Asymmetric synthesis of bicyclo[n.1.0]alkanes by the enantioselective 1,3-CH insertion reaction of chiral magnesium carbenoids

Treatment of enantiomerically pure 1-chlorovinyl p-tolyl sulfoxides, derived from cyclic ketones and (R)-chloromethyl p-tolyl sulfoxide, with the lithium enolate of tert-butyl carboxylates gave adducts in quantitative yields as single diastereomers. The adducts were treated with i-PrMgCl in toluene to afford optically active bicyclo[n.1.0]alkanes bearing a tert-butyl carboxylate moiety in up to 99% enantiomeric excess through the enantioselective 1,3-CH insertion reaction of the generated chiral magnesium carbenoids. This is the first example of the enantioselective 1,3-CH insertion reaction of magnesium carbenoid.

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(1′S,5′R)-Bicyclo[3.1.0]hex-1-ylacetic acid tert-butyl esterC12H20O2Ee = 96%[α]D29=-4.9 (c 0.39, acetone)Source of chirality: (−)-chloromethyl p-tolyl sulfoxideAbsolute configuration: (1′S,5′R)

(1′S,6′R)-Bicyclo[4.1.0]hept-1-ylacetic acid tert-butyl esterC13H22O2Ee = 92%[α]D30=+1.7 (c 0.69, acetone)Source of chirality: (−)-chloromethyl p-tolyl sulfoxideAbsolute configuration: (1′S,6′R)

(1′S,7′R)-Bicyclo[5.1.0]oct-1-ylacetic acid tert-butyl esterC14H24O2Ee = 99%[α]D30=-56.6 (c 0.52, acetone)Source of chirality: (−)-chloromethyl p-tolyl sulfoxideAbsolute configuration: (1′S,7′R)

(1′S,8′R)-Bicyclo[6.1.0]non-1-ylacetic acid tert-butyl esterC15H26O2Ee = 99%[α]D31=-86.8 (c 0.45, acetone)Source of chirality: (−)-chloromethyl p-tolyl sulfoxideAbsolute configuration: (1′S,8′R)

(2R,1′R,6′R)-2-Bicyclo[4.1.0]hept-1-yl-4-phenylbutyric acid tert-butyl esterC21H30O2Ee = 98%[α]D28=-41.5 (c 0.22, EtOH)Source of chirality: (−)-chloromethyl p-tolyl sulfoxideAbsolute configuration: (2R,1′R,6′R)

(2R,1′R,7′R)-2-Bicyclo[5.1.0]oct-1-yl-4-phenylbutyric acid tert-butyl esterC22H32O2Ee = 99%[α]D30=-26.2 (c 0.27, EtOH)Source of chirality: (−)-chloromethyl p-tolyl sulfoxideAbsolute configuration: (2R,1′R,7′R)

(2R,1′R,8′R)-2-Bicyclo[6.1.0]non-1-yl-4-phenylbutyric acid tert-butyl esterC23H34O2Ee = 99%[α]D22=-18.7 (c 0.98, EtOH)Source of chirality: (−)-chloromethyl p-tolyl sulfoxideAbsolute configuration: (2R,1′R,8′R)