Branched-Selective Alkene Hydroboration Catalyzed by Earth

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Branched-Selective Alkene Hydroboration Catalyzed by Earth-Abundant Metals WEIWEI FAN, Li Li, and Guoqi Zhang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00550 • Publication Date (Web): 24 Apr 2019 Downloaded from http://pubs.acs.org on April 24, 2019

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The Journal of Organic Chemistry

Branched-Selective Alkene Hydroboration Catalyzed by EarthAbundant Metals Weiwei Fan, †,‡ Li Li,*,† and Guoqi Zhang,*,‡ †

College of Chemical Engineering and Pharmacy, Jingchu University of Technology, Jingmen 448000, China Department of Sciences, John Jay College and Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, 10019 NY, USA * Corresponding Author. Email address: [email protected] (L. L.); [email protected] (G. Z.) ‡

ABSTRACT: Catalytic hydroboration of alkenes is a well-established method to access borane-functionalized hydrocarbons. While linear-selective hydroboration was predominantly reported, catalysts enabling opposite selectivity (branched-selective) are attracting considerable interests, especially when Earth-abundant metals are utilized. This Synopsis summarizes recent progress in Earth-abundant-metal-catalyzed, branched-selective hydroboration of alkenes, while overviewing the historical contributions to this reaction using precious metals. Lessons learned from the current state of this topic that can guide future catalyst design are presented, alongside with challenging issues remaining to be addressed.

1. INTRODUCTION Since its first observation by H. C. Brown in 1956,1 the hydroboration of alkenes has been recognized as one of the most powerful ways to access borane-functionalized hydrocarbons, namely, organoboranes that have found prominent applications in pharmaceutical, petroleum and fine chemical industries. 2 Originally used borane reagents for hydroboration include highly reactive boranes such as diborane (B 2H6), BH3-THF complex and some alkylboranes that typically enable alkene hydroboration at ambient temperature without a catalyst.3 However, issues associated with these methods are the high reactivity and extreme air-sensitivity of the resulting organoborane products that largely limit their applications in practical synthesis. To address this, milder and easy-to-handle dialkoxyborane reagents including catecholborane (HBcat) and pinacolborane (HBpin) have been introduced to replace the highly active boranes or alkylboranes, but reactions usually require elevated temperature and/or a catalyst, perhaps due to the weakened Lewis acidity of the boron centers. 4 Scheme 1. The Model Hydroboration of Alkenes with Regioselective Products

Thanks to the pioneering work by Mannig, Nöth and coworkers on the discovery of a metal-catalyzed hydroboration of alkenes and alkynes with HBcat using a (PPh3)3RhCl complex, the well-known Wilkinson’s catalyst in 1985,5 transition metal catalyzed hydroboration of alkenes has experienced tremendous growth in the past three decades. The regioselectivity relevant to a typical hydroboration reaction of terminal alkenes with alkoxyboranes refers to two forms of products: the linear product (popularly labelled as ‘anti-Markovnikov’ selectivity in the literature) and the branched one (‘Markovnikov’ selectivity) as depicted in Scheme 1. Comparing to the linear selectivity that is more commonly observed in uncatalyzed and metal-catalyzed versions of alkene hydroboration, branched-selective hydroboration is still a challenge and examples were scarcely reported with precious metal catalysts over decades. Several comprehensive review articles focusing on transition-metal-catalyzed hydroboration of alkenes were published earlier between 1991-2005.3,4,6,7 Since then, much increased efforts have been made in this area using transition metals, in particular Earth-abundant metals as catalysts. A few reviews emerged, where the general (asymmetric) hydrofunctionalization of alkenes and alkynes catalyzed by Earth-abundant metals has been discussed in 2018-2019.2,8-11 We noticed that a more specific review on branched-selective hydroboration of alkenes is lacking in the literature. Therefore, in this Synopsis we focus on the recent progress of branched-selective hydroboration of

