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    Home > The intramolecular cyclization of α - carbonyl thioylide on (hetero) aryl

    The intramolecular cyclization of α - carbonyl thioylide on (hetero) aryl

    • Last Update: 2019-09-25
    • Source: Internet
    • Author: User
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    In recent years, as a safe substitute of diazo compounds, the application of thioylide in metal catalytic reactions has attracted much attention At present, there are many reports about metal catalysis of sulfur ylide to form carbon heteroatom bond, especially in large-scale industrial environment In addition, the researchers also developed a metal catalyzed reaction of α - carbonyl sulfur ylide to form carbon carbon bond from carbon carbon bond However, most strategies require the use of guiding groups On the contrary, the examples of C-H functionalization without guiding group are limited to the reaction of α, β - unsaturated β - amino ester Recently, the Christophe a ϊ SSA group of the University of Liverpool in the UK reported the intramolecular cyclization of α - carbonylthiofulide on (hetero) aromatic rings without the participation of metals and guiding groups (Figure 1) The cyclization process is promoted by alkali and HFIP (1,1,1,3,3,3-hexafluoro-2-propanol) On the contrary, the cyclization of pyrrole and n-methylindole needs to be carried out in the presence of [{IR (COD) Cl} 2] The related research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 201910821) (source: angelw Chem Int ed.) in the study of rhodium catalyzed C-H cross coupling of α - carbonyl thioylide, the author found that when HFIP and alkali were used to treat substrate 2 at 60 ℃, cyclization product 3 could be obtained in the absence of metal Among them, K 2CO 3 is the best, and the yield is 91% (EQ 1) It is worth noting that the control experiment shows that HFIP is necessary and the reaction will not be carried out in other solvents (Table 1) (source: angelw Chem Int ed.) under the optimal reaction conditions, the author investigated the application scope of the substrate (Figure 2) Ninhydrin-2-one (5a-5f, 5H) can be obtained in good yield from the substrate with electron absorption or electron donor, but the corresponding 5g product can not be obtained from the 4 g of gemodimethylation The substrate 4H - 4N can also be cyclized regioselectively, and 5I - 5m can be obtained with excellent yield However, 4O produces two possible regional isomers 5O equimolar (source: angelw Chem Int ed.) the author speculates that the reaction mechanism is as follows At first, 4A - 4O formed intermediate I in alkaline condition, which was in equilibrium with II and III III is cyclized to IV via (a) and then aromatized to give product 5A - 5O However, the author found that the oxo allylic cation V may be an intermediate product from III to IV, and thought that pathway (b) is a more likely pathway First of all, HFIP is a very strong H-bond donor, which can promote the cleavage of C-S bond in III In addition, it is reported that the combination of HFIP and base can promote the formation of o-allylic cations in the presence of other leaving groups Secondly, when R 1 is me and R 2 (h, p-ibu, p-ome, p-cl) is changed, the relative rate obtained has a good correlation with the Hammett σ P parameter (R 2 = 0.97), and the reaction constant is - 0.6, which is consistent with the results of five center 4 π - electrocyclization of cationic intermediates in other examples Therefore, a similar mechanism may apply to the rearrangement of V to IV Thirdly, when R2 is p-ome, the equilibrium between V and VI leads to the formation of a single solvent decomposition product 7 in 54% yield This side reaction can only be partially avoided if R1 is methyl, such as 4C reaction to obtain a mixture of 5C and 6 In addition, when R 1 does not exist and R 2 is p-cf 3, the cycloacetone part of VII is rearranged by Favorskii to get product 8 When the substrate is 4f, the R 1 substituent completely prevents the reforskii rearrangement The 4 π - electrocyclization of o-allylic cations also explains the absence of 5g and the 5K - 5m regioselectivity of the product, which is due to the fact that another regional isomer cannot follow this mechanism (source: angelw Chem Int ed.) in addition, indole derivative 9 can generate cyclized products 10 and 11 in this reaction system, among which 10 may be intermediates, which can be converted into 11 (scheme 1) under the same conditions However, benzofuran 12 obtained a single product 13 with excellent yield However, pyrrole-14 can only form solvated product-15 under standard conditions The reason may be that 9, 12 and 14 can form o-allyl cations, but 14 can not undergo five center 4 π - electrocyclization (source: angelw Chem Int ed.) later, based on previous patent reports, the author optimized the cyclization conditions of thiophyllide on pyrrole, and found that the product 18 could be obtained successfully under microwave heating with 1 mo% of [{IR (COD) Cl} 2] as catalyst The corresponding cyclized product 18C - 18e can be obtained from various substrates, and it has excellent selectivity for the functionalization of pyrrole C-H bond It is important that the six to eight membered ring compounds 18F - 18h can also be selectively obtained in good yield under iridium catalysis (source: angelw Chem Int ed.) in order to further understand the mechanism of iridium catalytic reaction, the author carried out deuterium labeling experiment The parallel experiments of 21 and [D 1] 21 show that there is no kinetic isotope effect (KH / Kd = 1.0) These results show that in the presence of catalyst, thioyelide produces carbene VIII, which is attacked by nucleophilic attack to form IX, then x is formed by rapid 1,2-deuterium migration, then the product [D n] 22 is obtained by reduction elimination and re aromatization Alternatively, VIII is cyclopropanized to form XII, which becomes the zwitterion XIII, which can also undergo 1,2-migration to generate Xi This reaction path can also explain the deuterium labeling results (source: angelw Chem Int ed.) in a word, the author has developed the chemical specific intramolecular cyclization of α - carbonylthioylide on (hetero) aromatic ring This shows that α - carbonyl thioylide not only has good safety, but also has different reactivity from α - diazone or other precursors.
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