Synthesis of optically active (+)-2-benzyl-, (+)-2-octyl-, and (+)-2-tetradec-5′-enylcyclobutanones via metallated chiral imines or hydrazones

A practical asymmetric synthesis of (R)-2-benzyl-, (S)-2-octyl-, and (S)-2-tetradec-5′-enylcyclobutanones was investigated using enantiopure (S)-α-methylbenzylamine, (R)-methoxymethylbenzylamine, or hydrazine (RAMP). These amines were treated with cyclobutanone to afford the corresponding imines or hydrazones, respectively. Metallation of these imine derivatives followed by alkylation with n-octylbromide, benzylbromide, or tetradec-5-enylbromide gave, after hydrolysis, (S)-2-octylcyclobutanone and for the first time optically active (R)-2-benzylcyclobutanone and (S)-2-tetradec-5′-enylcyclobutanone (TECB) with 67–87% ee. The absolute configuration was also established.

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2-BenzylcyclobutanoneC11H12OEe = 79%[α]D20=+124 (c 1, CHCl3)Source of chirality: RAMP-hydrazineAbsolute configuration: (2R)

2-OctylcyclobutanoneC12H20OEe = 87%[α]D20=+42.7 (c 1, CHCl3)Source of chirality: RAMP-hydrazineAbsolute configuration: (2S)

Z-2-Tetradec-5′-enylcyclobutanoneC18H32OEe = 67%[α]D20=+22.7 (c 0.4, CHCl3)Source of chirality: RAMP-hydrazineAbsolute configuration: (2S)