Navigation

0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login or sign up for a free trial to access the full content.
2.15 Asymmetric Morita–Baylis–Hillman Reaction and Its Aza Analogue

DOI: 10.1055/sos-SD-202-00390

Masson, G.; Zhu, J.Science of Synthesis: Stereoselective Synthesis, (20112735.

General Introduction

The MoritaBaylisHillman (MBH)[‌1‌,‌2‌] reaction has been recognized as one of the most effective CC bond-forming processes. It generates densely functionalized compounds from simple starting materials under catalytic conditions without loss of atoms. This reaction involves the condensation of an electron-deficient alkene with an aldehyde in the presence of a catalytic amount of an organic nucleophilic base, such as a tertiary amine or phosphine. Imines can also participate in an analogous reaction, which is commonly referred to as the aza-MoritaBaylisHillman (aza-MBH) reaction (Scheme 1).[‌3‌] These operationally simple and atom-economic CC bond-forming reactions afford α-methylene-β-hydroxycarbonyl or α-methylene-β-aminocarbonyl derivatives, respectively, which can serve as valuable building blocks for the synthesis of medicinally relevant compounds as well as complex natural products.[‌4‌‌10‌] The synthetic potential of this reaction is illustrated by its application in industrial processes, such as the synthesis of tert-butyl 2-(hydroxymethyl)propenoate, a key intermediate in Pfizerʼs synthesis of the zinc-metallaprotease inhibitor Sampatrilat.[‌11‌]

Meeeee 8 Mee MeeeeeMeeeeeMeeeeee Meeeeeee[‌8‌‌8‌]

Meeeeeee eeee eeeeeeee eee eeeeeeeeeeeee eeeeeeee eeee eeee eeeeeeee eeeee eee eeee eeeeeeeeeee[‌88‌,‌88‌] ee eeee ee eee eeeeeeeeeeeeeeeeeeee, eeeee 8888 eeeee eee eeee eeee eeeeeeee ee eeeeeeee eeeeee, eeeeeee ee eeeeeeeee eeeeeeee eeeee, eeeeeeeeeeeeeeeeeeeeee, eee eeeee. Me eeeeeeeeee, eeeeeee eeeeee ee eee eeeeeeeeeee ee eeeee, eeee-eeeeeeee eeeeeeeee eeee eeeeeeeeeeee eee eeeeeeee eeee-eeeeeeeeeeee eeeeee ee eeeeee eeeeeeee.[‌88‌‌88‌] Meeeeee, eeeeeeee ee eee eeeeeeeeeee ee ee eeeeeeeeeeeeeeee eeeeeee eee eeee eeee, eeeeeeeeee eee eeeeeeeeeeee ee eeee eeee.[‌88‌‌88‌] Mee ee eee eeee eeeeee ee eee eeeeeeeeee ee eee eeeeeeee eeeeeeeee, eeeeeee ee eeeeeeeee eeeeeeeee, eee eee eeeeeeeeeeeeee eeeeeeeeeee eeee eeee eeeeeeee eeee eeeeee eeee ee eeeee eeeeeeeee.[‌88‌,‌88‌] Meeeeeee eee eeeeeeee eeeeeeee eeeee ee eee MeeeeeMeeeeeMeeeeee eeeeeeeee eeee eeeeeeeee eeeeeeeeee ee eee eeeeeee eeeeeeeeeeee, eeeeee eeeeeeeee eee eeeeeeee eeeeeeeeeee eeeeeee ee eee eeeeeeee eeeeeeeee eeeee. Me eeeeeeeeee, eee eeee-eeeeeeeeeee eeee eeee eeeeeeeeee eee eeeeeeeeee eeeeeeeee eee eeee eeeeeeeeeee eeee eeeeeeee. Meeeeeee, eee MeeeeeMeeeeeMeeeeee eeeeeeee eeeeeeee e eeeeeeee ee eeeee eeeeeeeeeeeeeee (Meeeee 8): Meeeeee eeeeeeee, eeeee ee Meeeeee eeeeeeee, eee β-eeeeeeeeeee. Mee eeeeeeee eee eeeeeeee ee eeeeeee ee eee eeeeeeeeee eeeeeeeee eeeeeeee ee eee eeeeeeeeeeee eeeeeeee 8 ee eee Meeeeee eeeeeeee 8 ee eeeeeeee e eeeeeeeeeeee eeeeeee 8 (eeee 8). Meee eeeeee eeeeeee eeee eeeeeeeee eeeeeeeeeeee eeeeeeee ee eeeeeeee 8 (ee ee ee eeeee ee eee eeee ee eee eee-MeeeeeMeeeeeMeeeeee eeeeeeee), eeeeeeeeee e eeeeee eeeeeeeeeeee eeeeeeeeeeee 8 (eeee 8). Meeeeeeeee eeeeee eeeeeeee, ee eeee 8, eeeeeeee ee eeeeeee ee eee eeeeeeee eeeee eeee eeeeeee eee eeeeeee eeeeeee 8. Mee eeeeeeeeeee ee eeee ee eeeee eeeeeee eee eeee eeeeeeeee ee eee eeeeeeeee ee eee eeeeeeee eeeeeeeeeeeee[‌88‌] eeeeeee ee 8 eee 8 ee eeee ee ee eeeeee MMM,[‌88‌,‌88‌] MMM-MM,[‌88‌,‌88‌‌88‌] eee eeeeeeeeeeeee eeeeeee.[‌88‌,‌88‌] Mee eeeee eeeeeeee eeeeeee 8 eee 8, eeeeeeeeee eee eeeeeeeeeee eeeeeee (eeee 8), eee eee e eeee eeee eeee eeeeeeeeee ee eee eeee-eeeeeeeeeee eeee.[‌88‌,‌88‌] Me eeeee ee eee eeeeeeeeee eeeeeeeeeeee ee eeeeeeeeeeeeeeee eeeee eeeeeeeee,[‌88‌,‌88‌] eee eeeee eeeeee eeee e eeeeee eeeeeeeeeeeeeeee MeeeeeMeeeeeMeeeeee eeeeeeee eeeeee eeeeee ee eeeeeeeeee. Meeeeee, eee eeeeeee ee eeee eeee e eeeeeeeeeeeeeeeeee MeeeeeMeeeeeMeeeeee eeeeeeee eee eeee eeeeeeeee ee eeeeeee eeeee eeeeee eeeeeeeee ee eeeeee Meeeeee eeeeeeeee ee eeeeeeee eeeeeeee, eeeee eeeee ee eeeeeeee eeee eee MeeeeeMeeeeeMeeeeee eeeeeeee ee eeee eeeeeeeeeee eeee eeee eeeeeeeeeeeeee eeeeeeeeeee eeee.[‌88‌,‌88‌]

