Use of nitrogen and oxygen dipole ylides for alkaloid synthesis

Abstract

As highlighted in this mini review, a growing area of interest in organic synthesis involves the use of substituted azomethine and carbonyl ylides as 1,3-dipoles for the preparation of alkaloidal natural products. Cascade reactions proceeding by an intramolecular 1,3-dipolar cycloaddition of nitrogen and oxygen dipole ylides are of particular interest to the synthetic organic community because of the increase in molecular complexity involved and the high isolated yields.

Switchable Cycloadditions of Mesoionic Dipoles: Refreshing up a Regioselective Approach to Two Distinctive Heterocycles

“…This class of masked thiocarbonyl ylide dipoles are willing partners against a broad range of dipolarophiles (double and triple bonds and heterocumulenes). 2b , 6 Reactions of thioisomünchones with alkynes provide straightforward access to either pyrid-2-one or thiophene nuclei, two privileged scaffolds in drug design, as witnessed by a series of blockbuster drugs ( Figure 1 ), 7 with thiophenes being common bioisosteres of the phenyl ring. 8 …”

“…The simultaneous incorporation of O, N, and S heteroatoms into mesoionic dipoles enhances the diversity toward highly functionalized heterocyclic targets, which is well portrayed by thiazol-3-ium-4-olates (widely dubbed thioisomünchnones). This class of masked thiocarbonyl ylide dipoles are willing partners against a broad range of dipolarophiles (double and triple bonds and heterocumulenes). , Reactions of thioisomünchones with alkynes provide straightforward access to either pyrid-2-one or thiophene nuclei, two privileged scaffolds in drug design, as witnessed by a series of blockbuster drugs (Figure ), with thiophenes being common bioisosteres of the phenyl ring …”

Asymmetric formal C–C bond insertion into aldehydes via copper-catalyzed diyne cyclization

“…Alternatively, we suppose that the highly reactive carbonyl ylides [28][29][30][31][32][33][34][35] could be potentially applicable to the formal C-C bond insertion into aldehydes. In recent years, special attention were drawn to the formation of carbonyl ylides via the reaction of aldehydes with metal carbenes, which provided efficient access to a variety of 1,3dioxolanes [36][37][38][39][40][41][42][43][44][45][46][47] and epoxides [48][49][50] .…”

Five-Step Total Synthesis of (±)-Aspidospermidine by a Lactam Strategy via an Azomethine Ylide

“…Our research group has proposed that easily available amides can serve as synthetic equivalents of 1,3-dipoles through reduction or nucleophilic addition (Scheme A). − In 2016, we documented the first example using an iridium-catalyzed reduction of N -hydroxyamides 5a to give nitrones 6 . , We also reported the synthesis of fully substituted cyclic nitrones 7 by nucleophilic addition of organolithium reagents to N -OSEM amides 5b . This method was successfully applied to the total synthesis of cylindricine C. In this communication, we report that amides can be transformed into azomethine ylides, which are also important 1,3-dipoles . An iridium-catalyzed reductive Michael addition of a lactam and subsequent [3+2] cycloaddition accomplished the five-step total synthesis of (±)-aspidospermidine ( 1 ).…”