Highly efficient trialkylsilylcyanation of aldehydes, ketones and imines catalyzed by a nucleophilic N-heterocyclic carbene

Article abstract of DOI:10.1016/j.tetlet.2006.04.141

The synthetic utility of N-heterocyclic carbenes was demonstrated by the trialkylsilylcyanation of aldehydes, ketones and imines. In the presence of a catalytic amount of 3a, the reactions with Me₃SiCN proceeded smoothly to give the corresponding cyanohydrin trimethylsilyl ethers or amino nitrile derivatives in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2006.04.141

Tetrahedron Letters 47 (2006) 4615–4618
Highly efficient trialkylsilylcyanation of aldehydes, ketones and
imines catalyzed by a nucleophilic N-heterocyclic carbene
Taichi Kano, Kouji Sasaki, Teppei Konishi, Haruka Mii and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Received 5 April 2006; revised 24 April 2006; accepted 27 April 2006
Abstract—The synthetic utility of N-heterocyclic carbenes was demonstrated by the trialkylsilylcyanation of aldehydes, ketones and
imines. In the presence of a catalytic amount of 3a, the reactions with Me3SiCN proceeded smoothly to give the corresponding
cyanohydrin trimethylsilyl ethers or amino nitrile derivatives in good to excellent yields.
Ó 2006 Elsevier Ltd. All rights reserved.
In the past few years, nucleophilic N-heterocyclic carb-
SiMe3
R1
SiR22Cl2
enes have been utilized not only as a ligand for metal
salts,1 but also as an organocatalyst2 for the benzoin
condensation,3 Stetter reaction4 and the transesterifica-
tion between esters and alcohols.5,6 Recently, in our
and other laboratories, the chiral carbene catalysts gen-
erated from the corresponding imidazolium salts were
also independently found to effectively catalyze the
enantioselective acylation of secondary alcohols to give
the highly enantiomerically enriched alcohols.7 To date,
however, the applicability of N-heterocyclic carbenes as
a nucleophilic organocatalyst for other transformation
reactions has not been fully investigated.8 For example,
N-heterocyclic carbenes were already reported to react
with trimethylsilyl iodide or polychlorosilanes to afford
the corresponding ionic 2-(trimethylsilyl)imidazolium
salt 1 or pentavalent silicon species 2, respectively
(Scheme 1).9 To the best of our knowledge, however,
these types of silicon–carbene complexes have rarely
been utilized in organic transformations.10 Accordingly,
we are interested in the possibility of activating Me3-
SiCN by complexation with nucleophilic N-heterocyclic
carbenes as a Lewis base. Very recently, Song reported
the study of trimethylsilylcyanation of aldehydes and
ketones catalyzed by nucleophilic N-heterocyclic carb-
enes,11 and this report prompted us to disclose our
own result on the synthetic utility of carbenes. In this
letter, we describe a new application of the N-hetero-
cyclic carbene as a highly efficient Lewis base catalyst
R1
R1
R1
R1
Me3SiI
R22SiCl2
R1
N
N
N
N
N
N
N
I
1
2
Me3SiCN
SiMe3
R1
R1 = Et
R1 = Et
R2 = Me, Ph, Cl
R1
N
CN
Scheme 1.
for the trimethylsilylcyanation of aldehydes, ketones
and imines.12–14 One of the most characteristic features
of this catalyst system is the ability to provide sterically
congested cyanohydrin trimethylsilyl ethers with rela-
tively low catalyst loadings. The resulting products can
be readily converted into a variety of important
synthetic intermediates, including a-hydroxy acids,15 b-
amino alcohols,16 a-amino acids17 and 1,2-diamines.18
The requisite carbene catalysts 3 were generated in situ
by the treatment of the corresponding imidazolium salts
with potassium tert-butoxide in THF at room tempera-
ture.19,20 Thus, in the presence of 10 mol % of N-hetero-
cyclic carbene 3a, acetophenone was treated with
2 equiv of Me3SiCN in THF at 0 °C for 1 h, and the
desired cyanohydrin trimethylsilyl ether was obtained
in an excellent yield (Table 1, entry 1).21 Interestingly,
the combination of commercially available thiazolium
salt 4 with triethylamine, which would generate an
N,S-heterocyclic carbene,22 exhibited a very low cata-
lytic activity (entry 2). N-Heterocyclic carbene 3 as a
Keywords: Cyanation; N-Heterocyclic carbene.
