Borane-Catalyzed C(sp³)–F Bond Arylation and Esterification Enabled by Transborylation

Abstract

The activation and functionalization of carbon-fluorine bonds represents a significant synthetic challenge given the high thermodynamic barrier to C-F bond cleavage. Stoichiometric hydridoborane-mediated C-F functionalization has recently emerged, but has yet to be rendered catalytic. Herein, the borane-catalyzed coupling of alkyl fluorides with arenes (carbon-carbon bond formation), and carboxylic acids (carbon-oxygen bond formation) has been developed using transborylation reactions to achieve catalytic turnover. Successful C-C and C-O coupling across a variety of structurally and electronically differentiated arenes and carboxylic acids was achieved using 9-borabicyclo[3.3.1]nonane (H-B-9-BBN) as the catalyst and pinacolborane (HBpin), with broad functional group tolerance. Experimental and computational studies suggest a mechanistic dichotomy for the carbon-carbon and carbon-oxygen coupling reactions. B-F transborylation (B−F/B−H metathesis) between F-B-9-BBN and HBpin enabled catalytic turnover for carbon-carbon bond formation whereas direct exchange between the alkyl fluoride and acyloxyboronic ester (C-F/B-O metathesis) was proposed for carbon-oxygen coupling, where H-B-9-BBN catalyzed the dehydrocoupling of the carboxylic acid with HBpin. ASSOCIATED CONTENTThis material is available free of charge via the Internet at http://pubs.acs.org. Crystallographic data (CIF) General experimental; system optimization; substrate synthesis; general reaction setup and procedure; product data; synthesis of reactive intermediates; single-turnover experiments; crystal data and experimental; computational details; NMR spectra; associated references (PDF)

Selective Csp3–F Bond Functionalization with Lithium Iodide

“…With a set of successful reaction conditions in hand, we continued to investigate the transformation of the benzylic substrate 2. Very efficient conversion into 4-nitrobenzyl iodide (4) was observed in dichloromethane or toluene at room temperature or upon heating (entries [18][19][20][21][22]. In analogy to the previously reported reaction with ytterbium iodide, we assume that the LiI mediated iodination follows an ionic mechanism that is likely to favor either an S N 1 or S N 2 pathway based on the substitution in the substrate structure.…”

Developing organoboranes as phase transfer catalysts for nucleophilic fluorination using CsF

“…1 Many of the most widely used boranes, such as BX3 (X = halide) and B(C6F5)3, are indeed strong Lewis acids towards fluoride and form robust fluoroborates, 2 with [BF4]being an archetypal weakly coordinating anion. 1 Furthermore, boranes such as B(C6F5)3, and even HBR2, 3 are increasingly applied in defluorinative functionalisation of fluorocarbons, with fluoride abstraction by the borane to form a fluoroborate anion a key step (Figure 1). 4 However, by controlling the relative Lewis acidity of the carbon and boron electrophiles it is possible to effect fluoride transfer from fluoroborates to carbon electrophiles.…”

Developing simple boranes as phase transfer catalysts for nucleophilic fluorination using CsF

“…The established dogma is that boranes (BY3) are strong Lewis acids towards fluoride, with the derived fluoroborates, [F-BY3] -, being highly stable towards loss of fluoride.1 Many of the most widely used boranes, such as BX3 (X = halide) and B(C6F5)3, are indeed strong Lewis acids towards fluoride and form robust fluoroborates, 2 with [BF4]being an archetypal weakly coordinating anion. 1 Furthermore, boranes such as B(C6F5)3, and even HBR2, 3 are increasingly applied in defluorinative functionalisation of fluorocarbons, with fluoride abstraction by the borane to form a fluoroborate anion a key step (Figure 1). 4 Thus using fluoroborates to transfer fluoride to carbon electrophiles appears counter intuitive.…”