Suero group, Catalonia Institute of chemistry, Spain: new rhodium Carbyne intermediate initiated simple olefin carbon double bond breaking reaction

Introduction: Dr Marcos g suero of the Institute of chemistry of Catalonia (iciq), Spain, has been committed to the study of catalytic formation and reaction activity of new carbon atom intermediates The research group has prepared a kind of diazomethylation reagent based on the framework of high valent iodine, which is activated by photo oxidation-reduction and generates diazomethyl radical RN 2C under mild conditions It is used as the intermediate (R-C ̇: ）Equivalent, it realizes the diazomethylation of electron rich aromatics, further derivatization of the newly introduced diazo group, and finally modular introduction of carbon atom containing specific functional group substitution (nature 2018, 554, 86) Recently, the research group selectively activated the diazo group in Carbyne precursor reagent by transition metal catalysis, resulting in a metal carbene species with high leaving trivalent iodine group, which is the equivalent of metal Carbyne intermediate R ≡ M This active species has the double reactivity of carbene (r 2c:) and carbocation (r 3C +), and can cyclopropane with the double bond of carbon and carbon in simple olefins- Ring opening reaction generates allylic positive ions, which are subsequently captured by nucleophiles to obtain functional rich allylic compounds In form, it realizes the cutting off of inert carbon double bonds and the introduction of single carbon atom, and efficiently and quickly completes the reconstruction of the original molecular skeleton (Fig 1) Relevant research results were published in j.am Chem SOC (DOI: 10.1021 / JACS 9b08632) Figure 1 Catalytic generation of rhodium Carbyne intermediate equivalent to realize carbon carbon double bond cutting (photo source: Dr J am Chem SOC.) Marcos g suero and brief introduction of the research team（ Tarragona), about 100 km (one hour train) from Barcelona Iciq is a highly international, world-class chemical research institute, which publishes about 40 top journals every year Dr Marcos g suero was founded in October 2014 Dr suero, the team leader, is a very nice young chemist who has studied in Cambridge, Harvard and other famous universities His grasp of the subject is very accurate and in place, and he can give very effective guidance to the problems encountered in the course of the subject The research group has published many papers in nature, J am Chem SOC., angel Chem Int ed and other journals within 5 years since its establishment It has made great achievements in the field of carbon atom intermediate chemistry Now there are three members of the research group, one Chinese postdoctoral student and two Spanish doctors At present, the research group is developing and expanding, and hopes to apply for doctor's degree (CSC doctoral joint training or doctoral degree) or postdoctoral program (CSC postdoctoral visiting scholar program or Marie Curie scholarship) together with more domestic scholars Dr suero has a very strong command of chemical frontier and application writing ability He can give the applicant comprehensive proposal writing guidance (the current post doctoral student of the research group is Mary Curie scholar), and the applicant who is interested in this can contact him In addition, full scholarship can also be provided for the outstanding after passing the corresponding assessment Dr suero contact email: mgsuero@iciq.es research group home page: http:// scientific research achievements: new rhodium Carbyne intermediate initiated simple olefin carbon carbon double bond fracture reaction "carbon" Elements are the basic elements of organic chemistry It is of great significance to study the formation, transformation, stability and various influencing factors of various carbon atom active intermediates for understanding and developing novel organic chemical reactions In general, carbon atoms can combine with four different atoms to achieve a stable tetravalent structure If one or two bonds of the tetravalent carbon atoms are broken, a series of active intermediates centered on carbon atoms will be formed, including trivalent positive carbon ions (r 3C +, negative carbon ions (r 3C -), carbon free radicals (r 3C ·) and bivalent carbene (R 2 C:), corresponding to the active organic metal intermediates R-M and metal carbene r = M These carbon containing active intermediates are the stages that many organic chemical reactions need to go through in the process The research on these active intermediates constitutes the basis of the whole organic carbon chemistry at present However, the research on Carbyne carbon intermediates (R-C ̇:) and metal Carbyne R ≡ m active species is far behind Through the transition metal catalyst, Dr Marcos g suero selectively activated the diazo group in Carbyne precursor reagent, and generated a metal carbene species with high leaving trivalent iodine group, which is the equivalent of metal Carbyne intermediate R ≡ M This species undergoes cyclopropanation ring opening reaction with carbon carbon double bond in simple olefins to generate allylic positive ions, which are subsequently captured by nucleophiles to obtain allylic compounds rich in functional groups (Fig 2) Figure 2 Speculated reaction mechanism (photo source: J am Chem SOC.) the researchers used cyclohexene as standard substrate for a series of condition screening and optimization (Figure 3) They dissolved the previously developed pseudo cyclic carbamate precursor 2a in dichloromethane, and slowly added it to the dichloromethane solution