Metal-catalyzed silylene transfer to imines: Synthesis and reactivity of silaaziridines

Article abstract of DOI:10.1021/ol701424a

Metal-catalyzed silylene transfer to imines provides an efficient synthesis of silaaziridines. These strained cyclic silanes undergo selective bond-forming reactions, permitting the synthesis of nitrogen-containing compounds after protodesilylation of the

Full text of DOI:10.1021/ol701424a

ORGANIC
LETTERS
2007
Vol. 9, No. 19
3773-3776
Metal-Catalyzed Silylene Transfer to
Imines: Synthesis and Reactivity of
Silaaziridines
Zulimar Neva´rez and K. A. Woerpel*
Department of Chemistry, UniVersity of California, IrVine,
IrVine, California 92697-2025
kwoerpel@uci.edu
Received June 18, 2007
ABSTRACT
Metal-catalyzed silylene transfer to imines provides an efficient synthesis of silaaziridines. These strained cyclic silanes undergo selective
bond-forming reactions, permitting the synthesis of nitrogen-containing compounds after protodesilylation of the resulting vinyl silane.
The chemistry of three-membered ring compounds composed
of silicon, nitrogen, and carbon atoms remains unexplored
because these compounds have proven to be challenging to
synthesize. Brook prepared silaaziridines from isocyanides
and photolytically generated silenes, but the generality of
this method is limited.1 Although silaaziridines have been
proposed as reactive intermediates in thermal2 and photo-
chemical3 silylene transfer reactions to imines, the strained-
ring silanes were not isolated; instead, rearranged products
were obtained. Because no general synthesis of silaaziridines
has emerged, the reactivity of these intermediates has not
been explored,4-6 and no applications to organic synthesis
have appeared.
bond-forming reactions that can be applied to the synthesis
of nitrogen-containing products.
An indication that stable silaaziridines could be prepared
from imines emerged from our studies of thermal silylene
transfer. Heating a mixture of imine 1 and silacyclopropane
2 provided silaaziridine 3 in 45% yield along wih 27% of a
dimer byproduct7 (Scheme 1). We surmised that the elevated
Scheme 1. Thermal Silylene Transfer to Imines
In this paper, we demonstrate that silver-catalyzed silylene
transfer to imines provides a general method for the synthesis
of stable silaaziridines. These compounds engage in selective
(1) Brook, A. G.; Young, K. K.; Saxena, A. K.; Sawyer, J. F.
Organometallics 1988, 7, 2245-2247.
temperatures required to transfer t-Bu2Si caused the dimer-
ization and that milder conditions would permit the isolation
of silaaziridines without unwanted side products.
The mild silver-catalyzed silylene transfer reaction allowed
for the clean conversion of a variety of imines to silaaziri-
(2) Belzner, J.; Ihmels, H.; Pauletto, L. J. Org. Chem. 1996, 61, 3315-
3319.
(3) Weidenbruch, M.; Piel, H. Organometallics 1993, 12, 2881-2882.
(4) Brook, A. G.; Saxena, A. K.; Sawyer, J. F. Organometallics 1989,
8, 850-852.
(5) Brook, A. G.; Azarian, D.; Baumegger, A.; Hu, S. S.; Lough, A. J.
Organometallics 1993, 12, 529-534.
(6) Brook, A. G.; Habtemariam, A. Can. J. Chem. 2003, 81, 1164-
1167.
(7) Bodnar, P. M.; Palmer, W. S.; Ridgway, B. H.; Shaw, J. T.;
Smitrovich, J. H.; Woerpel, K. A. J. Org. Chem. 1997, 62, 4737-4745.
10.1021/ol701424a CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/22/2007

