Science of Synthesis

Westbrook, J. A.; Schaus, S. E., Science of Synthesis, (2007) 20, 1125.

There has been extensive use of transition metals to mediate C—C bond formation during the incorporation of difluoromethyl groups into organic compounds. Alkyl 2,2-difluoro-2-haloacetates are the most common compounds used for delivery of the difluoromethylene moiety. ‌Scheme 9‌ summarizes the numerous reaction modes in which metals have been employed to facilitate such additions. Copper(0) is most commonly used during the cross coupling of vinyl halides, e.g. ‌38‌[‌50‌] and ‌39‌,[‌51‌] to either 2-bromo-2,2-difluoroacetates or 2,2-difluoro-2-iodoacetates (‌Scheme 9‌). Reformatsky-type reactions are also prevalent in the literature. For example, the nickel(0)-catalyzed coupling between the styrylzirconocene species ‌40‌ and isopropyl 2-bromo-2,2-difluoroacetate gives the 2,2-difluoro-substituted ester ‌41‌ in 65% yield.[‌52‌] More nucleophilic zirconium and zinc species have been generated from ethyl 2-chloro-2,2-difluoroacetate and ethyl 2-bromo-2,2-difluoroacetate; such species add to benzaldehyde (‌42‌)[‌53‌] and alkynylaldehydes such as ‌43‌ (‌Scheme 9‌).[‌54‌]

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Meeeeeeeeeee Meeeeeeee

Meeeeeeee (M)-8,8-Meeeeeee-8-eeeeeeeee-8-eeeeee (‌88‌); Meeeeee Meeeeeeee:[‌88‌]

M 88-eM eeeee-eeeeeeee eeeee eee eeeeeee eeee Me(Me)8MeM (Meeeeeee'e eeeeeee, 8 eeee), eeeeee eeeee eeeeeeeeeee eeeeee/eeeee (8 ×), eee eeee eeeeeeeee ee MMM (8 eM). Meeeeeeeeeeeeee (8 eeee) eee eeee eeeee eee eeeeeee eee eee eeeeeee eee eeeeeee ee eee eeee (eeeeeee eeee Me eeee) eeeee eeeee eee 88 eee. Me e eeeeeeee 88-eM eeeee, MeMe8(MMe8)8 (8.88 eeee) eee Me8M (8.88 eeee) eeee eeeeeeeeee eeeeeeee, eee eeee eeeeeeeee ee MMM (8 eM) eeeee eeeee. 8.8 M MeMe ee eeeeeee (8.88 eeee) eee eeee eeeee eeeeeeee, eee eee eee eeeeeee eee eeeeeee eee ee eeeeeeeeee 8 eee. Mee eeeeeeee eee eeee eeeee eee eeeeeee, eeeeeeeeeeeeee eeee eeeeeeeee 8-eeeee-8,8-eeeeeeeeeeeeeee (8.8 eeee) eeeeeee ee MMM (8.8 eM), ee eee eeeeeeeee eeeeeeeeeeeeeeeee eeeeeee ee ee. Mee eeeee eeeeeee eee eeeeeee ee ee eee 8 e, eeee eeeeeeee eeee 8 M MMe (8 eM), eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeeeee eeee eeeeee eeee eeeee (8 × 88 eM), eeeee (MeMM8), eeeeeeee eeee e eee ee eeeeee eee (88 × 88 ee) eeee MeMMe eeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee; eeeee: 88%.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8e, 888.
• 8.Meeeee-Meee, (8888) M 88-8, 8888.
• 8.Meeeee-Meee, (8888) M 88e, 888.
• 8.Meeeee-Meee, (8888) M 88e, 888.