Novel and efficient procedure for the regiocontrolled preparation of α-(phenylsulfanyl) carbonyl compounds

Article abstract of DOI:10.1002/jccs.200800097

A new procedure for the regiocontrolled synthesis of α- (phenylsulfanyl) carbonyl compounds has been developed, making use of lithium naphthalenide induced reductive sulfenylation of α-cyano carbonyl compounds as a key operation. Through this protocol, a variety of α-(phenylsulfanyl) carbonyl compounds has been prepared in moderate to high yields. The completely regioselective sulfenylation was observed in most of the cases.

Full text of DOI:10.1002/jccs.200800097

654
Journal of the Chinese Chemical Society, 2008, 55, 654-658
Novel and Efficient Procedure for the Regiocontrolled Preparation of
a-(Phenylsulfanyl) Carbonyl Compounds
Fa-Yen Lee (
Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 974, Taiwan, R.O.C.
) and Jia-Liang Zhu* (
)
A new procedure for the regiocontrolled synthesis of a-(phenylsulfanyl) carbonyl compounds has
been developed, making use of lithium naphthalenide induced reductive sulfenylation of a-cyano car-
bonyl compounds as a key operation. Through this protocol, a variety of a-(phenylsulfanyl) carbonyl
compounds has been prepared in moderate to high yields. The completely regioselective sulfenylation
was observed in most of the cases.
Keywords: Nitriles; Sulfur; Lithium naphthalenide; Reductive sulfenylation.
INTRODUCTION
a-(Phenylsulfanyl) carbonyl compounds are of con-
interested in extending this strategy into the syntheses of
a-(phenylsulfanyl) carbonyl compounds. Herein, we wish
to report the first examples of the LN-induced reductive
sulfenylation of the a-cyano carbonyl compounds to yield
the corresponding a-(phenylsulfanyl) carbonyl compounds.
siderable importance in synthetic chemistry where they can
be used to great advantage in a variety of organic transfor-
mations.1,2 In view of their broad synthetic utility, there
have been numerous procedures developed for the prepara-
tion of these substrates,3 with most of them highlighting di-
rect sulfenylation of enolates4 or enol derivatives5 and SN2
displacement of a-halogenated carbonyl compounds with
the sulfide.6 However, even with these precedents, the re-
gioselective synthesis of some a-(phenylsulfanyl) ketone
compounds is still not easily achieved due to difficult ac-
cess into the regiodefined precursors, thus making the de-
velopment of more efficient synthetic strategies necessary.
In conjunction with our studies on addition and cyclization
reactions involving carbon-centered radicals resulting from
C-Se bond cleavage, we have recently developed a highly
efficient procedure for the regiocontrolled preparation of
a-(phenylselanyl) ketones.7 Our approach is based on the
reductive decyanation of a-cyano ketones using lithium
naphthalenide (LN) as the reducing reagent, followed by
the rapid one-pot selenenylation of the resulting enolates
with phenylselenenyl bromide (PhSeBr); this gives the cor-
responding a-(phenylselanyl) ketones in the overall re-
placement of the cyano group with a phenylselanyl group.
Through this protocol, a wide range of a-cyano ketones
were efficiently converted into the corresponding a-(phen-
ylselanyl) ketones with the complete control over the regio-
chemistry. Meeting with these promising results, we were
RESULTS AND DISCUSSION
Our original investigation was conducted on a-cyano
ketone 1a under the reaction conditions developed earlier
for the reductive selenenylation reaction,7 except for re-
placing PhSeBr with commercially available diphenyl
disulfide (PhSSPh) as a sulfenylating reagent.4 Thus, 1a
was first treated with LN (5 equiv)8,9 in THF at -40 °C for
20 minutes to give the corresponding ketone enolate. The
subsequent addition of 1.2 equivalents of PhSSPh to the re-
action mixture followed by further reaction at the same
temperature for an additional 30 minutes afforded the de-
sired sulfenylated product 2a in 56% yield, and 2-benzyl-
cyclohexanone in 30% yield resulted from the decyanation.
