Stereoselective Phenylation of Allylic Alcohol Derivatives by Palladium-Catalyzed Cross-Coupling with Hypervalent Silicon Complexes

Full text of DOI:10.1021/jo980069d

3156
J . Org. Chem. 1998, 63, 3156-3157
Sch em e 1
Ster eoselective P h en yla tion of Allylic Alcoh ol
Der iva tives by P a lla d iu m -Ca ta lyzed
Cr oss-Cou p lin g w ith Hyp er va len t Silicon
Com p lexes†
Marc-Raleigh Brescia and Philip DeShong*
Department of Chemistry and Biochemistry, The University of
Maryland, College Park, Maryland 20742
Sch em e 2
Received J anuary 14, 1998
Palladium-catalyzed alkylation of allylic alcohol deriva-
tives has been widely used in organic synthesis.1 We and
Curran have recently reported Pd-catalyzed reactions of
dihydropyran derivatives in the synthesis of biologically
active compounds such as pseudomonic acid A.2 During the
course of our studies, it was observed, however, that phen-
ylstannanes did not couple efficiently to dihydropyran
derivatives, such as 1 (Scheme 1). For example, Stille coup-
ling3 of pyran 1 with phenyltributylstannane gave <10% of
dihydropyrans 2 and 3. Homocoupling of the tin reagent
led to the major product in the reaction mixture. Extensive
experimentation did not improve the yields of phenylated
materials.
Tin derivatives have several serious limitations as re-
agents for applications in cross-coupling reactions. Stille
noted that the reactivity of the tin reagent is strongly
affected by the nature of the substituents attached to tin.3
As a practical concern, tin(IV) derivatives are also toxic, and
the removal of tin byproducts is problematic. Recently,
Fouquet has shown that stannylene derivatives can be
employed in Pd(0)-catalyzed coupling reactions because
these reagents yield tin byproducts that are easily removed
from the reaction mixture.4 An alternative strategy for the
removal of tin reagents and byproducts has been reported
by Curran using fluorous workup procedures.5
groups have been coupled under these conditions, and
Hiyama has postulated that these cross-couplings proceed
through a pentavalent silicate complex.8 Hiyama’s in situ
preparation of fluorosilicates followed by Pd-catalyzed cross
coupling has three limitations: (1) the synthesis of fluorosi-
lanes is a multistep process, (2) the polyfluorosilane deriva-
tives are hydrolytically unstable, and (3) reaction conditions
of the coupling protocol are strongly basic, precluding the
use of base-sensitive functionalities.
In an effort to develop an efficient phenylation protocol
for allylic alcohol derivatives employing silane rather than
stannane reagents, the Pd(0)-catalyzed reaction of stable
fluorosilicate complexes such as tetrabutylammonium tri-
phenyldifluorosilicate (TBAT) was investigated. There are
several attractive properties of fluorosilicates as transmeta-
lating agents. For example, tetrabutylammonium triphen-
yldifluorosilicate (TBAT) is an air-stable, nonhygroscopic,
nontoxic crystalline material. Previous studies have dem-
onstrated that TBAT is an efficient fluoride source in organic
synthesis,9 and here we report that it is also an effective
phenylation reagent in Pd-catalyzed coupling reactions.
A typical example of this process is shown in Scheme 2.
The conditions for the coupling are 5 mol % of both Pd(dba)2
and PPh3 and 2 equiv of TBAT in refluxing THF for 12 h.
In contrast, standard conditions for the coupling with
phenyltrimethylstannane (1.3 equiv) are 3 equiv of LiCl, 5
mol % of Pd(dba)2 in DMF at rt for 24-48 h.3
It should be noted that 1 equiv of phosphine is tolerated
in the TBAT reaction, whereas phosphine strongly inhibits
the reaction with tin reagents.3 Excess phosphine com-
pletely inhibits the TBAT coupling. Substitution of various
phosphine ligands for triphenylphosphine was also investi-
gated. Although electron-deficient phosphines enhance the
cross-coupling in Stille coupling,1d we found coupling using
TBAT failed with 2-trifurylphosphine. Electron-rich phos-
phines such as dppe and PPh3 provided the highest yields
of phenylated adducts, while low yields of products were
obtained with highly nucleophilic n-tributylphosphine. Re-
duced yields of phenylation products were obtained with any
of the typical Pd(0) sources (Pd(PPh3)4, Pd(dppe)2, or
PdCl2(CH3CN)2) under these conditions.
