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. 2015 Mar 11;137(9):3237-40.
doi: 10.1021/jacs.5b01909. Epub 2015 Mar 2.

Enantioselective cross-coupling of meso-epoxides with aryl halides

Yang Zhao  1 , Daniel J Weix
Affiliations

Enantioselective cross-coupling of meso-epoxides with aryl halides

Yang Zhao et al. J Am Chem Soc. .

Abstract

The first enantioselective cross-electrophile coupling of aryl bromides with meso-epoxides to form trans-β-arylcycloalkanols is presented. The reaction is catalyzed by a combination of (bpy)NiCl2 and a chiral titanocene under reducing conditions. Yields range from 57 to 99% with 78-95% enantiomeric excess. The 30 examples include a variety of functional groups (ether, ester, ketone, nitrile, ketal, trifluoromethyl, sulfonamide, sulfonate ester), both aryl and vinyl halides, and five- to seven-membered rings. The intermediacy of a carbon radical is strongly suggested by the conversion of cyclooctene monoxide to an aryl [3.3.0]bicyclooctanol.

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Figures

Scheme 1
Scheme 1. Enantioselective Arylation of meso-Epoxides
Scheme 2
Scheme 2. Enantioselective Arylation of Cyclohexene Oxide
Reactions were run with 1.0:2.0:0.1:0.1:0.1 Et3N·HCl/Mn0/titanocene/NiCl2(dme)/bipyridine in DMPU with stirring for 12 h at rt. Assay yields (GC area %) are shown, with an isolated yield in parentheses. Enantiomeric excesses were determined by chiral-phase GC or SFC analysis.
Scheme 3
Scheme 3. Epoxide and Aryl Halide Scope
As in Scheme 2 footnote a. The yield in parentheses is for a racemate obtained with catalyst 1. The absolute configuration of 13 was determined by X-ray analysis (see the Supporting Information). Other products were assigned by analogy. The same reaction conducted with 3 equiv of Mn was finished in 4 h vs 8 h (see Table S1 in the Supporting Information).
Scheme 4
Scheme 4. Aryl Halide Scope
As in Scheme 2, footnote a. Extended reaction time resulted in hydrodehalogenation of the product. Product was isolated after 7 h. Product was isolated after 7.5 h.
Scheme 5
Scheme 5. Formation of [3.3.0]Bicyclooctanol Products from Cyclooctadiene Monoxide
As in Scheme 2, footnote a. Absolute configurations were assigned by X-ray analysis of camphanic acid esters.
Scheme 6
Scheme 6. Proposed Catalytic Cycle
See this image and copyright information in PMC

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    1. For a review of transition-metal-catalyzed cross-coupling with epoxides, see ref (1b). Although no enantioselective examples have been reported, several enantiospecific reactions are known.

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