Cyanation of alcohols with diethyl cyanophosphonate and 2,6-dimethyl-1,4-benzoquinone by a new type of oxidation-reduction condensation

Article abstract of DOI:10.1246/bcsj.79.1106

Cyanation of various alcohols by a new type of oxidation-reduction condensation is described. Primary alkyl diphenylphosphinites, 2,6-dimethyl-1,4-benzoquinone (DMBQ), and diethyl cyanophosphonate gave the corresponding nitriles in high yields. During the above experiment on cyanation of 4-phenylbutan-2-ol, the unexpected formation of a mixture of nitrile and isocyanide was observed. After careful examination of the reaction conditions, selective synthesis of isocyanides from secondary alcohols was successfully accomplished by the use of zinc oxide (ZnO) as an additive. Reaction of tertiary alcohols provided the corresponding isocyanides exclusively in the absence of an additive. Cyanation of optically active alcohols was tried in order to clarify the stereochemistry of this reaction, and the reaction was thus proved to proceed with the inversion of configuration.

Full text of DOI:10.1246/bcsj.79.1106

1106 Bull. Chem. Soc. Jpn. Vol. 79, No. 7, 1106–1117 (2006)
ꢀ 2006 The Chemical Society of Japan
Cyanation of Alcohols with Diethyl Cyanophosphonate
and 2,6-Dimethyl-1,4-benzoquinone by a New Type
of Oxidation–Reduction Condensation
ꢀ1;2
Kouta Masutani,1 Tomofumi Minowa,1 Yoshiaki Hagiwara,1 and Teruaki Mukaiyama
1Center for Basic Research, The Kitasato Institute, 6-15-5 Toshima, Kita-ku, Tokyo 114-0003
2Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
Received January 10, 2006; E-mail: mukaiyam@abeam.ocn.ne.jp
Cyanation of various alcohols by a new type of oxidation–reduction condensation is described. Primary alkyl
diphenylphosphinites, 2,6-dimethyl-1,4-benzoquinone (DMBQ), and diethyl cyanophosphonate gave the corresponding
nitriles in high yields. During the above experiment on cyanation of 4-phenylbutan-2-ol, the unexpected formation of a
mixture of nitrile and isocyanide was observed. After careful examination of the reaction conditions, selective synthesis
of isocyanides from secondary alcohols was successfully accomplished by the use of zinc oxide (ZnO) as an additive.
Reaction of tertiary alcohols provided the corresponding isocyanides exclusively in the absence of an additive. Cyana-
tion of optically active alcohols was tried in order to clarify the stereochemistry of this reaction, and the reaction was
thus proved to proceed with the inversion of configuration.
The aliphatic nucleophilic substitution reaction is one of the
most important processes in organic reactions.1 Among the nu-
cleophiles used in such substitution reactions, anions such as
enolate, nitrite, and cyanide anions exhibit very characteristic
behaviors. These anions are known as ambident nucleophiles2
because they possess two different reactive sites within a sin-
gle molecule. Although reactions with electrophiles proceed at
either position of the nucleophiles, various factors such as their
counter cations, solvents, and the nature of electrophiles influ-
ence the intrinsic reactivities of the nucleophiles. For example,
alkali metal cyanides such as sodium and potassium cyanides
react preferentially with alkyl halides at the C-position and
form nitriles.3 On the other hand, heavy metal cyanides such
as silver and copper cyanides react at the N-position and form
isocyanides predominantly.4
The oxidation–reduction condensation is recognized as one
of the most convenient and useful synthetic methods in organic
synthesis since the reaction is performed under neutral and
mild conditions.5 Recently, a newer type of oxidation–reduc-
tion condensation was reported from our laboratory; that is,
a combination of alkyl diphenylphosphinites prepared readily
from various alcohols, and quinones such as 2,6-dimethyl-
1,4-benzoquinone (DMBQ) and 2,6-di-t-butyl-1,4-benzoqui-
none (DBBQ) made many kinds of organic transformations
such as esterification,6 etherification,7 amination,8 and thio-
etherification9 possible. In order to extend the scope of this
condensation reaction, the carbon–carbon bond-forming reac-
tion using a cyanide ion, the simplest carbon nucleophile of
all, was tried.
sponding halides or sulfonates and the following substitution
with inorganic cyanides has generally been employed. When
secondary and tertiary alcohols were used in this reaction,
however, high temperature or the presence of strong bases
was needed in some cases, which often caused the undesirable
elimination reaction. Therefore, procedures such as one-pot
cyanation of alcohols according to the Mitsunobu reaction
were employed for the transformation under mild condi-
tions.10 Further, the conversion of alcohols into nitriles by
using a PPh3/DDQ/nBu4NCN system has also been reported
recently.11
As described above, a cyanide ion is an ambident nucleo-
phile that reacts alternatively at the C- or N-position in accord-
ance with the reaction conditions. If a cyanide ion reacted at
the N-position, isocyanides are formed instead of nitriles. Iso-
cyanides are the compounds that formally possess divalent car-
bon with unique reactivities.12 By making the best use of their
characteristics, isocyanides are employed in multicomponent
reactions such as Passerini13 and Ugi14 reactions, and synthesis
of heterocycles15 besides being used as ligands of transition-
metal complexes.16 There are various methods for the prepara-
tion of these isocyanides such as nucleophilic displacement
of alkyl halides by silver cyanide,4a,b dehydration of form-
amides,17 carbylamine reaction,18 or reduction of isocyanates
or isothiocyanates.19 Since these reactions are often carried
out under basic conditions or at high reaction temperatures,
it is desired to develop more convenient synthetic reactions
that proceed under mild conditions.
