A Decade of Advance in the Asymmetric Vinylogous Mannich Reaction

Abstract

When the principle of vinylogy is applied to imines as electrophiles, the so-called vinylogous Mannich reaction (VMR), γ-aminocarbonyl (such as butenolides) and β-aminocarbonyl compounds are generated in a very efficient manner. The asymmetric version of this vinylogous Mannich reaction gives access to highly functionalized chiral synthons, which are suitable for further transformations. The versatility of this methodology is exemplified with the synthesis of several alkaloids and natural products. 1 Introduction 2 Asymmetric Vinylogous Mannich Reactions (VMR) with 2-Silyloxyfurans and 2-Silyloxypyrroles 3 Asymmetric VMR with Acyclic Silyl Dienolates and Silyl Dienol Ketene Acetals 4 Asymmetric VMR with γ-Butenolides and γ-Butyrolactams 5 Asymmetric VMR with α,α-Dicyanoolefins 6 Miscellaneous Donors in Asymmetric VMR 7 Application of the VMR to Natural Product Synthesis 8 Conclusions

Chiral N,N′‐Dioxide/Tm(OTf)3 Complex‐Catalyzed Asymmetric Bisvinylogous Mannich Reaction of Silyl Ketene Acetal with Aldimines

“…The asymmetric Mannich and vinylogous Mannich‐type reactions, in which cyclic or acyclic enolates as nucleophiles add to preformed or in situ‐ generated imines, are powerful and straightforward carbon‐carbon bond‐forming processes for the synthesis of important chiral nitrogen‐containing carbonyl compounds ,. The enolates can generate in situ (by organic amine or organometallic catalysts), or indirect protocols (mostly built upon preformed silyl enol ethers) from carbonyl compounds.…”

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

“…A s an important branch of Mannich reaction, the α-aminomethylation of carbonyl compounds constitutes a powerful protocol for introducing aminomethyl groups to simple organic molecules [1][2][3][4][5][6][7][8] . The resulting β-amino carbonyl compounds are versatile synthetic building blocks for a wide variety of natural products and biologically active compounds 9 .…”

Synthesis of 4-(1,3,5-Thiadiazinan-2-ylidene)-2-(3,4- dihydro-2H-1,3,5-thiadiazin-6-yl)pent-2-enedinitriles

“…The Mannich reaction is an effective tool to build C-C-N and X-C-N bonds (where X = N, O, S, Se, P, etc. ), and therefore it is often used in the synthesis of a wide variety of heterocyclic compounds (for the reviews on the various modifications of the Mannich reaction, see [1][2][3][4][5][6][7][8][9]. 1,3,5-Thiadiazines belong to an important class of heterocyclic compounds.…”