Unusually accelerated silylmethyl transfer from tin in stille coupling: Implication of coordination-driven transmetalation

Article abstract of DOI:10.1021/ja0160593

The palladium-catalyzed cross-coupling reaction of 2-PyMe₂SiCH₂SnBu₃ with aryl iodide (Ar-I) exclusively produced the 2-PyMe₂SiCH₂ transferred product 2-PyMe₂SiCH₂Ar. The relative transfer ability of organic group from tin was found to be 2-PyMe₂SiCH₂ ? Ph > Me > Bu ? PhMe₂SiCH₂, which implies the beneficial pyridyl-to-palladium coordination effect. Thus, the transfer of the silylmethyl group from tin to palladium was remarkably accelerated by simply appending the 2-pyridyl group on silicon. The pyridyl-to-palladium coordination was validated in the palladium(II) complex 2-PyMe₂SiCH₂PdClPPh₃ by ¹H NMR and X-ray crystal structure analysis. The cross-coupling product was used for further transformations. The C - Si oxidation of the cross-coupling product 2-PyMe₂SiCH₂Ar afforded ArCH₂OH in high yield. The fluoride ion-catalyzed 1,2-addition of 2-PyMe₂SiCH₂Ar to carbonyl compound (RR′C=O) gave ArCH₂C(OH)RR′ in high yield.

Full text of DOI:10.1021/ja0160593

J. Am. Chem. Soc. 2001, 123, 8773-8779
8773
Unusually Accelerated Silylmethyl Transfer from Tin in Stille
Coupling: Implication of Coordination-Driven Transmetalation
Kenichiro Itami, Toshiyuki Kamei, and Jun-ichi Yoshida*
Contribution from the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Yoshida, Kyoto 606-8501, Japan
ReceiVed April 20, 2001. ReVised Manuscript ReceiVed July 9, 2001
Abstract: The palladium-catalyzed cross-coupling reaction of 2-PyMe2SiCH2SnBu3 with aryl iodide (Ar-I)
exclusively produced the 2-PyMe2SiCH2 transferred product 2-PyMe2SiCH2Ar. The relative transfer ability of
organic group from tin was found to be 2-PyMe2SiCH2 . Ph > Me > Bu . PhMe2SiCH2, which implies the
beneficial pyridyl-to-palladium coordination effect. Thus, the transfer of the silylmethyl group from tin to
palladium was remarkably accelerated by simply appending the 2-pyridyl group on silicon. The pyridyl-to-
palladium coordination was validated in the palladium(II) complex 2-PyMe2SiCH2PdClPPh3 by 1H NMR and
X-ray crystal structure analysis. The cross-coupling product was used for further transformations. The C-Si
oxidation of the cross-coupling product 2-PyMe2SiCH2Ar afforded ArCH2OH in high yield. The fluoride ion-
catalyzed 1,2-addition of 2-PyMe2SiCH2Ar to carbonyl compound (RR′CdO) gave ArCH2C(OH)RR′ in high
yield.
Introduction
The palladium-catalyzed cross-coupling reaction of organotin
compounds with organic halides (Migita-Kosugi-Stille cou-
pling) has emerged as one of the most important methods for
the catalytic carbon-carbon bond formation.1,2 Noteworthy and
advantageous features of this coupling process are that (1)
organotin compounds are readily available, (2) organotin
compounds are quite air and moisture stable, and (3) cross
coupling tolerates a variety of functional groups on either
coupling partner. In recent years the Stille coupling has been
well recognized as a powerful method for natural product
synthesis.3 Moreover, the cross coupling using aryl chlorides,
a long-standing challenge, has been accomplished very recently
by utilizing electron-rich and bulky supporting ligands.4 How-
ever, there are still several serious limitations associated with
the Stille coupling methodology. While aryl, alkenyl, alkynyl,
allyl, and benzyl groups are efficiently transferred into the cross-
Figure 1. Relative transfer ability of the organic group on tin in Stille
coupling.
coupling product, the low transfer ability of the alkyl group
from tin has been a bane in this chemistry (Figure 1).2 For
example, synthetically useful silylmethyl groups exhibit ex-
tremely low transferring ability and, thus, are not transferred
from tin usually. If the silylmethyltin reagents could be
effectively cross-coupled with alkenyl or aryl halides, availability
of synthetically useful allyl- and benzylsilanes,5 which bear
various functional groups, should be enormously enhanced.6
The low transfer ability of the simple alkyl group from tin
has currently been alleviated by several methods. In 1992,
Vedejs7 and Brown8 have independently discovered that the
intramolecular coordination of amine to tin greatly accelerates
* To whom correspondence should be addressed: (phone) (81)-75-753-
5651; (fax) (81)-75-753-5911; (e-mail) yoshida@sbchem.kyoto-u.ac.jp.
(1) (a) Kosugi, M.; Shimizu, Y.; Migita, T. Chem. Lett. 1977, 1423. (b)
Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636.
(2) For reviews, see: (a) Farina, V.; Krishnamurthy, V.; Scott, W. J.
The Stille Reaction; Wiley: New York, 1999. (b) Mitchell, T. N. In Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: Weinheim, Germany, 1998, Chapter 4. (c) Stanforth, S. P.
Tetrahedron 1998, 54, 263. (d) Stille, J. K. Angew. Chem., Int. Ed. Engl.
1986, 25, 508.
(3) (a) Hegedus, L. S. Transition Metals in the Synthesis of Complex
Organic Molecules, 2nd ed.; University Science Books: Sausalito, CA,
1999. (b) Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis;
VCH: Weinheim, 1996. (c) Gyorkos, A. C.; Stille, J. K.; Hegedus, L. S. J.
Am. Chem. Soc. 1990, 112, 8465. (d) Kalivretenos, A.; Stille, J. K.; Hegedus,
L. S. J. Org. Chem. 1991, 56, 2883. (e) Evans, D. A.; Black, W. C. J. Am.
Chem. Soc. 1992, 114, 2260. (f) Han, Q.; Wiemer, D. F. J. Am. Chem. Soc.
1992, 114, 7692. (g) Shair, M. D.; Yoon, T.; Danishefsky, S. J. J. Org.
Chem. 1994, 59, 3755. (h) Nicolaou, K. C.; Sato, M.; Miller, N. D.; Gunzer,
J. L.; Renaud, J.; Unterstetter, E. Angew. Chem., Int. Ed. Engl. 1996, 35,
887. (i) Smith, A. B., III; Condon, S. M.; McCauley, J. A.; Leazer, J. L.,
Jr.; Leaky, J. W.; Maleczka, R. E., Jr. J. Am. Chem. Soc. 1997, 119, 962.
(j) Smith, A. B., III; Ott, G. R. J. Am. Chem. Soc. 1998, 120, 3935.
(4) (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411.
(b) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3, 119.