*
Corresponding author. Tel./fax: +81 75 753 4041; e-mail: maruoka@
kuchem.kyoto-u.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.141

4616
T. Kano et al. / Tetrahedron Letters 47 (2006) 4615–4618
Table 1. Lewis base-catalyzed trimethylsilylcyanation of acetophen-
onea
Table 2. Trimethylsilylcyanation of various aldehydes and ketones
catalyzed by carbene 3aa
O
O
catalyst
THF
NC OSiMe3
Ph
Bn
1 mol% 3a
NC OSiMe3
R'
Me3SiCN
+
Me3SiCN
+
Ph
R
R'
THF
R
Cl
Entry
1
Substrate
PhCHO
Conditions (°C, h)
Yieldb (%)
89c
N
S
3a: R = cyclohexyl
R
R
0, 0.5
N
N
3b:
3c:
R = i-Pr
R = mesityl
99c
99c
CHO
CHO
OH
2
3
0, 0.5
0, 0.5
4
Ph
Entry Catalyst
(mol %) Conditions (°C, h) Yieldb (%)
Ph
O
1
3a
10
10
10
10
0, 1
97
15
26
0
5
0
90
12
99
95
97
4
5
0, 0.5
0, 1
99
87
2c
3
4/Et3N
KOBut
PBu3
rt, 24
rt, 24
rt, 24
rt, 24
rt, 24
0, 1.5
0, 1
0, 0.5
0, 0.5
0, 0.5
Ph
O
4
5
6
7
8d
9d
10d
11d
DABCO 10
Ph
t-Bu
DMAP
DBU
DBU
3a
10
10
1
1
1
O
6
7
8
0, 1; rt, 1
0, 1
93
90
99
Ph
3b
3c
O
1
n-heptyl
a Unless otherwise specified, acetophenone (0.2 mmol) was treated with
2 equiv of Me3SiCN in the presence of a catalyst in 2 mL of THF
under the given reaction conditions under an argon atmosphere.
b Isolated yield.
c Catalyst was generated by treatment of
triethylamine.
d Reaction performed with acetophenone (1.0 mmol) and 1.2 equiv of
Me3SiCN in 5 mL of THF.
O
0, 2; rt, 2
4 with 10 equiv of
O
9
0, 0.5
0, 1
99
89
O
10
CO2Et
nucleophilic organocatalyst was then evaluated by
comparison with other Lewis base catalysts in the tri-
methylsilylcyanation of acetophenone. The reaction
with 10 mol % of KOBut at room temperature for 24 h
afforded the addition product in 26% yield (entry 3).
The use of tributylphosphine, DABCO or DMAP gave
poor results (entries 4–6); in contrast, the reaction using
DBU gave a high yield of the product (entry 7). While
the use of a catalyst level as low as 1 mol % of DBU
resulted in a significant decrease in yield (entry 8),
1 mol % of N-heterocyclic carbene 3a was enough to
achieve an excellent yield (entry 9). Additionally, other
N-heterocyclic carbenes 3b and 3c were also found to
show similar catalytic activity (entries 10 and 11).
a An aldehyde or a ketone (1 mmol) was treated with 1.2 equiv of
Me3SiCN in the presence of carbene 3a in 5 mL of THF under the
given reaction conditions under an argon atmosphere.
b Isolated yield.
c Isolated yield of the cyanohydrin after hydrolysis with 2 N HCl.
the presence of 5 mol % of 3a, the reaction of 2-methyl-
cyclohexanone with t-BuMe2SiCN proceeded smoothly
to give the sterically congested cyanohydrin t-butyldi-
methylsilyl ether in excellent yield (Eq. 1). In sharp
contrast, the reaction using 30 mol % of N-methyl-
morpholine-N-oxide (NMO) as a catalyst under the
reported conditions provided the cyanohydrin exclu-
sively (Eq. 2).12i
With these initial results in hand, we next investigated
the efficiency of N-heterocyclic carbene 3a in the reac-
tions of various aldehydes and ketones, and the results
are summarized in Table 2. Aromatic, olefinic and ali-
phatic aldehydes as well as ketones were found to be
suitable substrates. In general, trimethylsilylcyanation
of the carbonyl compounds proceeded to give the corre-
sponding cyanohydrin trimethylsilyl ether in good to
excellent isolated yields. It should be noted that only
the 1,2-addition products were observed with the a,b-
unsaturated aldehyde and ketone (entries 2 and 6).