Compared with the high yield (87%) of the corresponding
reductive a-selenenylation reaction of 1a,7 the relatively
low-yielding formation of 2a in this case could be possibly
attributed to the weaker electrophilicity of PhSSPh than
that of PhSeBr to the enolate intermediate. After examining
several reaction conditions, we found that 84% yield of 2a
could be obtained when the sulfenylation reaction was per-
formed by using 2 equivalents of PhSSPh and with the re-
action mixture being slowly warmed up from -40 to -10 °C
within 30 minutes (Scheme I). Following this, the reaction
* Corresponding author. Tel: +886-3-8633583; Fax: +886-3-8630475; E-mail: jlzhu@mail.ndhu.edu.tw

Synthesis of a-(Phenylsulfanyl) Carbonyl Compounds
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 655
Table 1. LN-Induced reductive a-sulfenylation of a-cyano
Scheme I
compounds
Entry
1
Substrate
Product
Yield (%)a
90
O
O
LN (5 eq), THF, -40 oC, 20 min
Bn
Bn
O
O
then PhSSPh (2 eq), -40 oC to -10 oC,
30 min 84%
CN
SPh
SPh
CN
2a
1a
2b
1b
O
O
SPh
CN
conditions depicted in Scheme I were further applied to a
variety a-cyano carbonyl compounds (1b-i).10 The experi-
mental results are compiled in Table 1.
2
3
4
5
83
95
65
50
2c
1c
O
O
SPh
CN
As shown in Table 1, when subjected to the reductive
sulfenylation conditions, both monocyclic and acyclic a-
cyano ketones 1b-f were smoothly converted into the cor-
responding sulfenylated products 2b-f in good to high
yields (50-95%) (entries 1-5). Also, the reactions of 1b-c
and 1e-f proceeded in a completely regiocontrolled fashion
to afford 2b-c and 2e-f as the only detectable regioisomers
(entries 1, 2 and 4, 5). As for the bicyclic cyano ketone 1g,
the desired product 2g was produced in a moderate yield
under the conditions (entry 6), along with a complex by-
product mixture presumably resulting from polysulfenyl-
ation. The attempts of using reduced amounts of LN and/or
PhSSPh only resulted in incompletion of the reactions in-
stead of the improvement on the yield of 2g. In addition to
the ketone precursors, the reductive sulfenylation process
was also applied to a-cyano ester 1h and a-cyano aldehyde
1i. Following a reported procedure,11 compound 1h was
prepared by the alkylation of ethyl cyanoacetate with 3-
bromopropyl tert-butyldimethylsilyl12 ether and 1,8-dizao-
bicylo[5.4.0]undec-7-ene (DBU) in benzene, followed by
the reaction of the resulting monoalkylated intermediate
with benzyl bromide and DBU in DMF. On the other hand,
compound 1i was constructed from the Diels-Alder reac-
tion of isopropylidenemalononitrile13 with 2,3-dimethyl-
1,3-butadiene (20 equiv) in the presence of ZnCl2 (2 equiv)
as catalyst (benzene, 80 °C, 2 days), and the subsequent re-
duction of the resulting adduct with DIBAL-H.14 As illus-
trated in entries 7 and 8, 1h underwent the reaction effi-
ciently to furnish 2h in 85% yield, while the reaction of 1i
afforded a-(phenylsulfanyl) aldehyde 2i only in 29% yield,
together with a significant amount of unidentified byprod-
ucts.
2d
2e
2f
1d
1e
1f
O
O
SPh
CN
Et
Et
O
O
SPh
CN
Bn
Et
Bn
Et
O
O
SPh
H
CN
H
6
7
8
32b
85
2g
1g
O
O
SPh
CN
Bn (CH2)3OTBDMS
1h
EtO
EtO
Bn (CH2)3OTBDMS
2h
O
O
SPh
CN
H
H
29
2i
1i
a Yield refers to isolated product.
b cis-Addition product is temporarily assigned based on previous
similar examples.7
tivity as well as good to high yields were observed for the
reactions.
EXPERIMENTAL
Unless otherwise stated, all of the starting materials
were obtained from commercial suppliers and used without
further purification. Reactions were performed under an at-
mosphere of nitrogen. Tetrahydrofuran (THF) was distilled
from sodium-benzophenone, and benzene and dimethyl
formamide (DMF) were distilled from calcium hydride be-
fore use. TLC analysis was carried out on Merck 25 DC-
Alufolien Kieselgel 60F254 aluminum-backed plates visual-
ised by using UV light, or by means of an ethanolic solution
of vanillin (5%) with sulphuric acid (5%). All of the prod-
In summary, we have demonstrated that the LN-in-
duced reductive a-sulfenylation of a-cyano carbonyl sub-
strates can serve as an efficient method for the synthesis of
a number of structurally diverse a-(phenylsulfanyl) car-
bonyl compounds. In most cases, the complete regioselec-

656 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
Lee and Zhu
ucts were purified by flash chromatography using Merck
Art.9385 Kiesegel 60 silica gel (230-400 mesh). NMR
spectra (1H, 13C) were recorded on a Brücker 400 spec-
trometer using deuteriochloroform (CDCl3) as solvent.