(5) For silicon-based organic synthesis, see: (a) Brook, M. A. Silicon
in Organic, Organometallic, and Polymer Chemistry; John Wiley & Sons:
New York, 2000. (b) Fleming, I.; Barbero, A.; Walter, D. Chem. ReV. 1997,
97, 2063. (c) Langkopf, E.; Schinzer, D. Chem. ReV. 1995, 95, 1375.
(6) For the synthesis of allyl- and benzylsilanes through Ni- or Pd-
catalyzed cross coupling of Me3SiCH2MgCl with alkenyl and aryl halides,
see: (a) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.; Fujioka, A.;
Kodama, S.; Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem. Soc. Jpn.
1976, 49, 1958. (b) Negishi, E.; Luo, F. T.; Rand, C. L. Tetrahedron Lett.
1982, 23, 27. (c) Hayashi, T.; Kabeta, K.; Kumada, M. Tetrahedron Lett.
1983, 24, 2865.
(7) Vedejs, E.; Haight, A. R.; Moss, W. O. J. Am. Chem. Soc. 1992,
114, 6556.
(8) Brown, J. M.; Pearson, M.; Jastrzebski, J. T. B. H.; van Koten, G. J.
Chem. Soc., Chem. Commun. 1992, 1440.
10.1021/ja0160593 CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/16/2001

8774 J. Am. Chem. Soc., Vol. 123, No. 36, 2001
Itami et al.
Scheme 1
Scheme 2
Table 1. Pd-Catalyzed Cross Coupling of 1a with Aryl Iodide
the transfer of the alkyl group from tin (Scheme 1a).9 It has
been assumed that activation of the alkyl group stems from the
coordination-induced alkyl-tin bond elongation.10 Recently, the
activation utilizing externally coordinating ligands such as a
fluoride ion has also appeared (Scheme 1b).11 All these methods
are based on the hypervalent organotin strategy.
Recently, we have been engaged in employing the 2-pyridyl-
dimethylsilyl (2-PyMe2Si) group as an excellent removable
intramolecular ligand (directing group) for various metal-
catalyzed and -mediated processes.12,13 We envisioned that the
use of the 2-PyMe2Si group might have some interesting effects
on the alkyl group transfer from tin in Stille coupling. During
the course of this investigation, we unexpectedly discovered
that the 2-PyMe2SiCH2 group behaves quite unusually in Stille
coupling where the intramolecular ligand (2-PyMe2SiCH2 group)
itself transfers from tin (Scheme 1c). In this paper, we report
on the palladium-catalyzed cross-coupling reaction using 2-PyMe2-
SiCH2SnR3 with some mechanistic investigations (Scheme 2).
Further transformations of the cross-coupling products are also
described.
entry
ligand
PPh3
P(C6H4CF3-4)3
P(C6H4CF3-4)3
P(C6F5)3
PPh3
P(C6H4CF3-4)3
P(C6F5)3
temp (°C)
product
yield (%)
1
2
3
4
5
6
7
50
50
70
50
50
50
50
2a
2a
2a
2a
2b
2b
2b
13
46
64
56
49
76
84
utilizing 2-PyMe2SiCH2SnBu3 (1a) as a substrate, which can
be easily prepared by the reaction of 2-PyMe2SiCH2Li with Bu3-
SnCl.12g Treatment of 1a with 1.2 equiv of iodobenzene in the
presence of 5 mol % of PdCl2(CH3CN)2 and 10 mol % of PPh3
in THF at 50 °C afforded the coupling product 2a in 13% yield
after 24 h (Table 1, entry 1). Screening of the phosphine ligand
revealed that the use of more π-accepting ligands such as
P(C6H4CF3-4)3 and P(C6F5)3 provided 2a in higher yields
(entries 2-4). This may be rationalized by assuming that these
electron-withdrawing ligands rendered the Ph-Pd(L)n-I inter-
mediate more electrophilic, thereby enhancing the rate of the
slow transmetalation step.14 Similarly, the coupling with 4-iodo-
acetophenone was found to be more efficient when those ligands
were employed (entry 5 vs entries 6 and 7). In all cases, we
observed only a trace amount of Bu transferred product in the
reaction mixture.
It was quite unexpected and interesting to observe that the
2-PyMe2SiCH2 group was selectively transferred from tin to
give the coupling product with aryl halides. As can be seen in
the original report of Stille, the silylmethyl group is one of the
hardest groups to transfer from tin in cross coupling.15 For
example, when Me3SiCH2SnMe3 is used as an organotin
nucleophile, the methyl group is selectively transferred (eq 1).
Results and Discussion
Palladium-Catalyzed Cross Coupling of 2-PyMe2SiCH2-
SnBu3 with Aryl Iodide. Our initial attempt was made by
(9) For a recent application in natural product synthesis, see: Jensen,
M. S.; Yang, C.; Hsiao, Y.; Rivera, N.; Wells, K. M.; Chung, J. Y. L.;
Yasuda, N.; Hughes, D. L.; Reider, P. J. Org. Lett. 2000, 2, 1081.
(10) For an excellent review on the intramolecular coordination to tin,
see: Jastrzebski, J. T. B. H.; van Koten, G. AdV. Organomet. Chem. 1993,
35, 241.
(11) (a) Garc´ıa Mart´ınez, A.; Os´ıo Barcina, J.; de Fresno Cerezo, AÄ .;
Subramanian, L. R. Synlett 1994, 1047. (b) Fouquet, E.; Pereyre, M.;
Rodriguez, A. L. J. Org. Chem. 1997, 62, 5242. (c) Fouquet, E.; Rodriguez,
A. L. Synlett 1998, 1323. (d) Fugami, K.; Ohnuma, S.; Kameyama, M.;
Saotome, T.; Kosugi, M. Synlett 1999, 63. (e) Garc´ıa Mart´ınez, A.; Os´ıo
Barcina, J.; del Rosario Colorado Heras, M.; de Fresno Cerezo, AÄ . Org.
Lett. 2000, 2, 1377. (f) Garc´ıa Mart´ınez, A.; Os´ıo Barcina, J.; del Rosario
Colorado Heras, M.; de Fresno Cerezo, AÄ . Organometallics 2001, 20, 1020.
(12) (a) Yoshida, J.; Itami, K.; Mitsudo, K.; Suga, S. Tetrahedron Lett.
1999, 40, 3403. (b) Itami, K.; Mitsudo, K.; Yoshida, J. Tetrahedron Lett.
1999, 40, 5533. (c) Itami, K.; Mitsudo, K.; Yoshida, J. Tetrahedron Lett.
1999, 40, 5537. (d) Itami, K.; Nokami, T.; Yoshida, J. Org. Lett. 2000, 2,
1299. (e) Itami, K.; Mitsudo, K.; Kamei, T.; Koike, T.; Nokami, T.; Yoshida,
J. J. Am. Chem. Soc. 2000, 122, 12013. (f) Itami, K.; Nokami, T.; Yoshida,
J. Tetrahedron 2001, 57, 5045. (g) Itami, K.; Kamei, T.; Mitsudo, K.;
Nokami, T.; Yoshida, J. J. Org. Chem. 2001, 66, 3970. (h) Itami, K.;
Mitsudo, K.; Yoshida, J. Angew. Chem., Int. Ed. 2001, 40, 2337. (i) Itami,
K.; Nokami, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 5600. (j) Itami,
K.; Koike, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 6957. See also:
(k) Itami, K.; Nokami, T.; Yoshida, J. Angew. Chem., Int. Ed. 2001, 40,
1074.
