One-Pot, Asymmetric and Diastereoselective Four-Component Synthesis of Polyfunctional (Z)-Alkenyl Methyl Sulfones with Three Stereogenic Centers

Abstract

The reaction of 1-(trimethylsilyloxy)cyclopentene (9) with (±)-1,3,5-triisopropyl-2-(1-(RS)-{[(1E)-2-methylpenta-1,3-dienyl]oxy}ethyl)benzene ((±)-4a) in SO2/CH2Cl2 containing (CF3SO2)2NH, followed by treatment with Bu4NF and MeI gave a 3.0 : 1 mixture of (±)-(2RS)-2{(1RS,2Z,4SR)-2-methyl-4-(methylsulfonyl)-1-[(RS)-1-(2,4,6-triisopropylphenyl)ethoxy]pent-2-en-1-yl}cyclopentanone ((±)-10) and (±)-(2RS)-2-{(1RS,2Z)-2-methyl-4-[(SR)-methylsulfonyl]-1-[(SR)-1-(2,4,6-triisopropylphenyl)ethoxy]pent-2-en-1-yl}cyclopentanone ((±)-11). Similarly, enantiomerically pure dienyl ether (−)-(1S)-4a reacted with 1-(trimethylsilyloxy)cyclohexene (12) to give a 14.1 : 1 mixture of (−)-(2S)-2-{(1S,2Z,4R)-2-methyl-4-(methylsulfonyl)-1-[(S)-1-(2,4,6-triisopropylphenyl)ethoxy]pent-2-enyl}cyclohexanone ((−)-13a) and its diastereoisomer 14a with (1S,2R,4R) or (1R,2S,4S) configuration. Structures of (±)-10, (±)-11, and (−)-13a were established by single-crystal X-ray crystallography. Poor diastereoselectivities were observed with the (E,E)-2-methylpenta-1,3-diene-1-ylethers (+)-4b and (−)-4c bearing (1S)-1-phenylethyl and (1S)-1-(pentafluorophenyl)ethyl groups instead of the Greene's auxiliary ((1S)-(2,4,6-triisopropylphenyl)ethyl group). The results demonstrate that high α/β-syn and asymmetric induction (due to the chiral auxiliary) can be obtained in the four-component syntheses of the β-alkoxy ketones. The method generates enantiomerically pure polyfunctional methyl sulfones bearing three chiral centers on C-atoms and one (Z)-alkene moiety.