American Chemical Society
ja0672932_si_002.pdf (2.63 MB)

Intramolecular Cyclopropanation of Unsaturated Terminal Epoxides and Chlorohydrins

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journal contribution
posted on 2007-04-11, 00:00 authored by David M. Hodgson, Ying Kit Chung, Irene Nuzzo, Glòria Freixas, Krystyna K. Kulikiewicz, Ed Cleator, Jean-Marc Paris
Lithium 2,2,6,6-tetramethylpiperidide (LTMP)-induced intramolecular cyclopropanation of unsaturated terminal epoxides provides an efficient and completely stereoselective entry to bicyclo[3.1.0]hexan-2-ols and bicyclo[4.1.0]heptan-2-ols. Further elaboration of C-5 and C-6 stannyl-substituted bicyclo[3.1.0]hexan-2-ols via Sn−Li exchange/electrophile trapping or Stille coupling generates a range of substituted bicyclic cyclopropanes. An alternative straightforward cyclopropanation protocol using a catalytic amount of 2,2,6,6-tetramethylpiperidine (TMP) allows for a convenient (1 g−7.5 kg) synthesis of bicyclo[3.1.0]hexan-2-ol and other bicyclic adducts. The synthetic utility of this chemistry has been demonstrated in a concise asymmetric synthesis of (+)-β-cuparenone. The related unsaturated chlorohydrins also undergo intramolecular cyclopropanation via in situ epoxide formation.