The use of (Me3SiCH2)4Sn resulted in the recovery of starting
material even under forcing conditions.15 Therefore, under the
usual situation, the silylmethyl group can be considered as a
“dummy” ligand in Stille coupling.16 Quite similarly, Bertz has
(13) For the use of removable directing group in metal-catalyzed
reactions, see: (a) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem.
Soc. 1988, 110, 6917. (b) Breit, B. Angew. Chem., Int. Ed. Engl. 1996, 35,
2835. (c) Jun, C. H.; Lee, H.; Hong, J. B. J. Org. Chem. 1997, 62, 1200.
(d) Breit, B. Angew. Chem., Int. Ed. 1998, 37, 525. (e) Breit, B. Eur. J.
Org. Chem. 1998, 1123. (f) Jun, C. H.; Lee, H. J. Am. Chem. Soc. 1999,
121, 880. (g) Buezo, N. D.; Mancheno, O. G.; Carretero, J. C. Org. Lett.
2000, 2, 1451.
(14) (a) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585.
(b) Farina, V. Pure Appl. Chem. 1996, 68, 73.
(15) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987, 109, 5478.
(16) To the best of our knowledge, there is only one example of
silylmethyl group transfer from tin in Stille coupling. See ref 7.

Silylmethyl Transfer from Tin in Stille Coupling
J. Am. Chem. Soc., Vol. 123, No. 36, 2001 8775
Table 2. Pd-Catalyzed Cross Coupling of 2-PyMe2SiCH2SnR3
with 4-Iodoacetophenone
the identical conditions for 2-PyMe2SiCH2SnBu3 (1a). Clearly,
the pyridyl group in 1a enhanced not only the selectivity but
also the reactivity. The huge transferring ability difference
between 2-PyMe2SiCH2 and PhMe2SiCH2 groups can also be
observed in the intramolecular competitive reaction with 1e (eq
3). The 2-PyMe2SiCH2 transferred product 2b was exclusively
relative transfer ability
(2-PyMe2SiCH2/R)
entry
R
yield (%)
2b/3
1
2
3
Bu (1a)
Me (1b)
Ph (1c)
87
52
53
96/4
58/42
45/55
99/1
81/19
71/29
recently discovered that silylmethyl group serves as an excellent
“dummy” ligand in organocuprate chemistry.17,18
obtained while PhMe2SiCH2 transferred product 4 was not
detected at all. We next subjected the hydrochloride of 2-PyMe2-
SiCH2SnBu3 (1f) to cross coupling (eq 4). The coupling product
These conspicuous and seminal results (Table 1) clearly
brought to light several critical questions which have to be
addressed: (1) Why was the Bu group not transferred in our
system, (2) how facile does the 2-PyMe2SiCH2 group transfer
from tin compared to the other common transferring group, (3)
is there any beneficial coordination effect of the pyridyl group
during the catalytic cycle, and (4) if so, is the pyridyl group
coordinating to tin, as observed by Vedejs and Brown, or
coordinating to palladium?
was not detected at all, presumably due to the blocking of the
pyridyl coordination site by protonation. These results clearly
suggest that the beneficial effect of the pyridyl group is attributed
to the coordinating aptitude to either tin or palladium.
Relative Transfer Ability of the 2-PyMe2SiCH2 Group.
Having observed the unusually accelerated 2-PyMe2SiCH2 group
transfer, we next set out to compare the relative transfer ability
of the 2-PyMe2SiCH2 group with other organic groups (Table
2). The cross coupling was performed by stirring a mixture of
2-PyMe2SiCH2SnR3 (1a: R ) Bu; 1b: R ) Me; 1c: R ) Ph),
4-iodoacetophenone (1.2 equiv), PdCl2(CH3CN)2 (5 mol %),
and P(C6F5)3 (10 mol %) in THF at 50 °C for 24 h. The coupling
with 1a afforded 2-PyMe2SiCH2 transferred product 2b and Bu
transferred product 3a (entry 1). The ratio of 2b/3a was
determined to be 96/4 by 1H NMR analysis. The relative transfer
ability of these two groups (2-PyMe2SiCH2 and Bu groups) was
determined to be 99/1 by dividing the yield of 2b or 3 by the
number of groups attached on tin (one for 2b and three for 3,
respectively). Subjection of 1b and 1c to the cross coupling
afforded the cross-coupling products in 52% and 53% yield,
respectively (entries 2 and 3). In both cases, the relative transfer
ability of the 2-PyMe2SiCH2 group was found to be greater than
that of Me and Ph groups (81/19 and 71/29, respectively). The
observed relative transfer ability (2-PyMe2SiCH2 . Ph > Me
> Bu) was apparently unusual when considering the previously
reported transferring ability order (Ph > Me > Bu . Me3-
SiCH2).2
119Sn NMR Study of Organotin Compounds. As already
mentioned, Vedejs7 and Brown8 have reported that the intra-
molecular coordination of amine to tin greatly accelerates the
transmetalation step (transfer of the organic group from tin to
palladium).19 If the pyridyl group is coordinating to tin in our
system, the Bu group instead of the 2-PyMe2SiCH2 group should
be selectively transferred from tin (Scheme 1a). Since this is
not the case, the pyridyl group is likely not coordinating to tin
in our system. To verify if the pyridyl group is coordinating to
tin or not in solution, 119Sn NMR spectra of 2-PyMe2SiCH2-
SnBu3 (1a) and PhMe2SiCH2SnBu3 (1d) were taken. Organotin
1a showed resonance at -0.70 ppm in its 119Sn NMR spectrum
that is similar to that of 1d (-0.55 ppm). The minor chemical
shift difference seems to support the notion that the complex-
ation of the pyridyl group to tin is not a viable explanation for
the selective 2-PyMe2SiCH2 group transfer and for the enor-
mously different reactivities between 1a and 1d.
Stoichiometric Reaction of 2-PyMe2SiCH2SnBu3 with Pd-
(II) Complex. We next conducted the stoichiometric reaction
of 2-PyMe2SiCH2SnBu3 (1a) with palladium(II) complex. First,
1a was treated with PhPdI(PPh3)2 to see if the pyridyl group is
coordinating to palladium after the Sn/Pd transmetalation.
However, because of rapid reductive elimination, we obtained
the coupling product 2-PyMe2SiCH2Ph (2a) instead of the
To better ascertain the beneficial effect of the pyridyl group
in silylmethyl group transfer, several control experiments were
conducted (eqs 2-4). First, PhMe2SiCH2SnBu3 (1d) was
subjected to cross coupling (eq 2). However, none of the organic
(17) Bertz, S. H.; Eriksson, M.; Miao, G.; Snyder, J. P. J. Am. Chem.
