PdII-catalyzed oxidative 1,1-diarylation of terminal olefins

Article abstract of DOI:10.1021/ol1009575

(Figure presented) Evaluation of the scope of a Pd^II-catalyzed oxidative 1,1-diarylation reaction of terminal olefins using aryl stannanes is reported. The reaction is shown to be tolerant of functionality commonly encountered in organic synthesis; however, the reaction outcome was found to be dependent on the nature of the aryl stannane used. A mechanistic rationale for the observation of this influence is provided.

Full text of DOI:10.1021/ol1009575

ORGANIC
LETTERS
PdII-Catalyzed Oxidative 1,1-Diarylation
of Terminal Olefins
2010
Vol. 12, No. 12
2848-2851
Erik W. Werner, Kaveri B. Urkalan, and Matthew S. Sigman*
Department of Chemistry, UniVersity of Utah, 315 South 1400 East,
Salt Lake City, Utah 84112
sigman@chem.utah.edu
Received April 27, 2010
ABSTRACT
Evaluation of the scope of a PdII-catalyzed oxidative 1,1-diarylation reaction of terminal olefins using aryl stannanes is reported. The reaction
is shown to be tolerant of functionality commonly encountered in organic synthesis; however, the reaction outcome was found to be dependent
on the nature of the aryl stannane used. A mechanistic rationale for the observation of this influence is provided.
The rapid introduction of molecular complexity through the
formation of multiple carbon-carbon bonds in a single
synthetic step can be a powerful tool for organic chemists.
In order to accomplish this using palladium catalysis, the
interception of reactive PdII-alkyl intermediates is typically
required prior to ꢀ-hydride elimination.1-6 Recently, we
reported a catalytic system that installs two aryl groups on
an olefin substrate (Scheme 1a).7 The proposed mechanism
of this reaction is similar to that of the oxidative Heck
reaction8,9 in that after initial transmetalation an alkene inserts
into the Pd-aryl bond. Critical to the success of the
diarylation reaction is the exploitation of the stability of the
(1) For an overview of palladium-catalyzed difunctionalization reactions,
see: (a) Jensen, K. H.; Sigman, M. S. Org. Biomol. Chem. 2008, 6, 4083–
4088. For an example of palladium-catalyzed arylhalogenation, see: (b)
Kalyani, D.; Sanford, M. S. J. Am. Chem. Soc. 2008, 130, 2150–2151.
(2) For examples of palladium-catalyzed dialkoxylation, see: (a) Chevrin,
C.; Le Bras, J.; Henin, F.; Muzart, J. Sythesis 2005, 261, 5–2628. (b) Schultz,
M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006, 128, 1460–1461. (c) Thiery,
E.; Chevrin, C.; Le Bras, J.; Harakat, D.; Muzart, J. J. Org. Chem. 2007,
72, 1859–1862. (d) Zhang, Y.; Sigman, M. S. J. Am. Chem. Soc. 2007,
129, 3076–3077. (e) Jensen, K. H.; Pathak, T. P.; Zhang, Y.; Sigman, M. S.
J. Am. Chem. Soc. 2009, 131, 17074–17075.
(5) For examples of nucleopalladation-alkene insertion stratagies, see:
(a) Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai, H. J. Am. Chem. Soc. 2001,
123, 2907–2908. (b) Minami, K.; Kawamura, Y.; Koga, K.; Hosokawa, T.
Org. Lett. 2005, 7, 5689–5692. (c) Kawamura, Y.; Imai, T.; Hosokawa, T.
Synlett 2006, 3110–3114. (d) Yip, K.-T.; Yang, M.; Law, K.-L.; Zhu, N.-
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C. C.; Stahl, S. S. Org. Lett. 2006, 8, 3251–3254
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(6) For difunctionalization reactions using a PdII-PdIV catalytic cycle,
see: (a) Streuff, J.; Hovelmann, C. H.; Nieger, M.; Muniz, K. J. Am. Chem.
Soc. 2005, 127, 14586–14587. (b) Muniz, K. J. Am. Chem. Soc. 2007, 129,
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Soc. 2008, 130, 763–773. (d) Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006,
128, 7179–7181. (e) Desai, L. V.; Sanford, M. S. Angew. Chem., Int. Ed.
2007, 46, 5737–5740. (f) Tong, X.; Beller, M.; Tse, M. K. J. Am. Chem.
Soc. 2007, 129, 4906–4907. (g) Welbes, L. L.; Lyons, T. W.; Cychosz,
K. A.; Sanford, M. S. J. Am. Chem. Soc. 2007, 129, 5836–5837. (h) Li, Y.;
(3) For examples of hydrofunctionalization using a similar strategy, see:
(a) Gligorich, K. M.; Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc.
2006, 128, 2794–2795. (b) Gligorich, K. M.; Cummings, S. A.; Sigman,
M. S. J. Am. Chem. Soc. 2007, 129, 14193–14195. (c) Podhajsky, S. M.;
Sigman, M. S. Organometallics 2007, 26, 5680–5686. (d) Iwai, Y.;
Gligorich, K. M.; Sigman, M. S. Angew. Chem., Int. Ed. 2008, 47, 3219–
3222. (e) Urkalan, K. B.; Sigman, M. S. J. Am. Chem. Soc. 2009, 131,
18042–18043.
Song, D.; Dong, V. M. J. Am. Chem. Soc. 2008, 130, 2962–2964
.
(7) (a) Urkalan, K. B.; Sigman, M. S. Angew. Chem., Int. Ed. 2009, 48,
3146–3149. For an example of palladium-catalyzed diarylation of a chelating
vinyl ether, see: (b) Trejos, A.; Fardost, A.; Yahiaoui, S.; Larhed, M. Chem.
Commun 2009, 7587–7589.
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.
10.1021/ol1009575  2010 American Chemical Society
Published on Web 05/19/2010