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alkenes catalyzed by Earth-abundant transition metals such as Cu, Co, Fe, Ni, and Mn. One single example on the main group element, Mg, is also included. The synthetic utilization of branched alkylboronate esters obtained from branched hydroboration, if any, is discussed as well. Of note is that the current state-of-the-art branched-selective hydroboration is limited to vinylarene substrates, except in the cases of several Cu catalysts. 2. OVERVIEW OF PRECIOUS-METAL-CATALYZED ALKENE HYDROBORATION Shortly after the discovery of Wilkinson’s catalyst, Hayashi and Ito reported branched-selective hydroboration of styrene with HBcat using cationic phosphine-Rh(I) catalysts.12,13 As BINAP/[Rh(COD)2]BF4 brought considerable advance in asymmetric induction, several new RhI systems containing chiral P-ligands have also been developed.14-19 Evans20 and Dai21 reported branched-selective styrene hydroboration with HBcat using Wilkinson’s catalyst. Later on, Burgess and coworkers underlined the complexity of Wilkinson’s catalyst/HBcat system and performed a preliminary mechanistic study to understand the origin of branched-selectivity.22 Furthermore, Marder’s and Baker’s groups employed Rh(η3-2-Me-allyl){(Pri2PCH2)2} as a precatalyst for highly branched-selective hydroboration of vinylarenes with HBcat, while linear selectivity was observed for aliphatic alkenes.23 Supercritical-CO2 enhanced regioselectivity was also reported by Baker and Tumas.24 Recently, Aggarwal and coworkers developed a chiral (NCN)-RhIII precatalyst for enantioselective and branched-selective hydroboration of unactivated terminal alkenes while using a sp2-sp3 diboron reagent and water as proton source.25 Takacs also reported asymmetric RhIII-catalyzed regioselective hydroboration of γ,δ-unsaturated amide derivatives.26 3. COBALT-CATALYZED BRANCHED-SELECTIVE ALKENE HYDROBORATION Cobalt-based catalysts for branched-selective hydroboration of alkenes have been one of the most developed systems among Earth-abundant metal catalysts observed to date. Table 1 illustrates the structures of molecular cobalt (pre)catalysts that are effective for branched-selective hydroboration and summarizes the results on the model reaction of styrene with HBpin. In 2015, Chirik’s group reported the first cobalt(II)monoalkyl complex (1) based on a redox-active 2,2′;6′,2′′-terpyridine (tpy) ligand for hydroboration of alkenes. 27 While linear-selectivity was revealed for aliphatic alkenes, they also showed that in the case of styrene branched selectivity was obtained with 25:1 branched to linear (b/l) ratio. However, no further examples of vinylarenes were reported in this work. A few months later, the same group developed a simple catalyst, (Ph3P)3CoH(N2) (2), that enabled branched-selective hydroboration of styrene with comparable regioselectivity (b/l = 20:1). 28 Interestingly, this catalyst promoted the isomerization−hydroboration of terminal alkenes, allowing boron incorporation adjacent to π-systems even in alkene substrates where the C=C bond is at a remote position (Chart 1).

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Table 1. Recent Advance of Cobalt Catalysts for BranchedSelective Hydroboration of Vinylarenes.a

A summary of regioselective hydroboration of styrene using 1-8

catalyst solvent time (mol %) 1 1 (1.0) MTBE 98) 85 (>98) (>99) 90 (>95) (99) (90) (92) 82 (99)

b/l

ref.

25:1 20:1 20:1 32:1 19:1 19:1 24:1 12:1

27 28 29 30 31 34 35 37

Later on, the Hollis group reported air-stable CoIII(CCC) pincer complexes of N-heterocyclic carbene (NHC) ligands. It was revealed that complex 3 (Table 1) acted as a precatalyst for hydroboration of styrene in the presence of an activator, LiHBEt3.29 The observed b/l ratio was 20:1 (Table 1, Entry 3). Despite its potential, no further reactivity tests were reported with this catalyst system. Chart 1. Catalytic Alkene Isomerization-Hydroboration Promoted by 2, by Chirik28, a

A more general cobalt-catalyzed branched-selective hydroboration of alkenes was developed by the Thomas group in 2017.30 The authors introduced a stable CoII complex (4) based on bipyridyl-oxazoline ligand and NaOtBu as an activator for alkene hydroboration. They observed that for a range of