Chemical shifts measurements are reported in delta (d)
units. Splitting patterns are described as singlet (s), doublet
(d), triplet (t), quartet (q) or multiplet (m). Coupling con-
stants (J) are reported in Hertz (Hz). Infrared (IR) spectra
were recorded on an IR-FT JASCO 410 spectrophotometer
(neat) and resonances are reported in wave numbers (cm-1).
High resolution mass spectra (HRMS) were determined by
using a A. E. I. model MS-50 mass spectrometer in fast
atom bombardment (FAB) mode. GC-MS spectra were re-
corded on a Thermo Finnigan TRACE Gas Chromatogra-
phy mass spectrometer in electron ionization mode.
(dq, J1 = 14.5 Hz, J2 = 7.4 Hz, 1H), 1.69 (dq, J1 = 14.5 Hz,
J2 = 7.4 Hz, 1H), 1.86-1.98 (m, 1H), 1.98-2.08 (m, 2H),
2.09-2.25 (m, 2H), 2.62-2.72 (m, 1H), 7.28-7.44 (m, 5H);
13C NMR (100 MHz, CDCl3): d = 8.8, 18.0, 25.8, 33.9,
36.0, 61.4, 128.7, 129.4, 130.2, 137.0, 211.9; HRMS-FAB:
m/z [M+H]+ calcd. for C13H17OS: 221.1000; found:
221.1002.
2-Allyl-2-phenylsulfanyl-cycloheptanone (2c)
The typical procedure for the preparation of 2a was
followed; 1c (150 mg, 0.85 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 20:1)
afforded 2c as a colorless oil. Yield: 183 mg (83%).
IR (neat): 3074, 2927, 2856, 1697, 1637, 1439, 750,
692 cm-1; 1H NMR (400 MHz, CDCl3): d = 1.12-1.28 (m,
1H), 1.34-1.49 (m, 2H), 1.55-1.63 (m, 1H), 1.76-1.88 (m,
2H), 1.88-2.00 (m, 1H), 2.15-2.28 (m, 2H), 2.36-2.49 (m,
2H), 3.21 (broad, t, J = 11.9 Hz, 1H), 5.06 (broad, d, J =
17.0 Hz, 1H), 5.14 (broad, d, J = 10.1 Hz, 1H), 6.01 (dm, J
Synthesis of 2-benzyl-2-phenylsulfanyl-cyclohexanone
(2a); General procedure of reductive a-sulfenylation
A 0.365 M solution of LN in THF (9.6 mL, 3.52
mmol)8 precooled to -40 °C was quickly added by syringe
to a solution of 1a (150 mg, 0.70 mmol) in anhydrous THF
(10 mL) at -40 °C under a N2 atmosphere. The resulting
dark-green mixture was stirred at -40 °C for 20 min, and then
solid diphenyl disulfide (307 mg, 1.41 mmol) was added in
one portion. The stirring mixture was slowly warmed to -10
°C within 30 min and quenched with H2O (10 mL) and ex-
tracted with ethyl acetate (2 ´ 15 mL). The combined ex-
tracts were washed with saturated aqueous NaCl (10 mL),
dried with Na2SO4 and concentrated. Purification by chro-
matography on silica gel (hexane-ethyl acetate 30:1) af-
forded 2a as a viscous oil (175 mg, 84%).
IR (neat): 3060, 2937, 1699, 1581, 750, 692 cm-1; 1H
NMR (400 MHz, CDCl3): d = 1.43-1.53 (m, 1H), 1.64
(broad, d, J = 13.4 Hz, 1H), 1.81-1.97 (m, 2H), 1.97-2.18
(m, 2H), 2.33 (broad, d, J = 15 Hz, 1H), 2.82 (d, J = 13.9
Hz, 1H), 3.29 (d, J = 13.9 Hz, 1H), 3.31-3.36 (m, 1H),
7.15-7.25 (m, 5H), 7.31-7.40 (m, 3H), 7.43 (broad, d, J =
7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): d = 21.0, 26.3,
36.0, 37.9, 41.6, 61.5, 126.4, 127.9, 129.0, 129.3, 130.8,
131.2, 135.9, 137.3, 206.3; HRMS-FAB: m/z [M]+ calcd.
for C19H20OS: 296.1235; found: 296.1235.
