ACS catalyst: regioselective ammonolysis of 3,4-epoxicol catalyzed by boric acid

The C-3 selective stereospecific ammonolysis of 3,4-epoxy alcohol is a direct way to produce enantiomers to enrich amino alcohol A large number of natural products and bioactive compounds contain amino alcohol structure Although the amino alcohol structure can be obtained by high regioselective ring opening reaction of epoxy structure, there are few examples of high regioselective ring opening of 3,4-epoxy alcohol Professor Hisashi Yamamoto of the University of Chicago and Professor Wang Chuan of the University of science and technology of China have reported a nickel catalyzed C-4 selective ring opening of 3,4-epoxiol Therefore, it is very challenging to find suitable catalyst to realize the selective ring opening of C-3 Recently, Professor Wang Chuan's research group of University of science and technology of China proposed using 3,4,5-trifluorobenzoic acid as catalyst to realize the C-3 ammonolysis of epoxyphenyl alcohol, and used this method to synthesize amino alcohol (scheme 1) with high yield and high selectivity Relevant articles were published in ACS catalyst under the title of "boronic acid catalyzed regioselective aminalysis of 3,4-epoxy alcools" (DOI: 10.1021 / acscalal 8b02591) (source: ACS catalyst.) firstly, racemic trans-3,4-epoxy-1-hexanol (1a) and o-methoxyaniline (2a) were used as substrates to optimize the reaction conditions (Table 1) A series of organoboron catalysts were screened When 3,4,5-trifluorobenzoic acid was used as catalyst, the target product (entry 22) was obtained with excellent yield and regioselectivity After that, the solvent was simply selected The results showed that the target product could be obtained in 98% yield with 15 mol% of 3,4,5-trifluorobenzoic acid as catalyst and toluene or hexafluoroisopropanol as solvent, and the selective ring opening ratio of c3:c4 was more than 99:1 (entry 26, 27) (source: ACS catalyst.) Different primary and secondary amines are reacted with epoxide 1a The results show that the aniline compounds with electron donating groups can get the product 3a-3e in good to excellent yield In contrast, the aniline with electron absorbing groups has poor reactivity, but when the catalyst loading is increased to 25 At mol%, the product 3F - 3I can also be obtained from aniline containing electron withdrawing substituents in a good yield The method is also suitable for β - naphthylamine, secondary aromatic amine and heterocyclic amine, and the corresponding products 3j - 3l, 3M - 3P are obtained in good to excellent yields Among the aniline compounds containing phenol or alcohol, the boric acid showed excellent chemical selectivity (3q and 3R), while the aliphatic amines showed poor activity (3S) In addition, the ring opening reaction between aminoluminate (2t) and steroid containing amine 2U can be carried out successfully, which proves that this method is beneficial to the late functionalization of aromatic amines with complex structures (source: ACS catalyst.) the author further explored the substrate range of boric acid catalytic reaction, and investigated a series of representative epoxyphenol and amine compounds (Table 3) under the optimal conditions As a whole, the target product can be obtained in medium to good yield In terms of regioselectivity, products 3v-3ac, 3aE and 3af were constructed with complete C-3 selectivity It is worth noting that the CIS substituted epoxides have lower reactivity than the trans substituted epoxides (source: ACS catalyst.) finally, the author proposed a response mechanism (scheme 4) 3,4-epoxy alcohol reacts with boron catalyst to form borate, which acts as Lewis acid to activate amine in the transition state of six membered ring, and promotes nucleophilic reagent to attack adjacent C-3 position to form C-3 selective product The repulsion between the R 2 substituent of epoxide and the R 4 group of nucleophilic amine hinders the formation of transition state, which may be the reason for the low efficiency of ring opening reaction of CIS substituted epoxide (source: ACS catalyst.) Summary: the selective ammonolysis of c-3-epoxyphenyl alcohol was carried out with 3,4,5-trifluorobenzoic acid as catalyst Under the standard conditions, all kinds of aromatic amines and 3,4-epoxy alcohols can react successfully, and the reaction can produce high yield and high selectivity amino alcohols.