membered ring adducts. Treatment of R,â-unsaturated imine
8 to the silylene transfer conditions resulted in the formation
of enamine 9 in 80% yield by 1H NMR spectroscopy
(Scheme 2).10 Attempted isolation of the enamine 9, however,
Table 1. Silver-Catalyzed Silylene Transfer Followed by
Methanolysis
Scheme 2. Silylene Transfer to Conjugated Imines
resulted in dimerization to yield compound 10 as a single
diastereomer. The relative stereochemistry of 10 was deter-
mined by X-ray crystallography.11 This transformation likely
occurred through nucleophilic addition of the enamine 9 to
its conjugate acid I to form iminium ion II, which underwent
electrophilic aromatic substitution.
a
As determined by 1H NMR spectroscopic analysis of the product
relative to an internal standard (PhSiMe3). b Isolated yields after purification
by flash chromatography. Some decomposition was observed during
c
purification. Silaaziridines were isolated by bulb-to-bulb distillation in
Silylene transfer to N-acylimines also led to five-
membered ring products. Treatment of carbamate-protected
imine 11 under silver-catalyzed conditions provided oxa-
zoline 12 in 46% yield.12 The low yield of this reaction may
be the result of binding of the product to the catalyst, which
would inhibit turnover.13 Concentration of 12 resulted in
reaction with remaining imine 11 to yield 13 as a single
diastereomer. The relative stereochemistry was determined
by X-ray crystallography.11
the corresponding yields in parentheses. d 13:1 mixture of isomers with 7e
as the major isomer. The minor isomer is the result of cleavage of the Si-C
bond; characterization data are provided as Supporting Information.
dines (Table 1).8 Imines with aromatic and benzyl substit-
uents on the nitrogen atom underwent silylene transfer to
provide silaaziridines in good yields. Silylene transfer
occurred to alkyl imines (entries 1 and 2) and even to a
sterically hindered ketimine 5b (entry 2). The reactivity of
the trisubstituted C-N double bond contrasts with the
observations that trisubstituted alkenes are unreactive to the
silylene transfer conditions.9 Despite the sensitivity of these
compounds to air and water, silaaziridines 6a, 3, and 6c could
be isolated in good yields (entries 1, 3, and 4). In general,
however, silaaziridines were characterized as their metha-
nolysis products.
A mechanism for silylene transfer to imines can be
proposed to account for both three- and five-membered ring
products (Scheme 3). Addition of the nucleophilic heteroatom
to the electrophilic silylene13 or silylenoid would generate
ylides III or IV. Intermediate III can undergo a 4π-
electrocyclic reaction to form silaaziridine products 3 and
(10) Formal [4+1] products have been observed for other silylene transfer
reactions to unsaturated imines and dienes: (a) Bobbitt, K. L.; Gaspar, P.
P. J. Organomet. Chem. 1995, 499, 17-26. (b) Vinylsilacyclopropanes,
however, have been prepared: Zhang, S.; Conlin, R. T. J. Am. Chem. Soc.
1991, 113, 4272-4278.
(11) The details are provided as Supporting Information.
(12) The analogous reaction was observed for R,â-unsaturated esters and
ketones: Calad, S. A.; Woerpel, K. A. J. Am. Chem. Soc. 2005, 127, 2046-
2047 and references therein.
Silylene transfer to conjugated imines did not provide
three-membered ring products, but instead afforded five-
(8) Other silver catalysts such as AgOCOCF3, AgBF4, and AgOTf gave
products in comparable yields. Copper catalysts at higher temperatures also
provided products, although in low yields.
(9) For examples of metal-catalyzed silylene transfer to mono- and
disubstituted alkenes, see: CÄ irakovic´, J.; Driver, T. G.; Woerpel, K. A. J.
Am. Chem. Soc. 2002, 124, 9370-9371.
(13) Driver, T. G.; Woerpel, K. A. J. Am. Chem. Soc. 2004, 126, 9993-
10002.
3774
Org. Lett., Vol. 9, No. 19, 2007

