Highly stereoselective synthesis of anti, anti -dipropionate stereotriads: A solution to the long-standing problem of challenging mismatched double asymmetric crotylboration reactions

Article abstract of DOI:10.1021/ja300472a

The stereocontrolled synthesis of the β-branched anti,anti- dipropionate stereotriad 4 via aldol or crotylmetal chemistry represents a historical challenge to the organic synthesis community. Here we describe a general solution to the long-standing problem associated with the synthesis of 4 by utilizing mismatched double asymmetric crotylboration reactions of enantioenriched α-methyl substituted aldehydes with the chiral, nonracemic crotylborane reagent (S)-(E)-22 (or its enantiomer). This method not only provides direct access to anti,anti-dipropionate stereotriads 24 [a synthetic equivalent of 4] with very good (5-8:1) if not excellent (≥15:1) diastereoselectivity from β-branched chiral aldehydes with ≥50:1 intrinsic diastereofacial selectivity preferences but also provides a vinylstannane unit in the products that is properly functionalized for use in subsequent C-C bond-forming events. We anticipate that this method will be widely applicable and will lead to substantial simplification of strategies for synthesis of polyketide natural products.