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. 2018 Oct 5;8(10):9537-9542.
doi: 10.1021/acscatal.8b02928. Epub 2018 Sep 13.

Cu-Catalyzed Decarboxylative Borylation

Jie Wang  1 , Ming Shang  1 , Helena Lundberg  1 , Karla S Feu  1 , Scott J Hecker  2 , Tian Qin  1 , Donna G Blackmond  1 , Phil S Baran  1
Affiliations

Cu-Catalyzed Decarboxylative Borylation

Jie Wang et al. ACS Catal. .

Abstract

A simple method for the conversion of carboxylic acids to boronic esters via redox-active esters (RAEs) is reported using copper catalysis. The scope of this transformation is broad, and compared with the known protocols available, it represents the most inexpensive, rapid, and operationally simple option. In addition to a full exploration of the scope, a kinetic study was performed to elucidate substrate and reagent concentration dependences.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Decarboxylative borylation to access vaborbactam. (B) Discovery of a Cu-catalyzed decarboxylative borylation and optimization of reaction conditions. B2pin2 = bis(pinacolato)diboron, TMEDA = N,N,N′,N′-tetramethylethylenediamine.
Scheme 1
Scheme 1. Scope of the Cu-Catalyzed Decarboxylative Borylation with NHPI Redox-Active Esters
Reaction conditions: (a) RAE (1.0 equiv), Cu(acac)2 (30 mol %), LiOH·H2O (15.0 equiv), MgCl2 (1.5 equiv), B2pin2 (3.0 equiv), dioxane/DMF, rt, 10 min. (b) Cu(acac)2 (20 mol %) and B2pin2 (1.5 equiv) were used. (c) 3.5 mmol scale. (d) In situ reaction with NHPI (1.0 equiv) and DIC (1.0 equiv). (e) [Ni] yield referred to reported yield in ref (2). (f) [hν] yield referred to reported yield in ref (3). (g) [PET] yield referred to reported yield in ref (4). (h) solvent MTBE/DMF was used. Ts = tosyl, Boc = tert-butyloxycarbonyl, Fmoc = fluorenylmethyloxycarbonyl. NHPI = N-hydroxyphthalimide, DIC = N,N’-diisopropylcarbodiimide.
Scheme 2
Scheme 2. Cu-Catalyzed Decarboxylative Borylation to Synthesize Target Compound 2 and Cost Comparisons with Other Methods
(a) 0.1 mmol scale. (b) 2.5 mmol scale. (c) The cost of raw materials for one mole reaction setup. See the Supporting Information for details. (d) B2cat2 prepared from B2(NMe2)4 and catechol. e) Ir[(ppy)2dtbpy]PF6 prepared from IrCl3 × H2O in 2 steps.
Scheme 3
Scheme 3. (A) Kinetic Studies of Cu-Catalyzed Decarboxylative Borylation and Concentration Dependences for This Transformation; (B) Reactions Orders in [Cu] for Formation of Product and Major Byproduct; (C) Relationship between the Relative Rates of Productive and Side Reactions to mol % Cu
Selectivity to desired product is enhanced by high [Cu] and low [RAE]. Yields were determined by LC-UV.
Scheme 4
Scheme 4. Proposed Cu-Catalyzed Borylation Mechanism
See this image and copyright information in PMC

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