catalyzed hydrostannation of nonhindered 1-alkynes by
modifying the Pd catalyst.5 The lack of activity in this area
may be attributable to an observation made during some of
the early work on metal-catalyzed hydrostannations that
“attempts to modify the regiochemistry by changing the
catalyst and, in particular, the steric bulk of the ligands, met
with no success.”2 Thus, more circuitous routes such as the
use of 1-halo-1-alkynes were developed.2,6 More recently,
strategies involving modified stannanes such as trineophyltin
hydride7 and Bu2SnClH have been reported.8 For select
substrates such as R,â-acetylenic carbonyl compounds,
copper-catalyzed hydrostannations proceed with high regio-
selectivities.9 We now report that substitution of other
phosphine ligands in place of Ph3P in Pd-catalyzed hy-
drostannations gives considerably improved regioselectivities.
We chose to begin our studies with a propargylic alcohol,
3-butyn-2-ol, partly since we expected that the regioisomeric
products would be readily separable from each other and
from nonpolar stannane byproducts by flash chromatography.
We were delighted to find that the phosphine ligand does,
in fact, dramatically influence the regiochemistry (Table 1).
selectivities reported previously for similar 2° propargylic
alcohols (trans:gem ) 76:24 to 80:20). Bulky trialkylphos-
phines all gave substantially higher regioselectivities in favor
of the desired trans-isomer (entries 3-5). Somewhat per-
plexingly, while t-Bu3P gave none of the gem isomer 3a
(entry 5), the isolated yield of 2a with this ligand was
significantly lower than when (Cy3P)2PdCl2 was used,
suggesting the possibility of an undetected side reaction.
To probe for possible side reactions, alkyne 1b was chosen
to be sterically representative of a straight-chain alkyne but
contained an alcohol group to facilitate the chromatographic
separation of products. This compound was treated with Bu3-
SnH under a variety of conditions with very enlightening
results (Table 2). By using the “usual” (Ph3P)2PdCl2 catalyst,
Table 2. Hydrostannation of 1b under Various Conditions
Table 1. Hydrostannation of 1a with Various Catalysts
2b:3b:4b
ratiob
entry
conditionsa
1
2
1% (Ph3P)2PdCl2
1% (Cy3P)2PdCl2
66:33:1
69:4:27
3
0.5% Pd2(dba)3, 2% t-Bu3PHBF4, 4% i-Pr2NEt 46:1:53
2a:3a
yield of
4
5
6
7
8c
9
10
0.5% Pd2(dba)3, 2% Cy3PHBF4, 2% i-Pr2NEt
0.5% Pd2(dba)3, 2% Cy3PHBF4, 4% i-Pr2NEt
0.5% Pd2(dba)3, 2% Cy3PHBF4, 20% i-Pr2NEt
0.5% Pd2(dba)3, 2% (2-PhC6H4)PCy2
0.5% Pd2(dba)3, 2% ArPCy2
0.5% Pd2(dba)3, 2% n-Bu3P, 2% i-Pr2NEt
0.5% Pd2(dba)3, 2% (2-furyl)3P, 2% i-Pr2NEt
84:4:12
92:4:4
93:4:3
78:8:14
92:5:3
86:10:4
57:42:1
entry
catalysta,b
ratioc
2ad (%)
1
2
3
4
5
6
7
8
(Ph3P)2PdCl2
(o-tol3P)2PdCl2
(Cy3P)2PdCl2
t-Bu2PCH2t-Bu
t-Bu3P
68:32
80:20
95:5
57
60
84
70
72
22
45
63
96:4
100:0
40:60
47:53
77:23
(2-furyl)3P
a Mol % of catalyst and additives, toluene, rt, 2 h. b Determined by H
NMR analysis of crude reaction mixtures. c Ar ) 2-(2′,6′-dimethoxybiphe-
nyl).
1
TTMPPe
f
ArPCy2
a 1% Pd, 2% phosphine, toluene, rt, 2 h. b Catalyst precursor or ligand
used with Pd2(dba)3. c Determined by 1H NMR analysis of crude
reaction mixtures. d Isolated yield after flash chromatography. e Tris(2,4,6-
trimethoxyphenyl)phosphine. f Ar ) 2-(2′,6′-dimethoxybiphenyl).
hydrostannation of either 1a or 1b gave virtually identical
results, i.e., a 2:1 mixture of regioisomers (entry 1). However,
while hydrostannation of 1b with (Cy3P)2PdCl2 proceeded
with the same regioselectivity as that observed for 1a (entry
2, trans:gem ) 95:5), a substantial amount of reduction
product 4b was also formed. Moreover, with t-Bu3P, while
only a trace of gem-product 3b was detected, the major
product formed was 4b.10 With other propargylic alcohols
examined, up to 40% reduction was observed when t-Bu3P
was used. Thus it seems likely that reduction (producing
relatively volatile and thus undetected 3-buten-2-ol) may
have been a significant side reaction with use of t-Bu3P with
alkyne 1a.
The observed regioselectivity with (Ph3P)2PdCl2 as catalyst
precursor (entry 1, 2a:3a ) 68:32) was in line with
(4) Recent examples: (a) Volgraf, M.; Gorostiza, P.; Szobota, S.; Helix,
M. R.; Isacoff, E. Y.; Trauner, D. J. Am. Chem. Soc. 2007, 129, 260-261.
(b) Hosoya, T.; Sumi, K.; Doi, H.; Wakao, M.; Suzuki, M. Org. Biomol.
Chem. 2006, 4, 410-415. (c) Go´mez, A. M.; Barrio, A.; Amurrio, I.;
Valverde, S.; Jarosz, S.; Lo´pez, J. C. Tetrahedron Lett. 2006, 47, 6243-
6246.
(5) The effect of different catalysts on the hydrostannation of a
propargylglycine derivative has been reported: Crisp, G. T.; Gebauer, M.
G. J. Organomet. Chem. 1997, 532, 83-88.
(6) Boden, C. D. J.; Pattenden, G.; Ye, T. J. Chem. Soc., Perkin Trans.
1 1996, 2417-2419.
For hydrostannations of 1b involving Cy3P, the amount
of reduction product could be dramatically decreased by
(7) Dodero, V. I.; Koll, L. C.; Mandolesi, S. D.; Podesta´, J. C. J.
Organomet. Chem. 2002, 650, 173-180.
(8) Miura, K.; Wang, D.; Hosomi, A. Synlett 2005, 406-410.
(9) (a) Leung, L. T.; Leung, S. K.; Chiu, P. Org. Lett. 2005, 7, 5249-
5252. (b) Leung, L. T.; Chiu, P. Pure Appl. Chem. 2006, 78, 281-285. (c)
Miao, R.; Li, S.; Chiu, P. Tetrahedron 2007, 63, 6737-6740.
(10) To test if 4b might arise from protiodestannylation of 2b, 2b was
isolated and re-subjected to the reaction conditions (Table 2, entry 3). No
4b was detected.
862
Org. Lett., Vol. 10, No. 5, 2008