= 17.0 Hz, 1H), 7.27-7.32 (m, 2H), 7.32-7.38 (m, 3H); 13
C
NMR (100 MHz, CDCl3): d = 24.5, 26.5, 30.4, 32.3, 36.3,
39.6, 62.4, 118.2, 128.8, 129.4, 130.6, 134.4, 136.6, 207.9;
HRMS-FAB: m/z [M+H]+ calcd. for C16H21OS: 261.1313;
found: 261.1309.
1-Benzoyl-1-phenylsulfanyl-3,4,6,6-tetramethyl-3-cyclo-
hexene (2d)
The typical procedure for the preparation of 2a was
followed; 1d (116 mg, 0.43 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 70:1)
afforded 2d as a yellow oil. Yield: 144 mg (95%).
IR (neat): 3055, 2962, 1674, 1653, 1265, 741, 704
cm-1; 1H NMR (400 MHz, CDCl3): d = 1.00 (s, 3H), 1.01 (s,
3H), 1.41 (s, 3H), 1.61 (s, 3H), 1.77 (d, J = 18.2 Hz, 1H),
1.92 (d, J = 18.2 Hz, 1H), 2.37 (d, J = 21.0 Hz, 1H), 2.43 (d,
J = 21.0 Hz, 1H), 7.21-7.25 (m, 2H), 7.29-7.39 (m, 5H),
7.39-7.46 (m, 1H), 7.89 (broad, d, J = 7.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3): d = 18.2, 18.5, 25.6, 27.2, 37.0,
37.4, 46.6, 67.2, 122.0, 124.6, 127.7, 128.7, 128.9, 129.1,
130.0, 131.1, 136.8, 143.2, 203.4; HRMS-FAB: m/z
[M+H]+ calcd. for C23H27OS: 351.1783; found: 351.1781.
2,4-Dimethyl-4-phenylsulfanyl-3-hexanone (2e)
The typical procedure for the preparation of 2a was
followed; 1e (136 mg, 0.89 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 50:1)
afforded 2e as a colorless oil. Yield: 136 mg (65%).
IR (neat): 2972, 1699, 748, 692 cm-1; 1H NMR (400
MHz, CDCl3): d = 0.93 (t, J = 7.4 Hz, 3H), 1.16 (d, J = 7.1
Hz, 3H), 1.18 (d, J = 7.1 Hz, 3H), 1.37 (s, 3H), 1.70 (dq, J1
2-Ethyl-2-phenylsulfanyl-cyclopentanone (2b)
The typical procedure for the preparation of 2a was
followed; 1b (110 mg, 0.80 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 30:1)
afforded 2b as a colorless oil. Yield: 159 mg (90%).
IR (neat): 3057, 2966, 1730, 1587, 752, 692 cm-1; 1H
NMR (400 MHz, CDCl3): d = 0.99 (t, J = 7.4 Hz, 3H), 1.49

Synthesis of a-(Phenylsulfanyl) Carbonyl Compounds
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 657
= 14.2 Hz, J2 = 7.2 Hz, 1H), 1.83 (dq, J1 = 14.2 Hz, J2 = 7.2
Hz, 1H), 3.38, (septet, J = 6.7 Hz, 1H), 7.27-7.35 (m, 5H);
13C NMR (100 MHz, CDCl3): d = 9.1, 20.3, 20.7, 21.2,
29.2, 34.2, 60.6, 128.3, 128.7, 131.4, 135.5, 211.8; HRMS-
FAB: m/z [M+H]+ calcd. for C14H21OS: 237.1313; found:
237.1311.
3H), 1.19 (s, 3H), 1.65 (s, 3H), 1.67 (s, 3H), 1.86 (d, J =
18.4 Hz, 1H), 2.17 (d, J = 18.4 Hz, 1H), 2.35 (d, J = 17.8
Hz, 1H), 2.53 (d, J = 17.8 Hz, 1H), 9.45 (s, 1H); 13C NMR
(100 MHz, CDCl3): d = 18.3, 19.0, 23.3, 25.9, 33.7, 35.3,
43.9, 56.0, 118.5, 119.8, 125.3, 195.1; MS (EI, 70 eV): m/z
191.2 [M]+.
