Department of Chemistry, Scripps Florida, Jupiter, Florida 33458, USA.
J Am Chem Soc. 2012 Feb 29;134(8):3925-31. doi: 10.1021/ja300472a. Epub 2012 Feb 14.
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.
通过醛醇或烯丙基金属化学的立体控制合成β-支链反式，反式-二丙酸立体三联体 4 一直是有机合成界的一个历史挑战。在这里，我们通过利用非对映过量的α-甲基取代醛与手性非外消旋的烯丙基硼烷试剂 (S)-(E)-22（或其对映体）的不匹配的双不对称烯丙基硼化反应，为 4 的合成相关的长期问题提供了一个通用的解决方案。这种方法不仅可以直接获得反式，反式-二丙酸立体三联体 24 [4 的合成等价物]，而且β-支链手性醛的非对映选择性非常好（5-8:1），如果不是极好的（≥15:1），而且产物中具有适当官能化的乙烯基锡烷单元，可用于随后的 C-C 键形成事件。我们预计这种方法将具有广泛的适用性，并将大大简化聚酮天然产物合成的策略。