Soc. 1996, 118, 10906.
(18) The Me3SiCH2 group has received particular attention in the metal
alkyl chemistry because of lacking â-hydrogen, thus increasing the stability
of alkylmetal complexes: (a) Wilkinson, G. Pure Appl. Chem. 1972, 30,
627. (b) Davidson, P. J.; Lappert, M. F.; Pearce, R. Acc. Chem. Res. 1974,
7, 209. (c) Baird, M. C. J. Organomet. Chem. 1974, 64, 289.
(19) Farina, V.; Krishnan, B.; Marshall, D. R.; Roth, G. P. J. Org. Chem.
1993, 58, 5434.
groups including the PhMe2SiCH2 group were transferred under

8776 J. Am. Chem. Soc., Vol. 123, No. 36, 2001
Itami et al.
Mechanistic Rationale Based on Pyridyl-to-Palladium
Coordination. On the basis of the 119Sn NMR study, it is
reasonable to conclude that the pyridyl group is not coordinating
to tin in the cross coupling with 1a as an organotin nucleophile.
Instead, we favor the mechanistic rationale based on the pyridyl-
to-palladium coordination at the transmetalation step (Figure
3). Although the mechanism of the transmetalation step is still
uncertain,24 there are two major pathways proposed for this step,
namely the SE2(cyclic) mechanism (intermediate A)25,26 and the
SE2(open) mechanism (intermediate B).27 Very recently, Espinet
has proposed that the SE2(cyclic)-type mechanism fits for the
palladium-catalyzed cross-coupling reaction of organotin com-
pound with aryl iodide in THF based on the kinetic studies on
catalytic reactions, and on the reactions with isolated intermedi-
ates.26 Thus we favor the SE2(cyclic)-type mechanism for the
cross-coupling reaction with 2-PyMe2SiCH2SnBu3 at the present
time. Whichever mechanism is operating, the coordination of
the pyridyl group to palladium brings tin into the proximity of
the palladium and renders the subsequent transmetalation
intramolecular in nature, thereby facilitating the transfer of the
bridging 2-PyMe2SiCH2 group (A or B). Although experimental
evidence was not provided, similar coordination effects were
proposed in the alkenyl group transfer from tin by several
groups.28 In addition to this kinetic preference, stabilization of
the palladium(II) intermediate (C) by complexation with the
pyridyl group might also contribute to accelerate the 2-PyMe2-
SiCH2 group transfer. A similar coordination effect was
proposed in the Cu-catalyzed cross-coupling reaction of R-het-
eroatom-substituted organotin compounds.29
Figure 2. ORTEP drawing of 5. Thermal ellipsoids are drawn at the
40% probability level and hydrogen atoms are omitted for clarity.
Selected bond lengths (Å): Pd(1)-Cl(1) ) 2.392(2), Pd(1)-P(1) )
2.248(2), Pd(1)-N(1) ) 2.150(5), Pd(1)-C(1) ) 2.088(7), C(1)-Si-
(1) ) 1.873(7), Si(1)-C(4) ) 1.900(8), C(4)-N(1) ) 1.385(9).
Selected bond angles (deg): Cl(1)-Pd(1)-P(1) ) 95.46(7), Cl(1)-
Pd(1)-N(1) ) 90.6(2), N(1)-Pd(1)-C(1) ) 86.6(2), C(1)-Pd(1)-
P(1) ) 87.3(2).
desired bis(organo)palladium(II) complex.20 Thus, we next
examined the stoichiometric reaction of 1a with PdCl2(CH3-
CN)2 and PPh3, and the palladium(II) complex 5 was isolated
in 69% yield (eq 5).21 In complex 5, the coordination of the
Transformations of Coupling Product. The cross-coupling
product 2 can be used for further transformations (Scheme 3).
We have already reported that the 2-PyMe2Si group can be
converted to the hydroxyl group by the H2O2/KF system.30,31
By using this protocol, 2a can be converted into the corre-
sponding alcohol 6a in 94% yield (Scheme 3). By combining
this C-Si oxidation with the Stille coupling, the overall process
can be regarded as a nucleophilic hydroxymethylation of aryl
halides.32 It should be mentioned that such processes have
emerged as important transformations in natural product syn-
(23) Similar amine-to-palladium coordination after Sn/Pd transmetalation
was reported by van Koten: Steenwinkel, P.; Jastrzebski, J. T. B. H.;
Deelman, B. J.; Grove, D. M.; Kooijman, H.; Veldman, N.; Smeets, W. J.
J.; Spek, A. L.; van Koten, G. Organometallics 1997, 16, 5486.
(24) (a) Morita, D. K.; Stille, J. K.; Norton, J. R. J. Am. Chem. Soc.
1995, 117, 8576. (b) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117,
11598.
(25) (a) Eaborn, C.; Odell, K. J.; Pidcock, A. J. Chem. Soc., Dalton Trans.
1978, 357. (b) Cross, R. J. AdV. Inorg. Chem. 1989, 34, 219. (c) Fukuto, J.
M.; Jensen, F. R. Acc. Chem. Res. 1983, 16, 177.
(26) Casado, A. L.; Espinet, P. J. Am. Chem. Soc. 1998, 120, 8978.
(27) (a) Labadie, J. W.; Stille, J. K. J. Am. Chem. Soc. 1983, 105, 6129.
(b) Hatanaka, Y.; Hiyama, T. J. Am. Chem. Soc. 1990, 112, 7794. (c)
Casado, A. L.; Espinet, P.; Gallego, A. M. J. Am. Chem. Soc. 2000, 122,
11771.
(28) (a) Crisp, G. T.; Gebauer, M. G. Tetrahedron Lett. 1995, 36, 3389.
(b) Quayle, P.; Wang, J.; Xu, J.; Urch, C. J. Tetrahedron Lett. 1998, 39,
485. (c) Dom´ınguez, B.; Pazos, Y.; de Lera, A. R. J. Org. Chem. 2000, 65,
5917.
pyridyl group to palladium was highly indicated by the
noticeable changes of the pyridine ring chemical shift in the
1H NMR spectrum (see the Experimental Section).22
X-ray Crystal Structure of 5. The molecular structure of 5,
determined by X-ray crystallographic analysis, revealed the
coordination of the pyridyl group to palladium (Figure 2). The
palladium has a square-planar geometry and PPh3 sits trans to
the pyridyl group. Interestingly, the pyridine ring deviates from
the coordination plane (tortion angle C(1)-Pd(1)-N(1)-C(4)
) -26.3°) presumably because of the envelope-like conforma-
tion of five-membered metallacycle (C-Pd-N-C-Si). From
these data, it might be reasonable to presume that the pyridyl-
to-palladium coordination is a driving force for the facile
2-PyMe2SiCH2 group transfer.23
(29) (a) Falck, J. R.; Bhatt, R. K.; Ye, J. J. Am. Chem. Soc. 1995, 117,
5973. (b) Linderman, R. J.; Stiedlecki, J. M. J. Org. Chem. 1996, 61, 6492.
