Mechanism for basic hydrolysis of α-chloronitrile to ketone?

[![enter image description here](https://i.stack.imgur.com/xAWlI.png)](https://i.stack.imgur.com/xAWlI.png)


In Corey's 1969 prostaglandin synthesis,1 compound **2** is formed from compound **1** by:



> 
> [...] treatment with 2.5 equiv of potassium hydroxide (added as a hot saturated aqueous solution) in dimethyl sulfoxide for 14 hr at 25-30°.
> 
> 
> 


Can anybody explain the mechanism of this reaction? I thought of an $\mathrm{S\_N2}$ reaction, followed by nitrile hydrolysis and elimination of $\ce{CO2}$. But $\mathrm{S\_N2}$ there seems impossible, and the elimination of HCl should be more reasonable than decarboxylation.


### Reference


(1) Corey, E. J.; Weinshenker, N. M.; Schaaf, T. K.; Huber, W. Stereo-controlled synthesis of dl-prostaglandins F2α and E2. *J. Am. Chem. Soc.* **1969,** *91* (20), 5675–5677. [DOI: 10.1021/ja01048a062.](http://doi.org/10.1021/ja01048a062)




Your analysis is slightly incorrect, actually. If you do a $\mathrm{S\_N2}$ on the chloride, hydrolyse the nitrile, and decarboxylate, you end up with the wrong oxidation state:


[![Proposed substitution, hydrolysis and decarboxylation route leads to an alcohol.](https://i.stack.imgur.com/XVZw4.png)](https://i.stack.imgur.com/XVZw4.png)


Instead, if you actually get to the cyanohydrin, you could (in theory) simply lose $\ce{CN-}$ to form the ketone:


[![A marginally better but still incorrect route: loss of cyanide ion from cyanohydrin](https://i.stack.imgur.com/TDWXJ.png)](https://i.stack.imgur.com/TDWXJ.png)


However, a $\mathrm{S\_N2}$ reaction at that centre is going to be difficult, to say the least.


The reaction has been studied by Shiner *et al.*,1 who determined that the primary site of attack is likely to be the nitrile. They wrote:



> 
> No mechanistic studies of the hydrolysis step have previously been reported, although pathways involving nucleophilic displacement of chloride or cyanide, affording intermediate cyano- or chlorohydrins, have been proposed. *A priori* we regarded both $\mathrm{S\_N2}$ and $\mathrm{S\_N1}$ displacements as improbable in these systems. 
> 
> 
> 


The immediate product of nitrile hydrolysis is the amide, and the α-chloroamide intermediates were actually isolated:


[![Hydrolysis of nitrile to amide](https://i.stack.imgur.com/HDATo.png)](https://i.stack.imgur.com/HDATo.png)


The mechanism after this involves a cyclisation of the amide onto the $\ce{C-Cl}$. The exact steps are not entirely clear. However, the following was proposed:


[![enter image description here](https://i.stack.imgur.com/7IRvY.png)](https://i.stack.imgur.com/7IRvY.png)




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### Reference


(1) Shiner, C. S.; Fisher, A. M.; Yacoby, F. Intermediacy of α-chloro amides in the basic hydrolysis of α-chloro nitriles to ketones. *Tetrahedron Lett.* **1983,** *24* (51), 5687–5690. [DOI: 10.1016/S0040-4039(00)94173-X.](http://doi.org/10.1016/S0040-4039(00)94173-X)


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