Stereoselective Monofluoromethylation of Primary and Secondary Alcohols by Using a Fluorocarbon Nucleophile in a Mitsunobu Reaction

Abstract

OH is exchanged: An efficient Mitsunobu reaction that uses a fluorinated carbon pronucleophile for the facile synthesis of monofluoromethyl derivatives of alcohols is reported (see scheme; DIAD=diisopropyl azodicarboxylate). This reaction can be performed under mild conditions and is highly feasible for primary, secondary, allylic, benzylic, and alicyclic alcohols. Excellent enantiospecificity is observed for chiral alcohols.

Patterns of recurrence in patients with acute diverticulitis

“…In the same year, Prakash and Olah reported on the phosphine‐ or base‐catalyzed Michael addition of α‐substituted fluoro(phenylsulfonyl)methane derivatives to a variety of α,β‐unsaturated compounds (again with the exception of α,β‐unsaturated aldehydes) 4. The same authors had previously disclosed an enantiospecific monofluoromethylation of secondary alcohols by using a fluorocarbon nucleophile in a Mitsunobu reaction 5. There are, however, very few asymmetric nucleophilic fluorination methods reported in literature.…”

Efficient 1,4-addition of α-substituted fluoro(phenylsulfonyl)methane derivatives to α,β-unsaturated compounds

“…Hence, compound 2d was synthesized from another known procedure [ 29 ]. Fluorobis(phenylsulfonyl)methane 3f was prepared following a literature procedure by fluorinating bis(phenylsulfonyl)methane, which is commercially available [ 11 ].…”

Selective Nucleophilic Fluoroalkylations Facilitated by Removable Activation Groups

“…The reaction can also be carried out in K 2 CO 3 /DMF system, and it was found to be applicable for various a,b-unsaturated compounds such as ketones, esters, nitriles, and sulfones. 40 The successful use of 41 in Mitsunobu reaction reported by Prakash and co-workers 41 is another impressive example for the mediation of NFE. The reaction was performed under mild conditions and was amenable to primary, secondary, allylic, benzylic, and alicyclic alcohols (Scheme 16, eq.…”