Bryostatin 7 synthesis chiral auxiliaries

Another example of this methodology has appeared recently from Masamune and coworkers in connection with a total synthesis of bryostatin (equation 67). The salient point here is the demonstrated utility of the thiol ester, prepared directly through stereoselective boron enolate aldol condensation. Notice Aat no further activation or removal of a chiral auxiliary is necessary for this transformation, unlike other related aldol methodology. 

Evans synthesis of bryostatin 2 (113) also relied upon asymmetric aldol reactions for the introduction of most of the 11 stereocenters [58], At different points, the synthesis used control from an auxiliary, a chiral Lewis acid, chiral ligands on the enolate metal and substrate control from a chiral aldehyde. Indeed, this represents the current state of the art in the aldol construction of complex polyketide natural products. 

The synthesis of the C1-C9 fragment 120 began with an auxiliary controlled aldol reaction of the chloroacetimide 121, where chlorine is present as a removable group to ensure high diastereoselectivity in what would otherwise have been a non-selective addition (Scheme 9-39). The Lewis acid-catalyzed, Mukaiyama aldol reaction of dienyl silyl ether 122 with / -chiral aldehyde 123 proceeded with 94%ds, giving the 3-anti product 124, as predicted by the opposed dipoles model [3]. Anti reduction of the aldol product and further manipulation then provided the C1-C9 fragment 120 of the bryostatins. 

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