Meeeee 8 Meeeeeee Meeeeeeee eee MeeeeeMeeeeeMeeeeee eee Mee-MeeeeeMeeeeeMeeeeee Meeeeeeee[‌88‌‌88‌]

Me eeeeee eeeee, eeee eeeeeeeeeee eee eeeeeeeeeeee eeeeeee eeee eeee eeeeeeee eeeee ee ee-eeeeeeeeee eeee eeeeeeee eeeeeeeee. MeMeeee eee ee-eeeeeee eeee eeeeeeeeeee eeee eee MM eeee eeeeeeeee ee eee eee eeee-eeeeeeee eeee ee eee MeeeeeMeeeeeMeeeeee eeeeeeee eeeee eeeeeee eeeeeeeeee.[‌88‌] Me eeeeeeeeee eeeeeeee eeeeeeee eee eeeeeee eeeeeeeeeee ee eeeeeeee-eeeee MeeeeeMeeeeeMeeeeee eeeeeeeee, eeee eeee eeeeeeee eeee eee eeeeeeee ee eeeeee eeeee ee eeeeeeee eee eeee eee eeeeee eeeeeeee eeee eeeeeeee ee eee α-MM eeee ee eeeeeeee ee eee eeee-eeeeeeeeeee eeee. Meeee ee eeeee eeeeeeeeeeee, e eeeeeeee eeeeeeeee eee eeee eeeeeeee eeee eeeeeeee eee eeeeeeeee ee eeeeeeeeee eeeeeeeeeeee 8 ee eeeeeeeeeeee ee eeeeeeeeeeee eeeeeeeeeeee 8 eeee e eeeeee eeeeeeeeee ee eeeeeeee. Meeeeeeeeeeeee eeeeee eeeeeeee eee e eee-eeeeeeee eeeeeeeeee eeeee eeeeeeee ee β-eeeeeeeeeee eeeee eeee eeeeeee eee MeeeeeMeeeeeMeeeeee eeeeee 8 (Meeeee 8). Mee eeeeeeee eeeeeeeee ee eeeeeeeee 8 ee e eeee eeeeeee ee MeeeeeMeeeeeMeeeeee eeeeeeeee eeee eeeee eeeeeeee ee eeee eeeeeeeeee.[‌88‌]

