Recent Applications of Ammonium Ylide Based [2,3]-Sigmatropic and [1,2]-Stevens Rearrangements To Transform Amines into Natural Products

Abstract

Ammonium ylide based [2,3]-sigmatropic and [1,2]-Stevens rearrangements enable the transformation of tertiary amines into rearranged and functionalized intermediates en route to many polycyclic natural product targets. Herein, we summarize recent applications of these rearrangement reactions in formal and total synthesis endeavors while highlighting innovative improvements to these transforms.1 Introduction2 Ammonium Ylide Based [2,3]-Sigmatropic Rearrangements in Natural Product Synthesis2.1 (–)-Cephalotaxine2.2 (±)-Amathaspiramide F2.3 (–)-Cephalezomine G and Its C3 Epimer2.4 (±)-Strictamine2.5 (–)-Doxycycline3 [1,2]-Stevens Rearrangements Toward Natural Products3.1 Ring-Expanding [1,2]-Stevens Rearrangements en route to (±)-Tylophorine, (±)-7-Methoxycryptopleurine, and (±)-Xylopinine3.2 Enantioselective Synthesis of Iboga Alkaloids and (+)-Vinblastine4 Selected Methodology4.1 Ammonium Ylide Based [2,3]-Sigmatropic Rearrangements To Form Natural Product Cores4.2 Cascade Reactions Involving [1,2]-Stevens Rearrangement/ Hofmann-Type Elimination Events5 Conclusions

Recent asymmetric synthesis of natural products bearing an α-tertiary amine moiety via temporary chirality induction strategies

“…With an envelope-like ve-membered transition state, these rearrangements provide high stereoselectivity, 77 and are therefore extensively applied in natural product synthesis to generate stereocenters. 78,79 A notable aspect of this strategy, compared with Seebach's SRS strategy, is the positively charged intermediate quaternary nitrogen, which facilitates the easy deprotonation of adjacent protons. This characteristic allows the use of weaker bases such as DBU or t BuOK instead of the commonly employed LDA in the SRS strategy.…”

Deaminative ring contraction for the synthesis of polycyclic heteroaromatics: a concise total synthesis of toddaquinoline

“…1b). 8 The experimental replication of this biogenic pathway 8c reveals the potential of dehydroamination toward familylevel access to these phenanthrenes from tertiary amine precursors, 8,9 and highlights the utility of amine-derived molecular rearrangements 10,11 for the convergent synthesis of densely substituted polycyclic aromatics.…”

“… 26 We drew inspiration from strategies that are also tolerant of Lewis basic arenes that use a Z -selective Wittig olefination to build the alkene, followed by a transition-metal catalyzed cyclization to forge the biaryl bond. 27 The recognition of pseudosymmetry and knowing that tertiary amines can react to form alkenes guided our retrosynthetic analyses, 11,28 leading to the development of a convergent approach to polycyclic (hetero)aromatics by the reductive cyclization and deaminative contraction of appropriately halogenated tertiary amine precursors ( Fig. 1c ).…”

Transition-metal catalyzed reactions of diazo compounds and N,N-dialkylnitrosoamines

“…Transition-metal catalyzed reactions of carbenes with tertiary amines and nitrogen-heterocycles have undergone significant development for the synthesis of drugs, fine chemicals and natural products. 1 These transformations prominently entail the formation of ammonium ylides and the subsequent rearrangements. The typical transformations involve 1,2-Steves rearrangement and 2,3-sigmatropic rearrangements.…”