ORGANIC
LETTERS
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Vol. XX, No. XX
Pd(0)-Catalyzed 1,1-Diarylation of
Ethylene and Allylic Carbonates
000–000
Vaneet Saini, Longyan Liao, Qiaofeng Wang, Ranjan Jana, and Matthew S. Sigman*
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City,
Utah 84112, United States
Received August 14, 2013
ABSTRACT
An efficient protocol for the one-step synthesis of biologically relevant 1,1-diarylalkanes has been described. This reaction introduces two
different aryl groups across the terminal end of simple feedstock alkenes such as ethylene and allylic carbonates. The propensity to generate
π-benzylpalladium intermediates dictates the exclusive 1,1-regioselectivity observed in the product.
The 1,1-diarylalkane structural motif is present in
numerous biologically active compounds, which have
notable efficacy profiles against a diverse range of ther-
apeutic targets. Inthisregard, we haverecently disclosed a
1,1-diarylalkane (Scheme 1a, C-6) that is active against
patient-derived metastatic and chemoresistant breast can-
2
cer cells. Additionally, C-6 is highly selective in that
minimal cell death is observed in patient-derived non-
tumorigenic cells. Preliminary mechanistic investigations
indicate that the promising selectivity of C-6 is not due to
interruption of commonly targeted therapeutic signal-
ing pathways. The exciting possibility of identifying new
breast cancer target(s) using C-6 has stimulated a focused
effort on the synthesis of 1,1-diarylalkane analogues.
Our original synthesis of C-6 employed an oxidative
3,4
Pd(II)-catalyzed hydroarylation of styrenes (Scheme 1a).
This method allows access to various diarylethanes as it is
limited to terminal styrenes and also requires rather complex
1
5
reaction conditions. Many attractive alternative methods
have been reported to access diarylalkanes, including
6
enantioselective hydrogenation of 1,1-diarylalkenes,
7
rhodium-catalyzed TsujiꢀWilkinson decarbonylation, and
8
enantiospecific metal-catalyzed cross-coupling reactions.
(
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0.1021/ol4023358 r XXXX American Chemical Society