Catalytic, Asymmetric Vinylogous Mukaiyama Aldol Reactions of Pyrrole‐ and Furan‐Based Dienoxy Silanes: How the Diene Heteroatom Impacts Stereocontrol

Abstract

Denmarks chiral bisphosphoramide/silicon tetrachloride system performs as an excellent Lewis base-Lewis acid catalyst for the vinylogous Mukaiyama aldol reaction of pyrrole-and furan-based dienoxy silanes with aromatic and heteroaromatic aldehydes. This asymmetric methodology provides a powerful synthetic entry to a variety of d-hydroxylated g-butenolide-type frameworks with high efficiency and valuable margins of regio-, diastereo-, and enantioselectivity. Notably, the nature of the heteroatom within the vinylogous dienoxy silane donor heavily impacts the diastereocontrol, with syn-configured aldol adducts emerging from pyrroles bearing electron-withdrawing N-protecting groups (Boc, Ts, and Cbz) and anti-configured adducts prevailing when furan-or N-alkyl/alkenylpyrrole donors are involved.

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

“…Lactams offer the possibility of reactivity tuning by choosing an appropriate protecting group at the nitrogen atom. Since initial experiments with unprotected pyrrolin-2-one were not promising the respective tert -butyloxycarbonyl (Boc) and 4-toluenesulfonyl (Ts) derivatives 18a and 18b were prepared [ 52 ]. In CH 2 Cl 2 as the solvent, the attempted addition reaction of N -methyl- N -((trimethylsilyl)methyl)aniline ( 5 ) turned out to be sluggish.…”

The Vinylogous Aldol and Related Addition Reactions: Ten Years of Progress

“…227,228 After an initial survey of a prototypical reaction between TBSOP 163 and benzaldehyde (90) in the presence of a set of several chiral metal-based catalysts, it was discovered that the previously disclosed Denmark bisphosphoramide/SiCl 4 couple 399 was a superior catalyst candidate, with the expected (5S,1 0 S)-configured vinylogous aldol product syn-517 obtained in high yield and outstanding levels of site-, diastereo-, and enantioselectivities (Scheme 95, eq 1).…”

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…Following their longstanding experience in the use of the popular heterocyclic silyloxy dienes, in 2010 Curti, Zanardi, et al reported a study focused on the catalytic vinylogous aldol reaction of pyrrole- and furan-based silyl dienolates (the latter being already cited in section 5 ) with aromatic and heteroaromatic aldehydes. 344 After a preliminary screening of various metal-based catalyst systems, it was found that the bisphosphoramide L12 /SiCl 4 couple was the optimal catalyst system to promote and govern the VMAR between silyloxy pyrroles 842 and aldehydes 843 , producing the expected lactams 844 with high efficiency and stereocontrol ( Scheme 213 ). It is noteworthy that the study revealed that the nature of the heteroatom substituents in the silyloxy diene scaffolds heavily affected the stereochemical reaction outcome; that is, the syn -configured adducts syn- 844 were preferentially obtained with pyrroles bearing electron-withdrawing N -protecting groups (Boc, Ts, Cbz), while the use of dienes N -substituted with electron-donating groups (Bn, allyl, PMB) (as in the case of furans, vide supra) provided reversal of stereocontrol, giving rise to anti - 844 adducts, preferentially.…”