See also: (c) Ye, J.; Bhatt, R. K.; Falck, J. R. J. Am. Chem. Soc. 1994,
116, 1. (d) Linderman, R. J.; Graves, D. M.; Kwochka, W. R.; Ghannam,
A. F.; Anklekar, T. V. J. Am. Chem. Soc. 1990, 112, 7438.
(30) Itami, K.; Mitsudo, K.; Yoshida, J. J. Org. Chem. 1999, 64, 8709.
(31) For excellent reviews on oxidative cleavage of the carbon-silicon
bond, see: (a) Tamao, K. In AdVances in Silicon Chemistry; Larson, G. L.,
Ed.; JAI Press Inc.: London, UK, 1996; Vol. 3, p 1. (b) Fleming, I.
ChemTracts: Org. Chem. 1996, 1. (c) Jones, G. R.; Landais, Y. Tetrahedron
1996, 52, 7599. For a recent theoretical study on mechanism, see: (d) Mader,
M. M.; Norrby, P.-O. J. Am. Chem. Soc. 2001, 123, 1970.
(32) Tamao, K.; Ishida, N.; Kumada, M. J. Org. Chem. 1983, 48, 2120.
(20) For successful isolation of such transmetalated bis(organo)palladium-
(II) complexes, see: Mateo, C.; Ca´rdenas, D. J.; Ferna´ndez-Rivas, C.;
Echavarren, A. M. Chem. Eur. J. 1996, 2, 1596.
(21) Fuchita, Y.; Nakashima, M.; Hiraki, K.; Kawatani, M.; Ohnuma,
K. J. Chem. Soc., Dalton Trans. 1988, 785.
(22) Eaborn and Smith have recently established the coordination of the
related 2-PyMe2C(SiMe3)2 group to various metals: (a) Al-Juaid, S. S.;
Eaborn, C.; Hitchcock, P. B.; Hill, M. S.; Smith, J. D. Organometallics
2000, 19, 3324. (b) Eaborn, C.; Hill, M. S.; Hitchcock, P. B.; Smith, J. D.
Chem. Commun. 2000, 691. (c) Al-Juaid, S. S.; Avent, A. G.; Eaborn, C.;
Hill, M. S.; Hitchcock, P. B.; Patel, D. J.; Smith, J. D. Organometallics
2001, 20, 1223.

Silylmethyl Transfer from Tin in Stille Coupling
J. Am. Chem. Soc., Vol. 123, No. 36, 2001 8777
Figure 3. Pyridyl-to-palladium coordination at the transmetalation step.
Scheme 3
remarkably accelerated by simply appending the 2-pyridyl group
on silicon. This appears to be the general and practical
silylmethyl group transfer from tin in Stille coupling. The
relative transfer ability of the organic group was found to be
2-PyMe2SiCH2 . Ph > Me > Bu . PhMe2SiCH2, which
implies the beneficial pyridyl-to-palladium coordination effect.
The pyridyl-to-palladium coordination was validated in the
1
transmetalated palladium complex 5 by H NMR and X-ray
crystal structure analysis. Further transformations of the coupling
product clearly augment the synthetic utility of the cross
coupling using 2-PyMe2SiCH2SnBu3. The utility of 2-PyMe2-
SiCH2SnBu3 as synthons, its ease of preparation (two steps from
2-bromopyridine), and the resultant opportunity for sequential
reactions distinguish this chemistry and suggest multiple pos-
sibilities for further development. Moreover, we believe that
the coordination-driven transmetalation demonstrated herein may
be a useful alternative to the hypervalent organotin strategy for
enhancing the transfer of otherwise nontransferring organic
groups from tin in Stille coupling. If this goal could be
accomplished, the utility of Stille coupling methodology will
be enormously heightened.
thesis.33 Moreover, this procedure may have some advantages
over the direct hydroxymethylation with Bu3SnCH2OH,34
because the Bu3SnCH2OH protocol often requires the use of
HMPA as a solvent and suffers from the occurrence of
considerable Bu group transfer.35
The fluoride ion-catalyzed addition of 2 to carbonyl com-
pound was found to take place giving alcohol 7 in high yield
(Scheme 3).36 Not only simple aldehydes, but also R,â-
unsaturated aldehydes and ketones were found to be good
electrophiles in this reaction. In the case of R,â-unsaturated
aldehyde, we observed only the 1,2-addition product 7b.
Experimental Section
1
General. H, 13C, 31P, and 119Sn NMR spectra were recorded on
Varian GEMINI-2000 (1H 300 MHz, 13C 75 MHz), JEOL A-500 (1H
500 MHz, 13C 125 MHz), and JEOL A-400 (31P 162 MHz, 119Sn 149
MHz) spectrometers in CDCl3 with chemical shifts referenced to internal
1
standards (7.26 ppm H, 77.0 ppm 13C), H3PO4 (0 ppm), or Me4Sn (0
ppm). EI mass spectra were recorded on a JMS-SX102A spectrometer.
FAB mass spectra were recorded on a JMS-HX110A spectrometer.
Infrared spectra were recorded on a Shimadzu FTIR-8100 spectropho-
tometer. Unless otherwise noted, all materials were obtained from
commercial suppliers and used without further purification. Diethyl ether
(Et2O) and tetrahydrofuran (THF) were freshly distilled under argon
from sodium benzophenone ketyl prior to use. 2-Pyridyltrimethylsilane
was prepared according to the literature procedures.37
[(2-Pyridyldimethylsilyl)methyl]tributylstannane (1a). To a solu-
tion of 2-pyridyltrimethylsilane (5.56 g, 36.8 mmol) in dry Et2O (50
mL) was added dropwise a solution of t-BuLi (40.4 mmol, 1.37 M
solution in pentane) at -78 °C under argon. The mixture was stirred
Conclusion
In summary, we have found that the transfer of the syntheti-
cally useful silylmethyl group from tin to palladium was
(33) (a) Chen, X. T.; Zhou, B.; Bhattacharya, S. K.; Gutteridge, C. E.;
Pettus, T. R. R.; Danishefsky, S. J. Angew. Chem., Int. Ed. 1998, 37, 789.
(b) Chen, X. T.; Bhattacharya, S. K.; Zhou, B.; Gutteridge, C. E.; Pettus,
T. R. R.; Danishefsky, S. J. J. Am. Chem. Soc. 1999, 121, 6563.
(34) Kosugi, M.; Sumiya, T.; Ohhashi, K.; Sano, H.; Migita, T. Chem.
Lett. 1985, 997.
(35) Yasuda, N.; Yang, C.; Wells, K. M.; Jensen, M. S.; Hughes, D. L.
Tetrahedron Lett. 1999, 40, 427.