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vinylarenes, the b/l ratios of hydroborated products were up to 98:2, with 45-92% isolated yields (Chart 2). However, the regioselectivity of hydroboration decreased to 70:30 (b/l) for carbonyl-functionalized alkene, 5-hexen-2-one, where the ketone part remained intact during the reaction (10w). Additionally, 1,1-disubstituted aliphatic alkene was converted to the linear boronate ester 10x with moderate yield and linear selectivity. In 2017, Zhang’s group reported dinuclear CoII-alkyl complexes based on flexible NNN ligands for hydroboration of alkenes.31 Catalytic experiments confirmed the high activity of 5 (0.5 mol%) in promoting branched-selective hydroboration of styrene without additional activators (Table 1, Entry 5). The reactivity and regioselectivity were, however, substrate-dependent (Chart 3). For 4-halo-substituted styrenes (11b-11d), moderate isolated yields of branched products was obtained and the regioselectivity for 4-chlorostyrene and 4-bromostyrene was reasonable, yet it was poor for 4-fluorostyrene (b/l, 55:45). In addition, styrenes bearing electron-donating or electron-withdrawing groups (11e-11g) underwent hydroboration with good yields and high branched-selectivities. For aliphatic alkenes (11j-11m), the reactions offered linear-selectivity. In contrast, exclusively linear selectivity was found for both aromatic and aliphatic terminal alkenes when a related Co-PNP pincer catalyst was employed.32,33 Chart 2. Select Product Scope for Hydroboration of Alkenes Catalyzed by 4, by Thomas30, a

Chart 3. Select Product Scope for Hydroboration of Alkenes Catalyzed by 5, by Zhang31, a

Chart 4. Select Product Scope for Hydroboration of Alkenes

Catalyzed by Co(acac)3, by Findlater34, a

In 2018, the Findlater group reported the branched-selective hydroboration of alkenes catalyzed by commercially available Co(acac)3 in the presence of organic ligands (mainly phosphines) and NaOtBu as an activator.34 They found that four ligands (12-15, Chart 4) were effective while combined with Co(acac)3/NaOtBu to give good branched-selectivity for a range of alkenes. Particularly, triphenylphosphine (PPh3, 12) was found to promote the reaction with highest yield and selected for the examination of substrate scope. In this method, a variety of vinylarenes bearing electron-donating and electronwithdrawing groups, halogen, and ester substituents (16a-16g) were hydroborated with good to excellent yields and high branched selectivity. It was found that increased steric hindrance caused opposite regioselectivity (16h). They also tested one aliphatic substrate, 1-hexene (16m), and linear-selectivity was observed. In an effort to develop new ligand scaffolds for cobalt-catalyzed hydroboration of alkenes, the Gomes group reported the synthesis of substituted mono(2-iminopyrrolyl) cobalt(II) complexes for alkene hydroboration.35 Whereas high linear-selectivity was observed for aliphatic terminal alkenes, the regioselectivity proved to be poor for styrene. Tuning steric bulkiness on the 5-position of pyrrolyl group appeared to affect the regioselectivity. However, the best results showed only slight excess of branched product (b/l = 4:3). Recently, Geetharani’s group reported branched-selective hydroboration of vinylarenes using an NHC-supported cobalt(I) catalyst (7, Table 1).36 In this method, branched-selectivity for a good substrate scope of vinylarenes was demonstrated, while using 7 (3 mol%) at 50 °C without the presence of an activator. Good yields and regioselectivities were obtained for vinylarenes bearing electron-donating groups (17a-17h, Chart 5), yet electron-withdrawing substituents led to lower branched-selectivities (17i-17k). This catalyst is effective for 1,1-disubstituted (17l, 17m) and 1,1,2-trisubstituted (17n) vinylarenes affording tertiary boronate esters with high branched-selectivity, which was not disclosed in previous cobalt-based systems. Sterically congested 1,3,5-trimethyl-2-vinylbenzene was hydroborated with good effectiveness, yet poor selectivity (b/l = 46:54, 17n). The method was also applied to internal alkenes (17o-q)



and in the case of 1-phenylpropene, the branched product was exclusively obtained (17p). Again, for aliphatic alkenes as well as N-vinylcarbazole linear-selectivities were afforded. Chart 5. Select Product Scope for Hydroboration of Alkenes Catalyzed by Co(IMes)2Cl, by Geetharani36, a

Chart 6. Select Substrate Scope for Hydroboration of Alkenes Catalyzed by Complex 8, by Zhang37, a

