Kochi modification

Another valuable alternative to the Hunsdiecker reaction is the Kochi modification,3 which employs a Pb(IV) reagent. It is a one-carbon oxidative degradation of carboxylic acids and is suitable for synthesis of secondary and tertiary chlorides as exemplified by the transformation of carboxylic acid 10 to cyclobutyl chloride (11) mediated by lead tetra-acetate (LTA).16 Further improvement of the Kochi modification employs LTA under milder conditions where N-chlorosuccinimide (NCS) is used as chlorinating agent and a mixture of DMF and HOAc as solvent.17... 

Andrus et al. (109) proposed a stereochemical rationale for the observed selec-tivities in this reaction. The model is based on the Beckwith modification (97) of the Kochi mechanism, suggesting that the stereochemistry-determining event is the ally lie transposition from Cu(III) allyl benzoate intermediates 152 and 153, Fig. 13. Andrus suggests that the key Cu(III) intermediate assumes a distorted square-planar geometry. Steric interactions are decreased between the ligand substituent and the cyclohexenyl group in Complex 152 as opposed to Complex 153 leading to the observed absolute stereochemistry. 

During the final stages of the asymmetric total synthesis of antimitotic agents (+)- and (-)-spirotryprostatin B, the C8-C9 double bond had to be installed, and at the same time the carboxylic acid moiety removed from C8. R.M. Williams et al. found that the Kochi- and Suarez modified Hunsdiecker reaction using LTA or PIDA failed and eventually the Barton modification proved to be the only way to achieve this goal. After the introduction of the bromine substituent at C8, the C8-C9 double bond was formed by exposing the compound to sodium methoxide in methanol. This step not only accomplished the expected elimination but also epimerized the C12 position to afford the desired natural product as a 2 1 mixture of diastereomers at C12. The two diastereomers were easily separated by column chromatography. 

Liu Y, Kochi A, Pithadia AS, Lee S, Nam Y, Beck MW et al (2013) Tuning reactivity of diphenylpropynone derivatives with metal-associated amyloid-p species via structural modifications. Inorg Chem 52 8121-8130... 

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