Synthesis 2009(21): 3708-3718  
DOI: 10.1055/s-0029-1216999
PSP
© Georg Thieme Verlag Stuttgart ˙ New York

Cyclopropanation with Dibromomethane under Grignard and Barbier Conditions

Gerhard Brunner, Laura Eberhard, Jürg Oetiker, Fridtjof Schröder*
Research Chemistry Department, Givaudan Schweiz AG, 8600 Dübendorf, Switzerland
Fax: +41(44)8242976; e-Mail: fridtjof.sch[email protected];
Further Information

Publication History

Received 22 June 2009
Publication Date:
08 September 2009 (online)

Abstract

Tertiary Grignard reagents and dibromomethane efficiently cyclopropanate allylic (and certain homoallylic) magnesium and lithium alcoholates at ambient temperature in ether solvents. Lithium (homo)allyl alcoholates are directly cyclopropanated with magnesium and dibromomethane under Barbier conditions at higher temperatures. The reaction rates depend on the substitution pattern of the (homo)allylic alcoholates and on the counterion with lithium giving best results. Good to excellent syn-selectivities are obtained from α-substituted (homo)allyl alcohols. In tandem reactions, cyclopropyl carbinols are obtained from allyloxylithium or -magnesium intermediates, generated in situ by alkylation of conjugated aldehydes, ketones, and esters as well as from allyl esters and carbonates or vinyloxiranes. [¹]

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3

The reactivity order of dihalomethanes is in accordance with that of the radical halogen abstraction from these compounds.

9

Among other byproducts identified by GC/MS: 2,2,4,4-tetramethylpentane (CAS 1070-87-7), 2,2,6,6-tetramethyl-4-methyleneheptane (CAS 141-70-8), 2-tert-butyltetra-hydrofuran (CAS 38624-45-2), 2,2-dimethyldecane (CAS 17302-37-3), 2,2,8-trimethyldecane (CAS 62238-01-1), 2,2-dimethylundecane (CAS 17312-64-0), tert-butyl bromide (CAS 507-19-7), 1-bromo-2,2-dimethylpropane (CAS 630-17-1), 2-bromotetrahydrofuran (CAS 59253-21-3), 3-bromo-2,2,4,4-tetramethylpentane (CAS 107713-49-5).

11

Allylic alcohols, which underwent incomplete conversions with the system CH2Br2 (3 equiv)/t-BuMgCl (4 equiv) (GC conversion to the corresponding cyclopropanes after 18 h in brackets): (E)-hex-2-enol (35%), (Z)-hex-2-enol (65%), nonadienol (50%), geraniol (50%), nerol (10%), oct-1-en-3-ol (50%), linalool (40%), and nerolidol (50%).

17

2-Hexylcyclopent-2-enone = isojasmone B 11. Commercial available from Oxford Chemicals.

25

A possible explanation for this rate enhancement is the more covalent character of the Mg-O bond of the MgX-alcoholates versus the lithium alcoholate ion pair. For mechanistic details see ref. 1.

26

The syn-selectivities are in accord with a staggered Houk model.²7

28

GC-analysis on a 5% phenyl-95% dimethylpolysiloxane column.