Cycloadditions of Nonstabilized2-Azaallyllithiums (2-Azaallyl Anions) and Azomethine Ylides withAlkenes: [3+2] Approaches to Pyrrolidinesand Application to Alkaloid Total Synthesis

Abstract

The [3+2] cycloaddition of 2-azaallyl anions with alkenes represents an attractive strategy for the synthesis of substituted pyrrolidines. Although cycloadditions of 2-azaallyl anions stabilized by aryl and ester groups have been known for more than three decades, only recently have versions bearing simply hydrogen or alkyl groups been discovered. These nonstabilized 2-azaallyl anions are generated by the low temperature transmetalation of (2azaallyl)stannanes with alkyllithiums. The resulting nonstabilized 2-azaallyllithiums undergo cycloaddition with certain alkenes and alkynes in both intra-and intermolecular modes to yield pyrrolidine or pyrroline cycloadducts. The methodology has been extended to 2-azapentadienyllithiums, heteroatom-substituted 2-azaallyllithiums, and polymer-supported 2-azaallyllithiums. Asymmetric 2azaallyl anion cycloadditions have also been investigated. Nonstabilized azomethine ylides may also be generated from (2-azaallyl)stannanes via an N-alkylation/destannylation or N-protonation/ destannylation sequence. Together, the cycloaddition of nonstabilized 2-azaallyllithiums and azomethine ylides with alkenes allows access to a broader range of pyrrolidines, since these species have complimentary reactivity profiles. 7.1.5 Approach to 6a-Epipretazettine 7.2 Intermolecular Cycloadditions 7.2.1 Lepadiformine Isomers 7.2.2 Lapidilectine B 7.2.3 Indolizidine 239CD 8 Commentary

1,3‐Dipolar Cycloaddition of Azomethine Ylides to Aldehydes: Synthesis of anti α‐Amino‐β‐Hydroxy Esters

“…Aziridine 9a and benzaldehyde (8) were chosen as model substrates for the initial optimization of the cycloaddition. When the substrates were heated at reflux in toluene for 18 h oxazolidines 10a and 10b were obtained with good Scheme 2.…”

“…[4][5][6][7][8] For example, pyrrolidines can be made by a 1,3-dipolar cycloaddition between an azomethine ylide (AMY) and an olefin, often setting two or more stereocenters, and this approach is one of the most important methods for the construction of this class of compounds. [6][7][8] However, the analogous addition of AMYs to aldehydes is much less explored.…”

“…[4][5][6][7][8] For example, pyrrolidines can be made by a 1,3-dipolar cycloaddition between an azomethine ylide (AMY) and an olefin, often setting two or more stereocenters, and this approach is one of the most important methods for the construction of this class of compounds. [6][7][8] However, the analogous addition of AMYs to aldehydes is much less explored. [9][10][11][12][13][14][15][16] This type of reaction would deliver oxazolidine 2, which can readily be transformed into α-amino-β-hydroxy ester 1 by hydrolysis of the N,O-acetal functionality (Scheme 1).…”

A Versatile Aminobenzannulation Method Based on the Deprotonation of 2‐(1‐Alkynyl)benzaldimines and Similar 2‐Aza‐2,4‐heptadienyl‐6‐ynes: A Multistep Rearrangement Cascade

“…The preparation of the metal compounds by transmetalation of appropriate tin compounds, as investigated by Pearson et al, [16] is expected to increase the scope of this reaction even more, especially with respect to less acidic imines as starting compounds.…”

Eine vielseitige Aminobenzanellierungsmethode durch Deprotonierung von 2‐(1‐Alkinyl)benzaldiminen und ähnlichen 2‐Aza‐2,4‐heptadienyl‐6‐inen: eine mehrstufige Umlagerungskaskade

“…Dieser erste Schritt verläuft analog zu dem Ringschluss, den wir bei der verwandten Elektrocyclisierung der jeweiligen Alkenylimine beobachten konnten (Schema 1). [5] [12][13][14] In [16] lässt erwarten, dass das Anwendungsspektrum auf weniger acide Imine als Ausgangsstoffe erweitert werden kann.…”