Tetrahedron report number 594 Nitrile anion cyclizations Fraser F. Fleming p and Brian C. Shook ² Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282-1530, USA Received 1 October 2001 Contents 1. Introduction 1 1.1. Recent structural studies of nitrile anions 2 2. Cyclization by nucleophilic intramolecular displacements S N i) 2 2.1. Cyclizations to cyclopropanes 3 2.2. Cyclizations to cyclobutanes 3 2.3. Cyclizations to cyclopentanes 8 2.4. Cyclizations to cyclohexanes 8 2.5. Cyclizations to medium-sized rings 9 2.6. Cyclizations with epoxides 9 3. Stereoselective cyclizations 11 3.1. Monocyclic carbonitriles 11 3.2. Bicyclic carbonitriles 13 4. Thorpe±Ziegler cyclizations 14 5. Cyclizations with esters, ketones and lactones 14 6. Domino reactions 17 7. Synopsis 17 1. Introduction Alkylationofstabilizedcarbanionsisthemostfundamental carbon±carbon bond-forming reaction in organic chemistry. 1 Recent NMR and X-ray analyses, stimulated by the central role of stabilized carbanions, identify most `carbanions' as being complex aggregates, 2 although the common term carbanion succinctly encapsulates the observed reactivity and may actually exist in highly polar media. 3 Numerous stabilized carbanions provide reactive intermediates for C±C bond construction, among which nitrile-stabilized anions occupy a unique position as being particularly powerful nucleophiles, ideally suited for installing hindered quaternary centers. 4 Nitrile-stabilized carbanions are extremely important synthetic intermediates. 4 Despite the long history of nitrile anion alkylations 4 the exact nature of the `anion' remains elusive, re¯ecting a complex interplay between solvation, charge delocalization, and inductive stabilization. Con- ceptually, the powerful electron-withdrawing effect of the nitrile is most consistent with an sp 3 hybridized carbanion 2a), as either a contact or separated ion pair, whereas the greater electronegativity of nitrogen over carbon suggests an sp 2 hybridized `keteniminate' 2b) as the preferred structure Scheme 1). In the extreme these species might be envisaged as C- or N-metallated nitriles 2c and 2d, respectively. Tetrahedron 58 2002) 1±23 Pergamon TETRAHEDRON 0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved. PII:S0040-402001)01134-6 p Corresponding author. Tel.: 11-412-396-6031; fax: 11-412-396-5683; e-mail: ¯emingf@duq.edu ² Present address: University of Rochester, Rochester, NY, USA. Scheme 1.