Racemic 2,3-dihydro-1-phenylbenzo[b]phosphole was obtained by reduction of 1-phenylbenzo[b]phosphole-1-oxide, itself derived by ring-closing metathesis of phenylstyrylvinylphosphine oxide. The title compound was then reoxidized under asymmetric Appel conditions. Comparison of the sense and degree of the stereoselectivity to those obtained with an open-chain analogue indicated that the ring system does not affect the selectivity of the process. This in turn strongly suggests that the stereoselection is not related to pseudorotamer preferences in putative phosphorane intermediates.
1b Recently Rashatasakhon and Harmata 2 synthesised a rigid analog of the inhibitory neurotransmitter gamma-aminobutyric acid via an initial exhaustive dechlorination of the PCA adduct with a 2-substituted furan. However, as far as we know, this chemical is not available in laboratory chemicals suppliers' catalogues. To our knowledge, the only reported procedure for making polychlorinated acetone uses chlorine gas in the presence of an organic base for the non-selective substitution of hydrogen atoms in acetone. This results in a mixture of products that has to be separated in a tedious distillation step to give PCA in low yield.3 Therefore, we believe it is useful to disclose our results for the preparation of PCA under Appel conditions, 4 which can be performed with readily available starting materials at room temperature with work-up by filtration and simple distillation.Our interest in PCA arose through our discovery of the dynamic resolution of phosphines through asymmetric oxidation under Appel conditions with chiral non-racemic alcohols, such as menthol.5 In our studies we found that the electrophilic chlorine source used in the reaction plays a major role in determining the selectivity. 6 Notably there was 40% increase in selectivity when switching from carbon tetrachloride to hexachloroacetone (HCA). 7 Since PCA is produced in these reactions, we then wished to study the reaction using PCA as a cross-check on the chlorine source. In contemporary organic chemistry it remains a substantial challenge to perform selective dechlorination 8 and, to our knowledge, there are no reports of the replacement of one chlorine atom out of six with hydrogen. It was therefore pleasing to discover that the Appel reaction itself could be manipulated to make PCA exclusively.In preliminary investigations triphenylphosphine (TPP) was used in our standard process with HCA in the presence of menthol and various other alcohols. The alcohol has to be chosen judiciously with respect to its reaction by-product, which can complicate the purification of the PCA -e.g. in the case of menthol the product neomenthyl chloride made the isolation of PCA by distillation tedious. However, much more seriously, we also found that, commonly, multiple declorination occurs, producing an inseparable mixture of HCA, PCA and symmetrical tetrachloroacetone (sym-TCA). 9 We gained some insight into this problem on monitoring the reaction by 31 P NMR. We concluded that the PCA formed in the reaction via the intermediate chlorophosphonium salt (CPS A, δ P 64.5 ppm) 10 on route to the alkoxyphosphonium salt, (APS-1, δ P 58.9 ppm) 11 probably competes with HCA for phosphine via the intermediate CPS B (δ P 73.3 ppm) to form TCA, leaving behind unreacted HCA (Scheme 1). We assume that the rates of reaction of TPP with both HCA/PCA would be similar but the PCA can build up in the presence of HCA if the reaction of CPS-A with the alcohol is faster. A R T I C L E I N F O A B S T R A C TArticle history: Received Received in revised form Accepted Available onlin...
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