PAPER
Cyanation Reaction of Ketones and Ketimines
2651
HRMS (EI): m/z calcd for C14H19NOSi: 245.1236; found: 245.1232.
In summary, N-heterocyclic carbene 2a was found to
function as a good catalyst in cyanation reaction of ke-
tones and ketimines with TMSCN. This contribution
should provide a new synthetic strategy for the construc-
tion of tetrasubstituted carbon by organocatalyst under
mild reaction conditions. Ongoing efforts are focused on
developing an asymmetric version8 of this reaction with a
chiral N-heterocyclic carbene.
Cyanation of Ketimine: Representative Procedure
To a stirred solution of 1,3-bis(2,4,6-trimethylphenyl)imidazolium
chloride (1a; 5.1 mg, 15 mmol) in DMF (1.0 mL) was added t-BuOK
(1.4 mg,13 mmol) and the mixture was stirred for 15 min at r.t. After
dissolving the imidazolium chloride 1a completely, 4-methyl-N-(1-
phenylethylidene)benzenesulfonamide (5a; 82.0 mg, 0.30 mmol)
and TMSCN (56.5 mL, 0.45 mmol) were added to this mixture. The
reaction mixture was stirred for 3 h at r.t., then quenched with H2O
at 0 °C and extracted with EtOAc. The organic extracts were suc-
cessively washed with H2O and brine, dried (Na2SO4) and concen-
trated. Purification by silica gel chromatography (hexane–EtOAc,
4:1) gave N-(1-cyano-1-phenylethyl)-4-methylbenzenesulfon-
amide (6a; 83.7 mg, 93%) as a white solid; colorless needles; mp
130–132 °C (CHCl3–hexane).
IR spectra were measured on a JASCO IR Report-100 diffraction
grating IR spectrophotometer. 1H NMR (270 MHz) and 13C NMR
(68 MHz) spectra were measured on a JEOL JNM-EX-270 NMR
spectrometer. EI–MS, HRMS, and FAB–MS spectra were mea-
sured on a JEOL JMS-SX-102A instrument. Commercially avail-
able imidazolium salts, TMSCN and t-BuOK were used without
any purification. Tetrahydrofuran was distilled from Na/benzophe-
none ketyl under a nitrogen atmosphere. N,N-Dimethylformamide
was distilled from CaH2 under reduced pressure. Silica gel column
chromatography was performed on Fuji silysia PSQ 60B.
IR (nujol): 3255, 2250, 1339, 1155 cm–1.
1H NMR (CDCl3): d = 1.93 (s, 3 H), 2.41 (s, 3 H), 5.85 (s, 1 H), 7.21
(d, J = 8.1 Hz, 2 H), 7.20–7.34 (m, 3 H), 7.41–7.51 (m, 2 H), 7.57
(d, J = 8.1 Hz, 2 H).
13C NMR (CDCl3): d = 21.66, 30.33, 56.59, 118.92, 125.50, 127.29,
128.72, 129.05, 129.42, 136.96, 137.00, 143.86.
Cyanosilylation of Ketone; Typical Procedure
To a stirred solution of 1,3-bis(2,4,6-trimethylphenyl)imidazolium
chloride (1a; 5.1 mg, 15 mmol) in DMF (1.0 mL) was added t-BuOK
(1.4 mg, 13 mmol) and the mixture was stirred for 15 min at r.t. After
dissolving the imidazolium chloride 1a completely, acetophenone
(3a; 35 mL, 0.30 mmol) and TMSCN (56.5 mL, 0.45 mmol) were
added to this mixture. The reaction mixture was stirred for 15 min
at r.t., quenched with water and extracted with EtOAc. The organic
extracts were successively washed with H2O and brine, dried
(Na2SO4) and concentrated. Purification by silica gel chromatogra-
phy (hexane–EtOAc, 10:1; the silica gel was pretreated with 1%
Et3N in hexane) gave 2-phenyl-2-(trimethylsilanyloxy)propionitrile
(4a; 58.6 mg, 89%) as a colorless oil. The physical data were com-
parable to those reported.6a
FAB–MS: m/z = 301 [M+ + 1].
Anal. Calcd for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33. Found: C,
63.74; H, 5.38; N, 9.16.
N-(1-Cyano-1-p-tolylethyl)-4-methylbenzenesulfonamide (6b)
Colorless crystals; mp 129–130 °C (CHCl3–hexane).
IR (nujol): 3258, 2248, 1335, 1151cm–1.
1H NMR (CDCl3): d = 1.90 (s, 3 H), 2.30 (s, 3 H), 2.40 (s, 3 H), 6.09
(s, 1 H), 7.03 (d, J = 8.1 Hz, 2 H), 7.19 (d, J = 8.2 Hz, 2 H), 7.31 (d,
J = 8.1 Hz, 2 H), 7.55 (d, J = 8.2 Hz, 2 H).
