JACS: rhodium catalyzed addition cyclization rearrangement series reaction of alkynylhydrazone with organic boric acid

The addition cyclization reaction of alkynes with organic boric acid catalyzed by transition metals is an effective method for the synthesis of carbon rings and heterocycles In this series reaction, the intermolecular and intramolecular bonding experiences a single catalyst mediated nucleophilic reagent and alkyne substrate binding and ring closing process Due to the high efficiency of the reaction, there are many alkynyl substituted π - Systems (such as carbonyl, propadiene, nitrile, isocyanate, imine, etc.) under the action of rhodium catalyst The development of acceptors that can be further modified by catalytic cyclization will significantly expand the synthesis and application of this reaction, but this kind of acceptor has not been explored Recently, the chulbom Lee Group of Seoul University reported that rhodium catalyzed addition cyclization rearrangement series reaction of alkynylhydrazone and organic boric acid can realize the synthesis of cycloalkenes under mild conditions Relevant articles were published on J am Chem SOC (DOI: 10.1021 / JACS 8b05561) Because of the long-term efforts to develop a new cyclization strategy by using the reverse olefin reaction, the author speculates whether this method can be applied to the rhodium catalyzed addition cyclization reaction with n-sulfonylhydrazone as the acceptor It is expected that the catalytic addition of C = n bond between alkenyl and hydrazone is feasible, and the reaction can provide intermediate for the subsequent cyclization Therefore, the author designed a scheme according to the mechanism: allylhydrazide B was produced by cyclization of alkenylrhodium a, and allyldiazole C was obtained by elimination, and nitrogen (scheme 1) was released by migration of reducing alkene The combination of transition metal catalysis and ring rearrangement in series will provide a new method for the synthesis of inner ring olefins through a simple addition cyclization approach In addition, due to the high fidelity of stereochemistry, enantioselective addition of C = n and cis-c-rhodium of alkynes provide an opportunity for asymmetric induction (source: J Am Chem Soc.) at the beginning of the study, in the presence of rhodium catalyst, the feasibility of the series reaction was investigated with alkyne 1 and phenylboronic acid as the model substrate (Table 1) The reaction of ethyl alkyne 1 with n-toluenesulphonylhydrazone side chain and phenylboronic acid (RH (COD) OH] 2 as catalyst and THF as solvent) under the classical addition cyclization condition, the target cyclopentene product 2A can be obtained successfully, and the yield is only 27% (entry1) When the reaction was carried out in toluene or methanol, the yield was increased, but a large number of substrates were not reacted for a long time (entries 2 and 3) Interestingly, the monitoring results of the reaction process showed that 2A formed rapidly in a few minutes, and then the reaction rate dropped sharply, which indicated that the product formation process might be inhibited Subsequently, the author confirmed that the addition of p-tolso2h (10 mol%) would significantly inhibit the reaction, which may be due to the slow metal transfer between rh-o2 STL species and phenylboric acid Because hydrazide 2 'can not be separated, the author designed a temperature controlled "one pot" method to avoid the adverse effect of sulphite on rhodium catalysis: the addition cyclization of rhodium catalyzed 1 and phenylboronic acid was completed in methanol at 0 ℃, and then 2' formed in situ was eliminated at 60 ℃ and rearranged with allyldiazene to obtain cyclopentene 2a in high yield (source: J am Chem SOC.) after determining the optimal reaction conditions, the author discussed the application range of alkynylhydrazone (Table 2) The n-toluenesulphonylhydrazone with isopropyl, methylsubstituted alkynyl and terminal alkynyl is the suitable substrate, and the benzyl substituted cyclopentene product 3-5 is obtained in a good yield The alkynylhydrazone substituted by cyclohexane can also obtain spiro-6 and fused rings 7 and 8 The formation efficiency of six membered ring products 10 and 11 is low The substrate with n-toluenesulfonyl group can react with phenylboronic acid with different electronic properties to obtain pyrroline product 12 (source: J am Chem SOC.) next, the author used chiral diene to replace COD in rhodium catalyst to investigate the feasibility of asymmetric induction (scheme 3) The results show that, by using L1 ligand developed by Hayashi group and toluene water solvent, 2A can be formed asymmetrically in 81% yield and 93% ee value After determining the asymmetric reaction conditions, the mechanism of the reaction was studied with hydrazone 17 as the substrate Allylhydrazinecarboxylate 18 was synthesized from hydrazone 17 catalyzed by [Rh (L1) Cl] 2 in 94% yield and 93% ee value After that, the BOC Group was removed and oxidized to form 2A The EE value was 93% It is important to note that the products of the asymmetric reactions of 2a and n-ts-hydrazone-1 obtained by this route have the same configuration These results show that the reaction involves the C = n bond addition of alkenylrhodium and hydrazone to form allylhydrazide After allylhydrazide was converted to allyldiazene, cyclopentene was obtained by a simple inverse reaction (source: J am Chem SOC.) then, the author further investigated the substrate range of rhodium catalyzed enantioselective addition cyclization rearrangement reaction using a variety of organic boric acids Under the catalysis of [Rh (L1) Cl] 2, 1 can react with a variety of phenylboronic acids successfully to obtain the cyclopentene product 2B - 2G with secondary alkyl chiral center, and the yield of the product is good and the enantioselectivity is excellent Alkenyl boric acid and heterocyclic boric acid are also compatible, and the chiral product 2H - 2I is obtained with medium yield and excellent enantioselectivity (source: J am Chem SOC.) Summary: chulbom Lee research group has developed a new cyclization strategy, which can generate cycloalkenes from alkynylhydrazone and organic boric acid based on transition metal catalysis and rearrangement of cycloalkenes In the first stage, alkynes with n-toluenesulphonylhydrazone undergo rhodium catalyzed aromatization or alkenylation cyclization, in which the hydrazone is used as a guiding group and π - receptor The next stage involves in-situ elimination of n-toluenesulfonyl from cycloaddition products to produce allyldiazene intermediates, which are easy to reverse olefin reaction to form inner cycloalkene products In the process of rhodium catalysis and 1,5-σ rearrangement, it is very important to control the reaction temperature, which can avoid the product inhibition caused by the premature elimination of sulfite The new series addition cyclization rearrangement process can be carried out by enantiomeric control When the rhodium catalyst containing diene ligands is used for the reaction, the cycloalkenes with exo stereocenter can be obtained, which has high enantioselectivity.