Herein, we report an efficient isomerization–transfer hydrogenation reaction sequence based on a cobalt pincer catalyst (1 mol %), which allows the synthesis of a series of anti-Markovnikov alcohols from terminal and internal epoxides under mild reaction conditions (≤55 °C, 8 h) at low catalyst loading. The reaction proceeds by Lewis acid (3 mol % Er(OTf)3)-catalyzed epoxide isomerization and subsequent cobalt-catalyzed transfer hydrogenation using ammonia borane as the hydrogen source. The general applicability of this methodology is highlighted by the synthesis of 43 alcohols from epoxides. A variety of terminal (23 examples) and 1,2-disubstituted internal epoxides (14 examples) bearing different functional groups are converted to the desired anti-Markovnikov alcohols in excellent selectivity and yields of up to 98%. For selected examples, it is shown that the reaction can be performed on a preparative scale up to 50 mmol. Notably, the isomerization step proceeds via the most stable carbocation. Thus, the regiochemistry is controlled by stereoelectronic effects. As a result, in some cases, rearrangement of the carbon framework is observed when tri- and tetra-substituted epoxides (6 examples) are converted. A variety of functional groups are tolerated under the reaction conditions even though aldehydes and ketones are also reduced to the respective alcohols under the reaction conditions. Mechanistic studies and control experiments were used to investigate the role of the Lewis acid in the reaction. Besides acting as the catalyst for the epoxide isomerization, the Lewis acid was found to facilitate the dehydrogenation of the hydrogen donor, which enhances the rate of the transfer hydrogenation step. These experiments additionally indicate the direct transfer of hydrogen from the amine borane in the reduction step.
[Fe(PNP)(CO)HCl] (PNP=di-(2-diisopropylphosphanyl-ethyl)amine), activated in situ with KOtBu, is a highly active catalyst for the isomerization of allylic alcohols to ketones without an external hydrogen supply. High reaction rates were obtained at 80 °C, but the catalyst is also sufficiently active at room temperature with most substrates. The reaction follows a self-hydrogen-borrowing mechanism, as verified by DFT calculations. An alternative isomerization through alkene insertion and β-hydride elimination could be excluded on the basis of a much higher barrier. In alcoholic solvents, the ketone product is further reduced to the saturated alcohol.
Manganese PNP pincer complexes are excellent catalysts for the isomerization of allylic alcohols to the ketones. The reaction proceeds via a dehydrogenation/hydrogenation mechanism as shown by DFT calculations and deuterium labelling.
Catalytic isomerization of allylic alcohols in ethanol as ag reen solventw as achieved by using air and moisture stable cobalt (II) complexes in the absence of any additives. Under mild conditions, the cobaltP NP pincer complex substituted with phenyl groups on the phosphorusa toms appeared to be the most active. High rates were obtaineda t1 20 8C, even thought he addition of one equivalent of base increases the speed of the reaction drastically.A lthough some evidencew as obtained supporting ad ehydrogenation-hydrogenation mechanism, it was proven that this is not the major mechanism. Instead, the cobalt hydride complex formed by dehydrogenation of ethanol is capable of double-bond isomerization through alkene insertion-elimination.Isomerization reactions comply with the principles of green chemistry. [1] The catalytic isomerization of allylic alcohols into the saturated carbonyl compounds is an elegant synthetic process that eliminates the more conventional two-step oxidation and reduction pathway. [2] During the last half century, many preciousm etal catalysts for allylic alcoholi somerization, based on Ir,R u, Rh or Pd have been developed. [2, 3] Some of these even work well at ambient temperature. [4] Although noble metals playa ni ndispensable role in catalysis, they are rather expensive, less abundant and generally not used in the last step of drug synthesis. Thus, catalysts based on cheap metals like iron [5] and nickel [6] have been used for the isomerization of allylic alcohols recently.N evertheless, the requirement of either activateds ubstrates [5b] or the need for activation of the catalyst make those systemsl ess desirable. Recently,r eports have appeared on the sole use of base as catalystfor the isomerization of allylic alcohols to the corresponding ketones. [7] To the best of our knowledge,t here is only one report on the use of a cobalt catalyst[ HCo(CO) 4 ]t hat can promote the isomerization of an allylic alcohol to an aldehyde or ak etone, but harsh conditions including the use of toxic carbon monoxide were required to achievel ow conversionsa nd selectivities towards the desired products. [8] Recently,c obalt pincer complexes have been discovered to be effective catalysts [9] for hydrogenation, [10] dehydrogenation, [10g, 11] transfer hydrogenation, [12] hydrosilylations-hydroborations, [13] alkene isomerization [14] and N 2 activation. [15] Hanson and co-workersh ave reportedacationic cobalt(II) alkyl complex, which was appliedf or the hydrogenation of aldehydes, ketones and imines,a sw ell as for the isomerizationo fa lkenes. [16] Furthermore, Liu andc o-workers have recently reported impressive findings about pincerc obalt complexest hat are suitable catalysts for regioselective olefin isomerizationb yu sing ammonia borane as the activation source. [13] Althoughm any catalytic reactions have been performed with pincerc obalt catalysts, isomerization reactions of allylic alcohols with this type of complexes are still unknown.Herein, we report the first cobalt(II) catalyzed isomeri...
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