Imines difluoromethyl

The second asymmetric synthesis deals with the preparation of a C-difluoromethyl iminosugar. The key step of this synthesis is a hetero-Diels-Alder reaction with a chiral imine of difluoroacetaldehyde (Figure 6.32). ... 

However, difluoromethylation occurs when nucleophiles intercept difluoro-carbene generated under basic conditions, providing a route to difluoromethyl-ethers of phenols [33] and thiophenols [34]. The reaction with phosphite anion leads to the corresponding difluoromethyl phosphonate (see Sect. 2.3.2) while nucleophilic carbanions such as alkynes [35] also undergo formal alkylation, as do malonates [36,37]. An -difluoromethylaziridine was reported in a reaction with a glycine imine [38]. The scope of the established chemistry is summarised in Fig. 1. Bromodifluoromethylation occurs with a similar range of nucleophiles [39,40], and also with carbonyl-stabilised carbanions such as malonates [41,42]. 

C yclohcxyl-4-ethoxycarbony 1-2-methoxycarbonyl-2-methyl-3-trifluoromcthyl- ElOb,. 546 (FjC-en-COOR + Imin) l-Difluoromethyl-hcptafluoro-2H-ElOa, 668 (9H - 9F) 1-Difluoromethyl-octafluoro- F.lOa. 668 (10 H - 10 F)... 

Difluoromethyl-Substituted Imines, Imidoyl Chlorides, and Nitrones. These CF2H nitrogen-bound building blocks have received much recent interest. A few examples are given in Scheme 4.34, along with their fluorine, proton, and carbon NMR spectral data. 

Reaction of AT-methy lene-ftrr-bu tvl.i in i n c with octafluoroisobutylene in diethyl ether in the presence of water leads to unexpected l,3,7-oxadiazocan-4-one ring system 155 as a result of the complex sequence of reactions (Scheme 39 <1996ZOB344>). It is believed to include steps of imine hydration, cyclization accompanied by elimination of tert-butylamine, and final hydrolysis of difluoromethyl moiety into carbonyl group. 

An interesting variation of the aza-Corey-Chaykovsky reaction provides a pathway to difluoromethyl-substituted aziridines. Reduction of trifluoromethylimine 143 with magnesium in the presence of chlorotrimethylsilane gave the enamine 144. Treated with dimethyloxosulfonium methylide in DMSO, 144 hrst underwent desilylation and tautomerization to produce imine 145, which then afforded aziridine 146 via the aza-Corey-Chaykovsky reaction in 92% yield. 

Addition to Imines. An elegant diastereoselective fluoride-induced nucleophilic (phenylthio)difluoromethylation of (R)-(N-r-butylsulfinyl)imines with PhSCF2SiMc3 was reported by Li and Hu. The reaction afforded the corresponding products in 30-89%... 

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