The present method was also applicable to the sterically
congested ketones23 (entries 5 and 9) and an enolizable
ketone, such as ethyl pyruvate (entry 10).
NC OSiMe2But
O
5 mol% 3a
t-BuMe2SiCN
t-BuMe2SiCN
+
+
ð1Þ
ð2Þ
THF, 0 °C, 2.5 h
98% (dr = 6.7/1)
NC OH
O
30 mol% NMO
CH2Cl2, rt, 22 h
87% (dr = 2.3/1)
N-Heterocyclic carbene 3a also proved to be a reason-
ably effective catalyst for the cyanation of N-sulfonyl
imines derived from various aldehydes (Table 3, entries
The present reaction system is also applicable to a more
sterically demanding trialkylsilyl cyanide.24 Indeed, in

T. Kano et al. / Tetrahedron Letters 47 (2006) 4615–4618
4617
Table 3. Trimethylsilylcyanation of various imines catalyzed by
carbene 3aa
in good to excellent yields. Further investigations aimed
at the elucidation of the precise mechanism and the
scope of this reaction are currently underway.
NX
R'
NC NHX
1 mol% 3a
+
Me3SiCN
R
R'
R
THF
Acknowledgments
Entry
1
Substrate
Conditions (°C, h)
Yieldb (%)
NTs
This work was partially supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
rt, 4
92
92
Ph
H
NTs
H
2
3
4
5
6
7c
8
9
rt, 2
1-naphthyl
NTs
H
References and notes
rt, 3.5
rt, 5
83
82
25
2
Ph
1. For reviews, see: (a) Herrmann, W. A.; Ofele, K.; von
Preysing, D.; Schneider, S. K. J. Organomet. Chem. 2003,
687, 229; (b) Yong, B. S.; Nolan, S. P. Chemtracts 2003,
16, 205; (c) Herrmann, W. A. Angew. Chem., Int. Ed. 2002,
41, 1290.
2. For reviews, see: (a) Enders, D.; Balensiefer, T. Acc.
Chem. Res. 2004, 37, 534; (b) Nair, V.; Bindu, S.;
Sreekumar, V. Angew. Chem., Int. Ed. 2004, 43, 5130; (c)
Johnson, J. S. Angew. Chem., Int. Ed. 2004, 43, 1326.
3. (a) Breslow, R. J. Am. Chem. Soc. 1958, 80, 3719; For
recent representative papers, see: (b) Gerhard, A. U.;
Leeper, F. J. Tetrahedron Lett. 1997, 38, 3615; (c) Dvorak,
C. A.; Rawal, V. H. Tetrahedron Lett. 1998, 39, 2925; (d)
Knight, R. L.; Leeper, F. J. J. Chem. Soc., Perkin Trans. 1
1998, 1891; (e) Enders, D.; Kallfass, U. Angew. Chem., Int.
Ed. 2002, 41, 1743; (f) Tachibana, Y.; Kihara, N.; Takata,
T. J. Am. Chem. Soc. 2004, 126, 3438.
4. (a) Stetter, H. Angew. Chem., Int. Ed. Engl. 1976, 15, 639;
(b) Stetter, H.; Kuhlmann, H. Org. React. 1991, 40, 407;
(c) Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. Helv.
Chim. Acta 1996, 79, 1899; (d) Kerr, M. S.; Read de
Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 10298;
(e) Kerr, M. S.; Rovis, T. Synlett 2003, 1934; (f) Kerr, M.
S.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 8876.
5. (a) Grasa, G. A.; Kissling, R. M.; Nolan, S. P. Org. Lett.
2002, 4, 3583; (b) Nyce, G. W.; Lamboy, J. A.; Connor, E.
F.; Waymouth, R. M.; Hedrick, J. L. Org. Lett. 2002, 4,
3587; (c) Nyce, G. W.; Glauser, T.; Connor, E. F.; Mock,
A.; Waymouth, R. M.; Hedrick, J. L. J. Am. Chem. Soc.
2003, 125, 3046; (d) Grasa, G. A.; Singh, R.; Nolan, S. P.
Synthesis 2004, 971, and references therein.
