Cross silyl benzoin additions catalyzed by lanthanum tricyanide

Article abstract of DOI:10.1021/jo0496143

From a screen of (cyanide)metal complexes, an improved catalyst for the cross silyl benzoin addition was discovered. Several M(CN)₃ complexes (M = Ce, Er, Sm, Y, Yb, La) were evaluated and lanthanum tricyanide was identified as the optimal cata

Full text of DOI:10.1021/jo0496143

Cr oss Silyl Ben zoin Ad d ition s Ca ta lyzed by
La n th a n u m Tr icya n id e
SCHEME 1. P r op osed Mech a n ism for Cr oss Silyl
Ben zoin Ad d ition
Cory C. Bausch and J effrey S. J ohnson*
Department of Chemistry, University of North Carolina at
Chapel Hill, Chapel Hill, North Carolina 27599-3290
jsj@unc.edu
Received March 9, 2004
Abstr a ct: From a screen of (cyanide)metal complexes, an
improved catalyst for the cross silyl benzoin addition was
discovered. Several M(CN)3 complexes (M ) Ce, Er, Sm, Y,
Yb, La) were evaluated and lanthanum tricyanide was
identified as the optimal catalyst. The catalyst, prepared in
situ from LaCl3, effects the selective coupling of aryl and
alkyl acylsilanes with aryl, heteroaryl, R,â-unsaturated, and
aliphatic aldehydes. The reactions occur at ambient tem-
perature in less than 5 min to provide, depending on the
workup, R-hydroxy or R-silyloxy ketones in 48-93% isolated
yield.
produced lower yields for alkyl-aryl′ products (Ralkyl
-
COCH(OSiEt
ducts (RalkylCOCH(OSiEt
3
)Ar) and afforded <20% alkyl-alkyl′ ad-
)R′alkyl). The purpose of this
3
paper is to document progress in the discovery of transi-
tion metal cyanide catalysts for the cross silyl benzoin
reaction that provide enhanced reactivity for both aryl
and aliphatic substrates; the described systems should
provide a useful platform for the development of enan-
tioselective catalysts.
The benzoin condensation1 and its congeners6-11 are
important methods for the synthesis of R-hydroxy car-
bonyls. The reaction represents one of the most direct
routes to such compounds, but lack of regiochemical
control in the cross benzoin reaction of two different
aldehydes can be a limitation. The benzoin condensation
tends to be reversible, and as such, the product distribu-
tion for dimerization of two aldehydes is often determined
by the relative thermodynamic stabilities of the four
possible isomeric products.1 The cross silyl benzoin
reaction between acylsilanes and aldehydes has been
reported as a kinetically controlled, regiospecific alterna-
tive to the traditional benzoin condensation.12 The reac-
tion relies on generation of an acyl anion equivalent via
-5
An implicit requirement for successful catalysis of the
cross silyl benzoin reaction is the ability of alkoxide 3 to
undergo retrocyanation. If the cyanation of aldehyde 2
is irreversible, 3 becomes a nonproductive shunt of the
M-CN catalyst and acylsilane cyanation (1 f 4a ) is not
possible. We initially considered the possibility that
(salen)Al-CN complexes might be effective catalysts based
on the recent observation that such species react with
acylsilanes to produce (silyloxy)nitrile anions 4b (M )
,4
18
Al(salen)); however, the absence of benzoin catalysis in
a test reaction (Table 1, entry 1) hinted at the stability
addition of CN to an acylsilane (1 f 4a ) followed by [1,2]-
of tetrahedral intermediate 3 (M ) Al(salen)). We evalu-
Brook rearrangement1
3-17
(4a f 4b, Scheme 1).
19
ated (cyanide)lanthanum complexes guided by the
The KCN/18-crown-6 catalyst system12 performed well
for aryl-aryl′ combinations (ArCOCH(OSiEt )Ar′) but
hypothesis that the derived alkoxide complexes 3 might
tend to form reversibly. Attempts with lanthanum i-
3
propoxides activated by Me
lysts with reproducible activity (entries 2 and 3); how-
3
SiCN failed to provide cata-
(
(
(
(
(
(
(
1) Ide, W. S.; Buck, J . S. Org. React. 1948, 4, 269-304.
2) Lapworth, A. J . Chem. Soc 1903, 83, 995.
20
ever, La(CN)
found to be an effective catalyst that provided consistent
yields. LaCl (0.1 equiv) was treated with n-butyllithium
0.3 equiv), nominally yielding a tributyllanthanum spe-
cies that upon subsequent addition of Me SiCN provided
3 3 3
generated from (n-Bu) La/Me SiCN was
3) Breslow, R.; Kim, R. Tetrahedron Lett. 1994, 35, 699-702.
4) Stetter, H.; Daembkes, G. Synthesis 1977, 403-404.
5) J ohnson, J . S. Angew. Chem., Int. Ed. 2004, 43, 1326-1328.
6) Rozwadowska, M. D. Tetrahedron 1985, 41, 3135-3140.
7) Ricci, A.; Degl’Innocenti, A.; Chimichi, S.; Fiorenza, M.; Rossini,
3
(
G. J . Org. Chem. 1985, 50, 130-133.
8) Heck, R.; Henderson, A. P.; Kohler, B.; Retey, J .; Golding, B. T.
Eur. J . Org. Chem. 2001, 2623-2627.
3
(
the active catalyst. Six different (cyanide)lanthanum
catalysts were evaluated in the reaction between benzoyl
dimethylphenylsilane (1a , prepared in one step from
benzoyl chloride) and 4-chlorobenzaldehyde (2a ); the
results are listed in Table 1.
(
9) Pohl, M.; Lingen, B.; M u¨ ller, M. Chem. Eur. J . 2002, 8, 5288-
5
295.
(
(
10) Cunico, R. F. Tetrahedron Lett. 2002, 43, 355-358.
11) Linghu, X.; Potnick, J . R.; J ohnson, J . S. J . Am. Chem. Soc.
2
004, 126, 3070-3071.
(
534-2536.
(
12) Linghu, X.; J ohnson, J . S. Angew. Chem., Int. Ed. 2003, 42,
All catalysts were generated in situ, and the starting
materials 1a and 2a were added to the catalyst suspen-
2
13) Brook, A. G. Acc. Chem. Res. 1974, 7, 77-84.
14) Reich, H. J .; Holtan, R. C.; Bolm, C. J . Am. Chem. Soc. 1990,
(
1
12, 2, 5609-5617.
(18) Nicewicz, D. A.; Yates, C. M.; J ohnson, J . S. Angew. Chem.,
Int. Ed. 2004, 43, 2652-2655.
(19) Schaus, S. E.; J acobsen, E. N. Org. Lett. 2000, 2, 1001-1004.
(20) Matsubara, S.; Onishi, H.; Utimoto, K. Tetrahedron Lett. 1990,
31, 6209-6212.
(
15) Degl’Innocenti, A.; Ricci, A.; Mordini, A.; Reginato, G.; Colotta,
V. Gazz. Chim. Ital. 1987, 117, 645-648.
(16) Takeda, K.; Ohnishi, Y. Tetrahedron Lett. 2000, 41, 4169-4172.
17) Moser, W. H. Tetrahedron 2001, 57, 2065-2084.
(
1
0.1021/jo0496143 CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/19/2004
J . Org. Chem. 2004, 69, 4283-4285
4283

