Highly Stereoselective Synthesis of anti,anti-Dipropionate Stereotriads: A Solution to the Long-Standing Problem of Challenging Mismatched Double Asymmetric …

M Chen, WR Roush - Journal of the American Chemical Society, 2012 - ACS Publications
M Chen, WR Roush
Journal of the American Chemical Society, 2012ACS Publications
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 …
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.
ACS Publications
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