C O M M U N I C A T I O N S
alcohol substrate reacted efficiently with no observed olefin
isomerization (entry 4). In addition, 2-octyn-1-ol led cleanly to the
corresponding propargylic chloride without formation of allenic
product (entry 5). Activated secondary alcohols proved to be viable
substrates as well, with both cyclohexenol and methyl mandelate
serving as efficient participants (entries 6 and 7). Most notably,
unactivated substrates could also be employed. Thus, for example,
2-phenylethanol led to the production of (2-chloroethyl)benzene
in 15 min (entry 8). Unactivated secondary alcohols were found to
undergo efficient conversion, although higher reaction temperatures
(80 °C, CH3CN) were required in these cases (entries 9 and 10).
Finally, a tertiary alcohol substrate was investigated and found to
lead to the tertiary chloride in modest yield (45%) along with 33%
ꢀ,ꢀ-dimethylstyrene (entry 11).
demonstrating that substitution occurred primarily via the SN2
pathway. Notably, other more traditional methods of chlorination
often proceed with retention (SOCl2) or with poor stereoselectivity
(MsCl).9
Finally, as further support for the claim that substitution occurs
1
by way of a cyclopropenium-activated intermediate, we used H
NMR spectroscopy to monitor the reaction of 2-phenylethanol (10)
in CD3CN, a solvent in which the reaction is relatively slow. When
alcohol and 7 were mixed, the two starting-material methylene
triplet peaks immediately disappeared, and two new triplets took
their place (Figure 3). We attribute these new peaks to cyclopro-
penium ion 11. Notably, the oxygen-bearing methylene was shifted
downfield to δ 5.47, which is consistent with an alkoxycyclopro-
penium prepared by Breslow via an alternative method.10 Over the
course of the reaction, these new peaks decreased in intensity and
were replaced by the two methylene triplets of the chloride product
12.
Table 2. Substrate Scope Studies for Alkyl Chloride Formationa b
,
Figure 3. Chemical shifts of the alkoxycyclopropenium intermediate.
In conclusion, this work offers a convenient and efficient method
for converting alcohols to alkyl chlorides based on a novel paradigm
for the promotion of substitution reactions. Importantly, we have
also found aromatic cation activation to be effective for a broad
range of dehydration manifolds. The results of these studies will
be disclosed shortly.
Acknowledgment. We are grateful to the Turro Group for
generous use of their GC and Arun Sundaresan for his assistance.
Supporting Information Available: Experimental procedures and
product characterization data. This material is available free of charge
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a Reactions were performed by the addition of 7 to a solution of the
alcohol in CH2Cl2. For entries 1-6, 1.1 equiv of 7 was added. For
entries 7-11, 1.5 equiv of 7 was added. b Yields were determined on
isolated and purified products, unless otherwise noted. c Yield was
determined by H NMR analysis. d Reactions were perfomed in CH3CN.
1
e The ꢀ,ꢀ-dimethylstyrene yield was 33%.
To further demonstrate the utility of this method, we performed
the conversion of 1-phenylethanol to (1-chloroethyl)benzene on a
1.0 g scale (eq 1): The yield of this transformation was 90%, and
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