13C NMR (CDCl3): d = 21.03, 21.59, 30.23, 56.29, 119.09, 125.40,
127.21, 129.16, 129.23, 133.90, 137.02, 138.91, 143.59.
The physical data of the known silylated cyanohydrins shown be-
low were comparable to those of the corresponding literature: 2-(4-
chlorophenyl)-2-(trimethylsilanyloxy)propionitrile (4b),6a 2-(4-
methoxyphenyl)-2-(trimethylsilanyloxy)propionitrile (4c),6a 2-me-
thyl-4-phenyl-2-(trimethylsilanyloxy)butyronitrile (4d),9 (3E)-2-
methyl-4-phenyl-2-(trimethylsilanyloxy)but-3-enenitrile (4f).6a
FAB–MS: m/z = 315 [M+ + 1].
Anal. Calcd for C17H18N2O2S: C, 64.94; H, 5.77; N, 8.91. Found: C,
64.95; H, 5.96; N, 8.83.
N-(1-Cyano-1-p-methoxyphenylethyl)-4-methylbenzene-
sulfonamide (6c)
Colorless crystals; mp 152–154 °C (CHCl3–hexane).
IR (nujol): 3234, 2245, 1336, 1151 cm–1.
1H NMR (CDCl3): d = 1.91 (s, 3 H), 2.40 (s, 3 H), 3.77 (s, 3 H), 5.95
(s, 1 H), 6.74 (d, J = 8.8 Hz, 2 H), 7.20 (d, J = 8.2 Hz, 2 H), 7.34 (d,
J = 8.8 Hz, 2 H), 7.55 (d, J = 8.2 Hz, 2 H).
13C NMR (CDCl3): d = 21.60, 30.17, 55.34, 56.04, 113.85, 119.19,
126.97, 127.25, 128.74, 129.30, 137.09, 143.63, 159.84.
3-Methyl-2-phenyl-2-(trimethylsilanyloxy)butyronitrile (4e)
Colorless oil.
IR (neat): 2232, 1254, 1099 cm–1.
1H NMR (CDCl3): d = 0.10 (s, 9 H), 0.82 (d, J = 6.8 Hz, 3 H), 1.09
(d, J = 6.8 Hz, 3 H), 2.11 (sept, J = 6.8 Hz, 1 H), 7.29–7.41 (m, 3
H), 7.45–7.51 (m, 2 H).
13C NMR (CDCl3): d = 0.92, 17.25, 17.38, 41.54, 80.08, 119.80,
125.63, 128.14, 128.41, 140.07.
FAB–MS: m/z = 331 [M+ + 1].
EI–MS: m/z = 247 [M+], 204, 105.
Anal. Calcd for C17H18N2O3S: C, 61.80; H, 5.49; N, 8.48. Found: C,
61.51; H, 5.50; N, 8.43.
HRMS (EI): m/z calcd for C14H21NOSi: 247.1392; found: 247.1383.
2-(Trimethylsilanyloxy)-1,2,3,4-tetrahydronaphthalene-2-car-
bonitrile (4g)
Colorless oil.
IR (neat): 2232, 1254, 1127, 1103 cm–1.
1H NMR (CDCl3): d = 0.26 (s, 9 H), 2.00–2.30 (m, 2 H), 2.95–3.05
(m, 2 H), 3.09 (d, J = 16.4 Hz, 1 H), 3.31 (d, J = 16.4 Hz, 1 H), 6.90–
7.60 (m, 1 H), 7.07–7.17 (m, 3 H).
13C NMR (CDCl3): d = 1.45, 26.20, 35.69, 42.95, 68.45, 121.46,
126.15, 126.61, 128.49, 129.00, 131.13, 133.73.
N-(Cyanodiphenylmethyl)-4-methylbenzenesulfonamide (6d)
Colorless plates; mp 150–156 °C (CHCl3–hexane).
IR (nujol): 3264, 2244, 1335, 1166 cm–1.
1H NMR (CDCl3): d = 2.39 (s, 3 H), 5.88 (s, 1 H), 7.16 (d, J = 8.2
Hz, 2 H), 7.21–7.34 (m, 6 H), 7.36–7.47 (m, 4 H), 7.53 (d, J = 8.2
Hz, 2 H).
13C NMR (CDCl3): d = 21.62, 63.59, 118.36, 126.60, 127.32,
128.71, 129.03, 129.25, 137.09, 137.34, 143.71.
FAB–MS: m/z = 363 [M+ + 1].
EI–MS: m/z = 245 [M+], 155, 104.
Synthesis 2006, No. 16, 2649–2652 © Thieme Stuttgart · New York