromophenyl)acrylate]C58H66Br2O4[α]D25=+156.8 (c 0.31, CHCl3)Source of chirality: (−)-Menthol, chiral inductionAbsolute stereochemistry: (2Z,2′Z)-bis[(1R,2S,5R)-2,2′-[(1R,2R)]

(2Z,2′Z)-Bis[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl] 2,2′-[(1S,2S)-2-{(E)-styryl}-1,2,3,4-tetrahydro-(1,1′-biphenyl)-2,5-diyl]bis[3-(4-bromophenyl)acrylate]C58H66Br2O4[α]D25=-140.6 (c 0.33, CHCl3)Source of chirality: (−)-Menthol, chiral inductionAbsolute stereochemistry: (2Z,2′Z)-bis[(1R,2S,5R)-2,2′-[(1S,2S)]