Legros and Fiaud have reported that tetraphenylborate
underwent coupling with allylic alcohol derivatives in the
presence of a Pd catalyst to afford phenylated adducts in
good yields.6
Hiyama and Hatanaka have studied fluoride-promoted
cross-coupling of aryl- or vinylchloro- and fluorosilanes and
allylic alcohol derivatives.7 Aryl, vinyl, allyl, and alkyl
* To whom correspondence should be addressed: phone: 301-405-1892,
fax: 301-314-9121, email: pd10@umail.umd.edu.
† Dedicated to Carl J ohnson on the occasion of his 60th birthday.
(1) (a) Godleski, S. A. In Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon Press: New York, 1991; Vol. 4, pp 585-661. (b) Miyaura,
N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483. (c) Tsuji, J . Palladium
Reagents and Catalysts. Innovations in Organic Synthesis; J ohn Wiley &
Sons: New York, 1995; pp 290-421. (d) Farina, V. Pure Appl. Chem. 1996,
68, 73-78. (e) Hegedus, L. S. Coord. Chem. Rev. 1996, 147, 443-545.
(2) (a) Class, Y. J .; DeShong, P. Tetrahedron Lett. 1995, 36, 7631-7634.
(b) Balog, A.; Yu, M. S.; Curran, D. P.; Yu, G.; Carcangue, D. R.; Shue, Y.
K. Synth. Commun. 1996, 26, 935-944.
(3) Del Valle, L.; Stille, J . K.; Hegedus, L. S. J . Org. Chem. 1990, 55,
3019-3023.
(4) Fouquet, E.; Pereyre, M.; Rodriguez, A. L. J . Org. Chem. 1997, 62,
5242-5243.
(5) Hoshino, M.; Degenkolb, P.; Curran, D. M. J . Org. Chem. 1997, 62,
8341-8349.
(6) Legros, J .-Y.; Fiaud, J .-C. Tetrahedron Lett. 1990, 31, 7453-7456.
(7) Hiyama, T.; Hatanaka, Y. Pure Appl. Chem., 1994, 66, 1471-1478
and references therein.
(8) Preformed pentavalent silicates have been shown to couple with 4′-
iodoacetophenone but not allylic substrates. The stereoselectivity has been
studied with respect to double-bond geometry in acyclic alcohol derivatives
and in chiral silane derivatives coupled to aryl substrates but not with
respect to the leaving group in cyclic allylic alcohol derivatives. See ref 5
and references therein for additional details.
(9) (a) Pilcher, A. S.; Ammon, H. L.; DeShong, P. J . Am. Chem. Soc. 1995,
117, 5166-5167. (b) Pilcher, A. S.; DeShong, P. J . Org. Chem. 1996, 61,
6901-6905. TBAT is commercially available from Aldrich Chemical Co. and
Eburon Chemicals.
To assess the stereoselectivity in Pd-catalyzed cross-
coupling, the following substrates were tested under the
optimized conditions (vide supra). Benzoate 4 was converted
to cis-arene 5 in 60% yield (Scheme 2). The cis-benzoate
(not shown) was transformed into the trans-alkene. As
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Communications
J . Org. Chem., Vol. 63, No. 10, 1998 3157
Sch em e 3
Sch em e 4
Sch em e 5
distal (“distorted”) Pd complex (Scheme 5). The distal π-allyl
Pd complex is favored because it avoids the steric interac-
tions between Pd and methoxy present in the proximal Pd
complex. The preference for the distal Pd complex explains
the high degree of regioselectivity for the phenylation of 9a
to give 10a as the major product.
anticipated, alkene 5 was produced with complete inversion
of stereochemistry irrespective of whether tin or silicate
reagents were employed.1,3,10 Phenylation using phenyltri-
methylstannane gave slightly higher yields than TBAT
phenylation in this system, but removal of the tin byproducts
was again problematic.
