Asymmetric allylation of 1,3-dioxobronylheterocyclopentene catalyzed by JACS: PD
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Last Update: 2019-07-05
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Source: Internet
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Author: User
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Asymmetric functionalization of carbonyl compounds is one of the important methods to construct complex molecules and drugs The asymmetric allyl alkylation of α - hydroxyketone is a typical method, but there are some problems in the regioselectivity of c-alkylation and O-alkylation In order to solve this problem, Hartwig and other research groups reported the asymmetric allylic alkylation of O-protected hydroxycarbonyl compounds catalyzed by Pd or IR, but these asymmetric strategies greatly limited the range of substrates On the basis of the above research background, Professor Barry M Trost of Stanford University reported the asymmetric c-alkylation of unprotected second-order α - Hydroxyketones catalyzed by PD At the same time, the author speculated the possible mechanism: firstly, 1,3-dioxobronylheterocyclopentene 3 formed by the reaction of second-order α - hydroxyketone 1 with arylboronic acid 2 can be used as a pre nucleophilic reagent for PD catalyzed asymmetric alkylation Then, under the catalysis of PD, the pre nucleophilic reagent and π - allyl PD (II) form a counterion pair 5 Then, the c-alkylation product 7 (scheme 1) can be produced by the intramolecular alkylation of 5 and hydrolysis Due to the oxygen affinity of boron, the O-alkylation pathway can be completely avoided Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b04658) (photo source: J am Chem SOC.) firstly, the author optimized the reaction conditions with 1,3-dioxobronylcyclopentene (benzoin 1A condensed with phenylboronic acid) and allylmethyl carbonate as template substrate (Table 1) Through the selection of alkylation reagents, catalysts and solvents, the author found that the target product 7a can be obtained with 82% yield and 90% enantioselectivity by the reaction of 1,3-dioxobronylcyclopentene and allyl tert butylcarbonate in 2.5 mol% PD 2 (DBA) 3 · CHCl 3 and 7.5 mol% L1 (Figure 1) with DCM as the solvent at room temperature (photo source: J am Chem SOC.) then, the author focuses on the more challenging asymmetric α - hydroxyketone (Table 2) By optimizing the reaction conditions, the author found that 1,3-dioxobronylheterocyclopentene and allyl alcohol synthesized by condensation of α - hydroxyketone with p-methoxyphenylboronic acid can react at - 20 ℃ with 5 mol% (CP) Pd (ally) and 7.5 mol% L1 as catalyst, DMM as solvent, and the corresponding products can be obtained with 86% yield, 94% enantioselectivity and 5:1 regional selectivity (photo source: J am Chem SOC.) under the optimal reaction conditions, the author investigated the substrate range of α - hydroxyketone (Table 3) The electron absorption substituted α - hydroxyketone can adapt to the reaction conditions, and the corresponding products can be obtained with medium to good yield, excellent enantioselectivity and regioselectivity However, the regioselectivity of electron substituted α - Hydroxyketones is poor (photo source: J am Chem SOC.) next, the author examined the substrate range of allyl alcohol (Table 4) 1,3-dioxobronylheterocyclopentene can react with allyl alcohols substituted by various aromatic rings and heterocycles, and the corresponding product 10 can be obtained with good yield, high enantioselectivity and excellent regioselectivity (photo source: J am Chem SOC.) considering that there are few reports on the synthesis of asymmetric dienes, the author intends to use dienyl acetate instead of allyl alcohol to realize the synthesis of asymmetric dienes (Table 5) By optimizing the reaction conditions, the author found that 1,4,5-trifluoromethyl substituted α - hydroxyphenylacetone was condensed with 3,4,5-trifluorobenzoic acid, Under the condition of 2.5 mol% PD 2 (DBA) 3 · CHCl 3 and 7.5 mol% L1, CSCO 3 as base, THF as solvent, the reaction of 3-dioxoboroxyheterocyclopentene 11 with dienyl acetate 12 can yield asymmetric diene 13 with 67% yield, 98% enantioselectivity and 97:3 regioselectivity (photo source: J am Chem SOC.) the author speculated that the mechanism of asymmetric diene synthesis (scheme 3): PD catalyzed the conversion of dienyl ester to PD (II) - propadiene complex 14 The intermediate 16 formed by two isomerizations reacts with the nucleophile to obtain the main product 17 In the absence of alkali, the intermediate 16 is prone to generate by-product 19 through β - hydrogenation (photo source: J am Chem SOC.) under the optimal reaction conditions, the author investigated the range of substrates for the synthesis of asymmetric dienes (Table 6) All kinds of substituted α - hydroxyphenylacetone and dienyl ester have good tolerance, and can get various diene products with medium to good yield, excellent enantioselectivity, non enantioselectivity and regioselectivity (photo source: J am Chem SOC.) Summary: Professor Barry M Trost, Stanford University, USA, reported the asymmetric c-alkylation of 1,3-dioxobronylheterocyclopentene catalyzed by PD The asymmetric ketone product can be obtained with good yield, excellent enantioselectivity and regional selectivity At the same time, the asymmetric alkylation of 1,3-dioxobronylheterocyclopentene and dienyl ester can be realized by dynamic dynamic asymmetric conversion.
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