Gem-Difluoromethylation

For recent fluorinated nucleosides reviews, see (a) Meng, W-D. and Qing F-L. (2006) Fluori-nated nucleosides as antiviral and antitumor agents. Current Topics in Medicinal Chemistry, 6, 1499-1528 (b) Qing, F-L. and Qiu, X-L. (2007) Synthesis of gem-difluoromethylated sugar nucleosides. In Current Fluoroorganic Chemistry, ACS Symposium Series 949, pp. 305-322 and references cited therein. 

Table 1. gem-Difluorocyclopropanes from Bromo(difluoromethyl)-triphenylphosphonium Bromide... 

The electrogenerated base from pyrrolidone also promotes the introduction of a gem-difluoromethylen unit to aromatic aldehydes to give difluoromethyl carbinols in high yields (Scheme 4.4) [33],... 

Among the carbonate solvents used in practical lithium batteries, linear carbonates such as dimethyl carbonate (DMC), ethyl methyl carbonate (EMC), and diethyl carbonate (DEC) are well-known good co-solvents (thinner) for EC and PC. The direct fluorination of DMC gave fluorinated derivatives such as mono-fluorinated one, fluo-romethyl methyl carbonate (FDMC), two di-fluorinated ones (bis(fluoromelhyl) carbonate, DFDMC, and difluormethyl methyl carbonate, gem-DFDMC), and tri-fluorinated ones (difluoromethyl fluoromethyl carbonate, TFDMC) as shown in Scheme 2.6 [33]. Three kinds of partially fluorinated DMCs except gm-DFDMC were obtained by fractional distillation of the fluorinated sample. 

Burkholder R, Dolbier WR Jr, MedebieUe M (2001) Synthesis and reactivity of halogeno-difluoromethyl aromatics and heterocycles. Application to the synthesis of gem-difluorinated bioactive compounds. J Fluorine Chem 109 39-48... 

Prakash and co-workers have prepared monofluoro-methyl 3,5-bis(trifluoromethyl)phenyl sulfone and have used it in the fluoroalkenylation of aldehydes and ketones.They employ KOH or CsF as base in DMSO at 20°C. On their side, Hu and co-workers have developed TBTSO2CH2F as a versatile fluoromethylidene synthon. Difluoromethyl 2-pyridyl sulfone has been used for the gem-difluoromethylenation of aldehydes and ketones and was found to be a more efficient difluoromethyfidene synthon than BTSO2CF2H, PTSO2CF2H and TBTS02CF2H. ... 

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