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
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