4-Benzyl-2-methyl-4-phenylsulfanyl-3-hexanone (2f)
The typical procedure for the preparation of 2a was
followed; 1f (128 mg, 0.56 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 60:1)
afforded 2f as a viscous oil. Yield: 87 mg (50%).
IR (neat): 3060, 2974, 1693, 1603, 746, 692, cm-1; 1H
NMR (400 MHz, CDCl3): d = 1.04 (t, J = 7.3 Hz, 3H), 1.08
(d, J = 6.7 Hz, 3H), 1.18 (d, J = 6.7 Hz, 3H), 1.75 (q, J = 7.3
Hz, 2H), 3.02 (d, J = 14.6 Hz, 1H), 3.25 (d, J = 14.6 Hz,
1H), 3.37 (septet, J = 6.7 Hz, 1H), 7.16-7.25 (m, 5H), 7.28-
7.35 (m, 5H); 13C NMR (100 MHz, CDCl3): d = 9.1, 20.5,
21.2, 25.0, 34.6, 36.9, 65.3, 126.5, 128.0, 128.6, 128.8,
130.5, 131.5, 135.0, 137.0, 210.9; HRMS-FAB: m/z
[M+H]+ calcd. for C20H25OS: 313.1626; found: 313.1620.
(1R*,6S*)-1-Phenylsulfanyl-8,9-diemthylbicyclo[4.4.0]-
dec-8-en-2-one (2g)
2-Benzyl-2-phenylsulfanyl-5-(tert-butyl-dimethylsilanyl-
oxy)-pentanoic acid ethyl ester (2h)
The typical procedure for the preparation of 2a was
followed; 1h (138 mg, 0.37 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 40:1)
afforded 2h as a yellow oil. Yield: 143 mg (85%).
IR (neat): 3062, 2954, 1724, 1471, 1095, 835, 750
cm-1; 1H NMR (400 MHz, CDCl3): d = 0.02 (s, 6H), 0.88 (s,
9H), 1.17 (t, J = 7.1 Hz, 3H), 1.60-1.79 (m, 3H), 1.87-2.01
(m, 1H), 3.05 (d, J = 14.1 Hz, 1H), 3.33 (d, J = 14.1 Hz,
1H), 3.50-3.62 (m, 2H), 4.00-4.16 (m, 2H), 7.19-7.25 (m,
5H), 7.28-7.40 (m, 3H), 7.49 (broad, d, J = 7.5 Hz, 2H); 13C
NMR (100 MHz, CDCl3): d = -5.3, 14.0, 18.4, 26.0, 27.8,
29.4, 40.2, 60.0, 61.1, 63.1, 126.8, 128.1, 128.7, 129.2,
130.3, 131.2, 136.5, 136.7, 172.6; HRMS-FAB: m/z [M+H]+
calcd. for C26H39O3SiS: 459.2389; found: 459.2386.
3,4,6,6-Tetramethyl-1-phenylsulfanyl-cyclohex-3-ene-
carbaldehyde (2i)
The typical procedure for the preparation of 2a was
followed; 1g (100 mg, 0.49 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 40:1)
afforded 2g as a waxy solid. Yield: 45 mg (32%).
IR (neat): 2918, 2850, 1734, 1705, 1265, 739, 704
cm-1; 1H NMR (400 MHz, CDCl3): d = 1.25 (s, 3H), 1.55 (s,
3H), 1.56-1.58 (m, 3H), 1.58-1.66 (m, 1H), 1.75-2.03 (m,
2H), 2.07-2.23 (m, 1H), 2.24-2.53 (m, 3H), 3.40-3.52 (m,
1H), 7.27-7.40 (m, 5H). HRMS-FAB: m/z [M+H]+ calcd.
for C18H23OS: 287.1470; found: 287.1463.
The typical procedure for the preparation of 2a was
followed; 1i (120 mg, 0.63 mmol) was used as starting ma-
terial. Flash chromatography (hexane-ethyl acetate 40:1)
afforded 2i as a colorless oil. Yield: 50 mg (29%).
IR (neat): 3128, 3059, 2721, 1718, 1660, 1593, 1514,
1410 cm-1; 1H NMR (400 MHz, CDCl3): d = 0.97 (s, 3H),
1.10 (s, 3H), 1.56 (d, J = 19.6 Hz, 1H), 1.61 (s, 3H), 1.66 (s,
3H), 1.67 (d, J = 19.6 Hz, 1H), 1.74 (d, J = 17.6 Hz, 1H),
1.94 (d, J = 17.6 Hz, 1H), 6.96-7.53 (m, 5H), 9.79 (s, 1H);
13C NMR (100 MHz, CDCl3): d = 18.5, 19.1, 23.3, 28.7,
29.3, 32.0, 46.6, 55.7, 122.2, 124.5, 125.4, 129.1, 130.1,
137.6, 206.0; MS (EI, 70 eV): m/z 274.1 [M]+.
