Intramolecular cyclopropanation of unsaturated terminal epoxides and chlorohydrins.
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 (+)-beta-cuparenone. The related unsaturated chlorohydrins also undergo intramolecular cyclopropanation via in situ epoxide formation.
Hodgson
David M
DM
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK. david.hodgson@chem.ox.ac.uk
Chung
Ying Kit
YK
Nuzzo
Irene
I
Freixas
Gloria
G
Kulikiewicz
Krystyna K
KK
Cleator
Ed
E
Paris
Jean-Marc
JM
D000447:Aldehydes / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D002384:Catalysis; D002728:Chlorohydrins / Q000737:chemistry*; D003521:Cyclopropanes / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D006536:Heptanes / Q000737:chemistry; D006586:Hexanes / Q000737:chemistry; D007536:Isomerism; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry
D000447:Aldehydes; D001643:Bridged Bicyclo Compounds; D002728:Chlorohydrins; D003521:Cyclopropanes; D004852:Epoxy Compounds; D006536:Heptanes; D006586:Hexanes; D012717:Sesquiterpenes; C518145:alpha-cuparenone