Asymmetric synthesis of the 2,2,3-trisubstituted cyclopentanone, D-ring fragment of 9,11-secosterols

As a part of our studies on the total synthesis of 9,11-secosterols, the possibility of creating a substituted and functionalized D-ring fragment with three consecutive stereocentres, one of which was quaternary, was studied. The simple starting compound 2-methyl-cyclopent-2-ene-1-one was subjected to asymmetric 1,4-addition with (S,S)-crotyl phosphonamide and alkylation with methyl bromoacetate, resulting in a 2,2,3-substituted cyclopentanone in high diastereoselectivity. The covalently bonded chiral auxiliary was removed using oxidative methods. As a result, a stable D-ring fragment was obtained. The relative configuration of the substituents on the cyclopentane ring was assigned by comparison of the experimental with the quantum chemically calculated 1H-1H and 1H-13C J-coupling constants.