A new and more powerfully activating diamine for practical and scalable enantioselective aldehyde crotylsilylation reactions

Abstract

A new diaminophenol ligand for crotylsilylation reactions with cisand trans-crotyltrichlorosilane has been developed. The conformational constraints that result from the tethering of the phenol to one of the amino groups attenuate the stereoelectronic effects that reduce activity in the corresponding untethered diaminosilanes, and the resulting crotylsilane reagents are as active as our previously reported EZ-CrotylMix reagents, but without requiring the use of the Sc(OTf) 3 catalyst. In turn, this has allowed the development of an experimentally straightforward, sustainable, efficient, and scalable onepot procedure which may be carried out in #8 hours, and in which the diaminophenol activator ligand may be easily recovered in $90% yield by recrystallization.Scheme 1 (A) The procedure for the synthesis and isolation of the EZ-Cro-tylMixes. (B) Attempts to form and employ the EZ-CrotylMixes in situ are unsuccessful.

Direct, Mild, and General n-Bu4NBr-Catalyzed Aldehyde Allylsilylation with Allyl Chlorides

“…fluoride, catecholate) may be used to pre-form 5-coordinate allylsilicates that are activated for aldehyde allylsilylation reactions, 20 the effective use of more weakly coordinating anions as catalysts reported here is without precedent. We suggest that the key to accessing this mode of nucleophilic catalysis is the pre-activation of the silane by ligand 3, which induces Lewis acidity 7 sufficient for the reversible binding of less strongly nucleophilic anions.…”

Scalable synthesis of bryostatin 1 and analogs, adjuvant leads against latent HIV

“…The diastereoselective allylation of aldehyde 25 proceeded in 84% yield and 10:1 dr (decagram scale) using Leighton’s chiral diamine controller with silane 26 (42). The high efficiency of this Leighton allylation belies the many difficulties we experienced in surveying allylation platforms, most of which could not be extended to incorporate the sensitive trimethylsilyl moiety [e.g., Ipc method (43)] or did not react with the highly oxygenated and β-disubstituted aldehyde 25 [e.g., chiral allylstannane platforms (44, 45)].…”

Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1

“…The critical methodological challenge was thus the generation of versions of 8 and 10 possessed of the necessary reactivity to couple efficiently and highly stereoselectively with aldehydes 9 and 11 from simple and readily available precursors and in a way that does not require their isolation. We were optimistic that our diamine- and diaminophenol-activated crotyl- and allylsilanes 37 , 38 would, uniquely, be well-suited for the proposed reactions due both to their reliably excellent reactivity and broad generality and to the fact that the requisite crotyl- and allylsilanes 8 and 10 (M = Si) appeared accessible from the simple precursors diene 12 (ref. 39 ) and allylchloride 13 by way of mild, functional group-tolerant, and chemoselective transition metal-catalyzed hydrosilylation and allylic substitution reactions, respectively.…”