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    Home > The application of transition metal catalysis in free radical asymmetric reaction

    The application of transition metal catalysis in free radical asymmetric reaction

    • Last Update: 2018-10-28
    • Source: Internet
    • Author: User
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    Compared with ion reaction, free radical reaction has many advantages, such as relatively mild reaction conditions, good functional group tolerance, and the ability to assemble complex molecules efficiently and quickly However, due to the high reactivity and instability of free radicals, it is a challenging problem to control the enantioselectivity of free radical reactions Early studies focused on the use of the interaction between chiral Lewis acid and free radical acceptor or donor to control selectivity This strategy usually requires a chemical calculation of the amount of chiral reagent and is carried out at low temperature to inhibit the uncatalyzed background reaction Mukund P Sibi has done a lot of pioneering work in this field, and published many review papers [1] Another important strategy is to combine organic catalysis with free radical chemistry, including hydrogen bond catalysis [2], SOMO catalysis [3] and photo oxidation-reduction organic catalysis [4] In recent years, transition metal catalyzed highly enantioselective radical reactions have developed rapidly, and many important research results have emerged In this regard, Professor Kong Wangqing of the Institute of higher studies of Wuhan University summarized this field on chin J chem., and the article was selected as the cover of the magazine (chin J chem., 2018, 36, 247 Doi: 10.1002/cjoc.201700745) Fig 1 strategy of controlling stereoselectivity by transition metal catalysis (source: chin J chem.) the author mainly introduces three strategies of controlling stereoselectivity by transition metal catalysis: chelation of chiral metal complexes, reduction and elimination of the combination of chiral metal complexes and free radicals, substitution of the outer layer of chiral metal complexes by free radical intermediates Due to the author's limited energy, this paper mainly selects some representative examples to briefly introduce these strategies for readers' reference 1 Unlike the traditional Lewis acid catalysts, the transition metal catalysts can not only coordinate with the substrate to create a chiral environment, but also participate in the formation of free radicals The control of enantioselectivity in free radical reaction can be realized by using chiral titanium complex as catalyst In 2015, weix research group studied the enantioselective and non enantioselective coupling of Titanocene catalyzed aryl bromide with racemic epoxide (Fig 2) [5] The key step of the reaction is to obtain enantioselective β - titanium oxycarbon radical intermediate from the racemic epoxide The bicyclic radical 14 produced by the cyclization is intercepted by the phenyl nickel intermediate to form the nickel (III) intermediate 15 Finally, the two catalysts are reduced respectively to close the catalytic cycle Fig 2 enantioselective arylation of arylhalides and racemic epoxides (source: chin J chem.) in 2014, Meggers first found that the complexes 16-18 of iridium (III) and rhodium (III) can be used as chiral Lewis acid catalysts and photosensitizers for high enantioselective free radical conversion (Fig 3) [6] In the presence of 16 (2 mol%) iridium catalyst, 2-acylimidazole 19 can react with benzyl bromide or benzoyl bromide to obtain α - alkylation product 20 of > 99% ee Furthermore, they extended the reaction to highly enantioselective α - trifluoromethylation, α - perfluoroalkylation and α - Trichloromethylation of 2-acylimidazole [7] The reaction mechanism is as follows: oxygen atom in carbonyl group and nitrogen atom from imidazole group replace two unstable acetonitrile ligands in iridium catalyst to form intermediate 21, and then 21 forms iridium enol compound 22 during α - deprotonation; electrophilic free radicals generated by photoreduction are asymmetrically added to the enol double bond of iridium coordination to obtain the configuration determined 23 Finally, the required ketone 20 was formed by single electron transfer (set) and the activated iridium catalyst was released Figure 3 Enantioselective α - alkylation of 2-acylimidazole (source: chin J chem.) 2 Reduction and elimination of the combination of chiral metal complexes and free radicals Figure 4 Chiral bidentate nitrogen ligands (source: chin J chem.) (1) nickel catalyzed asymmetric Negishi coupling and reductive cross coupling In 2005, Ni was first reported by Fu /The high enantioselectivity Negishi cross coupling of racemic sec α - bromoamide catalyzed by pybox with organozinc reagent (Fig 5) [8] Moreover, various activated electrophilic reagents are also suitable for such reactions, including α - bromosulfonamide, α - CF 3 - substituted alkyl halide, α - halonitrile, α - haloalkyl borate, and benzyl, allyl and propargyl electrophilic reagents These reactions have good functional group tolerance, excellent yield and enantioselectivity Fig 5 enantioselective Negishi cross coupling catalyzed by nickel (source: chin J chem.) in 2013, Reisman team realized the enantioselective reduction coupling of acyl chloride and SEC benzyl chloride catalyzed by nickel for the first time [9] The reaction can be extended to the reduction cross coupling of vinyl bromide and aryl iodine with secondary benzyl chloride, and the enantioselective reduction coupling of α - chloronitrile with aryl iodine, both of which have good yield and excellent enantioselectivity (Fig 6) Figure 6 Enantioselective reduction cross coupling reaction catalyzed by nickel (source: chin J chem.) (2) asymmetric free radical reaction catalyzed by copper In 2013, Buchwald group first reported their pioneering work on asymmetric trifluoromethylation of olefins: chiral bisoxazoline (box) / copper (I) catalyzed alkenyl ester 38 and togni reagent 42 Free radical cyclization was carried out to prepare trifluoromethylated lactones with high yield 39 [10] When TMSN 3 is used as the precursor of azide radical and phi (OAC) 2 is used as oxidant, azide 40 is obtained Using TSCL as the source of sulfonyl radical, the oxidation sulfonation product 41 was obtained The mechanism of this kind of conversion is that copper (I) reacts with RX as a free radical source to obtain copper (II) species and free radical R, and R · p-olefin addition to obtain TERT alkyl radical 43, and finally enantioselective formation of C-O bond Figure 7 enantioselective oxidation functionalization of olefins (source: chin J chem.) in 2016, Liu Guosheng of Shanghai organic Research Institute and his collaborators reported the enantioselective cyanidation of benzyl C-H bond catalyzed by copper on science The reaction was carried out at room temperature, with a wide range of substrates and high enantioselectivity (Figure 8) [11] First, the in-situ active radical x grabs the hydrogen atom of substrate C (SP 3) - h to obtain benzyl radical 59; then, 59 is oxidized and added to the chiral copper (II) species 60 by a single electron transfer metallization process to form copper (III) 61; finally, 61 is reduced to get benzylnitrile Fig 8 enantioselective cyanidation of the C-H bond at the benzyl position (source: chin J chem.) Liu Guosheng's research team further developed a variety of enantioselective bifunctions of styrene and tmscn 3 catalyzed by chiral dioxazoline / copper, including asymmetric cyanotrifluoromethylation, cyanoamination and cyanazide (Fig 9) In addition, they also used the same box / copper (I) catalyst system to achieve high enantioselective arylamination and aryltrifluoromethylation of styrene and phenylboronic acid (FIG 10) Fig 9 enantioselective bifunctionalization of styrene (source: chin J chem.) Fig 10 asymmetric bifunctionalization of styrene (source: chin J chem.) 3 The outer layer of chiral metal complexes is replaced by free radical intermediates Most transition metal catalysis methods usually use catalysts with closed shell electronic structure, and metal free radical catalysis proposes metal centered free radicals as open shell catalysts to control enantioselective radical substitution reactions Zhang developed a series of D 2-Symmetric chiral cobalt (II) porphyrin complexes (FIG 11) [12] Among them, [CO (P1)] can effectively catalyze the asymmetric radical cyclization of diazo compounds, and [CO (P2)] can be used for the intramolecular bicyclization of allyl azido formate 76 [CO (P3)] can be used in asymmetric radical C-H bond alkylation to prepare five membered sulfolane 81 enriched with enantiomers Fig 11 d 2 symmetric chiral cobalt (II) porphyrin complex (source: chin J chem.) Fig 12 asymmetric reaction catalyzed by chiral cobalt (II) porphyrin complex (source: chin J chem.) in 2017, Liu and ready reported rhodium catalyzed olefin and brccl 3 The stereoscopic control step of the asymmetric bifunctionalization of [13] involves the outer layer substitution of alkyl radical chiral metal species The reaction mechanism is as follows: firstly, rhodium (I) catalyst reacts with brccl3 to produce CCL3 radicals and Rh (II) BrCl species 85; CCL3 radicals are added to double bonds to obtain alkyl radicals; finally, C-Br bonds are formed by enantioselective trapping of bromine atoms of chiral Rh (II) BrCl species Fig 13 asymmetric addition of brccl 3 to olefins (source: chin J chem.) finally, the author looks forward to the free radical asymmetric reaction catalyzed by transition metals, and summarizes the problems to be solved in this field: 1) the formation of bonds in the free radical reaction catalyzed by transition metals is still limited to certain positions, such as benzyl position, carbonyl α position, etc Therefore, the development of new catalytic systems to expand the bonding range is an important research direction in the future 2) Although transition metal catalyzed radical reactions have been used in the synthesis of natural products, they are still not universal 3) Although the preparation methods of high stereoselectivity have been developed, the detailed mechanism of some reactions is still not clear enough, and a deep understanding of the mechanism will help to design new catalysts 5849; (b) Bauer, A; Westkamper, F.;Grimme,
    S.; Bach, T Nature 2005 , 436 , 1139; (c)Muller, C.; Bauer,
    A.; Bach, T Angew Chem Int Ed 2009 , 48 , 6640
    [3] (a) Beeson, T D.; Mastracchio, A.; Hong, J B.;Ashton, K.; MacMillan, D W C Science 2007 , 316 , 582;(b) Jang, H Y.; Hong, J B.; MacMillan, D W C J Am Chem Soc 2007 , 129 , 7004; (c) Sibi, M P.; Hasegawa, M J Am Chem Soc 2007 , 129 , 4124
    [4] (a) Nicewicz, D A.; MacMillan, D W C Science 2008 , 322 , 77; (b) Nagib, D A.; Scott, M E.; MacMillan, D W C J Am.Chem Soc 2009 , 131 , 10875
    [5] Zhao, Y.; Weix, D J J Am Chem Soc 2015 , 137 , 3237
    [6] Huo, H.; Shen, X.; Wang, C.; Zhang, L.; Röse, P.;Chen, L.-A.; Harms, K.; Marsch, M.; Hilt, G.; Meggers, E Nature
    2014 , 515 , 100
    [7] (a) Huo, H.; Wang, C.; Harms, K.; Meggers, E J.Am Chem Soc 2015 , 137 , 9551; (b) Huo, H.; Huang, X.; Shen,X.; Harms, K.; Meggers, E Synlett 2016 , 27 , 749
    [8] Fischer, C.; Fu, G.C J Am Chem Soc 2005 , 127 , 4594
    [9] Cherney
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