Silaaziridines undergo regioselective palladium-catalyzed
alkyne insertion reactions to provide synthetically valuable
products in high yields. Treatment of selected silaaziridines
with terminal alkynes in the presence of Pd(PPh3)4 resulted
in the formation of azasilacyclopentenes 16 (Table 2).18 These
Scheme 3. Proposed Mechanism for Silylene Transfer to
Imines
Table 2. Palladium-Catalyzed Alkyne Insertions
entry
R1
R2
R3
producta,b
6a-e. In the case of conjugated imines, the resulting
intermediate IV could undergo a 6π-electrocyclic reaction
to provide five-membered ring products 9 and 12.12
Because little was known about the reactivity of silaaziri-
dines,4-6 we examined their reactions with various electro-
philes. Reaction of silaaziridine 6a with benzaldehyde
resulted in insertion into the Si-N bond to provide N,O-
acetal 14 (Scheme 4).14,15 The cis-stereochemistry of 14 was
1
2
3
4
5
6
i-Pr
i-Pr
i-Pr
i-Pr
Ph
Bn
Bn
Bn
Bn
Bn
Ard
Ph
16a, 90%
16a, 85%
16c, 94%
16d, 87%
16e, 95%
16f, 98%
CH2SiMe3
CH2OPc
CH2NMe2
Ph
Ph
Ph
a
Clean products were obtained after acetonitrile/hexane extractions.
b Purification by flash chromatography resulted in hydrolysis of the Si-N
bond. P ) SiMe2t-Bu. Ar ) p-MeC6H4.
c
d
Scheme 4. Chemoselective Ring Expansion Reactions
compounds are masked 1,3-amino alcohols,19 and embedded
in their structure is an allylic amine.20
A catalytic cycle that illustrates the palladium-catalyzed
C-C bond formation process between a silaaziridine and
an alkyne is shown in Scheme 5.21 Oxidative addition of
Scheme 5. Catalytic Cycle for Alkyne Insertion of
Silaaziridines
determined by NOE experiments. Insertion with the opposite
selectivity occurred with isocyanides. When silaaziridine 6a
was treated with tert-butyl isocyanide, insertion occurred
solely through the Si-C bond to give imine 15 in quantitative
yield.16 The chemoselectivity for these insertion reactions is
consistent with Pearson’s hard-soft acid-base theory.17 Hard
electrophiles such as PhCHO and MeOH reacted at the more
ionic Si-N bond, whereas the softer isocyanide electrophile
inserted at the more covalent Si-C bond.
the weaker Si-C bond22 of the silaaziridine would provide
azapalladasilacyclobutane 17. Migratory insertion of the
alkyne into the Si-Pd bond22 would lead to azapalladasila-
cyclohexene 18. The observed regioselectivity could result
from minimizations of steric interactions between the alkyne
substituent and the t-butyl groups on the silicon. Reductive
elimination from 18 would provide azasilacyclopentene 16
and regenerate the catalyst.23
(14) Product 14 was also obtained in the absence of a silver catalyst,
although the reaction was slower and low-yielding.
(15) Upon purification of 14 by flash chromatography, a significant
amount of N,O-acetal hydrolysis and elimination to form 14′ were observed.
Vinyl silane 14′ was isolated in 13% yield.
(16) Purification of 15 by flash chromatography gave a mixture of
hydrolyzed products. Compound 15′ was isolated in 55% yield.
The proposed palladium-catalyzed alkyne insertion mech-
anism is supported by data from a control experiment. When
silaaziridine 6a was treated with a catalytic amount of
(17) Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 1827-
1836.
Org. Lett., Vol. 9, No. 19, 2007
3775