We would like to report here the syntheses of respective
nitriles from primary alcohols and isocyanides from secondary
and tertiary alcohols via the corresponding alkyl diphenylphos-
phinites by a new type of oxidation–reduction condensation
using 2,6-dimethyl-1,4-benzoquinone and diethyl cyanophos-
phonate.20
Introduction of a cyano group with nucleophilic displace-
ment by a cyanide ion is considered a versatile method for car-
bon chain elongation and further functional group manipula-
tion. In order to perform this transformation, a two-step proce-
dure involving initial conversion of alcohols into the corre-
Published on the web July 4, 2006; doi:10.1246/bcsj.79.1106

K. Masutani et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006) 1107
Table 1. Cyanation of Benzyl Alcohol with Various Cya-
nides and DMBQ
Table 2. Cyanation of Various Primary Alcohols with
(EtO)2P(O)CN and DMBQ
nBuLi, Ph2PCl
XCN (1.0 equiv.)
(EtO)2P(O)CN (1.0 equiv.)
nBuLi, Ph2PCl
DMBQ (1.5 equiv.)
BnOPPh2
BnCN
BnOH
ROPPh2
2b-10b
RCN
ROH
DMBQ
THF, 0 °C, 1 h
CHCl3, rt, 24 h
THF, 0 °C, 1h
1a
1b
1c
2a-10a
2c-10c
Solvent, rt, 24 h
(1.5 equiv.)
BnOPPh2
/equiv
DMBQ Solvent Yield
/%a)
Entry
XCN
Yield/%
/equiv /mL
Entry
ROH
ROPPh2
RCN
CH2Cl2
/0.50
1
2
1.0
1.0
TMSCN
1.0
1.0
0
OH
1
2
2a
3a
99
64
73
HO CN
CH2Cl2
/0.50
OH
OH
OH
OH
75a)
96
20
35
49
73
82
Br
Cl
O
CH2Cl2
/0.50
3
4
4a
5a
86
70
3
4
5
6
1.0
1.0
1.5
1.5
1.0
1.0
1.5
1.5
(EtO)2PCN
89
O
CHCl3
/0.50
F3C
(EtO)2PCN
5
6
6a
7a
quant.
90
97
94
O
CHCl3
/0.50
OH
OH
(EtO)2PCN
O
CHCl3
/1.5
7
8
8a
9a
94
81b),c)
(EtO)2PCN
OH
O
a) A small amount of DMBQ was contained. Yield was deter-
1
84a)
96
mined by H NMR analysis.
MeO
THPO
OH
9
10a
78a)
83b)
Results and Discussion
Cyanation of Primary Alcohols. In the first place, cyan-
ation of benzyl diphenylphosphinite with DMBQ and TMSCN
(trimethylsilyl cyanide) was tried in CH2Cl2. The desired ni-
trile, however, was not obtained at all (Table 1, Entry 1). Even
in the case of using acetone cyanohydrin in place of TMSCN,
the yield of nitrile was 20% (Table 1, Entry 2), whereas it
increased up to 35% by using diethyl cyanophosphonate
(Table 1, Entry 3). After screening several reaction conditions,
the nitrile was eventually obtained in 82% yield when 1.5
equiv of benzyl diphenylphosphinite and 1.5 equiv of DMBQ
were used in CHCl3 (Table 1, Entries 4–6).
a) Preparation of alkyl diphenylphosphinite was carried out at
ꢁ78 ꢂC. b) The reaction was carried out in 5.0 mL of CHCl3
for 48 h. c) A small amount of DMBQ was contaminated.
1
Yield was determined by H NMR analysis.
O
O
O
OR
O
Ph
Ph
(EtO)2PCN
P
Ph2POR
O
Next, cyanation of several primary alcohols was tried by
using DMBQ and diethyl cyanophosphonate (Table 2). Benzyl
alcohols having various substituents also afforded the corre-
sponding nitriles in good yields (Table 2, Entries 1–4). In
addition, non-benzylic, hindered primary alcohols and mono-
protected diols having a p-methoxybenzyl group or a tetra-
hydropyranyl group also provided the desired nitriles in high
yields (Table 2, Entries 5–9).
11
R
O
CN
O
O
O
Ph
Ph
Ph
O
P
P
+
RCN
Ph
OP(OEt)2
O
OP(OEt)2
12
Scheme 1.
A proposed reaction mechanism is shown in Scheme 1:
Alkyl diphenylphosphinite reacted initially with DMBQ to
form the adduct 11,6a which in turn transformed to the phos-
phonium cyanide 12 by reaction with diethyl cyanophospho-
nate. By the attack of the cyanide anion to the alkyl group
of 12, the corresponding nitrile was formed.
Cyanation of Secondary Alcohols. Next, cyanation of
secondary alcohols was examined. It was unexpectedly found
that the isocyanide 13c was formed21 in 23% yield along with
the aimed nitrile 14 by the cyanation of 4-phenylbutan-2-ol
(13a) with diethyl cyanophosphonate in CHCl3 at room tem-
perature (Scheme 2).
nBuLi, Ph2PCl
OH
OPPh2
Ph
Ph
+
THF, 0 °C, 1 h
13a
13b
CN
NC
(EtO)2P(O)CN, DMBQ
CHCl3, rt, 24 h
Ph
Ph
13c: 23%
14: 65%
Scheme 2.

1108 Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006)
Cyanation of Alcohols
O
O
CN --- Mhard
RCN
RNC
Ph
Ph
O
P
+
OP(OEt)2
R
NC --- Msoft
O
Ph
Ph
O
P
O
OP(OEt)2
Mhard = Hard metal salts such as Li, Na, and Mg
Msoft = Soft metal salts such as Ag, Cd, and Hg
Scheme 3.
Table 4. Selective Formation of Isocyanides from Various
Secondary Alcohols with ZnO as an Additive
Table 3. Additive Effect
CN
NC
Ph2PCl, Et3N
DMAP
(EtO)2P(O)CN (1.0 equiv.)
DMBQ (1.5 equiv.)
Ph
Ph
(EtO)2P(O)CN (1.0 equiv.)
DMBQ (1.5 equiv.)
OPPh2
ROPPh2
RNC
ROH
14
ZnO (1.0 equiv.)
CH2Cl2, rt, 24 h
THF, rt, 2 h
15a-21a
15b-21b
(1.5 equiv.)
15c-21c
+
Ph
Additive (2.0 equiv.)