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hydroborated smoothly, yet regioselectivity was poor. For 5hexen-2-one, the hydroboration chemoselectively occurs on the alkene, showing linear selectivity different from Thomas’s catalyst 4.31 4. COPPER-CATALYZED BRANCHED-SELECTIVE ALKENE HYDROBORATION Earlier than the observation of cobalt-catalyzed branchedselective hydroboration of alkenes, regioselective copper-catalyzed hydroboration of styrene was reported by Yun’s group in 2009.38 The authors found that styrene reacted with HBpin in the presence of CuCl/KOtBu/dppbz (dppbz = 1,2-bis(diphenylphosphino)benzene) to give branched boronate ester with high conversion and regioselectivity. Encouraged by this finding, the authors investigated asymmetric hydroboration of alkenes by introducing a variety of chiral phosphine ligands and found out the best-performing ligand, P-chiral tangphos 19 (Chart 7). Enantioselective synthesis of 20a was achieved with high enantiomeric excess (ee, 92%) and excellent regioselectivity (b/l > 99:1). For a variety of vinylarenes, the regioselectivity of hydroboration was excellent, along with good enantioselectivities (Chart 7). However, relatively lower ee values were detected for 1- or 2-vinylnaphthalene. In later reports, the same group extended the copper-catalyzed reactions to hydroboration of vinyl boronates39 and norbornadienes.40 In both cases, high regioselectivity and enantioselectivity were achieved. Related copper-catalyzed enantioselective hydroboration of internal alkenes has been independently developed by Hartwig’s group.41,42 Chart 7. Copper-Catalyzed Enantioselective Hydroboration of Styrene Derivatives with Ligand 19, by Yun38, a

Zhang’s group also reported an efficient hydroboration of alkenes catalyzed by cobalt(II) coordination polymer using KOtBu as an activator (8, Table 1).37 This cobalt precatalyst, features a bench-stable coordination polymer exhibiting high turnover frequencies (TOFs) of up to 47520 h-1. The b/l ratio for hydroboration of styrene was found to be comparable to other discrete cobalt catalysts (Table 1, Entry 8). For sterically hindered 2-methylstyrene, high TOF was observed along with a slightly lower regioselectivity (18b, Chart 6). The method was applied to halogenated styrenes and styrenes bearing electrondonating groups in the 4-position, affording the corresponding products with appreciable branched selectivity. 2-Vinylnaphthalene, trans-β-methylstyrene and 2,3-benzofuran were suitable for this method, showing good conversion and regioselectivity. However, a 1,1-disubstituted terminal alkene, α-methylstyrene, appeared not suitable. Aliphatic alkenes could be

Schomaker and coworkers utilized boron reagents containing secondary alkylboranes to develop an elegant application towards further organic transformations.43 In their methodology, branched boronate esters obtained from Cu(I)-catalyzed hydroboration were initially treated with KOtBu to induce the cleavage of C-B bonds affording benzylic carbanions. Then, simply quenching the intermediates in one pot with CO 2, CS2, isocyanates, or isothiocyanates led to effective benzylic functionalization through a sequential hydroboration/carboxylation process. This method has been applied to other electrophiles,


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such as alkyl and benzyl halides for benzylic functionalization with alkyl or aryl groups. They also demonstrated the utility of this methodology through a three-step synthesis of anti-inflammatory drug (±)-flurbiprofen with 76 % overall yield. Later on, the Schomaker and Tantillo groups have found a novel (NHC)CuI-catalyzed 1,3-halogen migration while attempting to synthesize benzyl boronate ester via branched-selective hydroboration of 2-bromostyrene using the method reported by Yun.37 Through a combined computational and experimental studies, they illuminated the mechanism of this unusual transformation.44 It was found that the catalyst is monomeric and the rate-determining step is hydrometallation. As the energy gap between branched-selective hydroboration and 1,3bromine migration was very small (0.2 kcal/mol), minor changes in the nature of substrate always led to mixtures of products. To increase the energy barrier between these two pathways, (NHC)CuI complexes based on the flexible and bulky IPent (21) and IHept (22) ligands were used to substantially improve the effectiveness of 1,3-halogen migration methodology (Table 2).45 In general, reports of branched-selective hydroboration for aliphatic alkenes were relatively underexplored and the challenges have been seen even using the most active cobalt catalysts.28-37 The first copper(I)-catalyzed highly branched-selective hydroboration of alkyl-substituted terminal alkenes was achieved by Ito group (Scheme 2).46 In this contribution, bis(pinacolato)diboron (B2pin2, 25), instead of HBpin had to be used as the boron source, while alcohol was required to provide the proton. It was earlier believed that copper-catalyzed formal hydroboration using B2pin2 and an alcohol operates by a mechanism distinct with the copper-catalyzed hydroboration using HBpin.47

