An Efficient Protocol for the Enantioselective Preparation of a Key Polyfunctionalized Cyclohexane. New Access to (R)- and (S)-4-Hydroxy-2-cyclohexenone and (R)- and (S)-trans-Cyclohex-2-ene-1,4-diol

Abstract

Starting from very accessible raw materials such as p-methoxyphenol, ethylene glycol, and thiophenol, a protocol has been developed to prepare multigram quantities of the polyfunctionalized cyclohexane (+/-)- 7. A highly efficient resolution of (+/-)- 7 has been achieved through enantioselective acetylation catalyzed by Candida antarctica lipase B. Straightforward and enantioselective syntheses of 4-hydroxy-2-cyclohexenone, 1, trans-cyclohex-2-ene-1,4-diol, 2, and their O-protected derivatives 18 and 19 have been readily accomplished from 7.

Divergent Approach to Gabosines and Anhydrogabosines: Enantioselective Syntheses of (+)‐Epiepoformin, (+)‐EpoKformin, (+)‐Gabosine A, and Gabosines B and F

“…One of our goals was to design an easily available and versatile precursor of polyfunctionalized cyclohexanes in both antipodal forms. This objective was accomplished by developing the protocol depicted in Scheme , where, starting from very accessible raw materials such as p ‐methoxyphenol, 2 , ethylene glycol, and thiophenol, multi‐gram quantities of (±)‐ 3 can be readily prepared 18. The reduction of (±)‐ 3 with NaBH 4 gives the cis alcohol (±)‐ 4 exclusively.…”

“…Treatment of (±)‐ 4 with vinyl acetate and a catalytic amount of Novozyme 435 in diisopropyl ether furnishes the acetate (–)‐ 5 and the unreacted alcohol (+)‐ 4 . Methanolysis of the acetate (–)‐ 5 leads to recovery of the levorotatory alcohol (–)‐ 4 15,18. By silylation of alcohols (+)‐ 4 and (–)‐ 4 followed by hydrolysis of the acetal, the α‐phenylthioketones (4 R )‐ 6 and (4 S )‐ 6 are easily synthesized, respectively.…”

Stereoselective Synthesis of [4.3.1]Propellane Fragment of Phainanoids A–F

“…Treatment of 8 with 10% Pd/C under H 2 atmosphere allowed simultaneous hydrogenation of double bond and hydrogenolysis of benzyl ether moiety to provide the phenol 4 in 99% yield. PIFA oxidation of 4 in the presence of ethylene glycol delivered the ketal 9 in 74% yield …”

Efficient Asymmetric Synthesis of Chiral Monomer of Epoxyquinols and (-)-Phyllostine

“…9 We considered that chiral Diels-Alder adduct 5 could be a good starting material for the synthesis of 4. Initially, the enantioselective Diels-Alder reactions of cyclopentadiene with 1,4-quinone monoketal 7, which is easily prepared from p-methoxyphenol, 10 were attempted. The reaction was carried out at -78 o C by stirring 1,4-quinone monoketal 7 and cyclopentadiene in the presence of (S)-cationic chiral oxazaborolidium catalysts 6 11 (20 mol %) in CH2Cl2 under nitrogen atmosphere.…”