carbonꢀsilicon bond formations have been reported in a
short period of time.7 We have also contributed to this
chemistry, and our major focuses have been γ-selective
allylic (3fγ-4, upper)7d and propargylic (5 f γ-6, lower)7h
substitutions of linear precursors with chloride (and
phosphate) as leaving group(s) (Scheme 1).
from that with 2. In this Letter, we disclose a copper(I)-
catalyzed SN0 substitution of propargylic chlorides with the
silicon nucleophile released from easy-to-prepare (Me2PhSi)2-
Zn (1).11 The 1ꢀCuCN (5.0 mol %) combination also
allows for double addition with complete regiocontrol in
both steps, affording bifunctional building blocks with
allylic and vinylic silicon groups.
Our investigation began with the usual survey of leav-
ing groups using approximately equimolar amounts of
the propargylic precursor and 1 (Table 1). As expected, the
chloride leaving group was regioselectively displaced (γ:R g
99:1) in high yield (Table 1, entry 1). The outcome agreed
with that using the reported protocol with 2 (cf. Scheme 1,
lower),7h and the same was found with the bromide (γ:R =
59:41) and phosphate (γ:R g 99:1) as X groups (Table 1,
entries 2 and 3). With the latter, we found a new compound
with allylic and vinylic silicon groups, resulting from the
regioselective addition of 1 to the central carbon atom of the
intermediate allene (γ-6afγ-7a). To our surprise, the double
addition of the silicon nucleophile even became the major
reaction with the other oxygen leaving groups (Table 1,
entries 4ꢀ6). Also, these substitutions either were not going
to completion (phosphate, carbonate, and benzoate) or were
accompanied by substantial decomposition of the pro-
pargylic precursor(carbamate). Forthat reason, an excess of
1 is available for the subsequent addition. As detailed later,
deliberate addition of a two-fold excess of 1 resulted in full
consumption of the γ (except for the propargylic phosphate)
but not the R isomer (for the propargylic bromide).
Scheme 1. Copper(I)-Catalyzed γ-Selective Allylic and
Propargylic Substitution with either (Me2PhSi)2Zn (1) or
Me2PhSiBpin (2)
The protocol employing interelement compound 27d,8 as
the source of nucleophilic silicon is somewhat superior to
that with zinc reagent 14f in the allylic displacement (γ:R g
98:2 versus γ:R g 93:7 in 3fγ-4, Scheme 1, upper). The
related substitution of propargylic chlorides involving
activation of the SiꢀB bond also proceeds with excellent
levels of regiocontrol (γ:R = 100:0 in 5fγ-6, Scheme 1,
lower),7h,9,10 and those findings appeared to make an
investigation of the zinc chemistry seem unnecessary. We
found, however, for the propargylic displacement, unlike
similar trends for both protocols in the allylic substitution,
the copper(I) catalysis with 1 to be significantly different
Table 1. Copper-Catalyzed Propargylic Substitution
Competing with Subsequent Addition to the γ Adduct:
Survey of Leaving Groups
(7) (a) Lee, K.-s.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132, 2898–
2900 (conjugate addition). (b) Welle, A.; Petrignet, J.; Tinant, B.; Wouters,
J.; Riant, O. Chem.;Eur. J. 2010, 16, 10980–10983 (conjugate addition).
(c) Tobisu, M.; Fujihara, H.; Koh, K.; Chatani, N. J. Org. Chem. 2010, 75,
4841–4847 (nitrile insertion). (d) Vyas, D. J.; Oestreich, M. Angew.
Chem., Int. Ed. 2010, 49, 8513–8515 (allylic substitution). (e) Ibrahem,
ꢀ
I.; Santoro, S.; Himo, F.; Cordova, A. Adv. Synth. Catal. 2011, 353,
245–252 (conjugate addition). (f) Wang, P.; Yeo, X.-L.; Loh, T. P.
J. Am. Chem. Soc. 2011, 133, 1254–1256 (addition acrosstriple bonds). (g)
€
Vyas, D. J.; Frohlich, R.; Oestreich, M. Org. Lett. 2011, 13, 2094–2097 (1,2-
addition to imines). (h) Vyas, D. J.; Hazra, C. K.; Oestreich, M. Org. Lett.
2011, 13, 4462–4465 (propargylic substitution). (i) Kleeberg, C.; Feldmann,
E.; Hartmann, E.; Vyas, D. J.; Oestreich, M. Chem.;Eur. J. 2011, 17,
13538–13543 (1,2-addition to aldehydes). (j) Kleeberg, C.; Cheung, M. S.;
Lin, Z.; Marder, T. B. J. Am. Chem. Soc. 2011, 133, 19060–19063 (1,2-
addition to carbon dioxide).
(8) For an allylic substitution involving copper(I)-catalyzed SiꢀSi
bond activation, see: Ito, H.; Horita, Y.; Sawamura, M. Adv. Synth.
Catal. 2012, 354, 813–817.
propargylic
precursor
leaving
group X
γ:R:double
yield
(%)b
entry
ratioa
1
2
3
4
5
6
5a
Cl
>99:<1:0
58:41:1
82:0:18
4:17:79
3:11:86
2:4:94
93 (γ-6a)
77 (γ/R-6a)
87 (γ-6a)c
30 (γ-7a)d
48 (γ-7a)c
47 (γ-7a)c
8a
Br
9a
OP(O)(OEt)2
OC(O)NHPh
OC(O)OMe
OC(O)Ph
10a
11a
12a
(9) For a related propargylic substitution involving palladium(II)-
ꢀ
ꢀ
catalyzed SiꢀSn bond activation, see: Kjellgren, J.; Sunden, H.; Szabo,
K. J. J. Am. Chem. Soc. 2005, 127, 1787–1796.
a Ratio of regioisomers (γ and R) and double addition determined by
GLC analysis without internal standard prior to purification. b γ-6a and
R-6a separated from γ-7a by flash chromatography on silica gel.
c Considerable amounts of unreacted starting material remained. d Par-
tial decomposition of the propargylic precursor.
(10) With carbonate as a leaving group: (a) Ohmiya, H.; Ito, H.;
Sawamura, M. Org. Lett. 2009, 11, 5618–5620 (rhodium(I)-catalyzed
SiꢀB bond activation). For a related transformation, see: (b) Shimizu,
M.; Kurahashi, T.; Kitagawa, H.; Hiyama, T. Org. Lett. 2003, 5, 225–
227 (uncatalyzed SiꢀB bond cleavage by reaction with terminally
metalated propargyl substrates).
Org. Lett., Vol. 14, No. 15, 2012
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