Asymmetric hydrogenation of cyclohexane-1,2-dione over cinchonidine-modified platinum
Introduction
Heterogeneous enantioselective hydrogenation using chirally modified metal catalysts is a promising route for the synthesis of optically pure compounds using a heterogeneous process. One of the most investigated catalysts for such reactions is the platinum cinchona alkaloid system [1], [2], [3], [4], [5], [6], [7], and the mechanism of enantiodifferentiation is the target of ongoing research in several laboratories. The scope of the reaction is steadily increasing, although it is still rather limited to α-keto acid derivatives and “activated” ketones.
Here we investigate the heterogeneous enantioselective hydrogenation of a cyclic vicinal diketone, cyclohexane-1,2-dione. The enantioselective hydrogenation of vicinal diketones on Pt with cinchonidine as modifier has been in the focus of several studies. Investigated diketones include butane-2,3-dione [8], hexane-3,4-dione [9], and 1-phenylpropane-1,2-dione [10]. The reduction of diketones can be a helpful tool in deducing the stereochemical requirements for fast reaction, since several reaction pathways compete, as shown in the reaction network in Fig. 1. The vicinal diketones investigated so far show considerable structural flexibility. In particular they can exist in cis and trans conformation, which makes analysis of stereochemical requirement difficult. We therefore decided to investigate cyclohexane-1,2-dione (1), which has a fixed cis conformation of the keto groups.
Several applications of the chiral hydrogenation product cyclohexane-1,2-diol (3) have been reported. (R,R)-cyclohexane-1,2-diol is used in organic synthesis as a chiral auxiliary. The conjugate addition of organocuprate reagents and Grignard reagents to α,β-unsatured esters of chiral (R,R)-cyclohexane-1,2-diol proceed with high diastereoselectivity [11], [12]. For instance, it is used as an auxiliary for the enantio- and diastereoselective synthesis of β-substituted five-, or six-membered cyclohexanecarboxylates [13]. It is further used as a photocrosslinkable chiral doping agent in liquid-crystal mixtures and in optical devices [14] and in the preparation of carbohydrate mimetics having anti-adhesive properties [15], [16].
Section snippets
Experimental
A 5 wt% Pt/Al2O3 catalyst (Engelhard 4759) was prereduced in flowing hydrogen for 90 min at 400 °C. The platinum dispersion after heat treatment was 0.27 as determined by TEM measurements. Toluene and cinchonidine were used as received (Baker, Fluka). The reactant cyclohexane-1,2-dione (1) (Avocado >98%) was distilled before use. The hydrogenation reactions were carried out in a 100-ml stainless-steel autoclave equipped with a 50-ml glass liner and PTFE cover. The reactor was magnetically
General features of the reaction
The enantioselective hydrogenation of cyclohexane-1,2-dione(1) resulted in an 81.3% enantiomeric excess (ee) in favor of (1R,2R)-trans-cyclohexane-1,2-diol ((R,R)-3) at full conversion under standard conditions. The diastereomeric excess (de) of the cis-cyclohexane-1,2-diol ((R,S)-3,(S,R)-3)) was 22.9% at complete conversion. Due to kinetic resolution the ee of the (R)-intermediate (R)-2 reached very high values, close to 100%, toward the end of the reaction. We found that the purity of the
Discussion
Rate constants for the enantioselective hydrogenation of butane-2,3-dione, based on the same reaction network as the one in Fig. 1, have previously been reported [8], which allows a comparison of the reactions of the two diones. There are similarities but also important differences. A striking similarity is the finding that for the second reaction 2→3 the rate constant kSR is the largest, i.e., the (S)-2→(S,R)-3 reaction is the fastest. kSR is less than four times larger than the other rate
Conclusions
The racemic and asymmetric hydrogenation of cyclohexane-1,2-dione (1) was investigated and the reaction network analyzed. In the absence of modifier the first hydrogenation step is considerably faster than the second, leading to a high intermediate concentration of the 2-hydroxycyclohexanone (2). In the presence of cinchonidine the latter is never present at high concentration due to rate acceleration of the second hydrogenation step induced by the modifier. Kinetic analysis of the reaction
Acknowledgements
Financial support by the Swiss National Science Foundation is kindly acknowledged.
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