Scheme 2. Plausible Catalytic Cycle of Copper(I)-Catalyzed Branched-Selective Hydroboration of Aliphatic Alkenes, by Ito46

In 2018, Ito and coworkers developed an enantioselective version of copper(I)-catalyzed hydroboration for aliphatic alkenes.48 They used computational approach to design high-performance chiral bisphosphine ligands and carried out Cu I-catalyzed branched-selective hydroboration of unactivated aliphatic alkenes with high enantioselectivity (up to 99% ee). Notably, enantioselective (NHC)CuI-catalyzed branched-selective protoboration of functionalized α-olefins has been achieved by Shi’s group in the same year, where new buttressed NHC ligands were designed and a different diboron reagent other than B2pin2 and methanol were required for high regio- and stereoselectivities.49 Chart 8. Substrate Scope for Copper(I)-Catalyzed Branched-Selective Hydroboration of Alkenes, by Ito46, a

Table 2. Ligand Effects in 1,3-Chlorine Migration, by Schomaker45

In this work, the combination of CuCl with a sterically hindered bisphosphine ligand (26) was used to promote the hydroboration of aliphatic terminal alkenes with reasonable yields. They have demonstrated the application of this methodology for a range of unactivated and functionalized aliphatic alkenes, and generally high branched-selectivity was observed. However, for sterically congested terminal alkene, 3,3-dimethyl-1-butene, only low conversion and poor regioselectivity was obtained (27e). In addition, this method also showed regioselectivity for terminal alkene over internal alkene (Chart 8).46

In a separate contribution, the Montgomery group reported a (NHC)CuI-catalyzed branched-selective hydroboration of terminal and 1,1-disubstituted alkenes using diboron 25 and methanol.50 In their work, the NHC ligands previously utilized by Schomaker’s group44,45 were employed to catalyze hydroboration of a broad range of unactivated and functionalized aliphatic alkenes with high branched-selectivity. As shown in Chart 9, steric interactions between the ligand and alkene favored the formation of intermediate 28a over 28b that leads to the linear product. The method was tolerant of a range of functional groups and even 1,1-disubstituted alkenes (29a-p). The authors extended the utilization of as-obtained branched-alkylboranes for nickel-catalyzed photocatalytic cross-couplings with aryl bromides,50 demonstrating its applications in valuable crosscoupling reactions.



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Hydroboration of Vinylarenes, by Thomas51, a Chart 9. Branched-Selective Hydroboration of Terminal and 1,1-Disubstituted Alkenes, by Montgomery50, a

5. IRON-CATALYZED BRANCHED-SELECTIVE ALKENE HYDROBORATION The first iron-catalyzed branched-selective hydroboration of alkenes was reported by the Thomas group.51 They prepared two alkoxy-tethered NHC-iron(II) complexes (30a and 30b, Chart 10) involving Fe-phenoxy or Fe-alkoxy coordination, respectively, in addition to Fe-Ccarbene bonds. These complexes showed activator-free catalytic activity for hydroboration of vinylarenes with controlled and divergent regioselectivity. Interestingly, while catalyst 30a promoted the linear-selective hydroboration of alkenes with HBcat, 30b was effective for branched-selective hydroboration with HBpin. The authors investigated the substrate scope for 30b-catalyzed hydroboration of vinylarenes.51 Various vinylarenes generally furnished the reaction to afford branched products with good yields and high regioselectivity (30a-k, Chart 10), whereas bulkier 2,4-dimethylstyrene was found to be less effective in terms of both yield and selectivity (31e). However, 4cyanostyrene (31l) and alkyl-alkenes such as 4-phenyl-1-butene (31m) were not suitable substrates, indicating the limitation of this methodology. Chart

10.

(NHC)FeII-Catalyzed

Recently, Lu’s group52 developed a Fe-based system that can promote hydroboration of a broader range of vinylarenes with branched-selectivity. In this method, a tridentate amide ligand (32) was utilized to generate in situ an active iron catalyst in the presence of NaHBEt3 (Chart 11). A variety of styrene derivatives bearing electron-withdrawing and electron-donating groups were suitable substrates for this method (33a-33v), giving branched alkylboronates in good yields and excellent regioselectivities (b/l > 50:1 for most cases). However, ortho-substituted styrenes such as 2-methylstyrene, 2-bromostyrene, or 2chlorostyrene were not compatible. In addition, aliphatic alkenes were hydroborated with only moderate yields and poor regioselectivity.52 Chart 11. Select Product Scope for Hydroboration of Alkenes Catalyzed by Iron(II) Complex, by Lu52, a

Branched-Selective In addition, the Webster group reported on an iron-catalyzed hydroboration of alkenes by a β-diketiminate-FeII monoalkyl complex.53 While aliphatic alkenes showed high linear selectivity, branched-selective hydroboration of a few examples of vinylarenes has been achieved at higher temperature (60-90 °C). 6. MANGANESE-CATALYZED BRANCHEDSELECTIVE ALKENE HYDROBORATION


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The only example of manganese-catalyzed branched-selective hydroboration of vinylarenes was reported by Zhang’s group in 2016.54 They prepared three well-defined MnII-dialkyl complexes (34a-c, Chart 12) based on tpy and its derivatives, and tested the catalytic activity for styrene hydroboration without the use of activators. Although high regioselectivity was found using all three catalysts, 34a appeared most effective, affording branched boronate esters in quantitative conversion. The authors further utilized 34a for a broader substrate scope. Styrenes bearing methyl or halo groups on the para- or meta-position underwent branched-selective hydroboration with excellent regioselectivity and good yields (35b-35g, Chart 12). Examples of styrenes bearing electron-donating or electron-withdrawing group were also included and good yields and excellent regioselectivity were obtained (35h-35j). Limitations of the method were found for α-methylstyrene, 1H-indene, internal alkenes, and nitro- or cyano-substituted styrenes. In addition, although the catalyst was active for aliphatic alkenes, linear-selectivity was observed again. Chart 12. Select Substrate Scope of Manganese-Catalyzed Hydroboration of Alkenes, by Zhang54, a

IMes(Cy3P)NiCl2, by Schomaker55, a

8. MAGNESIUM-CATALYZED BRANCHEDSELECTIVE ALKENE HYDROBORATION Main group metals are important components of Earth-abundant elements and some of them have been frequently utilized in catalytic hydroboration of polar multiple bonds.56 However, they were unknown for promoting branched-selective hydroboration of alkenes until a recent report by Parkin’s group in 2017.57 The authors reported a terminal Mg-hydride compound (38a, Scheme 3). Preliminary catalytic tests revealed that this complex and its alkyl analogue (38b) catalyzed the hydroboration of styrene using HBpin with branched selectivity, albeit very low TOF (0.3 h-1 at 60 °C). No further details on the regioselectivity and substrate scope were disclosed. Of interest is that the authors elucidated experimentally the structure of a branched 1-phenylethyl-Mg intermediate resulting from the insertion of styrene to Mg-H bond of 38a. This provides valuable information on the origin of branched-selectivity related to mechanistic insights which are currently lacking details in Earth-abundant-metal-catalyzed alkene hydroboration. Scheme 3. Magnesium-Catalyzed Hydroboration of Styrene, by Parkin57

7. NICKEL-CATALYZED BRANCHED-SELECTIVE ALKENE HYDROBORATION In 2016, Schomaker’s group reported a nickel(II)-catalyzed branched-selective hydroboration of vinylarenes by using nickel complex with heteroleptic NHC/P-ligands (36, Chart 13).55 The reaction requires KOtBu as an activator as well as elevated temperature (60 °C). A range of vinylarenes were examined and branched-products were exclusively observed in most cases (37a-h and 37l). Of note is that the electronic effect of substituents in these substrates was not significant with regard to the yields obtained. This method was also applied to internal alkenes and vinylnaphthalenes, giving equally high yields and regioselectivity (37i-k). However, functional groups such as amino, phenylthio, ester, bromo and heterocycle were not well tolerated (38a-38f). Chart 13. Branched-Selective Hydroboration Catalyzed by

Scheme 4. Plausible Mechanism for Earth-AbundantMetal-Catalyzed Hydroboration with Branched-Selectivity