Scheme 1
.
Diarylation of Styrenes
Scheme 2. 1,1-Diarylation of Nonene
initial result and to determine the scope and limitations of
this new methodology.
Using the optimal conditions previously reported, this
reaction was found to be quite tolerant of functional groups
commonly encountered in organic synthesis (Table 1). A
proposed Pd-π-benyzl intermediate A.10 This interaction
slows ꢀ-hydride elimination, allowing for a second trans-
metalation, ultimately delivering the 1,2-diarylation product.
During this study, an interesting byproduct was observed
arising from A slipping to an η1 Pd-alkyl (Scheme 1c),
followed by ꢀ-hydride elimination and olefin reinsertion to
give a new Pd-π-benzyl D. This is proposed to undergo a
second transmetalation followed by reductive elimination to
give the 1,1-diarylation product. The observation of a linear
free energy relationship between the electronic nature of the
styrene substrates and the ratio of these two products revealed
the reaction’s high level of sensitivity to the stability of
π-benzyl intermediates. This led to the hypothesis that alkyl-
substituted olefins would give exclusively 1,1-diarylated
products, since the substrate cannot provide π-benzyl sta-
bilization, but this interaction would be accessible with the
arene originating from the aryl stannane via palladium
migration. To evaluate this hypothesis, nonene was subjected
to the conditions optimized for 1,2-diarylation of styrenes,
and this indeed resulted in the formation of the expected
1,1-diaryl product 3a (Scheme 2).7a The proposed mechanism
for this reaction is initiated by a Heck insertion, followed
by ꢀ-hydride elimination to give F. Hydride insertion at the
position ꢀ to the arene gives G, which can be stabilized as
a π-benyzl intermediate. A second transmetalation is pro-
posed to occur followed by reductive elimination to provide
the 1,1-diarylation product. Since the diarylmethine core
structure is a common motif in biologically active com-
pounds,11 we believed it would be valuable to pursue this
Table 1. Scope of 1,1-Diarylation
a Ar ) p-MeOC6H4. Yield is the average of two experiments performed
on 0.5 mmol scale. The remainder of the mass balance is largely an oxidative
Heck product, which was not quantified for these reactions. b Isolated as a
7.2:1 mixture with 1,3-diaryl product.
(9) For examples of oxidative Heck reactions, see: (a) Du, X.; Suguro,
M.; Hirabayashi, K.; Mori, A.; Nishikata, T.; Hagiwara, N.; Kawata, T.;
Okeda, T.; Wang, H. F.; Fugami, K.; Kosugi, M. Org. Lett. 2001, 3, 3313–
3316. (b) Parrish, J. P.; Jung, Y. C.; Shin, S. I.; Jung, K. W. J. Org. Chem.
2002, 67, 7127–7130. (c) Jung, Y. C.; Mishra, R. K.; Yoon, C. H.; Jung,
K. W. Org. Lett. 2003, 5, 2231–2234. (d) Andappan, M. M. S.; Nilsson,
P.; von Schenck, H.; Larhed, M. J. Org. Chem. 2004, 69, 5212–5218. (e)
Yoo, K. S.; Yoon, C. H.; Jung, K. W. J. Am. Chem. Soc. 2006, 128, 16384–
16393. (f) Delcamp, J. H.; Brucks, A. P.; White, C. M. J. Am. Chem. Soc.
2008, 130, 11270–11271.
substrate bearing a protected homoallylic alcohol leads to a
good yield of the desired product (3b). Similarly, a protected
allylic alcohol (3c) undergoes the diarylation reaction cleanly
Org. Lett., Vol. 12, No. 12, 2010
2849