(36) (a) Bennetau, B.; Dunogues, J. Tetrahedron Lett. 1983, 24, 4217.
(b) Bartoli, G.; Bosco, M.; Caretti, D.; Dalpozzo, R.; Todesco, P. E. J.
Org. Chem. 1987, 52, 4381.
(37) Anderson, D. G.; Bradney, M. A. M.; Webster, D. E. J. Chem. Soc.
B 1968, 450.

8778 J. Am. Chem. Soc., Vol. 123, No. 36, 2001
Itami et al.
for an additional 45 min to afford an orange ether solution of
(2-pyridyldimethylsilyl)methyllithium. To this solution was added a
solution of chlorotributylstannane (15.6 g, 47.8 mmol) in Et2O (20 mL)
at -78 °C. After being stirred at room temperature for 12 h, the reaction
mixture was quenched with H2O (50 mL). The aqueous phase was
extracted with Et2O (2 × 50 mL), and the combined organic phase
was washed with H2O (50 mL). Drying over MgSO4 and subsequent
silica gel chromatography (hexane/EtOAc ) 20/1 to 10/1) afforded 1a
(12.1 g, 74%) as colorless oil:1H NMR (300 MHz) δ -0.01 (s, JSn-H
) 65.1 Hz, 2 H), 0.31 (s, 6 H), 0.70-0.78 (m, 6 H), 0.85 (t, J ) 7.2
Hz, 9 H), 1.18-1.50 (m, 12 H), 7.15 (ddd, J ) 7.5, 5.1, 1.8 Hz, 1 H),
7.49 (dm, J ) 7.5 Hz, 1 H), 7.55 (td, J ) 7.5, 1.5 Hz, 1 H), 8.75 (dm,
J ) 5.1 Hz, 1 H); 13C NMR (75 MHz) δ -9.5, -0.5, 10.2, 13.5, 27.3,
29.0, 122.5, 128.6, 133.9, 150.1, 169.9; 119Sn NMR (149 MHz) δ -0.70.
IR (neat) 1576, 1559, 1464, 1456, 1418, 1375, 1246, 1138 cm-1. HRMS
(FAB) m/z calcd for C20H40NSiSn (M + H)+: 440.1952. Found:
440.1955. Anal. Calcd for C20H39NSiSn: C, 54.55; H, 8.93; N, 3.18.
Found: C, 54.39; H, 9.20; N, 3.25.
1246, 1113, 990, 816 cm-1. HRMS (FAB) m/z calcd for C25H43NSi2-
Sn2 (M + H)+: 534.2039. Found: 534.2023.
[(2-Pyridyldimethylsilyl)methyl]tributylstannane Hydrochloride
(1f). To 1a (213.5 mg, 0.48 mmol) was added HCl solution in Et2O (5
mL, 1 M, 5 mmol) at room temperature. After being stirred for 5 min,
the mixture was filtered. Drying the residue under reduced pressure
afforded 1f (229 mg, quant) as a colorless solid: 1H NMR (400 MHz,
DMSO-d6) δ 0.22 (s, JSn-H ) 63.0 Hz, 2 H), 0.44 (s, 6 H), 0.76-0.88
(m, 15 H), 1.18-1.30 (m, 6 H), 1.30-1.46 (m, 6 H), 7.68 (d, J ) 7.1
Hz, 1 H), 8.04 (t, J ) 6.8 Hz, 1 H), 8.19 (d, J ) 7.5 Hz, 1 H), 8.51 (t,
J ) 7.2 Hz, 1 H), 8.94 (d, J ) 5.3 Hz, 1 H); 13C NMR (100 MHz,
DMSO-d6) δ -10.1, -0.9, 10.0, 13.5, 26.6 (JC-Sn ) 56.2 Hz), 28.4,
126.8, 132.5, 143.1, 143.9, 161.5.
Procedure for the Palladium-Catalyzed Cross Coupling of 1 with
4-Iodoacetophenone (Table 2, Entry 1). To a solution of PdCl2(CH3-
CN)2 (4.1 mg, 0.016 mmol, 5 mol %) and P(C6F5)3 (16.9 mg, 0.032
mmol, 10 mol %) in THF (1.0 mL) were added 1a (145.0 mg, 0.33
mmol), 4-iodoacetophenone (93.6 mg, 0.38 mmol), and THF (1.0 mL).
After the mixture was stirred at 50 °C for 24 h, 1,8-diazabicyclo[5.4.0]-
undec-7-ene (ca. 0.1 mL) and Et2O (1.0 mL) were added to the mixture.
The catalyst and tin residue were removed by filtration through a short
silica gel pad (EtOAc). The filtrate was evaporated to give the crude
product. The yield of 2b and 3a was determined to be 87%, with the
ratio of 96/4, as judged by 1H NMR analysis with phenyl acetate as an
internal standard. Compound 2b was isolated in a pure form by the
acid-base extraction as follows. The solution of a crude mixture in
Et2O (2 mL) was extracted with 1 N aqueous HCl (5 × 1 mL). The
combined aqueous phase was neutralized by adding NaHCO3 and then
was extracted with EtOAc (3 × 20 mL). Drying over MgSO4 and
removal of solvents under reduced pressure afforded 2b (72.7 mg, 82%)
as a pale yellow oil.
[(2-Pyridyldimethylsilyl)methyl]trimethylstannane (1b). The title
compound was prepared by a similar procedure to that used for 1a
(83%). 1H NMR (300 MHz) δ 0.01 (s, JSn-H ) 54.0 Hz, 9 H), 0.06 (s,
2 H), 0.31 (s, 6 H), 7.16 (ddd, J ) 7.5, 5.1, 1.8 Hz, 1 H), 7.49 (ddd,
J ) 7.5, 1.8, 1.5 Hz, 1 H), 7.56 (td, J ) 7.5, 1.8 Hz, 1 H), 8.75 (ddd,
J ) 5.1, 1.8, 1.5 Hz, 1 H); 13C NMR (75 MHz) δ -8.0, -6.4, -0.6,
122.5, 128.4, 133.8, 149.9, 169.3. IR (neat) 1576, 1246 cm-1. HRMS
(FAB) m/z calcd for C11H22NSiSn (M + H)+: 316.0537. Found:
316.0547.
[(2-Pyridyldimethylsilyl)methyl]triphenylstannane (1c). The title
compound was prepared by a similar procedure to that used for 1a
(67%). 1H NMR (300 MHz) δ 0.28 (s, 6 H), 0.78 (s, JSn-H ) 74.4 Hz,
2 H), 7.10 (ddd, J ) 7.2, 4.8, 1.5 Hz, 1 H), 7.32-7.36 (m, 9 H), 7.46
(td, J ) 7.8, 1.8 Hz, 1 H), 7.51-7.54 (m, 6 H), 7.59-7.62 (m, 1 H),
8.59 (dm, J ) 4.8 Hz, 1 H); 13C NMR (75 MHz) δ -7.1, -0.5, 122.7,
128.2 (JSn-C ) 50.1 Hz), 128.5, 128.6, 133.8, 136.8 (JSn-C ) 36.5 Hz),
140.1, 149.7, 168.1. IR (neat) 1428, 1246, 1075, 1001 cm-1. HRMS
(EI) m/z calcd for C26H27NSiSn: 501.0940. Found: 501.0930.