Pd(PPh3)4, in the absence of alkyne, a slow rearrangement
was observed to form silane 19 (Scheme 6). Compound 19
thetic value of these intermediates. To release the allylic
amines embedded in structure 16a, the t-Bu2Si moiety was
removed by protodesilylation (Scheme 7).
Scheme 6. Palladium-Catalyzed Rearrangement
Scheme 7. Synthesis of Allylic Amines
was characterized by H NMR and IR spectroscopy.24 The
1
In conclusion, silver-catalyzed silylene transfer is a general
method for the synthesis of silaaziridines. These strained
compounds undergo selective insertion reactions to afford
ring-expanded products. The azasilacyclopentenes obtained
from palladium-catalyzed alkyne insertion can be converted
into allylic amines by protodesilylation of the vinyl silane
moiety.
rearranged product 19 likely results from â-hydride elimina-
tion of intermediate 17 followed by reductive elimination.21a,25
Synthetic manipulations of the vinylsilane functionality
of azasilacyclopentene products 16 demonstrated the syn-
(18) For other transition-metal-mediated alkyne insertion reactions of
strained intermediates, see: (a) Barluenga, J.; Rodr´ıguez, F.; AÄ lvarez-
Rodrigo, L.; Zapico, J. M.; Fan˜ana´s, F. J. Chem. Eur. J. 2004, 10, 109-
116. (b) Buchwald, S. L.; Watson, B. T.; Wannamaker, M. W.; Dewan, J.
C. J. Am. Chem. Soc. 1989, 111, 4486-4494. (c) Grossman, R. B.; Davis,
W. M.; Buchwald, S. L. J. Am. Chem. Soc. 1991, 113, 2321-2322. (d)
Gao, Y.; Yoshida, Y.; Sato, F. Synlett 1997, 1353-1354. (e) Ohkubo, M.;
Hayashi, D.; Oikawa, D.; Fukuhara, K.; Okamoto, S.; Sato, F. Tetrahedron
Lett. 2006, 47, 6209-6212. (f) Seyferth, D.; Shannon, M. L.; Vick, S. C.;
Lim, T. F. O. Organometallics 1985, 4, 57-62. (g) Ohshita, J.; Ishikawa,
M. J. Organomet. Chem. 1991, 407, 157-165. (h) Saso, H.; Ando, W.;
Ueno, K. Tetrahedron 1989, 45, 1929-1940. (i) Saso, H.; Ando, W. Chem.
Lett. 1988, 1567-1570.
Acknowledgment. This research was supported by the
National Institute of General Medical Sciences of the
National Institutes of Health (GM-54909). Z.N. thanks the
National Institutes of Health for a predoctoral fellowship.
K.A.W. thanks Amgen and Lilly for awards to support
research. We thank Dr. Phil Dennison (UCI) for assistance
with NMR spectroscopy, Dr. Joseph W. Ziller (UCI) for
X-ray crystallography, and Dr. John Greaves (UCI) for mass
spectrometry.
(19) (a) Kochi, T.; Tang, T. P.; Ellman, J. A. J. Am. Chem. Soc. 2003,
125, 11276-11282. (b) Ohno, H.; Hamaguchi, H.; Tanaka, T. Org. Lett.
2000, 2, 2161-2163. (c) O’Brien, P. Angew. Chem., Int. Ed. 1999, 38,
326-329.
(20) (a) Johannsen, M.; Jørgensen, K. A. Chem. ReV. 1998, 98, 1689-
1708. (b) Patel, S. J.; Jamison, T. F. Angew. Chem., Int. Ed. 2003, 42,
1364-1367. (c) Miller, K. M.; Molinaro, C.; Jamison, T. F. Tetrahedron:
Asymmetry 2003, 14, 3619-3625.
(21) (a) Palmer, W. S.; Woerpel, K. A. Organometallics 1997, 16, 1097-
1099. (b) Palmer, W. S.; Woerpel, K. A. Organometallics 1997, 16, 4824-
4827.
Supporting Information Available: Complete experi-
mental procedures and product characterization. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL701424A
(22) (a) Walsh, R. In The Chemistry of Organic Silicon Compounds,
Part 1; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1989; pp 371-
391. (b) Armitage, D. A. In The Chemistry of the Silicon-Heteroatom Bond;
Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1991; pp 245-439.
(23) For other metal-catalyzed reductive coupling strategies of imines
and alkynes, see: (a) Black, D. A.; Arndtsen, B. A. Org. Lett. 2006, 8,
1991-1993. (b) Black, D. A.; Arndtsen, B. A. Org. Lett. 2004, 6, 1107-
1110. (c) See ref. 20c.
(24) The proton chemical shift (δ 4.13 ppm) and IR band (V ) 2137
cm-1) for the Si-H are similar to other aminosilanes: Gu, T.-Y. Y.; Weber,
W. P. J. Organomet. Chem. 1980, 184, 7-11.
(25) A 1,3-dipolar cycloaddition between dipole III (Scheme 3) and an
alkyne would also account for the formation of compounds 16a-f. We
have not, however, observed the cycloaddition under thermal conditions
(120 °C).
3776
Org. Lett., Vol. 9, No. 19, 2007