with no products derived from Pd-π-allyl chemistry observed.
Substrates containing a ketone (3d) and an ester (3c) are
well tolerated, as are primary chlorides (3e). A substrate with
a distal free alcohol resulted in moderate yields of the 1,1-
diarylation product (3f), and allyl benzene gives a high yield
of diarylation products as a mixture of regioisomers (3g).
Allyl cyanide is a poor substrate for this reaction, providing
a 27% yield (3h). Importantly, an enantioenriched sample
of 1c suffered no erosion in enantiomeric excess when
converted to 3c using these conditions (eq 1).
Evaluation of the scope of the aryl stannane revealed a
clear trend between the electronic nature of the aryl stannane
and the yields of both the 1,1-diarylation and oxidative Heck
products. Specifically, as the aryl stannane became more
electron-deficient, the ratio of diarylation product (3) to the
oxidative Heck product (4) decreased. Intrigued, we ques-
tioned whether there was a direct relationship between these
parameters. The ratios of 1,1-diarylation to Heck products
1
was determined by H NMR integration performed on a
mixture where the tin byproducts had been chromatographi-
cally removed. Plotting log[1,1-diarylation]/[Heck] as a
function of the Hammett parameters of 2 (σ) indeed revealed
a linear free energy relationship with F ) -0.91 (Figure 1).
Next, the scope of the aryl stannane component of the
reaction was evaluated (Table 2). The reaction proceeds well
Table 2. Scope of 1,1-Diarylation
Figure 1. Hammett plot.
This relationship can be explained by noting that the cationic
metal center is stabilized by the π-electrons of the aryl group
in π-benzyl structure G and that electron-rich arenes provide
more stability and impart a longer lifetime to this intermedi-
ate than electron-poor arenes. This slows ꢀ-hydride elimina-
tion, allowing for a second transmetalation, which results in
a higher ratio of 1,1-diarylation to oxidative Heck products
when electron-rich aryl stannanes are used. It is interesting
to note that despite the different products delivered by the
1,2- and 1,1-diarylation reactions, the slope of the two
Hammett plots are nearly identical (F ) -0.88 for work
described in ref 7a), suggesting that they are affected to a
similar degree by the stability of Pd-π-benzyl intermediates.
This catalyst control can presumably be manipulated by the
nature of the dative ligand and counterions on the metal for
future applications.
a Yields are the average of two experiments performed on 0.5 mmol
scale except where noted. The remainder of the mass balance is isomerized
starting material. b One experiment performed on 0.42 mmol scale.
c Recovered 47% starting material.
using p-alkyl phenyl stannanes (entry 2) and PhSnBu3 (entry
3). p-Fluoro phenyl stannane gave a slightly diminished yield
of 3k, while use of more electron poor p-chloro phenyl
stannane 2e resulted in a further decrease in yield. Using
the highly electron deficient aryl stannane bearing a triflu-
oromethyl group gave very low yield with a greater amount
of the Heck product, and poor tolerance of steric hindrance
in the aryl stannane was observed (2f). The major byproduct
for these reactions is oxidative Heck products 4, presumably
arising from Pd-dissociation from intermediate F (Scheme
2), the yields of which are also reported in Table 2.
In conclusion, we have found that the PdII-catalyzed
oxidative diarylation reaction of terminal olefins is tolerant
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Coniglio, S.; Colagioia, S.; Beccari, A. R.; Bizzarri, C.; Cavicchia, M. R.;
Locati, M.; Galliera, E.; Di Benedetto, P.; Bigilante, P.; Bertini, R.;
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P.-H.; Liao, C.-H.; Huang, I.-S. J. Nat. Prod. 2007, 70, 1444–1448. (c)
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Org. Lett., Vol. 12, No. 12, 2010

of diverse functionality, and does not erode enantiomeric
excess in a substrate with a proximal stereocenter. The
reaction performs well using electron-rich aryl stannanes,
but yield and selectivity suffer when the aryl stannane is
electron-deficient or sterically hindered. We have reported
a linear free energy relationship quantifying this observation
and demonstrating the reaction’s high sensitivity to Pd-π-
benzyl stability. Future work will be directed toward the
development of a diarylation reaction capable of installing
two distinct aryl groups on a terminal olefin.
Acknowledgment. This research was supported by the
National Institutes of Health (NIGMS RO1 GM3540).
Supporting Information Available: Detailed experi-
mental procedures, characterization data, and copies of
1H and 13C NMR spectra for all products. This material
isavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
OL1009575
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