6. Recently, some communications describing the related
esterifications and lactonizations catalyzed by N-hetero-
cyclic carbenes have been reported: (a) Chow, K. Y.-K.;
Bode, J. W. J. Am. Chem. Soc. 2004, 126, 8126; (b)
Reynolds, N. T.; Read de Alaniz, J.; Rovis, T. J. Am.
Chem. Soc. 2004, 126, 9518; (c) Sohn, S. S.; Rosen, E. L.;
Bode, J. W. J. Am. Chem. Soc. 2004, 126, 14370; (d)
Burstein, C.; Glorius, F. Angew. Chem., Int. Ed. 2004, 43,
6205.
NTs
H
cyclohexyl
NBn
rt, 6
Ph
Ph
Ph
Ph
Et
H
NTs
rt, 12
rt, 1.5
rt, 4
NTs
NBn
49
76
69
NBn
Et
rt, 2
a An imine (1 mmol) was treated with 1.2 equiv of Me3SiCN in the
presence of carbene 3a in 2–3 mL of THF under the given reaction
conditions under an argon atmosphere.
b Isolated yield.
c Use of 10 mol % of 3a.
1–4).24–26 However, attempted cyanation of an N-benzyl
imine from benzaldehyde resulted in the formation of
the product in low yield (entry 5). Although the cyana-
tion of an N-sulfonyl imine derived from acetophenone
gave only trace amounts of the corresponding amino
nitrile (entry 6), employment of 3a at a high catalyst
loading (10 mol %) afforded the product in moderate
yield (entry 7). In comparison, the reaction of an
N-benzyl ketimine of acetophenone provided the desired
amino nitrile in 76% yield, even with 1 mol % of 3a
(entry 8). The present reaction was also applicable to
an N-benzyl ketimine of aliphatic pentan-3-one (entry
9). These reactions proceeded under neutral and mild
conditions without using Lewis acid or hazardous
HCN, either of which is usually required in catalytic
Strecker reaction, except for a few examples.14 In this
respect, our catalyst system would provide an alterna-
tive method for the synthesis of amino nitriles.
7. (a) Suzuki, Y.; Yamauchi, K.; Muramatsu, K.; Sato, M.
Chem. Commun. 2004, 2770; (b) Kano, T.; Sasaki, K.;
Maruoka, K. Org. Lett. 2005, 7, 1347.
8. Kuhn, N.; Kratz, T.; Bla¨ser, D.; Boese, R. Chem. Ber.
1995, 128, 245.
9. Singh, R.; Nolan, S. P. Chem. Commun. 2005, 5456, and
references therein.
10. N-Heterocyclic carbene catalyzed trifluoromethylation
using Me3SiCF3: Song, J. J.; Tan, Z.; Reeves, J. T.;
Gallou, F.; Yee, N. K.; Senanayake, C. H. Org. Lett. 2005,
7, 2193.
In conclusion, we have demonstrated that the N-hetero-
cyclic carbene efficiently catalyzes the trialkylsilylcyana-
tion of various aldehydes, ketones and imines with
Me3SiCN to give the corresponding addition products
11. Song, J. J.; Gallou, F.; Reeves, J. T.; Tan, Z.; Yee, N. K.;
Senanayake, C. H. J. Org. Chem. 2006, ASAP.

4618
T. Kano et al. / Tetrahedron Letters 47 (2006) 4615–4618
12. (a) Evans, D. A.; Truesdale, L. K. Tetrahedron Lett. 1973,
14, 4929; (b) Ohta, H.; Hayakawa, S.; Moriwaki, H.;
Harada, S.; Okamoto, M. Chem. Pharm. Bull. 1986, 34,
4916; (c) Kobayashi, S.; Tsuchida, Y.; Mukaiyama, T.
Chem. Lett. 1991, 20, 537; (d) Matsubara, S.; Takai, T.;
Utimoto, K. Chem. Lett. 1991, 20, 1447; (e) Ruble, J. C.;
Fu, G. C. J. Org. Chem. 1996, 61, 7230; (f) Kantam, M.
L.; Sreekanth, P.; Santhi, P. L. Green. Chem. 2000, 47; (g)
Wilkinson, H. S.; Grover, P. T.; Vandedbossche, C. P.;
Bakale, R. P.; Bhongle, N. N.; Wald, S. A.; Senanayake,
C. H. Org. Lett. 2001, 3, 553; (h) Wang, Z.; Fetterly, B.;
Verkade, J. G. J. Organomet. Chem. 2002, 646, 161;
(i) Kim, S. S.; Kim, D. W.; Rajagopal, G. Synthesis 2004,
213; (j) Kim, S. S.; Rajagopal, G.; Song, D. G.
