Iridium-Catalyzed 1,3-Hydrogen Shift/Chlorination of Allylic Alcohols**

Chlorinated compounds are among the most common and versatile building blocks in organic synthesis. Among these, achlorocarbonyl derivatives are of synthetic value owing to the variety of functional groups that can be introduced both at the chlorinated a-carbon atom and at the carbonyl functionality. For instance, they readily undergo substitution/addition reactions and cross-coupling reactions and are useful precursors to heterocycles. While a number of methods have been reported for the electrophilic halogenation of aldehydes or ketones containing only one enolizable position, the same reaction for unsymmetrical aliphatic ketones is challenging. Here, most methods rely on steric or electronic differentiation for regioselective functionalization of carbonyl compounds (Scheme 1a). However, many ketones lack the bias to enolize with complete regioselectivity, and the enolization cannot always be directed to the desired position. Importantly, the formation of mixtures of halocarbonyl compounds limits both the yield and the overall synthetic utility owing to the challenge of separating constitutional isomers. We envisaged that a-chloroketones could be synthesized with complete regiocontrol from allylic alcohols through a 1,3-hydrogen shift/chlorination catalyzed by transition metals. A considerable advantage of using allylic alcohols as enol equivalents is that the new bond (to the electrophile) is formed exclusively at the alkenylic carbon atom of the allylic alcohol [RCH(OH) CH=CHR; Scheme 1b]. This type of transformation has almost exclusively been investigated using carbon electrophiles (e.g. aldehydes or imines). A drawback with all these procedures has always been the undesired formation of unfunctionalized ketone by-products (Scheme 1b). Recently, we reported the first example of 1,3hydrogen shift/halogenation for the preparation of a-fluoroketones. While this represented a success in terms of merging a transition-metal-catalyzed isomerization with an electrophilic halogenation, the formation of nonfluorinated ketones (5–20%) could not be avoided and led to challenging separations. Herein, we describe the first chlorination of allylic alcohols, which affords single constitutional isomers of a-chloroketones in up to> 99% yield, and for the first time the formation of ketone by-products is completely suppressed (Scheme 1c). We first investigated the isomerization/chlorination of phenylpent-1-en-3-ol (2a) catalyzed by [{Cp*IrCl2}2] in the presence of N-chlorosuccinimide (NCS). In THFand at room temperature, only traces of the desired monochlorinated carbonyl compound 3a were formed together with a complicated mixture of by-products (Table 1, entry 1). However, introducing water as a cosolvent had a strong influence on the reaction outcome, and the yield of 3a gradually increased (entries 2,3). Notably, in THF/H2O= 1:2, a quantitative yield of 3a was obtained in 6 h with only 0.25 mol% of [{Cp*IrCl2}2] (entry 4). Under these conditions, 3a was formed with complete regiocontrol and nonchlorinated ketone 4a or enone 5a were not detected. Furthermore, the reactions do not require inert conditions. In the absence of THF, a low yield of 3a was obtained (entry 5). Chloramine-T or 1,3-dichloro-5,5-dimethylhydantoin afforded poor yields of 3a (entries 6–7). To evaluate the reaction scope, a variety of aliphatic and a-aryl allylic alcohols (2a–2o), including cyclic and function-