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Letter
Gold-Catalyzed Oxidative Coupling of Terminal Alkynes and Borane Adducts: Efficient Synthesis of #-Boryl Ketones Ji-Min Yang, Yu-Tao Zhao, Zi-Qi Li, Xuesong Gu, Shou-Fei Zhu, and Qi-Lin Zhou ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b02052 • Publication Date (Web): 05 Jul 2018 Downloaded from http://pubs.acs.org on July 5, 2018
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ACS Catalysis
Gold-Catalyzed Oxidative Coupling of Terminal Alkynes and Borane Adducts: Efficient Synthesis of α-Boryl Ketones Ji-Min Yang,1 Yu-Tao Zhao,1 Zi-Qi Li,1 Xue-Song Gu,1 Shou-Fei Zhu,1,* and Qi-Lin Zhou1,2,* 1
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China 2 Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China ABSTRACT: Herein, we report a gold-catalyzed oxidative coupling reaction of terminal alkynes and borane adducts for the synthesis of α-boryl carbonyl compounds, which are versatile organoboron reagents and could undergo various synthetic transformations. This efficient, regiospecific reaction showed good functional group tolerance and could be used for late-stage modification of structurally complex bioactive compounds. KEYWORDS: α-boryl ketones, alkynes, borane adducts, gold catalyst, organoboron
Organoborons are widely used in organic synthesis, materials science, medicine, and other fields.1 The new and efficient synthetic methodologies for organoborones are always highly desired. In particular, α-boryl carbonyl compounds have recently been shown to be versatile synthons,2 a result that constitutes significant progress in organoboron chemistry. However, reliable methods for the synthesis of α-boryl carbonyl compounds are scarce. These compounds are typically prepared by means of a hydroboration–oxidation–rearrangement sequence (Scheme 1a)3 that uses readily accessible and relatively stable alkynes as starting materials. However, the multistep nature of this method and the need for harsh reaction conditions limit its applications. Recently, a transition-metal-catalyzed B–H bond insertion reaction between α-diazo carbonyls and stable borane adducts was reported, providing an alternative route to α-boryl carbonyl compounds (Scheme 1b).4 This route is more straightforward, but α-diazo carbonyls are toxic, explosive, and difficult to make. Therefore, a more efficient synthetic method for α-boryl carbonyl compounds is highly desirable. Herein, we describe a novel method for the synthesis of α-boryl ketones by means of a goldcatalyzed oxidative coupling reaction of terminal alkynes and borane adducts (Scheme 1c). This efficient, regiospecific reaction features good functional group tolerance and can be used for late-stage modification of structurally complex bioactive compounds. Our study was inspired by previous reports of transition-metal-catalyzed alkyne oxidation coupling via metal carbenoid intermediates5 and transition-metal-catalyzed carbene insertion into the B–H bond of borane adducts.4,6 We reasoned that if metal carbenes generated from terminal alkynes could be trapped by borane adducts, αboryl carbonyls could be obtained in a straightforward manner from the alkynes.
Scheme 1. Synthesis of α-Boryl Carbonyl Compounds We began by studying the reaction of naphthyl acetylene 1a, 8-isopropylquinoline N-oxide (abbreviated Noxide hereafter), and trimethylamine-borane 2a (Table 1). First, several representative π-acid catalysts were tested (entries 1–7). Unlike CuCl, Cu(OTf)2, Rh2(OAc)4, and PtCl2, which failed to afford the desired product (entries 1–4), Au(I) catalysts gave α-boryl ketone 3aa in moderate to high yields (entries 5–7). Although Au(I) catalysts are reported to be easily reduced by borane adduct 2a,7 the bulky phosphine ligands (L1–L3) used in this study slowed down catalyst deactivation. Using L3AuNTf2 as the catalyst, we optimized the reaction conditions. A higher yield (90%) was achieved by increasing the amount of borane adduct 2a from 3 to 4 equiv (entry 8). In addition to dichloromethane (DCM), other chlorinated solvents, such as 1,2-dichloroethane (DCE), CHCl3, and PhCl, were also suitable for the reaction (entries 9–11). However, the high-
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ly coordinating solvent THF was not (entry 12). The steric and electronic properties of the borane adduct markedly affected the yield of the reaction. Tributylphosphineborane adduct 2c gave a yield comparable to that for trimethylamine-borane adduct 2a, whereas tributylamineborane adduct 2b and N-heterocyclic carbene (NHC)borane adduct 2d gave much lower yields (entries 13 and 15). The reaction could be performed on a gram scale without compromising the yield (entry 16), which demonstrates the potential utility of this protocol. Other Noxides were also tested as oxidants, but they did not improve the reaction outcome (see Table S1 for details).
3na), methoxy (3oa), trifluoromethyl (3ja), hydroxy (3ia), amino (3ha), amide (3ga), nitro (3ea), carbonyl (3ka, 3la), and ester (3fa). Notably, some of the above-mentioned functional groups (e.g., hydroxy, amino, carbonyl) are not amenable to the previously reported methods for the synthesis of α-boryl carbonyls.3,4 Alkynes bearing a heteroaromatic ring (3pa, 3qa) or an alkenyl group (3ra) also gave excellent yields of the corresponding products. The structure of 3na was confirmed by X-ray diffraction analysis of a single crystal.8
Table 1. Transition-Metal-Catalyzed Oxidative Coupling of Naphthyl Acetylene 1a and Borane Adducts 2: Optimization of the Reaction Conditions. a
entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16d
catalyst equiv of 2 CuCl 3 Cu(OTf)2 3 Rh2(OAc)4 3 PtCl2 3 L1AuNTf2 3 L2AuNTf2 3 L3AuNTf2 3 L3AuNTf2 4 L3AuNTf2 4 L3AuNTf2 4 L3AuNTf2 4 L3AuNTf2 4 L3AuNTf2 4 L3AuNTf2 4 L3AuNTf2 4 L3AuNTf2 4
solvent DCM DCM DCM DCM DCM DCM DCM DCM DCE CHCl3 PhCl THF DCM DCM DCM DCM
2 2a 2a 2a 2a 2a 2a 2a 2a 2a 2a 2a 2a 2b 2c 2d 2a
products 3aa 3aa 3aa 3aa 3aa 3aa 3aa 3aa 3aa 3aa 3aa 3aa 3ab 3ac 3ad 3aa
yield (%)b N.D.c N.D. N.D. N.D. 27 38 87 90 75 80 68