J. Organomet. Chem. 2004, 689, 1734; (k) Zhou, H.;
Chen, F.-X.; Qin, B.; Feng, X.; Zhang, G. Synlett 2004,
1077; (l) Li, Y.; He, B.; Feng, X.; Zhang, G. Synlett 2004,
1598.
13. Chiral catalysts: (a) Holmes, I. P.; Kagan, H. B. Tetra-
hedron Lett. 2000, 41, 7453; (b) Holmes, I. P.; Kagan, H.
B. Tetrahedron Lett. 2000, 41, 7457; (c) Choi, M. C. K.;
Chan, S.-S.; Chan, M.-K.; Kim, J. C.; Matsumoto, K.
Heterocycles 2002, 58, 645; (d) Tian, S.-K.; Hong, R.;
Deng, Li. J. Am. Chem. Soc. 2003, 125, 9900; (e) Hatano,
M.; Ikeno, T.; Miyamoto, T.; Ishihara, K. J. Am. Chem.
Soc. 2005, 127, 10776.
A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M.
Tetrahedron 1999, 55, 14523.
20. General procedure for the preparation of N-heterocyclic
carbene catalyst: A solution of 1,3-dicyclohexylimidazo-
lium tetrafluoroborate (3.2 mg, 0.01 mmol) in freshly
distilled THF (5 mL) was carefully degassed with argon
at ꢀ78 °C. To the solution was added a 1.0 M THF
solution of potassium tert-butoxide (10 lL, 0.01 mmol)
dropwise at room temperature. After being stirred for
0.5 h, the catalyst solution was used for the following
reactions without further purification.
21. General procedure for the trimethysilylcyanation of
ketones with trimethylsilyl cyanide by an N-heterocyclic
carbene catalyst: To a solution of N-heterocyclic carbene
catalyst (0.01 mmol) in 5 mL of THF was added a ketone
(1 mmol) and trimethylsilyl cyanide (1.2 mmol) dropwise
at 0 °C. The reaction mixture was stirred under the
conditions as indicated in Table 2. The resulting mixture
was then treated with aqueous saturated NH4Cl and
basified with aqueous saturated NaHCO3. After ethereal
extraction, the organic layer was dried over Na2SO4 and
concentrated under vacuum. The residue was purified by
column chromatography on silica gel (cooled by dry ice)
(ethyl acetate/hexane = 1:50–1:10 as eluent) to give the
corresponding cyanohydrin trimethylsilyl ether.
22. Murry, J. A.; Frantz, D. E.; Soheili, A.; Tillyer, R.;
Grabowski, E. J. J.; Reider, P. J. Am. Chem. Soc. 2001,
123, 9696.
14. Lewis base catalyst for imines: (a) Takahashi, E.; Fuji-
sawa, H.; Yanai, T.; Mukaiyama, T. Chem. Lett. 2005, 34,
318; (b) Takahashi, E.; Fujisawa, H.; Yanai, T.; Mukai-
yama, T. Chem. Lett. 2005, 34, 604.
23. 2,2-Dimethyl-1-(trimethylsilyloxy)cyclohexanecarbonitrile:
1H NMR (400 MHz, CDCl3)
d 1.96–1.90 (1H, m,
15. (a) Schwindt, M. A.; Belmont, D. T.; Carlson, M.;
Franklin, L. C.; Hendrickson, V. S.; Karrick, G. L.;
Poe, R. W.; Sobieray, D. M.; de Vusse, J. V. J. Org. Chem.
1996, 61, 9564; (b) Parisi, M. F.; Gattuso, G.; Notti, A.;
Raymo, F. M. J. Org. Chem. 1995, 60, 5174.
16. (a) Lu, Y.; Miet, C.; Kunesch, N.; Poisson, J. E.
Tetrahedron: Asymmetry 1993, 4, 893; (b) Brown, R. F.
C.; Donohue, A. C.; Jackson, W. R.; McCarthy, T. D.
Tetrahedron 1994, 50, 13739; (c) Zhao, X.; Wan, X. Org.