4-[(2-Pyridyldimethylsilyl)methyl]acetophenone (2b). 1H NMR
(300 MHz) δ 0.31 (s, 6 H), 2.51 (s, 2 H), 2.54 (s, 3 H), 7.00 (d, J )
8.1 Hz, 2 H), 7.25 (ddd, J ) 7.5, 4.8, 1.2 Hz, 1 H), 7.38 (dt, J ) 7.5,
1.2 Hz, 1 H), 7.59 (td, J ) 7.5, 1.2 Hz, 1 H), 7.76 (dt, J ) 8.4, 1.8 Hz,
2 H), 8.81 (ddd, J ) 4.8, 1.5, 1.2 Hz, 1 H); 13C NMR (75 MHz) δ
-4.1, 25.8, 26.4, 123.1, 128.2, 128.4, 129.4, 133.4, 134.1, 146.3, 150.1,
165.7, 197.8. IR (neat) 1680, 1603, 1271 cm-1. HRMS (EI) m/z calcd
for C16H19NOSi: 269.1236. Found: 269.1232. Anal. Calcd for C16H19-
NOSi: C, 71.33; H, 7.11; N, 5.20. Found: C, 71.16; H, 7.13; N, 5.11.
[(2-Pyridyldimethylsilyl)methyl]benzene (2a). 1H NMR (300 MHz)
δ 0.31 (s, 6 H), 2.42 (s, 2 H), 6.97 (dm, J ) 7.5 Hz, 2 H), 7.02-7.09
(m, 1 H), 7.12-7.24 (m, 3 H), 7.40 (dm, J ) 7.5 Hz, 1 H), 7.55 (td,
J ) 7.5, 1.5 Hz, 1 H), 8.82 (dm, J ) 5.1 Hz, 1 H); 13C NMR (75
MHz) δ -4.2, 24.8, 122.9, 124.1, 128.2, 128.3, 129.4, 134.0, 139.6,
[(Phenyldimethylsilyl)methyl]tributylstannane (1d). To a solution
of chlorotributylstannane (1.56 g, 4.79 mmol) in Et2O (1.0 mL) was
added a solution of PhMe2SiCH2MgCl (5.0 mmol, 2.77 M in Et2O,
prepared by the reaction of PhMe2SiCH2Cl with Mg). After the mixture
was stirred at room temperature for 7 h, H2O (3.0 mL) was added to
the mixture. The aqueous phase was extracted with Et2O (3 × 10 mL).
The combined organic phase was dried over MgSO4. Removal of
solvents under reduced pressure and subsequent silica gel chromatog-
raphy (hexane) afforded 1d (2.11 g, quant) as a colorless oil:1H NMR
(300 MHz) δ -0.07 (s, JSn-H ) 65.4 Hz, 2 H), 0.27 (s, 6 H), 0.75 (t,
J ) 8.1 Hz, JSn-H ) 50.4 Hz, 6 H), 0.86 (t, J ) 7.5 Hz, 9 H), 1.19-
1.31 (m, 6 H), 1.34-1.44 (m, 6 H), 7.33-7.35 (m, 3 H), 7.51-7.54
(m, 2 H); 13C NMR (75 MHz) δ -8.6, 0.2, 10.2, 13.7, 27.4, 29.1,
127.6, 128.5, 133.2, 141.9; 119Sn NMR (149 MHz) δ -0.55. IR (neat)
1248, 1113, 833, 814 cm-1. HRMS (FAB) m/z calcd for C20H37SiSn
(M - CH3)+: 425.1687. Found: 425.1683.
[(2-Pyridyldimethylsilyl)methyl][(phenyldimethylsilyl)methyl]-
dibutylstannane (1e). To a solution of dichlorodibutylstannane (1.51
g, 5.0 mmol) in Et2O (3.0 mL) was added a solution of PhMe2SiCH2-
MgCl (5.0 mmol, 2.77 M in Et2O) at 0 °C, and the mixture was stirred
at room temperature for 5 h. To this mixture was added a solution of
2-PyMe2SiCH2Li (5.1 mmol) in Et2O at -78 °C. After the mixture
was stirred for 3 h, H2O (10 mL) was added. The aqueous phase was
extracted with Et2O (3 × 30 mL). The combined organic phase was
dried over MgSO4. Removal of solvents under reduced pressure and
subsequent silica gel chromatography (hexane/EtOAc ) 10/1) afforded
1e (568 mg, 22%) as a colorless oil: 1H NMR (300 MHz) δ -0.07 (s,
JSn-H ) 67.5 Hz, 2 H), -0.01 (s, JSn-H ) 66.6 Hz, 2 H), 0.25 (s, 6 H),
0.31 (s, 6 H), 0.67 (t, J ) 7.8 Hz, 4 H), 0.82 (t, J ) 7.2 Hz, 6 H),
1.12-1.32 (m, 8 H), 7.18 (ddd, J ) 7.5, 4.8, 1.5 Hz, 1 H), 7.30-7.34
(m, 3 H), 7.46-7.51 (m, 3 H), 7.57 (td, J ) 7.5, 1.8 Hz, 1 H), 8.75
(ddd, J ) 4.8, 1.8, 1.2 Hz, 1 H); 13C NMR (125 MHz) δ -7.4, -6.5,
-0.3, 0.3, 11.9, 13.6, 27.3 (JC-Sn ) 66.5 Hz), 28.9 (JC-Sn ) 20.0 Hz),
122.5, 127.6, 128.5, 128.6, 133.2, 134.0, 141.8, 149.8, 169.4. IR (neat)
150.2, 166.8. IR (neat) 1599, 1574, 1493, 1451, 1418, 1248, 1208 cm-1
.
HRMS (EI) m/z calcd for C14H17NSi: 227.1130. Found 227.1129. Anal.
Calcd for C14H17NSi: C, 73.95; H, 7.54; N, 6.16. Found: C, 74.05; H,
7.61; N, 6.10.
