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The stereochemistry of the conversion 13 → 14, established by the identity of totally synthetic 1 with naturally formed salinosporamide A, is that predicted from a cyclic, chair-formed, six-membered transition state involving addition of the organozinc reagent to the sterically more accessible face of the formyl group. The use of 2-cyclohexenylzinc chloride is critical to successful formation of 14 because none of this product is obtained with 2-cyclohexenyllithium (probably because the initial carbonyl adduct undergoes retroaldol cleavage and decomposition; see: Corey, E. J.; Li, W.; Nagamitsu, T. Angew. Chem., Int. Ed. 1998, 37, 1676-1679).
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