Study group of Zhu Chen, Professor of Suzhou University, reported the ring opening functional group reaction of small tension naphthenic alcohol promoted by visible light

The author: Professor Zhu Chen's group C-C bond activation has always been a challenging problem in organic synthesis chemistry In the past few decades, the free radical promoted ring opening reaction of tension carbon ring has provided an effective strategy for the selective breaking of C-C bond Recently, the ring opening functionalization of Cyclopropanol and cyclobutanol involving free radicals has been widely reported Since the cycloalkanols such as Cyclopentanol, cyclohexanol, cycloheptanol, dodecyl alcohol and pentadecanol have lower ring tension, more stable carbon ring and more difficult and challenging ring opening than other cycloalkanols, the ring opening functional group reaction of small tension cycloalkanols has rarely been reported (scheme1) Scheme 1 strain energy of different rings (source: chem SCI.) recently, Professor Zhu Chen's research group of Suzhou University has developed an efficient and novel visible light promoted bromination reaction Cyclopentanol, cyclohexanol, cycloheptanol, dodecyl alcohol and Pentadecyl alcohol and other small tension cycloalkanols can be successfully opened to generate cycloalkanols that are difficult to prepare by conventional methods Distal brominated fatty ketone The C-Br bond of the product can construct C-N bond, C-I bond, C-B bond and C-C bond rapidly, and then it can be transformed into other valuable compounds through one or two steps of reaction, providing useful intermediates for organic synthesis and pharmaceutical development Relevant research results were published on chem SCI (DOI: 10.1039/c8sc01763h) First of all, 1-phenylcyclopentanol was used as the reaction substrate, NBS as the bromine source, PIDA as the oxidant, and photocatalyst was added Under the irradiation of 14W blue LED, the conditions were screened Finally, the target product was obtained in 78% yield Subsequently, the applicability of the naphthenic alcohol substrate (scheme 2) was investigated First, the ring opening bromination of Cyclopentanol was investigated In general, the electron deficient aryl substituent can produce δ - bromoaliphatic ketones in a good yield, and the change of substituent position (para, meta and ortho) will not affect the reaction Due to the electrophilicity of NBS, the aromatic substituent with high electron density can only obtain a small amount of products, but the reaction can be carried out smoothly by introducing additional electron absorbing groups into the aromatic ring to adjust the electric property, and finally the target product can be obtained in a medium yield The secondary fatty bromide can also be prepared by this method Next, the author studied the ring opening bromination of cyclohexanol more extensively In addition to the functional groups that have been investigated, other groups such as cyano and ester groups can also be compatible to produce corresponding products In addition to aryl substituted Cyclohexanols, alkyl substituted Cyclohexanols can also be reacted to form far-end bromodiketones When there are several substituents on cyclohexanol, the reaction can also be carried out smoothly to form alkyl substituted bromoaliphatic ketones Under the condition of light, hydrogen at the benzyl position is easy to react with NBS When 4 equivalent NBS was added into the reaction system, the toluene substituted arylcyclohexanol would undergo triple bromination, and the product with benzyl and distal position being brominated simultaneously could be obtained in medium yield The product of cyclohexanol derived from 1,4-cyclohexanedione by ring opening bromination is not stable, and it will be further debrominated to form unsaturated 1,4-dione In addition, the reaction is also suitable for ring opening bromination of cycloheptanol, dodecanol and pentadecanol In order to show the practicability of the reaction, the author transformed the products of ring opening bromination into a series of other useful compounds (scheme3) by one or two steps, such as nucleophilic substitution or cross coupling Further transformation of scheme 3 ring opening brominated product (source: chem SCI.), haloperidol is a kind of market antipsychotic drug widely used in the treatment of schizophrenia and Tourette's syndrome After obtaining a series of far-end brominated fatty ketones, the author has completed the preparation of haloperidol analogues with high yield, and is currently testing its biological activity (scheme 4) In addition to ring opening bromination, the method is also suitable for ring opening cyanation and Alkynylation of small tension naphthenic alcohols Under similar reaction conditions, 1-phenyldodecyl alcohol can be successfully converted into distal cyano or alkynyl substituted aliphatic ketones This reaction provides a rapid method to construct distal C-C bond (scheme 5) Scheme 5 cyclocyanation and Alkynylation of small tension naphthenic alcohols (source: chem SCI.) Conclusion: Professor Zhu Chen's research group realized the ring opening bromination of small tension naphthenic alcohol by visible light catalysis Cyclopentanol, cyclohexanol, cyclohexanol, cycloheptanol, dodecyl alcohol, pentadecanol and other substrates can be successfully ring opened to obtain far-end brominated fatty ketone by this method The C-Br bond of the product can be converted into a series of other valuable compounds by nucleophilic substitution or cross coupling This method is also suitable for the ring opening cyanogenation and Alkynylation of 1-phenyldodecyl alcohol with small tension ring It provides a simple and efficient method for the construction of remote C-C bond Review of previous reports of Professor Zhu Chen's research group: CBG information interview with Professor Zhu Chen of Suzhou University