Prep. Proced. Int. 1995, 27, 513; (d) Jackson, W. R.;
Jacobs, H. A.; Matthews, B. R.; Jayatilake, G. S.;
Watson, K. G. Tetrahedron Lett. 1990, 31, 1447; (e)
(TMSO)(CN)CCH2), 1.83–1.76 (1H, m, (TMSO)(CN)-
CCH2), 1.71–1.65 (1H, m, –CH2CH2CH2–), 1.61–1.39
(5H, m, –CH2CH2CH2–), 1.11 (3H, s, CH3), 0.96 (3H, s,
CH3), 0.23 (9H, s, (CH3)3SiO); 13C NMR (100 MHz,
CDCl3) d 121.3, 76.7, 38.5, 35.5, 34.7, 25.4, 22.2, 20.6, 1.3;
IR (neat) 2953, 2938, 1252, 1173, 1123, 1086, 978, 914,
889, 886, 843, 754 cmꢀ1; HRMS (ESI-TOF) Calcd. for
C12H23NNaOSi: 248.1441 ([M+Na]+). Found: 248.1441
([M+Na]+).
24. None of these results were mentioned in the previous
paper, see Ref. 11.
25. 2-Tosylamino-2-phenylacetonitrile: 1H NMR (400 MHz,
CDCl3) d 7.79 (2H, d, J = 8.4 Hz, SO2Ar–H), 7.44–7.34
(7H, m, Ar–H), 5.46 (1H, d, J = 9.2 Hz, PhCHCN), 5.26
´
´
´
Tellitu, I.; Badıa, D.; Domınguez, E.; Garcıa, E. J.
Tetrahedron: Asymmetry 1994, 5, 1567; (f) Effenberger,
F.; Eichhorn, J. Tetrahedron: Asymmetry 1997, 8,
469.
(1H, d, J = 9.2 Hz, TsNH), 2.45 (3H, s, SO2Ph–CH3); 13
C
NMR (100 MHz, CDCl3) d 144.6, 135.9, 132.0, 129.9,
17. (a) Strecker, A. Ann. Chem. Pharm. 1850, 75, 27; (b)
Williams, R. M.; Hendrix, J. A. Chem. Rev. 1992, 92, 889;
(c) Duthaler, R. O. Tetrahedron 1994, 50, 1539; (d) Arend,
M. Angew. Chem., Int. Ed. 1999, 38, 2873.
18. (a) Stout, D. M.; Black, L. A.; Matier, W. L. J. Org.
Chem. 1983, 48, 5369; (b) Hennion, G. F.; Reardon, J. E.
J. Org. Chem. 1967, 32, 2819; (c) Villacampa, M.;
129.8, 129.3, 127.2, 127.0, 116.2, 48.2, 21.8; IR (neat) 3292,
1331, 1157, 1088, 1070, 937, 903, 745, 669, 590 cmꢀ1
;
HRMS (ESI-TOF) Calcd. for C15H14N2NaO2S: 309.0668
([M+Na]+). Found: 309.0667 ([M+Na]+).
26. 2-Benzylamino-2-phenylpropanenitrile: 1H NMR (400
MHz, CDCl3) d 7.69 (2H, d, J = 8.4 Hz, NHCH2Ar–H),
7.43–7.24 (8H, m, Ar–H), 3.86 (1H, d, J = 12.6 Hz,
NHCH2Ph), 3.54 (1H, d, J = 12.6 Hz, NHCH2Ph), 1.76
(3H, s, CH3); 13C NMR (100 MHz, CDCl3) d 139.5, 138.8,
128.7, 128.4, 128.3, 128.0, 127.2, 125.3, 121.1, 60.4, 49.5,
31.3; IR (neat) 1493, 1447, 1152, 1074, 1026, 762, 737, 696,
ˆ
´
Martınez, M.; GonzaAlez-Trigo, G.; So¨llhuber, M. M.
Heterocycles 1992, 34, 1885; (d) Greenlee, W. L.; Allibone,
P. L.; Perlow, D. S.; Patchett, A. A.; Ulm, E. H.; Vassil, T.
C. J. Med. Chem. 1985, 28, 434.
19. (a) Huang, J.; Jafarpour, L.; Hillier, A. C.; Stevens, E. D.;
Nolan, S. P. Organometallics 2001, 20, 2878; (b) Craig, H.
567 cmꢀ1
237.1386 ([M+H]+). Found: 237.1382 ([M+H]+).
; HRMS (ESI-TOF) Calcd. for C16H17N2: