ACS catalyst: palladium catalyzed stereospecific cross coupling of a-boranyl copper with aryl bromide

Palladium catalyzed cross coupling reaction is one of the most effective tools to construct C-C bond At present, significant progress has been made in the cross coupling of SP 2 - hybrid organometallic nucleophiles and aryl halides, but the development of SP 3 - hybrid organometallic is relatively small In particular, due to the unstable configuration of alkyl nucleophiles, it is challenging to construct C-C bonds containing chiral centers by palladium catalyzed cross coupling with alkyl organic metals Recently, Morken's group extended the formation of C-C bond with chiral center to the cross coupling of 1,1-diborane alkane and aryl halide (scheme 1a) by using chiral catalyst Recently, brown and Liao Jian reported Pd / Cu co catalyzed asymmetric aryl boration of alkenyl aromatics, involving the stereospecific cross coupling of chiral organic copper intermediates with aryl halides (scheme 1b) So far, asymmetric cross coupling of organometallic nucleophiles using chiral heterobimetallic intermediates has not been reported α - boranyl copper is a useful intermediate in the synthesis of multifunctional compounds So far, it has not been reported that the csp2-csp3 bond can be constructed by coupling the chiral a-boranyl copper with csp2 electrophilic reagent Recently, jaesook Yun research group of chengjunguan University in South Korea has developed a palladium catalyzed scheme 1C method for the stereodirectional cross coupling of a-borane copper with aryl bromide, which was published in ACS catalyst (DOI: 10.1021 / acscalal 9b05213) Firstly, in the presence of imes CuCl, Pd (OAC) 2 and xphos catalysts, the author began to study the reaction between styrene based boron substrate (1a), brominated benzene (2a) and bis (pinacol) diboron (B2) The olefins containing bpin group can get the expected product in good yield, but the enantioselectivity is poor (D.R = 3:1); when using 1,8-diaminonaphthylboramide (bdan) substrate, a single enantiomer can be obtained in high yield Therefore, the palladium catalyzed stereospecific cross coupling reaction was further studied by using alkenyl boramide (picture source: ACS catalyst.) based on the racemic results, the author screened the chiral NHC ligand (Table 1) through the coupling between 1A - bdan and phenylbromide (2a), and found that in the presence of NHC Cu complex, L4 has the best reactivity and enantioselectivity When the reaction temperature was reduced to 40 ℃, the enantioselectivity was increased and the reaction was moderate; when CuCl was replaced with CuPc, the yield of the product was increased Finally, the product 3A was obtained with 81% yield and high enantiomeric ratio (92.5:7.5) at 30 ℃, and the optimum reaction condition was selected (picture source: ACS catalyst.) after determining the best reaction conditions, the author studied the scope of application of the reaction (scheme 3) When most of the aryl bromides are electrophilic coupling partners, the corresponding coupling products can be obtained with good yield and high enantioselectivity; the aryl bromides containing electron donating groups can obtain the expected products with high yield and high enantioselectivity, which are single non enantiomers; the electron deficient aryl bromides with fluorine, trifluoromethyl and chloro substituents can also be compatible with the catalytic conditions, and A good ratio of enantiomers was obtained The o-methyl substituted aryl bromides are not effective electrophilic coupling ligands, and the yield is moderate Subsequently, the author investigated the scope of application of alkenyl boramide (scheme 3) The alkenyl bdan substrate containing methoxy, chlorine and o-methyl substituents can tolerate the reaction conditions The alkenyl boramide containing heteroaryl group can obtain the corresponding product with medium yield and high enantioselectivity; the cyclohexyl substituted alkenyl boramide can react with good enantioselectivity, but the enantioselectivity of the primary alkyl substituted substrate is low (photo source: ACS catalyst.) the author found the limitation of its application during the investigation of substrate range The expected product (scheme 4a) could not be obtained from the substrate containing large steric substituents such as tert butyl When (z) - 1A is used, anti - 3A instead of syn - 3A can be obtained in 65% yield, but the enantioselectivity is poor (scheme 4b) Under the standard catalytic conditions, alkenyl bromide (4) is not an effective coupling mate (scheme 4C), and the product 5 can only be obtained with medium enantioselectivity (picture source: ACS catalyst.) finally, the author investigated the selective conversion of bpin group in the obtained chiral 1,2-dibromoalkane (scheme 5) As the Lewis acid of bdan is lower than that of corresponding borate ester, it can selectively convert bpin to potassium trifluoroaborate (BF 3K) to obtain 6 In addition, 3b was transformed into trans 1,2-dihydroxy compounds However, amination with 3b and Zweifel olefinization were not successful (picture source: ACS catalyst.) conclusion: jaesook Yun research group has developed a Cu / PD collaborative catalytic method of boronization coupling between alkenyl bdan and aryl bromide By introducing 1,8-naphthalene dimethylaminoborate (bdan) into α - carbon, the palladium catalyzed cross coupling of α - boranyl copper with aryl bromide has been realized for the first time, and has good enantioselectivity and non enantioselectivity In addition, in the presence of PD xphos catalyst, α - boranyl copper, as an effective ligand, can cross couple with aryl bromine, and obtain trans-1,2-dibromide with good enantioselectivity.