Meeeeeee eee Meeee-Meeee eeee eeeeeeee eeeee eeee ee eee eeeeeeee ee e eeeeee eeeeeeee, eeeeeeeeeee ee eee α-MM ee 8 ee eeee eeeeeeee, eee eeee eeeeeeeee eeeeeeeeeeee 88 ee eeeeeee eee eeeeee eeeee (Meeeee 8).[‌88‌] Me eee eeeeeee ee e eeeeee eeeeeeee, eeee eeeee eeee eee eeeeeeee ee eeeeeeeeeeeee, eeeeeee eee eeeeeee eeeeee eee eee ee e eeeeeeee-eeee eeeee ee eeeeeee eee eeeeee eeeeeeee eee eee eeee eeeeeeeeee eeeee 88 (Meeeee 8).[‌88‌‌88‌] Meeeeeeeeeee, ee eeee eeee eeeeeee eeeeeeeeeee eeeeeee eee eee eeeeeee ee eeeeeee eeeeeeee: ee ee eeeee eeeee ee eee eeeeeeee, ee eee eeeeeee ee eeeeeeeeee eeeeeeeeee ee eeeeeee, MeMeeeeʼe eeeeeee eeeeeeeee eee eeeeeeeeee eeeeeeeeeeee 8 eeeeeeee. Me eee eeeeeeee eeeeeeeeee (>88% eeeeeeeeee), eee eeeeeeeeee eeeee 88 eeeeeeeee eee MeeeeeMeeeeeMeeeeee eeeeee eee eeeee eeee eeeeee ee eeeeeee eee eeeeee eeeeeeee. Meeeee eeeeeee eeee eeee eeeeee eeee eee eeeeee eeeeeeee eeeeeee eee eeee-eeeeeeeeeee eeee eeee eeee eee MeeeeeMeeeeeMeeeeee eeeeeeee ee eeeeeee eee ee e eeeeee eeeeeee, eeee ee eeeee ee ee eeeeeee.[‌88‌]

Meeeee 8 Meeeeeee ee eee Meeeeeeee[‌88‌‌88‌]

Meeee eeeeeeeeeee eeeeeee eeeeeee eeee ee eeeeeeeee eeeeee eeeeeeeee eee eee MeeeeeMeeeeeMeeeeee eeeeeeee, eee eee eee eeee ee eeeeeeee eee eeeeeeeeeeeeeeeeee eee eee eeeeeeeeeeeeeeeeeeee ee eee eeeee-eeeeeeeeeeee eeee (eeee 8, Meeeee 8), eee eeee eee eeeeeeeee eeeee ee eee eeeeeeeeeeeee ee eee eeeeeeeeee eeeeee-eeeee eeee (eeee 8, Meeeee 8). Me e eeeeeeee eeeeee eeeee eeeee eee eeeeee eeeee ee eee ee eee eeee eeeeeeeeeeeee, e eeeeee eeeeeeeeeeeeeeee MeeeeeMeeeeeMeeeeee eeeeeeee eee eeeeee eeee ee eee eeeee eeeeeeee ee eeeeeeeeeeeeeeeeee.[‌88‌] Meee eeeee eeeee eeee eee eeeeee-eeeeeeeee eeee eeeeeeeeee eee eeeeeeeeeeeeeeeeee ee eee eeeeeeee, eee eeee eee eeeeeeee eeeeee eee ee eeeeeeee ee e eeeeeee eeeeeee eeeeeeeeee ee eeeeeeeeeeee 8 eeeeeeeeeee eee eeeeeeeeeeeee ee eee eeeee eeeeeeee. Meeeeee, eeeee ee eeeeee eeeeeeeeeeeee eeeeeee, Meeeeeee eee Meeeee eeee eeeee eeee eeee 8 ee eeeeee ee ee eeee eeeeeeeeee ee eeeeeeeeeeeee eeee eeeeeeeee eeeeeeeee, eeeeeeeee eeeeeeee eeeeeeeee, eee eeeeee. Me eeeeeee, eeeee eeeeeeeeeee eeeeeee eeeeeee eeee eee eeeeeeeeeee ee e eeeeeee eeeeeeeeee eeeeeee ee eee MeeeeeMeeeeeMeeeeee eeeeeeee eeeee eeeeeee eee eeeeeeeeeeeee ee eeee eeeee 8 eee 8 (Meeeee 8).[‌88‌]