CHCl3 (0.10 M), rt, 24 h
13b
Yield/%
ROPPh2
(1.5 equiv.)
Entry
ROH
13c
RNC
63a)
OH
Yield
(14:13c)/%a)
Yield
(14:13c)/%a)
1
2
15a
16a
quant.
95
Entry Additive
Entry Additive
Ph
OH
OH
OH
OH
1
2
3
4
5
None
Li2SO4
Na2CO3
Mg(OTf)2
CaO
88
(74:26)
6
7
Ag2O
HgO
CdO
ZnO
ZnO
0
89
63
72
Ph
88
(79:21)
0
3
4
17a
18a
82
PMBO
80
(82:18)
8
68
(<5:>95)
quant.
TBDPSO
72
(84:16)
9
57
(<5:>95)
82b),c)
(<5:>95)
5
19a
71
78
48
(81:19)
10
O
N
OH
a) Isolated as a mixture of isomers. Numbers in parentheses
are ratios of isomers determined by comparing the peak of
the methine proton of each isomer in 1H NMR analysis.
b) The reaction was carried out in CH2Cl2 (1.0 M). c) 1.0
equiv of ZnO was used.
6
7
20a
21a
86
99
81
OH
40b)
Ph
a) 1.5 mL of CH2Cl2 was used. b) The reaction time was 3 h.
Formation of isocyanides from secondary alcohols with
cyanide ions has not been reported yet.10 Since a cyanide anion
worked as an ambident nucleophile, it was figured that either
nitriles or isocyanides should be selectively formed in the
presence of an additive such as an inorganic salt taking the
Pearson’s HSAB principle22 into consideration: that is, hard
metal salts interact preferentially at the harder N-position of
the cyanide to form nitriles whereas soft metal salts interact
at the C-position of softer character to afford isocyanides
(Scheme 3).
The effect of inorganic salts was then examined in order to
selectively prepare either nitrile or isocyanide (Table 3). First,
reactions were tried by using various alkali metal salts and
alkaline earth metal salts (Table 3, Entries 2–5). Contrary to
our expectation, the yield of the desired nitrile was not good.
Then, the same reaction was tried in the presence of heavy
metal salts (Table 3, Entries 6–9). At that time, it was striking-
ly found that only the isocyanide was obtained in the case
when ZnO or CdO was used as an additive (Table 3, Entries
8 and 9). Although CdO afforded the isocyanide in higher
yield, further optimization of the reaction conditions in the ex-
istence of ZnO was tried from the environmental-benign point
of view. Under the optimized conditions (1.0 M of CH2Cl2 and
1.0 equiv of ZnO), the desired isocyanide was obtained in 82%
yield (Table 3, Entry 10).
Next, the cyanation of several secondary alcohols was tried
under the above optimized conditions (Table 4). Alkyl diphen-
ylphosphinites derived from 1-phenylpropan-2-ol and 1-phen-
ylpentan-3-ol provided the corresponding isocyanides in good
yields (Table 4, Entries 1 and 2). Monoprotected diols having
a p-methoxybenzyl group or a t-butyldiphenylsilyl group pro-
vided the desired isocyanides in satisfactory yields as well
(Table 4, Entries 3 and 4). On the other hand, heterocyclic
moieties contained in benzofuran and 1-methyl indole were
not affected under the above conditions (Table 4, Entries 5
and 6). In the case of 1-phenylethanol, the corresponding iso-
cyanide was obtained in 40% yield (Table 4, Entry 7).
Cyanation of an optically active secondary alcohol was next
tried in order to examine the stereochemistry of this reaction. It
was found that the inversion of configuration took place when
(R)-4-phenylbutan-2-ol was used as the substrate. The absolute
configuration of the isocyanide was determined by conversion
to the known amine 2523 and comparison of the sign of specific
rotation (Scheme 4).

K. Masutani et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006) 1109
OH
OPPh2
Ph2PCl, Et3N, DMAP
THF, rt
Ph
Ph
22
23
99% ee (R)
95%
NC
(EtO)2P(O)CN, DMBQ
ZnO, CH2Cl2, rt
2 M HCl-MeOH, H2O
MeOH
Ph
24
71%, 96% ee
NH2
[α]D23 = + 7.2 (c = 0.49, CHCl3)
Lit.23 for (S)-25: [α]D20 = + 6.4 (c = 0.47, CHCl3, 98% ee)
Ph
25
31%, (S)
Scheme 4.
(EtO)2P(O)CN, DMBQ
+
Ph
NC
Ph
CN
Ph
OPPh2
ZnO, CH2Cl2, rt, 24 h
7b
26
7c
< 40%
< 23%
Scheme 5.
Table 5. Cyanation of Tertiary Alkyl Diphenylphosphinite
Table 6. Synthesis of Isocyanides from Various Tertiary
Alcohols
OPPh2
NC
(EtO)2P(O)CN (1.0 equiv.)
DMBQ, CH2Cl2, rt
Ph2PCl, Et3N
DMAP
(EtO)2P(O)CN (1.0 equiv.)
DMBQ (2.0 equiv.)
+
Ph
Ph
ROH
ROPPh2
28b-33b
RNC
27b
27c
THF, rt, 2 h
CH2Cl2, rt, 12 h
28a-33a
28c-33c
+
(1.5 equiv.)
Ph
Ph
Yield/%
27d
27e
Entry
ROH
ROPPh2
82a)
RNC
Yield/%
27d + 27ec)
27b
/equiv
DMBQ
/equiv
Time
/h
Entry
OH
27c
1
2
3
4
28a
29a
30a
31a
59c)
60b)
71c)
67
Ph
Ph
1a)
2
3
4
1.5
1.5
1.5b)
1.5b)
1.5
1.5
1.5
2.0
24
24
12
12
40
44
50
70
39
29
33
26
OH
87a)
98
OH
OH
TBDPSO
a) 1.0 equiv of ZnO was used. b) Purified with basic silica-gel
chromatography. c) Yield based on 27b.
84
O
N
When the cyanation of a primary alcohol was examined un-
der the same conditions, however, a mixture of the correspond-
ing isocyanide21 and nitrile was obtained unexpectedly in a ca.