2-Benzyl-5-(tert-butyl-dimethyl-silanyloxy)-2-cyano-
pentanoic acid ethyl ester (1h)
IR (neat): 2243, 1741, 1471, 1388, 837 cm-1; 1H NMR
(400 MHz, CDCl3): d = 0.04 (s, 6H), 0.89 (s, 9H), 1.17 (t, J
= 7.2 Hz, 3H), 1.52-1.61 (m, 1H), 1.75-1.86 (m, 1H), 1.87-
1.95 (m, 1H), 2.04-2.13 (m, 1H), 3.07 (d, J = 13.5 Hz, 1H),
3.20 (d, J = 13.5 Hz, 1H), 3.64 (t, J = 6 Hz, 2H), 4.15 (q, J =
7.2 Hz, 2H), 7.29-7.34 (m, 5H); 13C NMR (100 MHz,
CDCl3): d = -5.4, 13.9, 18.3, 25.9, 28.7, 34.1, 43.2, 51.3,
62.1, 62.6, 119.0, 127.8, 128.5, 130.0, 134.2, 168.6; MS
(EI, 70 eV): m/z 318.1 [M – t-Bu]+.
ACKNOWLEDGEMENT
We are grateful to the National Science Council of
Republic of China and National Dong-Hwa University for
financial support.
Received November 30, 2007.
1-Formyl-3,4,6,6-tetramethyl-3-cyclohexenecarbonitrile
(1i)
REFERENCES
1. Trost, B. M. Chem. Rev. 1978, 78, 363.
2. Trost, B. M. Acc. Chem. Res. 1978, 11, 453.
IR (neat): 2968, 2733, 2663, 2241, 1728, 1454, 1373,
816, 719 cm-1; 1H NMR (400 MHz, CDCl3): d = 1.06 (s,

658 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
Lee and Zhu
3. For recent examples, see: (a) Wang, W.; Li, H.; Wang, J.;
Liao, L. Tetrahedron Lett. 2004, 45, 8229. (b) Pohmakotr,
M.; Leawsuwan, W.; Tuchinda, P.; Kongsaeree, P.; Prabpai,
S.; Reutrakul, V. Org. Lett. 2004, 6, 4547.
sults7 indicated that the use of less than 5 equivalents of LN
(e.g., 4 eq.) often resulted in incompletion of the reaction un-
der the specified conditions (-40 °C, 20 min).
10. For the preparation of 1a-g, see reference 7.
11. Shia, K. S.; Chang, N. Y.; Yip, J.; Liu, H. J. Tetrahedron Lett.
1997, 38, 7713.
4. Trost, B. M.; Salzmann, T. N.; Hiroi, K. J. Am. Chem. Soc.
1976, 98, 4887.
5. Magnus, P.; Rigollier, P. Tetrahedron Lett. 1992, 33, 6111.
6. Truce, W. E.; Knospe, R. H. J. Am. Chem. Soc. 1955, 77,
5063.
12. Dubowchik, G. M.; Vrudhula, V. M.; Dasgupa, B. Org. Lett.
2001, 3, 3987.
13. Chen, Y. L.; Mansbach, R. S.; Winter, S. M.; Brooks, E.; Col-
lins, J.; Corman, M. L.; Dunaiskis, A. R.; Faraci, W. S.;
Gallaschun, R. J.; Schmidt, G. A.; Schulz, D. J. Med. Chem.
1997, 40, 1749.
7. Zhu, J. L.; Ko, Y. C.; Kuo, C. W.; Shia, K. S. Synlett 2007,
1274.
8. For preparing a stock solution of LN, see: Liu, H. J.; Yip, J.;
Shia, K. S. Tetrahedron Lett. 1997, 38, 2253.
9. In theory, the reductive decyanation of a-cyanoketones re-
quires only 2 equivalents of LN. However, the previous re-
14. Ojima, J.; Masumoto, M.; Katsuyama, J.; Kitamura, K.;
Iyoda, M. Bull. Chem. Soc. Jpn. 1989, 62, 1188.