Département de chimie moléculaire

Nonracemic cis-disubstituted cyclobutanones I [R = Me, PhCH₂, H₂C:CHCH₂, Ph(CH₂)₃, PhCOO(CH₂)₄, TBDMSO(CH₂)₄, TIPSOCH₂, PhCH₂OCH₂, PhCOOCH₂; R₁ = R; R₂ = H; TBDMS = tert-butyldimethylsilyl; TIPS = triisopropylsilyl] or their enantiomers were prepd. in 61-81% yields and in 92:8->98:2 diastereoselectivities from the corresponding enol ethers II [R = Me, PhCH₂, H₂C:CHCH₂, Ph(CH₂)₃, PhCOO(CH₂)₄, TBDMSO(CH₂)₄, TIPSOCH₂, PhCH₂OCH₂, PhCOOCH₂; R₁ = H; R₂ = R] or their enantiomers contg. the Stericol chiral auxiliary by cycloaddn. with dichloroketene generated in situ from trichloroacetyl chloride followed by redn. in the same pot; trans-cyclobutanones I [R = H₂C:CHCH₂, TIPSOCH₂, PhCH₂OCH₂, PhCOOCH₂; R₁ = H; R₂ = R] were prepd. in 62-73% yields and in >98:2 diastereoselectivities by cycloaddns. of the corresponding trans-enol ethers II [R = H₂C:CHCH₂, TIPSOCH₂, PhCH₂OCH₂, PhCOOCH₂; R₁ = H; R₂ = R] with in situ redn. and isomerization. II [R = Me, PhCH₂, H₂C:CHCH₂, Ph(CH₂)₃, PhCOO(CH₂)₄, TBDMSO(CH₂)₄, TIPSOCH₂, PhCH₂OCH₂, PhCOOCH₂; R₁ = R; R₂ = H] were prepd. in two or three steps by reaction of (R)- or (S)-alpha-methyl-2,4,6-triisopropylbenzyl alc. (Stericol) with trichloroethylene followed by treatment with base, addn. of alkylating agents or paraformaldehyde, redn. of the intermediate alkynes with Lindlar catalyst, and in some cases protection of the hydroxy group; redn. of the intermediate alkynes with lithium aluminum hydride provided the corresponding trans enol ethers. I (R₁ = TIPSOCH₂; R₂ = H) was converted to the nucleoside analog cyclobut-G (Lobucavir) in ten steps.