2:1 ratio in the cyanation of the alkyl diphenylphosphinite 7b
derived from 3-phenylpropan-1-ol (Scheme 5).
Cyanation of Tertiary Alcohols. Next, the cyanation of
tertiary alcohols was tried (Table 5). Cyanation of 2-methyl-
4-phenylbutan-2-ol gave the corresponding isocyanide in 40%
yield when ZnO was used as an additive (Table 5, Entry 1). It
was unexpected that the corresponding isocyanide would be
obtained exclusively in the absence of ZnO (Table 5, Entry 2).
However, the above reaction conditions were not reproducible.
After intensive examination of reaction conditions, purification
with basic silica-gel chromatography was found most effective
for the reproduction of the reaction (Table 5, Entry 3). Finally,
OH
5
6
32a
33a
85
75
43b),c)
OH
33
Ph
a) ROPPh2 was prepared by using nBuLi as a base. b) 2.0
equiv of ROPPh2 was used. c) The reaction time was 7 h.
the corresponding isocyanide was obtained in 70% yield
(Table 5, Entry 4).
The cyanation of several tertiary alcohols was further tried
under the optimized conditions (Table 6) and alkyl diphenyl-
phosphinites derived from 3-methyl-1-phenylpentan-3-ol and

1110 Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006)
Cyanation of Alcohols
OPPh2
OH
Ph2PCl, nBuLi
Ph
Ph
THF, 0 °C
34
35
86%
80% ee (S)
1) 2 M HCl-MeOH, H2O
MeOH, rt then Boc2O
Et3N, DMAP, THF, reflux
NC
(EtO)2P(O)CN, DMBQ
CH2Cl2, rt
Ph
2) RuCl3, NaIO4
CCl4/CH3CN/H2O
reflux to rt
36
47%, 78% ee
O
[α]D20 = -5.8 (c = 0.89, benzene)
Lit.24 for (S)-37:
NH
[α]D29 = + 5.7 (c = 0.848, benzene)
37
16%, 2 steps (R)
Scheme 6.
tive to tetramethylsilane with the solvent resonance as the internal
standard (CDCl3; ꢀ ¼ 77:0 ppm). Carbon–31P coupling constants
are reported when possible. The optical rotations were measured
with a JASCO P-1020 polarimeter. High-resolution mass spectra
(HRMS) were recorded on a JEOL JMS-700V instrument
unless otherwise noted. High-performance liquid chromatography
(HPLC) was carried out using a Hitachi LC-Organizer, L-4000UV
Detecter, L-6200 Intelligent Pump, and D-2500 Chromato-
Integrator. Analytical TLC was performed on Merck preparative
TLC plates (silica gel 60 GF254, 0.25 mm). Column chromatogra-
phy was carried out on Merck silica gel 60 (0.063–0.200 mm)
or Fuji Silysia Chromatorexꢂ NH (100–200 mesh). Preparative
thin-layer chromatography (PTLC) was carried out on silica gel
Wakogel B-5F. All reactions were carried out under an argon at-
mosphere unless otherwise noted. Dry solvents (Dichloromethane,
MeOH, and EtOH) were prepared by distillation under appropriate
drying agents. Dehydrated solvents (THF, Dioxane, and Chloro-
form) were purchased from KANTO KAGAKU and were used
as received. ZnO (3N5) was purchased from KANTO KAGAKU
and was dried by a heatgun for 5 min prior to use. t-Butyldimeth-
ylsilyl chloride was purchased from Shin-Etsu Chemical. 10%
Pd/C was purchased from KAWAKEN Fine Chemicals. Other
reagents were purchased from Tokyo Kasei Kogyo, KANTO
KAGAKU, Kokusan Chemical, Wako Pure Chemical Industries,
Acros Organics, or Aldrich Chemical, and were used as received
unless otherwise noted.
3-ethyl-1-phenylpentan-3-ol was found to provide the corre-
sponding isocyanides in good yields (Table 6, Entries 1 and 2).
The desired products were obtained in high yields by using
phosphinites having a t-butyldiphenylsilyl group and benzo[b]-
furan-2-yl group (Table 6, Entries 3 and 4). On the other hand,
cyanation of an alcohol having a 1-methylindol-2-yl group and
benzylic tertiary alcohol afforded the corresponding isocya-
nides in moderate yield (Table 6, Entries 5 and 6).
In order to examine the stereochemistry of this reaction,
cyanation of an optically active tertiary alcohol, (S)-3-methyl-
1-phenylpentan-3-ol (34), was tried and the inversion of con-
figuration was confirmed similar to the case of a secondary
alcohol such as (R)-4-phenylbutan-2-ol (Scheme 6). The abso-
lute configurations of the isocyanide 36 were determined by
leading to the known lactam 3724 to compare with the sign
of specific rotation reported in the literature.
Conclusion
Cyanation of various alcohols via alkyl diphenylphosphin-
ites was established by a new type of oxidation–reduction con-
densation. Although the cyanation of primary alcohols provid-
ed the corresponding nitriles, isocyanides were formed exclu-
sively in the case when secondary alcohols were treated with
ZnO and tertiary alcohols in the absence of an additive. Con-
cerning the stereochemistry of the reaction, the inversion of
configuration was confirmed when the cyanation of optically
active alcohols was performed.
Preparation of Primary Alkyl Diphenylphosphinites. To a
stirred solution of alcohol (20 mmol) in dehydrated THF (60 mL)
was added a hexane solution of nBuLi (20 mmol) at 0 ꢂC dropwise
under an argon atmosphere. After the solution was stirred for 1 h,
PPh2Cl (20 mmol) was added dropwise. The solution was further
stirred for 1 h, then concentrated in vacuo. After the dilution of the
residue with a mixed solution of hexane (180 mL) and ethyl ace-
tate (20 mL), the suspension was filtered through a pad of alumina
and Celite. The filtrate was concentrated in vacuo to afford the
desired phosphinites.