9. MECHANISTIC CONSIDERATIONS Despite the lack of sufficient data for fully understanding the



mechanism of branched-selective alkene hydroboration using Earth-abundant metal complexes, a plausible catalytic cycle is proposed here (Scheme 4). According to limited deuterium-labelling experiments and kinetic data reported in Co-, Fe-, and Mg-catalyzed reactions,30,34,36,51-53,57 it is proposed that a key Mhydride as an active catalyst would generate upon activation of metal precatalyst by various hydride sources. The insertion of alkene into the M-hydride species would furnish the formation of an M-alkyl intermediate (40) which then experienced σ-bond metathesis involving HBpin to afford boronate ester, regenerating the M-hydride catalyst. While direct evidence for the formation of 40 has been found in Parkin’s Mg catalysis,57 a mechanism involving M-ƞ3-benzylic complex as key intermediate can not be excluded in other circumstances,36,55 considering the unique branched-selectivity applied only to vinylarenes. 10. CONCLUSION This Synopsis summarizes the recent advances in branched-selective hydroboration of alkenes catalyzed by complexes based on Earth-abundant metals such as Cu, Co, Fe, Mn, Ni and Mg. Except for sporadic examples that were reported before 2015, most progress has been made in the past 4 years. Despite having been explored for such a short term, early transition metal catalysts have displayed great promise as effective surrogates for rhodium catalysts in hydroboration process. Although Earth-abundant metal catalysts are playing a more important role than ever before in the field of regioselective alkene hydroboration, there are still challenges remaining to be addressed. The first issue relates to the substrate selectivity. While aromatic styrene derivatives achieved excellent branched-selectivity in most examples, unactivated aliphatic olefins often suffered from poor or reversed regioselectivity. Examples for aliphatic alkenes are limited to CuI/phosphine system when using diboron reagents and alcohols (or water) as proton sources. Base-metal-catalyzed branched-selective hydroboration of aliphatic alkenes with HBpin (or HBcat) remains unprecedented. Second, functional group tolerance is one of the major problems in all methodologies developed to date. For known examples of hydroboration with HBpin, only simply substituted styrenes showed good activity and branched-selectivity, some reducible functional groups such as nitrile, nitro, amide, alkyne, carbonyl, and heterocycle were either not compatible or not disclosed in detail. In addition, controlling regioselectivity in non-symmetrical 1,2-disubstituted olefins is a significant and unsolved problem. In this regard, it is worth noting that recent work by Lu’s group on asymmetric remote C-H borylation of internal alkenes catalyzed by cobalt through alkene isomerization sheds lights on the future development of this topic,58 while iron complexes also showed promising activity for isomerization/hydroboration of internal alkenes.59 Finally, more comprehensive mechanistic studies for branchedselective hydroboration of alkenes are still required. Both experimental and theoretical work for elucidating the originality of activity and selectivity are highly desired.

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AUTHOR INFORMATION Notes The authors declare no competing financial interest. Biographies

Weiwei Fan received Ph.D. in Polymer Chemistry in 2014 from Northwestern Polytechnical University and then joined the faculty of Jingchu University of Technology as a lecturer in 2015. He is now a visiting scholar in the group of Professor Guoqi Zhang at John Jay College, City University of New York (CUNY). His research focuses on the design of novel catalysts and development of synthetic methodology.

Li Li received his Ph.D. at the Technical Institute of Physics and Chemistry of the Chinese Academy of Sciences in 2010 and then join the faculty of Jingchu University of Technology. His research lies on the development of homogeneous catalysis and synthetic methods that allow improvement in chemical pharmaceutical technology.

Guoqi Zhang earned his doctorate from Institute of Chemistry of the Chinese Academy of Sciences in 2006. He conducted postdoctoral research at University of Basel and later the Los Alamos National Laboratory in the US as a Director’s Postdoctoral Fellow, before he joined John Jay College, CUNY as an Assistant Professor


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in 2013. His research interests include Earth-abundant metal catalysis and organometallic/inorganic chemistry.

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ACKNOWLEDGMENT This work is supported by the Nature Science Foundation of Hubei Province (2016CFB329) and Science and Technology Bureau of Jingmen (2018ZDYF006). We also acknowledge the support from the PSC-CUNY awards (61321-0049) and the Seed grant from the Office for Advancement of Research at John Jay College, CUNY.

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