Cyclization of Zincated α‐N‐Homoallylamino Nitriles: A New Entry to Enantiopure 2,3‐Methanopyrrolidines |
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Authors: | Sabrina Ouizem Dr. Sandrine Cheramy Dr. Candice Botuha Prof. Fabrice Chemla Dr. Franck Ferreira Dr. Alejandro Pérez‐Luna |
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Affiliation: | UPMC Univ Paris 06, UMR CNRS 7201, Institut Parisien de Chimie Moléculaire, Institut de Chimie Moléculaire (FR 2769), Case 183, 4 place Jussieu, 75005 Paris (France), Fax: (+33)?144‐27‐75‐67 |
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Abstract: | Stereoselective cyclization of zincated α‐N‐homoallylamino nitriles has been developed. Following treatment with lithium diisopropylamide (LDA) and transmetalation with zinc bromide, α‐N‐(1‐phenylethyl)‐N‐homoallylamino nitriles lead to 2,3‐methanopyrrolidines in moderate to good yields (up to 66 %) and excellent selectivities (up to >98:2). With substrates derived from α‐branched homoallylic amines, a stereospecific inversion of the homoallylic stereogenic center was observed. To account for this, a mechanistic rationale involving the formation of zincioiminium ions from zincated α‐amino nitriles is put forward. 2,3‐Methanopyrrolidines should then arise from a sequence involving an aza‐Cope rearrangement providing a configurationally stable (2‐azoniaallyl)zinc species that then undergoes a [3+2] cycloaddition reaction. |
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Keywords: | cyclization enantioselectivity metalation sigmatropic rearrangement ylides |
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