Experimental
General. Infrared (IR) spectra were recorded on a Shimadzu
FT-IR 8900 spectrometer or a SensIR Technologies TravelIRꢁ
portable FT-IR spectrometer. H NMR spectra were recorded on
1
a JEOL JNM-EX270L (270 MHz) spectrometer; chemical shifts
(ꢀ) are reported in parts per million relative to tetramethylsilane.
Splitting patterns are designated as s, singlet; d, doublet; t, triplet;
q, quartet; m, multiplet; br, broad. 13C NMR spectra were record-
ed on a EX270L (68 MHz) spectrometer with complete proton
decoupling. Chemical shifts are reported in parts per million rela-
Typical Experimental Procedure for Cyanation of Primary
Alkyl Diphenylphosphinites. To a mixture of alkyl diphenyl-
phosphinite (0.75 mmol) and diethyl cyanophosphonate (0.50

K. Masutani et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006) 1111
mmol) was added a chloroform solution (1.5 mL) of 2,6-dimethyl-
1,4-benzoquinone (0.75 mmol) at room temperature under an
argon atmosphere. After 24 h, the reaction mixture was quenched
with saturated aqueous NaHCO3 solution and the aqueous layer
was extracted with dichloromethane. The combined organic layer
was washed with saturated aqueous NaHCO3 solution and with
brine, and then dried over anhydrous Na2SO4. After filtration
and evaporation, the resulting residue was purified by preparative
TLC to afford the corresponding nitrile.
CDCl3) ꢀ 7.6–7.1 (14H, m), 4.83 (2H, d, J ¼ 9:2 Hz); 13C NMR
(68 MHz, CDCl3) ꢀ 141.32 (d, J ¼ 17:8 Hz), 137.12 (d, J ¼ 7:8
Hz), 133.37, 130.55, 130.22, 129.34, 128.69, 128.41, 128.29,
128.20, 70.78 (d, J ¼ 19:5 Hz); HRMS (EI positive) Found: m=z
325.0555. Calcd for C19H1635ClOP ꢁ H: 325.0549.
4-Chlorophenylacetonitrile (4c):29 Colorless oil; IR (KBr)
2941, 2920, 2257, 1493, 1410, 1090, 1015, 912, 841, 799, 664
cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.35 (2H, d, J ¼ 8:6 Hz),
7.26 (2H, d, J ¼ 8:6 Hz), 3.72 (2H, s); 13C NMR (68 MHz, CDCl3)
ꢀ 133.93, 129.14, 129.12, 128.21, 117.32, 23.12; HRMS (EI
positive) Found: m=z 151.0185. Calcd for C8H635ClN: 151.0189.
4-(Trifluoromethyl)benzyl Diphenylphosphinite (5b): Col-
orless oil; IR (ATR) 3056, 2865, 1620, 1587, 1480, 1434, 1419,
1372, 1323, 1162, 1121, 1065, 1043, 1013, 820, 790, 740, 694
cmꢁ1; 1H NMR (270 MHz, CDCl3) ꢀ 7.6–7.1 (14H, m), 4.90 (2H,
d, J ¼ 9:2 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 142.66 (d, J ¼ 8:3
Hz), 141.20 (d, J ¼ 17:9 Hz), 130.59, 130.27, 129.45, 128.21
(d, J ¼ 6:7 Hz), 127.24, 125.20 (q, J ¼ 270:6 Hz), 70.66 (d, J ¼
20:1 Hz); HRMS (EI positive) Found: m=z 359.0811. Calcd for
C20H16F3OP ꢁ H: 359.0813.
Benzyl Diphenylphosphinite (1b):6a Colorless oil; IR (ATR)
3054, 3030, 2926, 2861, 1953, 1887, 1585, 1495, 1479, 1453,
1434, 1373, 1306, 1210, 1179, 1157, 1094, 1079, 1034, 1006,
1
994, 912, 832, 783, 733, 692 cmꢁ1; H NMR (270 MHz, CDCl3)
ꢀ 7.6–7.2 (15H, m), 4.88 (2H, d, J ¼ 9:5 Hz); 13C NMR (68 MHz,
CDCl3) ꢀ 141.52 (d, J ¼ 17:8 Hz), 138.60 (d, J ¼ 8:4 Hz), 130.52,
130.20, 129.23, 128.20 (d, J ¼ 7:3 Hz), 127.61, 127.35, 71.54 (d,
J ¼ 19:5 Hz); HRMS (EI positive) Found: m=z 291.0941. Calcd
for C19H17OP ꢁ H: 291.0939.
Phenylacetonitrile (1c):25
Colorless oil; IR (KBr) 3067,
3034, 2922, 2343, 2251, 1956, 1603, 1587, 1497, 1456, 1416,
1339, 1186, 1157, 1078, 1030, 1003, 941, 899, 735, 696, 675,
4-(Trifluoromethyl)phenylacetonitrile (5c): Colorless oil;
IR (KBr) 2928, 2252, 2000, 1938, 1717, 1620, 1420, 1327, 1165,
1109, 1067, 1016, 943, 924, 868, 847, 818, 752, 719 cmꢁ1
;
615 cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.4–7.2 (5H, m), 3.76
;
(2H, s); 13C NMR (68 MHz, CDCl3) ꢀ 129.74, 128.97, 127.88,
127.76, 117.77, 23.72; HRMS (EI positive) Found: m=z 117.0573.
Calcd for C8H7N: 117.0578.
1H NMR (270 MHz, CDCl3) ꢀ 7.65 (2H, d, J ¼ 8:4 Hz), 7.47
(2H, d, J ¼ 8:1 Hz), 3.83 (2H, s); 13C NMR (68 MHz, CDCl3) ꢀ
133.76, 130.42 (q, J ¼ 32 Hz), 128.23, 126.02 (q, J ¼ 3:9 Hz),
125.66, 124.04 (q, J ¼ 323 Hz), 23.40; HRMS (EI positive)
Found: m=z 185.0453. Calcd for C9H6F3N: 185.0452.