Palladium Complex 5. To a solution of PdCl2(CH3CN)2 (78.0 mg,
0.30 mmol) in THF (2.0 mL) were added 1a (181.6 mg, 0.41 mmol)
and a solution of PPh3 (80.0 mg, 0.31 mmol) in THF (2.0 mL). After
the mixture was stirred at 40 °C for 13 h, the solvent was removed
under vacuum. The residue was washed with Et2O (5.0 mL) and the
filtrate was evaporated to give the solid, which was further washed
with hexane (5.0 mL). Addition of hexane to the solution of this residue
in CH2Cl2 afforded 5 (105.3 mg, 69%) as an orange solid: mp 169-
1
171 °C. H NMR (300 MHz) δ 0.21 (s, 6 H), 0.55 (s, JH-P ) 3.7 Hz,
2 H), 7.29 (ddm, J ) 7.5, 5.8 Hz, 1 H), 7.34-7.42 (m, 9 H), 7.46 (dm,
J ) 7.5 Hz, 1 H), 7.65 (td, J ) 7.7, 1.6 Hz, 1 H), 7.71-7.76 (m, 6 H),
9.63-9.65 (m, 1 H); 13C NMR (100 MHz) δ 0.0, 15.8 (d, JC-P ) 3.8
Hz), 123.9 (d, JC-P ) 3.0 Hz), 128.1 (d, JC-P ) 10.6 Hz), 129.1 (d,
JC-P ) 2.3 Hz), 130.2 (d, JC-P ) 2.3 Hz), 132.0 (d, JC-P ) 50.8 Hz),
134.5 (d, JC-P ) 11.4 Hz), 135.6, 152.4, 174.2 (d, JC-P ) 1.5 Hz); 31
P
NMR (162 MHz) δ 37.2. X-ray data for 5: C26H27NSiPClPd, M )
554.42, triclinic, space group P1h(No. 2), a ) 10.2144(7) Å, b ) 27.866-
(2) Å, c ) 9.4148(6) Å, V ) 2600.5(3) Å3, Z ) 5, Dc ) 1.77 g/cm3,
µ ) 11.72 cm-1. Intensity data were measured on a Rigaku RAXIS
imaging plate area detector with graphite-monochromated Mo KR
radiation (λ ) 0.71069 Å). The data were collected at 23 ( 1 °C to a
maximum 2θ value of 55.0°. A total of 9472 reflections were collected.

Silylmethyl Transfer from Tin in Stille Coupling
J. Am. Chem. Soc., Vol. 123, No. 36, 2001 8779
Two molecules were found in a unit cell. The structure was solved by
direct methods and expanded by using Fourier techniques. The non-
hydrogen atoms were refined anisotropically. Hydrogen atoms were
included but not refined. The final cycle of full-matrix least-squares
refinement on F was based on 8565 observed reflections (I > 3.00σ-
(I)) and 560 variable parameters and converged (largest parameter shift
was 0.00 times its esd) with unweighted and weighted agreement factors
of R ) 0.052 (Rw ) 0.068). The standard deviation of an observation
of unit weight was 1.32. All calculations were performed by using the
CrystalStructure crystallographic software package.
1,4-Diphenylbut-3-en-2-ol (7b).39 This compound was obtained in
68% yield from 2a (1.5 equiv) and trans-cinnamaldehyde (1.0 equiv)
in the presence of TBAF (5 mol %). H NMR (300 MHz) δ 1.64 (br
s, 1 H), 2.89 (dd, J ) 13.5, 7.8 Hz, 1 H), 2.99 (dd, J ) 13.8, 5.1 Hz,
1 H), 4.54 (ddd, J ) 12.0, 6.3, 1.2 Hz, 1 H), 6.29 (dd, J ) 15.9, 6.3
Hz, 1 H), 6.61 (d, J ) 16.2 Hz, 1 H), 7.22-7.40 (m, 10 H).
1
1,2-Diphenylpropan-2-ol (7c).38 This compound was obtained in
70% yield from 2a (1.5 equiv) and acetophenone (1.0 equiv) in the
1
presence of TBAF (5 mol %). H NMR (300 MHz) δ 1.57 (s, 3 H),
1.84 (br s, 1 H), 3.03 (d, J ) 13.2 Hz, 1 H), 3.14 (d, J ) 13.2 Hz, 1
Procedure for the C-Si Oxidation of 2a (Scheme 3). To a mixture
of KF (119 mg, 2.0 mmol) and KHCO3 (207 mg, 2.1 mmol) in MeOH
(2 mL) and THF (2 mL) were added 2a (256 mg, 1.1 mmol) and 30%
aqueous H2O2 (2.3 g, 20 mmol) and the reaction mixture was stirred at
50 °C for 12 h. After being cooled to room temperature, the reaction
mixture was treated with H2O (10 mL). The mixture was extracted
with Et2O (5 × 10 mL) and the combined organic phase was
successively washed with 15% aqueous Na2S2O3 (10 mL). Drying over
MgSO4 and removal of solvents under reduced pressure afforded crude
benzyl alcohol. The yield of benzyl alcohol (6a) was 94% as judged
by capillary GC analysis with n-pentadecane as an internal standard.
Procedure for the TBAF-Catalyzed Reaction of 2 with Carbonyl
Compound (Scheme 3). To a solution of benzaldehyde (52.8 mg, 0.50
mmol) and tetrabutylammonium fluoride (0.025 mmol, 5 mol %, 1.0
M solution in THF) in THF (1.0 mL) was added 2a (174.0 mg, 0.75
mmol) at room temperature. After the mixture was stirred for 4 h, 1 N
aqueous HCl (2 mL) was added to the mixture. The mixture was
extracted with Et2O (5 × 2 mL) and the combined organic phase was
dried over MgSO4. Removal of solvents under reduced pressure and
subsequent silica gel chromatography (hexane/EtOAc ) 5/1) afforded
1,2-diphenylethanol (7a) (92.6 mg, 94%) as colorless solid.
H), 6.99 (dd, J ) 6.0, 2.1 Hz, 2 H), 7.21-7.42 (m, 8 H).
4-(2-Hydroxy-2-phenyl)acetophenone (7d).40 This compound was
obtained in 54% yield from 2b (1.5 equiv) and benzaldehyde (1.0 equiv)
1
in the presence of TBAF (5 mol %). H NMR (300 MHz) δ 2.08 (br
s, 1 H), 2.58 (s, 3 H), 3.06 (dd, J ) 13.5, 6.0 Hz, 1 H), 3.11 (dd, J )
13.5, 7.5 Hz, 1 H), 4.93 (dd, J ) 7.2, 6.0 Hz, 1 H), 7.25 (m, 7 H), 7.87
(d, J ) 8.1 Hz, 2 H).
Acknowledgment. This research was supported by a Grant-
in-Aid for Scientific Research from the Japan Society for the
Promotion of Science.
Supporting Information Available: Tables of crystal-
lographic data for 5 (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA0160593
(38) Kim, S. H.; Rieke, R. D. J. Org. Chem. 2000, 65, 2322.
(39) Huang, Y. Z.; Liao, Y. J. Org. Chem. 1991, 56, 1381.
(40) Saito, S.; Shiozawa, M.; Ito, M.; Yamamoto, H. J. Am. Chem. Soc.
1998, 120, 813.
1,2-Diphenylethanol (7a).38 1H NMR (300 MHz) δ 2.08 (br s, 1
H), 3.00 (dd, J ) 13.8, 8.1 Hz, 1 H), 3.07 (dd, J ) 13.5, 5.1 Hz, 1 H),
4.90 (dd, J ) 8.4, 5.4 Hz, 1 H), 7.20-7.38 (m, 10 H).