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Synlett 2003(7): 0903-0921
DOI: 10.1055/s-2003-39285
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Cycloadditions of Nonstabilized 2-Azaallyllithiums (2-Azaallyl Anions) and Azomethine Ylides with Alkenes: [3+2] Approaches to Pyrrolidines and Application to Alkaloid Total Synthesis

William H. Pearson*, Patrick Stoy
Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109-1055, USA
Fax: +1(734)7632307; e-Mail: wpearson@umich.edu;
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Publikationsverlauf

Received 9 August 2002
Publikationsdatum:
20. Mai 2003 (online)

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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 (2-azaallyl)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 2-azaallyl 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.

  • 1 Introduction

  • 2 Background: 2-Azaallyl Anions

  • 2.1 Semistabilized 2-Azaallyl Anions

  • 2.2 Stabilized 2-Azaallyl Anions

  • 2.3 Nonstabilized 2-Azaallyl Anions

  • 3 Methodology Development

  • 3.1 Initial Attempts at Generating Nonstabilized 2-Azaallyl Anions

  • 3.2 Tin-Lithium Exchange on (2-Azaallyl)stannanes

  • 4 Cycloaddition of Simple Nonstabilized 2-Azaallyllithiums

  • 4.1 Preparation of (2-Azaallyl)stannanes

  • 4.2 Anionophiles and Quenches

  • 4.3 Mechanism and Stereoselectivity

  • 5 Variations on a Theme: Related Cycloadditions

  • 5.1 Cycloadditions on Solid Support

  • 5.2 2-Azapentadienyllithiums

  • 5.3 Heteroatom-Substituted 2-Azaallyllithiums

  • 5.4 Enantioselective Cycloadditions

  • 5.5 Higher-Order Cycloadditions

  • 6 Other Uses of (2-Azaallyl)stannanes

  • 6.1 Azomethine Ylide Generation and Cycloaddition

  • 6.2 Nucleophilic Additions to (2-Azaallyl)stannanes

  • 7 Synthesis of Alkaloids

  • 7.1 Intramolecular Cycloadditions

  • 7.1.1 Amabiline and Augustamine

  • 7.1.2 Mesembranes

  • 7.1.3 Coccinine

  • 7.1.4 Crinine and 6-Epicrinine

  • 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

Key words

organolithium - anionic cycloaddition - heterocycles - alkaloid synthesis - tin-lithium exchange