4-Methylbenzyl Diphenylphosphinite (2b): Colorless oil; IR
(ATR) 3051, 3006, 2920, 2862, 1895, 1616, 1586, 1515, 1479,
1434, 1370, 1307, 1205, 1179, 1095, 1026, 1006, 991, 802, 785,
1
739, 693 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.6–7.0 (14H, m),
2-Phenylethyl Diphenylphosphinite (6b): Colorless oil; IR
(ATR) 3055, 3027, 2942, 2868, 1951, 1885, 1811, 1603, 1586,
1495, 1479, 1453, 1434, 1377, 1305, 1180, 1156, 1092, 1054,
4.81 (2H, d, J ¼ 9:2 Hz), 2.27 (3H, s); 13C NMR (68 MHz,
CDCl3) ꢀ 141.63 (d, J ¼ 17:9 Hz), 137.15, 135.54 (d, J ¼ 8:3 Hz),
130.41, 130.10, 129.06, 128.85, 128.09 (d, J ¼ 6:7 Hz), 127.43,
71.39 (d, J ¼ 19:5 Hz), 21.18; HRMS (EI positive) Found: m=z
305.1113. Calcd for C20H19OP ꢁ H: 305.1095.
1016, 1001, 915, 886, 841, 737, 693 cmꢁ1 1H NMR (270 MHz,
;
CDCl3) ꢀ 7.5–7.2 (15H, m), 4.10 (2H, dt, J ¼ 8:4, 7.3 Hz), 3.03
(2H, t, J ¼ 6:8 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 141.77 (d, J ¼
18:4 Hz), 138.13, 130.37, 130.05, 129.06, 128.94, 128.13 (d, J ¼
8:9 Hz), 126.16, 70.70 (d, J ¼ 19:0 Hz), 38.01 (d, J ¼ 7:3 Hz);
HRMS (EI positive) Found: m=z 306.1180. Calcd for C20H19OP:
306.1174.
3-Phenylpropionitrile (6c):25 Colorless oil; IR (neat) 2868,
2359, 2340, 2245, 1497, 1454, 1423, 1339, 1078, 1030, 976,
905, 746, 700, 669 cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.4–
;
4-Methylphenylacetonitrile (2c):26 Colorless oil; IR (KBr)
3028, 3011, 2924, 2864, 2737, 2251, 1913, 1618, 1516, 1452,
1418, 1381, 1215, 1186, 1119, 1105, 1042, 1022, 953, 912, 839,
799, 752 cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.18 (4H, m),
;
3.68 (2H, s), 2.34 (3H, s); 13C NMR (68 MHz, CDCl3) ꢀ 137.60,
129.57, 127.61, 126.66, 117.97, 23.18, 21.05; HRMS (EI positive)
Found: m=z 131.0737. Calcd for C9H9N: 131.0735.
4-Bromobenzyl Diphenylphosphinite (3b): White solid; mp
50–51 ꢂC; IR (ATR) 3069, 2868, 1966, 1898, 1588, 1480, 1454,
1434, 1402, 1360, 1307, 1280, 1242, 1205, 1128, 1098, 1067,
7.2 (5H, m), 2.95 (2H, t, J ¼ 7:3 Hz), 2.61 (2H, t, J ¼ 7:6 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 137.88, 128.73, 128.12, 127.10,
119.04, 31.58, 19.42; HRMS (EI positive) Found: m=z 131.0741.
Calcd for C9H9N: 131.0735.
1006, 990, 944, 916, 834, 796, 743, 727, 693 cmꢁ1 1H NMR
;
(270 MHz, CDCl3) ꢀ 7.7–7.1 (14H, m), 4.86 (2H, d, J ¼ 9:2 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 141.26 (d, J ¼ 17:8 Hz), 137.58 (d,
J ¼ 7:8 Hz), 131.30, 130.50, 130.18, 129.30, 128.94, 128.21 (d,
J ¼ 7:3 Hz), 121.47, 70.73 (d, J ¼ 20:1 Hz); HRMS (EI positive)
Found: m=z 369.0051. Calcd for C19H1679BrOP ꢁ H: 369.0004.
4-Bromophenylacetonitrile (3c):27 White solid; mp 48–49 ꢂC
(lit.28 mp 47.5–48.5 ꢂC); IR (KBr) 2963, 2926, 2249, 1591, 1487,
1460, 1412, 1315, 1103, 1067, 1013, 926, 905, 837, 824,
3-Phenylpropyl Diphenylphosphinite (7b): Colorless oil; IR
(ATR) 3055, 2939, 2865, 2359, 1766, 1726, 1662, 1587, 1551,
1495, 1480, 1434, 1382, 1091, 1025, 938, 783, 738, 693 cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.6–7.1 (15H, m), 3.88 (2H, dt, J ¼
8:9, 6.5 Hz), 2.71 (2H, d, J ¼ 7:6 Hz), 2.00 (2H, m); 13C NMR
(68 MHz, CDCl3) ꢀ 142.03 (d, J ¼ 17:9 Hz), 141.52, 130.05,
129.11, 128.34, 128.22, 128.13, 125.70, 69.37 (d, J ¼ 6:8 Hz),
33.14 (d, J ¼ 7:8 Hz), 32.20, 30.36; HRMS (EI positive) Found:
m=z 320.1317. Calcd for C21H21OP: 320.1330.
791 cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.50 (2H, d, J ¼ 8:4
Hz), 7.10 (2H, d, J ¼ 8:1 Hz), 3.71 (2H, s); 13C NMR (68 MHz,
CDCl3) ꢀ 132.09, 129.44, 128.73, 121.99, 117.22, 23.20; HRMS
(EI positive) Found: m=z 194.9686. Calcd for C8H679BrN:
194.9684.
4-Phenylbutyronitrile (7c):30 Colorless oil; IR (KBr) 3086,
3063, 3028, 3005, 2939, 2866, 2247, 1603, 1497, 1456, 1423,
1
1350, 1082, 1030, 912, 845, 800, 748, 700 cmꢁ1; H NMR (270
MHz, CDCl3) ꢀ 7.4–7.1 (5H, m), 2.77 (2H, t, J ¼ 7:3 Hz), 2.31
(2H, t, J ¼ 7:0 Hz), 2.1–1.9 (2H, m); 13C NMR (68 MHz, CDCl3)
ꢀ 139.53, 128.51, 128.30, 126.35, 119.39, 34.37, 26.93, 16.42;
HRMS (EI positive) Found: m=z 145.0895. Calcd for C10H11N:
145.0891.
