JACS: nickel catalyzed stereoselective diarylation of arylolefins

The carbon carbon double bond in olefins is one of the most basic functional groups in organic compounds, and the olefin double functional reaction is also a kind of relatively common reaction However, the introduction of two different carbon containing functional groups on the double bond via bifunctionalization is rare and very attractive, especially the introduction of two aromatic groups One of the strategies to realize the diarylation of olefins is the cross coupling reaction based on the migration insertion process However, the challenge of this strategy lies in the existence of competitive direct cross coupling and β - hydrogen elimination (mizoroki Heck reaction) of alkyl metal intermediates, which can be alleviated by the use of active olefins It has been reported that the reaction of vinyl aromatics with arylation reagents is diarylation, but the range of substrates is limited Therefore, the heterodiarylation of simple styrene derivatives with 1,2-disubstituted arylalkenes is very challenging Recently, Professor M Kevin Brown of Indiana University in the United States has developed for the first time the stereoselective heterodiarylation of mono substituted, 1,1-disubstituted, 1,2-disubstituted arylalkenes with arylbromides and arylboron reagents catalyzed by Ni Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 8b05680) (source: J am Chem SOC.) firstly, the reaction conditions were screened with styrene (1), 4-tolylboron (2) and 3,5-dimethylbromobenzene (3) as substrates It is found that the target product 4 can be obtained in 77% yield by using toluene as solvent, 7.5 mol% NiCl2 as catalyst, 0.1 equivalent (bpin) 2 as reducing agent and 2.3 equivalent potassium alcohol as base (source: J am Chem SOC.) after determining the best reaction conditions, the author investigated the scope of application of the reaction (scheme 2) The electron donor and electron acceptor substituted styrene derivatives can react smoothly Naphthalene ring and indole ring substituted olefins are also compatible In addition, the author found that 1,1-disubstituted and 1,2-disubstituted alkenes are also suitable substrates, and the reaction mainly produces the CIS addition products of aryl groups However, trisubstituted alkenes and unactivated alkenes cannot react (source: J am Chem SOC.) then, the author studied the substrate range of aryl bromide (scheme 3) The results show that electron donor, electron acceptor and aryl bromide with steric hindrance can all react Ester group, amide group and tertiary amine group can be tolerated in the reaction However, heterocyclic aryl bromides, such as 3-bromopyridine, are not tolerated in this reaction Similarly, aryl boron reagents have a wide range of substrates (source: J am Chem SOC.) further, the author studied the practicability of the reaction (scheme 4) First of all, the reaction can be carried out in gram scale, and the yield and selectivity are similar to those of smaller scale In addition, the reaction was used to synthesize rac-laoxifene (48) Compared with the reported method, the advantage is that the heteroaryl group can be installed in the later stage (source: J am Chem SOC.) finally, the author proposed the possible reaction mechanism (scheme 5): firstly, NiCl2 was reduced to Ni (0) by (bpin) 2 and koet; Ni (0) and AR 2Br were oxidized and added to produce Ni II Brar 2 (56), 56 was transferred and inserted to obtain the complex 57; with the help of koet, 57 and AR 1B (NEO p ）Transition metallization took place to produce 58, 58 which was further reduced and eliminated to form diaryl products It is suggested that the reaction may not involve free radical intermediates Different enantiomers were obtained from the reactions of (E) - and (z) - olefins due to CIS addition (source: J am Chem SOC.) conclusion: Professor M Kevin Brown's research group of Indiana University has developed the Ni catalyzed diarylation of arylolefins for the first time Compared with the known arylation of vinyl aromatics, this method does not need special substrate, and is suitable for 1,2-disubstituted arylolefins The reaction can be used for the effective and modular synthesis of various polyaryl alkanes.