containing 5 equivalent cyclohexene and 1 mol% Rhodium octanoate using peristaltic pump The reaction solution was maintained at - 50 ℃ in cold bath during the whole dropping process, and then added 3 The yield of the target product was 17% according to NMR Later, the author found that the rhodium catalysts (rhodium adamantinate and Dubois RH 2 (ESP) 2) with larger steric hindrance can significantly increase the yield of the target product, accompanied by about 10% elimination of by-product formation In the aspect of Carbyne precursor reagent, the reactivity of Carbyne precursor reagent with cyclic and linear framework is poor, and the target product can be obtained with 76% nuclear magnetic yield after the conversion of anti ion from OTF to PF 6 Other nucleophiles such as tetrabutylphosphorium bromide and trimethylsilyl bromide did not give better results Figure 3 Screening of main reaction conditions (photo source: J am Chem SOC.) after determining the optimal reaction conditions, the researchers studied the reactivity of different types of nucleophiles with cyclohexene as olefin substrate, and realized a series of carbon heteroatom bonds such as carbon bromine (6a), carbon fluorine (6b), carbon oxygen (6c-6f) ）, construction of C-S (6g) and C-N (6h-6k) bonds (Fig 4) In addition, all kinds of carbon nucleophiles can react smoothly and form new carbon carbon bond (6l-6r) It is worth mentioning that in such a series of chemical conversion process, on the basis of carbon carbon double bond breaking of cyclohexene substrate, a new carbon carbon single bond and a carbon carbon double bond are formed, and a racemic chiral center is formed on one of the original carbon atoms of SP 2 hybrid double bond, which greatly increases the complexity of the raw material molecule Figure 4 Extension of various types of nucleophiles (photo source: J am Chem SOC.) next, the researchers examined the application scope of olefin substrate (Figure 5) Ethylene, as a chemical raw material with large output and wide application range, can be successfully converted into allyl bromide product with high added value for 6S This process includes the formation of cyclopropane intermediate 8, ring opening and subsequent nucleophilic bromine attack In addition to ethylene, other common chemical raw materials such as propylene, 1-butene, 1-hexene and styrene can all react smoothly to obtain the target allyl bromide (6T - 6W) with high regioselectivity and stereoselectivity The researchers believe that the regioselectivity is determined by the steric hindrances of two reaction sites (α and α ') of allylic cation intermediate 11 Nucleophiles tend to attack the α site with small steric hindrance to obtain linear products In addition, the olefin substituent R and trivalent iodine group tend to be CIS in the cyclopropane intermediate 10, so that the R and ester group (CO2 ET) are trans in the intermediate 11 obtained by ring unscrewing, so the double bond configuration in the product is mainly Z-type (Woodward Hoffmann DePuy rule) The reaction and empirical rules are also applicable to 1,2-disubstituted olefins, such as trans-2-butene and β - methylstyrene, and the target products are obtained with excellent regioselectivity and stereoselectivity The 7 -, 8 -, and 12 membered cyclic alkenes were also able to react successfully, resulting in the allyl bromide product (6Z - 6ab) inserted by a single carbon atom In addition, when 1,1-disubstituted alkenes are used as raw materials, the reaction can generate tetrasubstituted alkenes which are quite challenging in the synthesis field, showing the potential application prospect of this method Fig 5 Application scope of olefin substrate (photo source: J am Chem SOC.) when olefin substrate has nucleophilic reaction site, intramolecular carbon double bond insertion nucleophilic attack cross-linking reaction can take place (Fig 6), resulting in a series of heterocyclic compounds (14-18 ）The series of reactions also experienced the corresponding allylic carbonium intermediate (19 - 22) Fig 6 Intramolecular carbon double bond breaking ring closing reaction (photo source: J am Chem SOC.) finally, the researchers tried to confirm the formation of the key intermediate 4 speculated in Fig 2 through experiments, and then verify the reaction mechanism previously proposed They reacted the ethylene gas with the metal Carbyne intermediate containing long chain substituents at low temperature, and obtained the stable alkyl polyiodide 23 at room temperature for the first time, and determined its structure by single crystal diffraction Subsequent control experiments show that the compound can indeed be captured by nucleophilic tetrabutylammonium bromide to generate target allyl bromide products, thus confirming the whole reaction mechanism (Fig 7) Fig 7 Control experiment (photo source: J am Chem SOC.) Summary: Based on a new kind of carbamate precursor reagent developed by Dr suero group of Catalonia Institute of chemistry in Spain, metal carbamate intermediates are generated by metal catalytic activation, and cyclopropane is adopted- The open-loop series reaction leads to the double bond breaking of carbon and the insertion of single carbon atom The cheap and wide olefin raw materials are efficiently converted into allylic compounds with important application value, and the fixed-point editing at the molecular skeleton level is realized This research methodology has achieved new breakthroughs in the fields of inert carbon bond activation and allylic chemistry, providing new ideas and tools for synthetic chemistry Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of Chemistry