4-Chlorobenzyl Diphenylphosphinite (4b): White solid; mp
39–41 ꢂC; IR (ATR) 3069, 2943, 2866, 1898, 1593, 1484, 1454,
1434, 1404, 1360, 1307, 1275, 1241, 1206, 1090, 1068, 1008, 989,
944, 916, 837, 799, 743, 729, 712, 694 cmꢁ1; 1H NMR (270 MHz,

1112 Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006)
Cyanation of Alcohols
2-Phenylpropyl Diphenylphosphinite (8b): Colorless oil; IR
(ATR) 3055, 3028, 2963, 2927, 2868, 1951, 1886, 1602, 1586,
1493, 1480, 1452, 1434, 1384, 1305, 1180, 1156, 1094, 1067,
C15H19NO2: 245.1416.
Preparation of Secondary Alkyl Diphenylphosphinites. To
a stirred solution of alcohol (20 mmol) and DMAP (4-dimethyl-
aminopyridine) (6 mmol) in dehydrated THF (40 mL) was added
Et3N (24 mmol), and then PPh2Cl (22 mmol) was dropped into
the solution under an argon atmosphere. After stirring at rt for
2 h, the white slurry was concentrated in vacuo. After dilution
of the residue with a mixed solution of hexane (180 mL) and ethyl
acetate (20 mL), the suspension was filtered through a pad of alu-
mina and Celite. To remove a trace amount of DMAP, the filtrate
was concentrated and filtered through a pad of alumina and Celite
again. The filtrate was concentrated in vacuo to afford the desired
phosphinites.
Typical Experimental Procedure for Cyanation of Secon-
dary Alkyl Diphenylphosphinites. To a stirred suspension of
dry ZnO (0.50 mmol), alkyl diphenylphosphinite (0.75 mmol),
and diethyl cyanophosphonate (0.50 mmol) was added a dichloro-
methane solution (0.50 mL) of 2,6-dimethyl-1,4-benzoquinone
(0.75 mmol) at room temperature under an argon atmosphere. Af-
ter 24 h, the reaction mixture was quenched with saturated aque-
ous NaHCO3 solution and the aqueous layer was extracted with
dichloromethane. The combined organic layer was washed with
saturated aqueous NaHCO3 solution and with brine, and then
dried over anhydrous Na2SO4. After filtration and evaporation,
the resulting residue was purified by preparative TLC to afford
the corresponding isocyanide.
1013, 1000, 907, 798, 739, 693 cmꢁ1
;
1H NMR (270 MHz,
CDCl3) ꢀ 7.6–7.0 (15H, m), 4.0–3.7 (2H, m), 3.2–3.0 (1H, m),
1.30 (3H, d, J ¼ 7:0 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 143.53,
141.85 (d, J ¼ 17:9 Hz), 130.32, 130.27, 129.99, 129.95, 129.01,
128.97, 128.18, 128.12, 128.09, 128.02, 128.00, 127.37, 126.27,
75.39 (d, J ¼ 18:4 Hz), 41.44 (d, J ¼ 7:3 Hz), 18.07; HRMS (EI
positive) Found: m=z 320.1349. Calcd for C21H21OP: 320.1330.
3-Phenylbutyronitrile (8c):31 Colorless oil; IR (KBr) 3063,
3030, 2968, 2932, 2878, 2835, 2247, 1954, 1881, 1811, 1602,
1583, 1497, 1454, 1421, 1383, 1358, 1329, 1312, 1097, 1067,
1016, 999, 914, 764, 700 cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ
7.4–7.2 (5H, m), 3.16 (1H, m), 2.59 (2H, m), 1.46 (3H, d, J ¼
6:8 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 142.98, 128.74, 127.21,
126.42, 118.48, 36.57, 26.42, 20.74; HRMS (EI positive) Found:
m=z 145.0895. Calcd for C10H11N: 145.0891.
2-(4-Methoxybenzyloxy)ethyl Diphenylphosphinite (9b):
Colorless oil; IR (ATR) 3052, 3002, 2928, 2861, 1887, 1611,
1586, 1511, 1461, 1434, 1374, 1356, 1301, 1245, 1174, 1097,
1056, 1033, 922, 843, 817, 738, 695 cmꢁ1 1H NMR (270 MHz,
;
CDCl3) ꢀ 7.6–7.2 (10H, m), 7.19 (2H, d, J ¼ 6:8 Hz), 6.83 (2H,
d, J ¼ 6:5 Hz), 4.42 (2H, s), 4.1–3.9 (2H, m), 3.77 (3H, s), 3.7–
3.6 (2H, m); 13C NMR (68 MHz, CDCl3) ꢀ 158.96, 141.92 (d,
J ¼ 17:8 Hz), 130.39, 130.17, 130.07, 129.11, 129.07, 128.11
(d, J ¼ 6:6 Hz), 113.62, 72.74, 70.02 (d, J ¼ 7:3 Hz), 69.40 (d,
J ¼ 19:0 Hz), 55.24; HRMS (EI positive) Found: m=z 366.1378.
Calcd for C22H23O3P: 366.1385.
4-Phenylbutan-2-yl Diphenylphosphinite (13b): White sol-
id; mp 37–38 ꢂC; IR (ATR) 3055, 3027, 2961, 2933, 2868, 1602,
1491, 1478, 1453, 1434, 1373, 1349, 1311, 1191, 1124, 1097,
3-(4-Methoxybenzyloxy)propionitrile (9c): Colorless oil; IR
(ATR) 2936, 2872, 2251, 1612, 1586, 1512, 1462, 1413, 1361,
1302, 1245, 1175, 1097, 1031, 913, 820, 754, 731 cmꢁ1; 1H NMR
(270 MHz, CDCl3) ꢀ 7.26 (2H, t, J ¼ 6:2 Hz), 6.88 (2H, d, J ¼ 8:6
Hz), 4.49 (2H, s), 3.79 (3H, s), 3.63 (2H, t, J ¼ 6:5 Hz), 2.58 (2H,
t, J ¼ 6:2 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 159.21, 129.20,
129.11, 117.70, 113.75, 72.82, 64.17, 55.21, 18.87; HRMS (EI
positive) Found: m=z 191.0942. Calcd for C11H13NO2: 191.0946.