On the other hand, 9b proceeds through a trans-Pd
complex in which Pd and methoxy are on the opposite side
of the ring and no steric interaction occurs between these
two groups. Thus, the reaction proceeds through a sym-
metrical Pd complex. This symmetrical complex shows no
preference for either the proximal or distal Pd complex and
explains the lack of regioselectivity in the phenylation of cis-
benzoate 9b. The high degree of regioselectivity using trans-
substrates and the absence of regioselectivity with cis-
substrates is a general trend in these reactions (vide infra)
that has been noted in other Pd-catalyzed reactions in our
laboratory.11
The use of dppe as the Pd ligand is essential to maintain-
ing the stereochemistry of trans-benzoates such as 9b.
Ba¨ckvall has previously shown that the ligand change from
PPh3 to dppe minimizes the loss of stereochemistry when
adding stabilized carbon nucleophiles and amines to allylic
alcohol substrates.12 However, Stille has shown that the Pd-
catalyzed phenylation of allylic alcohol derivatives using
stannanes is inhibited by the presence of phosphine.3
Therefore, the ability of TBAT to cross-couple in the presence
of phosphines makes the cross-coupling of pentavalent
silicates superior to stannanes.
In summary, the hypervalent silicate complex TBAT has
been shown to be a highly effective reagent for the pheny-
lation of allylic benzoates. The Pd-catalyzed phenylations
with TBAT are completely stereoselective with inversion of
configuration and occur under mild reaction conditions.
With certain substrates, the phenylations occur with excel-
lent regioselectivity as well. The mild reaction conditions,
availability of the silicate reagent, low toxicity of the
silicates, and complete stereoselectivity of phenylation means
that this protocol is superior to its tin counterpart.
Ack n ow led gm en t. We thank Dr. Yiu-Fai Lam and Ms.
Caroline Ladd for their assistance in obtaining NMR and
mass spectral data. The generous financial support of the
University of Maryland and an unrestricted grant from
Lederle Laboratories are acknowledged.
Phenylation of benzoates 6a ,b (Scheme 3) was also
studied, and in this system, TBAT was shown to be signifi-
cantly more stereoselective than the stannane derivatives
in the coupling reaction. As shown in Scheme 3, coupling
of phenyltrimethylstannane with benzoate 6a gave a mix-
ture of all possible regio- and stereoisomers 7a -d , while the
silicate derivative gave exclusively the products of inversion
of configuration. We attribute the loss of stereoselectivity
in the tin coupling to intermediacy of a “distorted” π-allyl
palladium intermediate11 and the slow transmetalation from
tin to the π-allyl complex. Under these conditions, when
transmetalation from tin to palladium is slow, the initially
formed π-allyl palladium complex reacts with Pd(0), result-
ing in formation of the diastereomeric Pd-complex.12
Phenylation of benzoate 6b, in which there is a “sym-
metrical” π-allyl palladium complex as an intermediate,
occurred without loss of stereoselectivity with both the tin
and silicate reagent presumably due to facile transmetala-
tion from tin/silicon to palladium for the intermediate π-allyl
complex.
The generality of utilizing TBAT rather than tin reagents
as the aryl donor in Pd-catalyzed cross-coupling reactions
was further demonstrated using benzoates 9a ,b as sum-
marized in Scheme 4. As in the results shown above,
phenylation occurred with complete stereoselectivity with
both 9a and 9b to provide a mixture of regioisomeric pyrans
10 and 11. Again, one of the isomers, benzoate 9a , displayed
excellent regioselectivity in the phenylation process, while
the other isomer gave no selectivity in the coupling reaction.
The high degree of regioselectivity in the phenylation of
dihydropyran derivatives 6 and 9 can be explained by
invoking “distorted” and “nondistorted” π-allyl Pd-complex-
es.11 Examination of the Pd-complexes that precede reduc-
tive elimination showed that 9a must proceed through a cis-
(10) Although the reaction occurred with complete inversion of stereo-
chemistry with regard to the isopropylidene group, it should be noted that
the absolute stereochemistry of the molecule was lost during the phenylation
due to intermediacy of the achiral π-allyl complex.
(11) Brescia, M.-R.; Shimshock, Y. C.; DeShong, P. J . Org. Chem. 1997,
62, 1257-1263.
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures and spectral data for all novel compounds (5 pages).
(12) Granberg, K. L.; Ba¨ckvall, J .-E. J . Am. Chem. Soc. 1992, 114, 6858-
6863.
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