Synthesis of (3S)-(tert-butyldimethylsilyloxy)methylcyclopentan-1-one as a key intermediate of sphingosine 1-phosphate-1 receptor agonists

Herein we report the asymmetric synthesis of (3S)-(tert-butyldimethylsilyloxy)methylcyclopentan-1-one (S)-3 as a practical chiral synthon for a wide range of pharmaceutical and/or natural products, using Lipshutz’s asymmetric copper-catalyzed conjugate reduction. This method makes it feasible to prepare a conformationally constrained cyclopentane analogue 12, which is one of the key intermediates for the synthesis of novel sphingosine 1-phosphate-1 receptor agonists.