JACS: ruthenium catalyzed cross coupling of secondary alcohols
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Last Update: 2019-03-09
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Source: Internet
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Author: User
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The alkylation of carbonyl compounds and alkyl halides under strong base conditions (such as n Buli, LDA, etc.) is to prepare α - and β- The most commonly used method of substituted ketones, but there are some disadvantages in this method, such as: (I) the reaction will produce by-products such as stoichiometric metal halides and polysubstituted ketones; (II) the split coupling of carbonyl compounds reduces the atomic economy of the reaction; and (III) the high price of organic halides and carbonyl compounds (scheme 1a) Therefore, the use of cheap and environmentally friendly alcohols in alkylation is an ideal alternative Among them, the direct cross coupling of hydrogen free acceptor alcohols provides the most atom economical and environmentally friendly method (scheme 1b) for the construction of C-C bond The reported reactions include the catalytic self coupling of primary alcohols, the cross coupling of primary alcohols and secondary alcohols, and the self coupling of secondary alcohols However, the catalytic cross coupling of two different secondary alcohols has not been reported (scheme 1c) Recently, Professor Chidambaram gunanathan of niser, India, has developed a method of combining β - disubstituted ketones with two different cross couples of secondary alcohols The catalyst only needs the amount of alkali and ruthenium catalyst, and no stoichiometric oxidant H 2O and H 2 are the only by-products of the reaction Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b00025) (source: J am Chem SOC.) firstly, the reaction conditions were screened with 1-phenylethanol and cyclohexanol as substrates (Table 1) When the reaction is carried out under the conditions of 1 mol% catalyst, 1,5 mol% potassium TERT butanol and 125 ℃, the cross coupling products can be obtained with 86% separation yield The control experiment shows that catalyst and alkali are essential for the success of the reaction (source: J am Chem SOC.) later, the author studied the range of cross coupling reaction between various secondary alcohols and Cyclohexanols (scheme 2) The 1-phenylethanol substituted by methyl, methoxy and benzyloxy reacts well with cyclohexanol, and the yield decreases slightly when the electron absorption group is substituted In addition, heteroaryl and naphthalene substituted secondary alcohols were well tolerated in the reaction (source: J am Chem SOC.) in addition, the author explored a series of secondary alcohols (scheme 3) for cross coupling reaction Both cyclic and acyclic secondary alcohols can be directly coupled with benzyl secondary alcohols When the cyclohexyl ring contains substituents, the product is a mixture of non enantiomers Through X-ray single crystal structure diffraction, the author determined the single crystal structure of the main isomer 3b, and revealed that the two substituents on the cyclohexyl ring are in 1,4-cis conformation When the amount of catalyst and alkali is increased, the acyclic aliphatic secondary alcohols without activation can react smoothly Various secondary alcohols such as 2-propanol, 2-butanol, 2-pentanol, 3-pentanol and 4-heptanol are well tolerated and can be selectively converted into β - disubstituted ketone (3N - 3T) (source: J am Chem SOC.) finally, the mechanism of the reaction was studied (scheme 4) The olefin product 5A was selectively obtained by the reaction of 1-trimethylphenylethanol with 2-adamantane alcohol with large steric hindrance GC analysis showed that there was no alkylation product in the product The mixture of alkylation product 3T and olefin product 5B was obtained by the reaction of 1-trimethylphenylethanol with 4-heptanol These results show that the steric hindrance of catalyst 1 leads to the interruption of hydrogen path, and then the reaction is carried out through α, β - unsaturated ketone intermediates The results of deuterium labeling indicate that the dihydrogen released from cyclohexanol is preferentially added to the unsaturated intermediate These results clearly show that the catalytic cross coupling of secondary alcohols is sensitive to steric hindrance (source: J am Chem SOC.) based on the experimental results, the author proposed the reaction mechanism of cross coupling reaction (scheme 5) First, catalyst 1 reacts with alkali to form unsaturated active intermediate I, then reacts with two secondary alcohols to obtain alkoxy coordinated ruthenium intermediates II and II '; then β - hydrogen elimination leads to the formation of ketone intermediates a and B, and at the same time produces ruthenium complex III; a and B produce α, β - unsaturated carbonyl compound C through alkali mediated cross aldol condensation, and finally The β - disubstituted ketones were obtained by selective hydrogenation of III (source: J am Chem SOC.) conclusion: Professor Chidambaram gunanathan of niser, India, has developed a method for the preparation of β - disubstituted ketones by cross coupling of secondary alcohols The reaction has a wide range of substrates, and H 2O and H 2 are the only by-products This reaction provides a precedent for the development of new green and sustainable catalytic methods.
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