compounds may be prepared via C-acylation of carbanions
derived from suitably protected cyanohydrins.7,8 An asym-
metric variant of this reaction involving an auxiliary con-
trolled C-acylation of a chiral cyanohydrin phosphate with
benzoyl chloride was recently disclosed by Schrader.9
Takeda, Reich, and Degl’Innocenti have reported generation
of carbanionic cyanohydrin derivatives via reactions of
Table 1. Catalyst Evaluation for Cyanation/Brook
Rearrangement/C-Acylation Reactions of Acylsilanes (Eq 1)a
-
acylsilanes (1) with various CN sources.10-12 The nucleo-
philes derived from [1,2]-Brook rearrangement were trapped
in protonation and alkylation reactions, but the analogous
acylation reactions have not been reported to the best of our
knowledge.
The latter publications led us to consider the possibility
of employing cyanoformates13,14 as acylating agents for the
silyl cyanohydrin carbanions. The proposed catalytic cycle
that resulted from this idea is pictured in Scheme 2.
entry
catalyst
KCN
KCN/18-crown-6
KCN/Bu4NBr
KCN/Bu4PBr
quinuclidine
none
time (h)
yield (%)b
1
2
3
4
5
6
36
4-5
15
15
36
29c
86
83
74
69d
0
36
a PhC(O)SiEt3 (1.0 equiv), NCCO2Et (1.1 equiv). b Isolated yield of
analytically pure material. c Percent conversion based on 1H NMR spec-
troscopy of the unpurified reaction mixture. d Catalyst concentration ) 20
mol %, C7H8, 25 °C.
Scheme 2
ethyl cyanoformate in Et2O to afford the desired acylation
product 8 in low yield (entry 1). Speculating that the limited
solubility of the KCN in the medium was hindering reactiv-
ity, phase transfer catalysts were employed to increase the
concentration of -CN in solution. The commonly used KCN
cocatalyst, 18-crown-6,15 proved to be optimal for the Brook
rearrangement sequence and could be employed at relatively
low catalyst loadings (5 mol %, entry 2). The reaction also
proceeded with cocatalysis by tetrabutylammonium or tet-
rabutylphosphonium bromide, albeit at a slower rate (entries
3 and 4). The tertiary amine quinuclidine (entry 5) could
also be utilized as a catalyst in the absence of KCN, although
slower reaction times were observed relative to the KCN/
18-crown-6 system. The success of this experiment suggests
that a different mechanism, one analogous to O-acylation
reactions conducted by Deng, may be operative for this
catalyst.16 A control experiment demonstrated that 6 and 7
do not react in the absence of a catalyst (entry 6).
Nucleophilic addition of a metal cyanide to an acylsilane
(1) would generate a tetrahedral intermediate 1a poised to
undergo [1,2]-Brook rearrangement. Following migration of
silicon from carbon to oxygen, C-acylation of the resulting
nitrile enolate 1b with a cyanoformate ester (2) would give
the desired product and regenerate the metal cyanide,
completing the catalytic cycle.
To assess the viability of the proposed reaction scheme
(Scheme 2), a number of catalysts and cocatalysts were
evaluated (Table 1). In the presence of catalytic quantities
of KCN, phenyl triethylsilyl ketone (6) reacted slowly with
With the identification of 18-crown-6 and KCN as an
efficient catalyst system, the reaction scope was studied using
a variety of acylsilanes.17 Collectively, aryl acylsilanes gave
moderate to excellent yields (66-97%, Table 2, entries 1-5
and 9). The electron-poor aryl acylsilanes reacted faster (1-2
h) than their electron-rich counterparts (4-24 h), which
required more forcing conditions (toluene, 110 °C). Alkyl
acylsilanes gave moderate to good yields (49-73%, entries
6-8) with reaction times closer to that of the electron-
deficient aryl acylsilanes (1.5-4 h). Optimum yields for
enolization-prone alkyl acylsilanes were realized through
slow acylsilane addition to a solution of cyanoformate and
(7) Babler, J. H.; Marcuccilli, C. J.; Oblong, J. E. Synth. Commun. 1990,
20, 1831-1836.
(8) Hu¨nig, S.; Wehner, G. Chem. Ber. 1980, 113, 302-323.
(9) Schrader, T. Chem. Eur. J. 1997, 3, 1273-1282.
(10) Takeda, K.; Ohnishi, Y. Tetrahedron Lett. 2000, 41, 4169-
4172.
(11) Reich, H. J.; Holtan, R. C.; Bolm, C. J. Am. Chem. Soc. 1990, 112,
5609-5617.
(12) Degl’Innocenti, A.; Ricci, A.; Mordini, A.; Reginato, G.; Colotta,
V. Gazz. Chim. Ital. 1987, 117, 645-648.
(13) Mander, L. N.; Sethi, S. P. Tetrahedron Lett. 1983, 24, 5425-
5428.
(15) Evans, D. A.; Truesdale, L. K. Tetrahedron Lett. 1973, 4929-
4932.
(16) Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2001, 123, 6195-
6196.
(17) Acysilanes were prepared in three steps from the corresponding
aldehydes. See Supporting Information for details. For reviews on the
synthesis and chemistry of acylsilanes, see: (a) Cirillo, P. F.; Panek, J. S.
Org. Prep. Proc. Int. 1992, 24, 553-582. (b) Page, P. C. B.; Klair, S. S.;
Rosenthal, S. Chem. Soc. ReV. 1990, 19, 147-195. (c) Reference 2.
(14) Crabtree, S. R.; Mander, L. N.; Sethi, S. P. Org. Synth. 1991, 70,
256-264.
2958
Org. Lett., Vol. 4, No. 17, 2002