Palladium catalyzed oxidative esterifications of aldehydes and benzylic alcohols


Over the past 10 years there has been a successful effort on the direct esterification of aldehydes with alcohols  using palladium catalysts mainly using molecular oxygen as the oxidant as the most environmentally friendly variation.

The common proposed mechanism for the transformation is shown below

The first step is the reduction of the Pd(II) species to Pd(0) and recently Xu and co-workers (Chem. Com. 2012, 48, 8592-8594) have taken this in consideration and added hydrosilanes to the reaction mixture in order to accelerate the first catalytic step in the aerobic oxidation of benzylic acohols.

 

Polymethylhydrosiloxane (PMHS) was found to be the best performing hydrosilane and gave high chemoselective oxidation for benzyl alcohol.  However, the reaction was found to be substrate dependent and for other substituted benzylic alochols, the aldehyde was the major product (Table 1)

Further attempts to improve the conversion and selectivity on o-tolylmethanol lead to the discovery that addition of BiCl3 as co-catalyst resulted in complete conversion and excellent ester selectivity and reduction of the reaction time. The optimized bimetallic Pd/Bi catalyst in the presence of PMHS proceeded in high yield and excellent selectivities also on different benzylic alcohols (Scheme 1).

Scheme 1.

 In the former oxidative esterification there was no reported issue of dimeric esterification presumably because methanol is used as solvent and therefore in large excess.  A highly selective cross-oxidative esterification was reported earlier this year by Lei (Angew. Chem. Int. Ed. 2012, 51, 5662) where the esterification of an aldehyde with a benzylic alcohol occurred before any alcohol oxidation. This selective transformation was achieved by using benzyl chloride as the oxidant. Other organohalides selectively converted the benzylic alcohol to the corresponding aldehyde without any ester formation. (Table 2) The use of aryl halides for the oxidation of alcohols is well documented and Lei’s paper cites a review by Muzart from 2003 (Tetrahedron 2003, 59, 5789), although there have been more recent publications improving this reaction  (J. Org. Chem. 2011, 76, 1390; Org. Lett. 2003, 5, 2485)…but not cited.

The use of 2-chloroactophenone as oxidant of alcohols has not been reported before but a similar reactivity with a-bromo sulfoxide has been previuosly described by Asensio (Adv. Synth. Catal. 2007, 349, 987-991). Lei, however, describes the alcoholisis step to generate I2 in Scheme 1 to occcur at the Pd-enolate bond of I1 (A-B = Cl-enolate) whereas Asensio proposes the alcoholisis to occur at the Pd-Cl bond. In the case of benzyl chloride, the alcoholysis is proposed to occur at the Pd-Cl bond by Lei, and he confirms it by isotopic labeling experiments.

The benzyl group seems therefore to be the key for the selective esterification of aldehydes with alcohols and Lei proposes that it forms a n3-coordination to palladium and facilitates dissociation of one of the triphenyphosphine ligands favouring the coordination of the aldehyde to the palladium.

The high selectivity of this reaction allows the authors to use the reagents (aldehyde and alcohol) in a 1:1 ratio, rather than using the alcohol in excess as originally described by the authors who first described the oxidative esterification using benzyl chloride (Tetrahedron Lett. 2011, 52, 5319). By the way…no proper citation (again) to this reference in Lei’s paper!!.

As the original publication (Table 3), Lei’s procedure is suitable for electron-rich and electron-deficient aromatic aldehydes and also aliphatic aldehydes and a,b-unsaturated aldehyes, their novelty, however, is the use of various aliphatic, benzylic and allylic alcohols  without alcohol oxidation observed (Table 4), making this piece of work a general and selective oxidative esterification of aldehyde with alcohol in a 1:1 ration.

 

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