Meeeeeee eee eeeeeeeee ee eee MeeeeeMeeeeeMeeeeee eee eee-MeeeeeMeeeeeMeeeeee eeeeeeeee eeee eeee eeeeeeeeee ee eeeeeeeee eeeee eee, eeee eeeeeeeeeee eeee eeee eeeee. Meeeeee, ee eeeeeeee ee eee MeeeeeMeeeeeMeeeeee eeeeeeee, eee eee-MeeeeeMeeeeeMeeeeee eeeeeeee eeeeeeee eeeee-eeeee eeeeeeee eeee eeeeeee ee eeeee eee eeeeeeee ee eeeeeeeeeeeee ee eee eeeeeee ee eeeeee eeeeeee.[‌88‌] Me eeee eeee, ee eeeeeeeeeeeeee eeeeee eeee-eeeeee eeeeee eeeeeeee eee eeee eeeeeeee ee ee e eeee-eeeeeeeeeee eeee, eeee ee eeee eeeeeee ee eeeeeeeeee eeee eeee-eeeeeeeeeeee 8 eeeeeee ee eee eeeeeeeee eeeeeeeeeee. Meeeeee eeeeeeeeeeeeee eeeeeeeee ee Meeeeeee eee ee-eeeeeee eeee eeeeeeeee eeee eeeeeeeeeee eeeeeeee.[‌88‌] Me eee eeeee eeee, Meeeeee eee ee-eeeeeee eeee eeeee eeee eeeeeeee ee e Meøeeeee eeee eeeee ee eeeeeeeeeee eeee eeeeeeeeeeee eeeeeee eeeeeeeeeeee ee eee eeeeeeeeeee eeee eee eeee eee eeee eee eeeeeee, eeeeeee eeeee-eeeee eeeeeeeeee ee eee eeeee.[‌88‌] Meeee eeeee eeeeeeeeeeeee, eee eeeeee eeeeeeee eee e eee-eeeeeeee eeeeeeeeee eeeee ee ee eeeeee eeeeeeee ee eee eeee-eeeeeeeeeee eeee. Mee eeeeeeeeeee ee eeeee eeeeeeeeeeee ee eeee eeeeeeee ee eee eeeeeee ee eee eeeee (eeeeeeeeee ee eee) eeeee eeeeee eee eeeeeeeeeee-eeeeeeeeeee eeee ee eee eeeeeeee ee eeeee eeeeee eeeeeee.

Meeeeeeeeee, eee eeeeeeeee ee eee eeeeee eeeeeeeee eee eeee eeeeeeeee eee eeeeeeeeeee eeeeeeeeeeeee ee eee MeeeeeMeeeeeMeeeeee eee eee-MeeeeeMeeeeeMeeeeee eeeeeeeee. Meeeeeee eee eeeeeee eeeeeeeeeee eee eeeeeeeeeeeeee eee eee eeeee eeeee, eeeeeeeeeeeee eee eeeee eeeeeeeeee ee eeeeee eeeeeeee eee eeeeeee eeeee eee eeeeee ee eeeeeeeee eeeeeee eee eee MeeeeeMeeeeeMeeeeee eeeeeeee. Mee eeee eeeeeeeeee eeee eeee eeeeeeeeee eee eee eeeeeeeeeee ee eeeeeeeee eeeeeeeeeeeeeeee MeeeeeMeeeeeMeeeeee eee eee-MeeeeeMeeeeeMeeeeee eeeeeeeee; eee ee eee eee ee Meeee eeeee eeeeeeeee ee eee eeeeeeee ee eeeeee Meøeeeee ee Meeee eeeee eee eee eeeee eeeeeeee eee eee ee eeeeee Meeee eeeee eeeeeeeee eeee eeeeeeeeeee Meøeeeee eeeeee eeeeee (eeeeeeeeeeee eeeeeeeee). Meee eeeeee eeeeeeeeee eee eeeeeeeeeeee eeee ee eeee eeeeeeee eeeee.

References