Difluorohomoallyl alcohols

Indium mediates the coupling of a,a-difluoroallyl carbanion with aldehydes, to give geuz-difluorohomoallyl alcohols.89 hi contrast to many comparable allylations of carbonyl compounds, ketones do not react. 

Similarly, preparation of a,a-difluorohomoallylic alcohols has been achieved by zinc-mediated addition of CH2=CHCF2Br to carbonyl compounds.29 The reaction is successful with dialkyl ketones as well as aliphatic and aromatic aldehydes (Equation 4.12). The allylation products are particularly useful since the alkene may be oxidized to an aldehyde,32 epoxide,33 or converted to a 8-lactone34 via hydroformylation. 

With inspiration from extensive studies on the synthesis and biological activities of 2 -deoxy-2,2 -difluoronucleosides, 3 -dcoxy-3, 3 -di(luoro-i>-ara/mo-furanosyl nucleosides were stereoselectively synthesized, featuring a novel and efficient strategy to prepare 3-dcoxy-3,3-di(luoro-D-ara >m<9-furanosc 7 via chiral gem-A (1 uorohomoallyl alcohol 2 [4], In the presence of indium powder, the reaction of (7 )-glyceraldehyde acetonide 1 with 3-bromo-3,3-difluoropropene gave difluorohomoallyl alcohol 2 in 90% yield as a mixture of two diastereoisomers in a ratio of 7.7 1. Without separation, homoallyl alcohol 2 was subjected to benzylation. When 1.6 equivalents of NaH were used, benzylated compound... 

Boc group of 44, followed by the condensation of the resultant amine with 3-ethoxy-2-propenoyl isocyanate, afforded urea 45. The cyclization of 45 with sulfuric acid and the subsequent removal of the benzoyl group gave thionucleoside 46. Nucleoside 46 was further converted to thionucleoside 47. Meanwhile, gem-difluorohomoallyl alcohol 49, which was derived from (S)-glyceraldehyde acetonide 48 and 3-bromo-3,3-difluoropro-pene, was converted to thionucleosides 50a and 50b by applying the same strategy [13]. Thionucleosides 50a and 50b were further converted to thionucleosides 51a and 51b (see Scheme 8.7). 

Scheme 5.4). Conversion of cw-difluorohomoallyl alcohol 26 to the separable diastereoisomers 27a and 27b was accomplished by the kinetic resolution (NaH/ BnBr/TBAI) and subsequent Os-catalyzed dihydroxylation. Disilylation of isomer 27b furnished the compound 28 in 94% yield. SnCla-mediated removal of the... 

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