TABLE 1. Eva lu a tion of M(CN)n Com p lexes a s Cr oss
Silyl Ben zoin Ca ta lysts
TABLE 2. Ca ta lyzed Silyl Ben zoin Ad d ition Rea ction s
of Acylsila n es a n d Ald eh yd esa
entry
catalyst
% yielda
1
2
3
4
5
6
7
8
9
(salen)Al-CN
Er(iOPr)3/Me3SiCN
Yb(iOPr)3/Me3SiCN
0
42-66
30-55
40
50
75
51
5
68
b
Ce(CN)3
Er(CN)3
La(CN)3
b
b
b
Sm(CN)3
b
Y(CN)3
b
Yb(CN)3
a
Isolated yield. b Catalyst prepared via treatment of 0.1 equiv
of (n-Bu)3M with 0.3 equiv of Me3SiCN (see text).
SCHEME 2. Test for Rever sibility of Ald eh yd e
Cya n a tion
sion. Although all of the (cyanide)lanthanum complexes
delivered the desired R-hydroxy ketone 6a (after acidic
3
workup), La(CN) was the metal cyanide that afforded
the highest yield (entry 6). Having identified the optimal
cyanide)metal catalyst, the scope of the cross benzoin
(
reaction was further investigated (Table 2).
All reactions conducted with benzoyl trimethylsilane
2b) were subjected to subsequent silyl ether deprotection
with aqueous HCl upon completion of the reaction. The
reaction time for the KCN/18-crown-6 catalyzed cross
silyl benzoin additions ranged from 1 to 5 h, whereas La-
a
1
2
R C(O)SiR3 (1.0 equiv), R CHO (1.1 equiv), LaCN3 (0.1 equiv)
(
in THF at 25 °C for <5 min. See Supporting Information for
details. b Yield of isolated analytically pure material. c The silyloxy
ketone product was subjected to deprotection with 1 M HCl in
MeOH. d R C(O)SiMe (1.0 equiv), R CHO (1.5 equiv), LaCN (0.1
1
2
3
3
(
CN)
The La(CN)
the KCN/18-crown-6 catalyst previously reported for aryl-
aryl′ benzoin adducts (entries 1-3). The La(CN) system
gave excellent yields in coupling PhCOSiEt and het-
eroaromatic aldehydes (entries 4 and 5). PhCOSiMe
3
typically catalyzed the reactions in less than 5 min.
equiv) in THF at 25 °C for 15 min.
3
catalyst gave yields comparable to that of
that we are aware, cyanide catalysis has proven effective
(albeit in intermediate yield) for the synthesis of alkyl-
alkyl′ acyloins (entry 11). A large excess of aldehyde is
not required in this case.8
3
3
3
underwent selective catalyzed 1,2-addition to an R,â-
unsaturated aldehyde (entry 8). Compared with the KCN/
The reversibility of aldehyde cyanation in the present
reactions was verified through the use of mandelonitrile
1
8-crown-6 system, significant improvement has been
3
(7) as a catalyst precursor in conjunction with (n-Bu) La
observed for alkyl-aryl′ and alkyl-alkyl′ benzoin adducts.
In the previous report, catalyst loading and electrophile
concentration had to be significantly increased to achieve
satisfactory yields. La(CN) catalyzes the silyl benzoin
3
reaction of acetyl trimethylsilane and 4-chlorobenzalde-
hyde in reasonable yield (entry 10), and for the first time
(Scheme 2). Reaction of the (tributyl)lanthanum species
with the cyanohydrin should be rapid and irreversible
to generate tris(alkoxide) 8 (with concomitant generation
of butane). If aldehyde cyanation is reversible (8 f 9),
benzaldehyde extrusion should yield a competent cata-
3
lyst. Thus, a solution of freshly prepared (n-Bu) La (0.1
4
284 J . Org. Chem., Vol. 69, No. 12, 2004

equiv) was treated with a THF solution of PhCH(OH)-
CN, followed by a THF solution of (p-MeOPh)COSiEt
cyanide (3 equiv) was added, and the mixture was stirred for
0 min at the same temperature and then slowly warmed to
room temperature.
-(4-Ch lor op h en yl)-2-h yd r oxy-1-p h en ylet h a n on e (6a ).
Typ ica l Exp er im en ta l P r oced u r e. To a solution of La(CN)
was added via cannula a solution of benzoyl trimethylsilane (0.40
mmol, 1.0 equiv) and 4-chlorobenzaldehyde (0.44 mmol, 1.1
equiv) in 8 mL of THF. Upon completion of the reaction, 5 mL
3
3
and PhCHO. The cross benzoin product (p-MeOPh)-
COCH(OH)Ph was obtained in 73% yield after acidic
workup, consistent with our working hypothesis. It is
interesting to note the contrast to the classic benzoin
condensation, in which aldehyde cyanation is the crucial
initiating step: in the present reactions no productive
chemistry arises from M-CN addition to RCHO.
In summary, an improved catalyst for the cross silyl
benzoin addition has been developed. A (cyanide)lantha-
num complex is successful with a range of substrates and
allows for simple, regiospecific synthesis of R-hydroxy
ketones and their silyl-protected progenitors. The reac-
tion proceeds rapidly at ambient temperature with a
catalyst system that should provide a useful platform for
the development of enantioselective variants. To this end,
appropriate modifications of the (cyanide)metal com-
plexes are currently under investigation and will be
reported in due course.
2
3
of 1 M HCl was added at 23 °C. After 30 min, 10 mL of Et
were added, and the organic layer was washed twice with 10
mL of H O. The aqueous layer was extracted with three 20-mL
portions of Et O. The organic extracts were combined and dried
with MgSO . The solvent was removed with a rotary evaporator.
2
O
2
2
4
The residue was purified by flash chromatography, eluting with
20% EtOAc/hexanes to afford 74 mg (87%) of the known
compound 6a as a white solid:21 1H NMR (300 MHz, CDCl
7
) δ
.87 (d, J ) 7.5 Hz, 2H), 7.52 (t, J ) 7.5 Hz, 1H), 7.39 (t, J ) 7.5
Hz, 2H), 7.29-7.25 (m, 4H), 5.92 (s, 1H), 4.57 (br s, 1H).
3
Ack n ow led gm en t. The authors acknowledge par-
tial funding of this work by the donors of the Petroleum
Research Fund, administered by the American Chemi-
cal Society (PRF no. 37868-G1) and Research Corpora-
tion (Research Innovation Award). J .S.J . is the recipient
of a J ohnson and J ohnson Focused Giving Award.
Exp er im en ta l Section
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedures and compound characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
P r ep a r a t ion of La CN
dried 25-mL round-bottom flask with a magnetic stir bar was
charged with 0.04 mmol of LaCl and 3 mL of THF in a drybox.
The flask was removed and cooled to -78 °C under a N
3
a s a Solu t ion in THF . A flame-
3
2
atmosphere. After 15 min, n-butyllithium (1.6 M in hexanes, 0.12
mmol, 3.0 equiv) was added via syringe. The resulting solution
was stirred for 15 min at the same temperature before warming
to 0 °C. After 30 min of stirring, 0.12 mmol of trimethylsilyl
J O0496143
(21) Heilmann, S. M.; Rasmussen, J . K.; Smith, H. K., II. J . Org.
Chem. 1983, 48, 987-992.
J . Org. Chem, Vol. 69, No. 12, 2004 4285