2-Phenyl-3-(tetrahydropyran-2-yloxy)propyl Diphenylphos-
phinite (10b): Colorless oil; IR (ATR) 3055, 2939, 2869, 1737,
1603, 1494, 1479, 1453, 1434, 1380, 1352, 1322, 1280, 1260,
1200, 1182, 1156, 1133, 1121, 1073, 1024, 997, 970, 905, 869,
812, 739, 694 cmꢁ1; 1H NMR (270 MHz, CDCl3) ꢀ 7.1–7.5 (15H,
m), 4.6–4.5 (1H, m), 4.3–4.0 (3H, m), 3.7–3.6 (2H, m), 3.5–3.2
(2H, m), 1.9–1.3 (6H, m); 13C NMR (68 MHz, CDCl3) ꢀ 142.00,
141.97, 141.95, 141.73, 141.69, 141.68, 140.35, 140.34, 140.28,
140.26, 130.41, 130.39, 130.30, 130.28, 130.26, 130.09, 130.07,
129.99, 129.95, 129.93, 129.05, 129.00, 128.94, 128.32, 128.11,
128.01, 128.00, 127.98, 126.58, 98.70, 98.47, 71.12, 71.08, 71.07,
70.84, 70.80, 68.19, 67.90, 67.88, 61.77, 61.64, 47.52, 47.50,
47.46, 47.45, 47.41, 47.38, 47.35, 47.33, 30.55, 30.52, 30.51,
25.51, 25.50; HRMS (EI positive) Found: m=z 420.1863. Calcd
for C26H29O3P: 420.1854.
1080, 1049, 1017, 937, 911, 886, 791, 741, 723, 696 cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.7–7.0 (15H, m), 4.2–4.0 (1H,
m), 2.8–2.5 (2H, m), 2.1–1.7 (2H, m), 1.31 (3H, d, J ¼ 6:5 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 143.01 (d, J ¼ 16:7 Hz), 142.54
(d, J ¼ 16:1 Hz), 141.89, 130.57, 130.25, 130.10, 129.79, 129.08,
128.83, 128.19, 128.14, 128.10, 128.03, 125.61, 76.96 (d, J ¼
20:6 Hz), 40.12 (d, J ¼ 5:6 Hz), 31.89, 22.42 (d, J ¼ 5:6 Hz);
HRMS (EI positive) Found: m=z 334.1497. Calcd for C22H23OP:
334.1487.
4-Phenylbutan-2-yl Isocyanide (13c):
Colorless oil; IR
(ATR) 3063, 3028, 2984, 2936, 2862, 2137, 1734, 1717, 1699,
1684, 1650, 1604, 1558, 1541, 1521, 1496, 1454, 1382, 1347,
1185, 1129, 1052, 1031, 918, 858, 798, 775, 743, 698 cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.4–7.1 (5H, m), 3.6–3.5 (1H, m),
2.9–2.6 (2H, m), 2.0–1.7 (2H, m), 1.38 (3H, dt, J ¼ 6:8, 2.2 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 154.57 (t, J ¼ 5:0 Hz), 140.02,
128.41, 128.25, 126.14, 49.42 (t, J ¼ 5:6 Hz), 38.31, 31.94, 21.69.
2-Methyl-4-phenylbutyronitrile (14):32
Colorless oil; IR
(ATR) 3028, 2981, 2936, 2863, 2239, 1603, 1496, 1454, 1383,
1123, 1051, 1030, 742, 699 cmꢁ1 1H NMR (270 MHz, CDCl3)
;
ꢀ 7.4–7.1 (5H, m), 2.9–2.6 (2H, m), 2.6–2.5 (1H, m), 2.0–1.7
(2H, m), 1.32 (3H, d, J ¼ 7:0 Hz); 13C NMR (68 MHz, CDCl3)
ꢀ 139.98, 128.50, 128.27, 126.67, 122.65, 35.76, 33.21, 24.89,
18.06; HRMS (EI positive) Found: m=z 159.1049. Calcd for
C11H13N: 159.1048.
3-Phenyl-4-(tetrahydropyran-2-yloxy)butyronitrile (10c):
Colorless oil; IR (ATR) 2942, 2870, 2246, 1496, 1454, 1440,
1385, 1352, 1322, 1280, 1260, 1201, 1183, 1155, 1123, 1071,
1-Phenylpropan-2-yl Diphenyphosphinite (15b): Colorless
oil; IR (ATR) 3055, 3027, 2970, 2927, 1951, 1587, 1495, 1480,
1452, 1434, 1376, 1351, 1303, 1212, 1180, 1126, 1093, 1068,
1029, 977, 904, 869, 814, 759, 732, 700 cmꢁ1 1H NMR (270
;
MHz, CDCl3) ꢀ 7.4–7.2 (5H, m), 4.7–4.5 (1H, m), 4.1–3.9 (1H,
m), 3.8–3.4 (3H, m), 3.3–3.2 (1H, m), 3.0–2.6 (2H, m), 1.9–1.4
(6H, m); 13C NMR (68 MHz, CDCl3) ꢀ 139.07, 139.00, 128.66,
127.56, 127.36, 127.34, 118.45, 99.26, 98.47, 69.76, 69.27, 62.32,
62.03, 42.31, 42.28, 30.47, 30.43, 25.35, 21.28, 21.23, 19.43,
19.26; HRMS (EI positive) Found: m=z 245.1413. Calcd for
1061, 998, 948, 879, 859, 738, 693 cmꢁ1 1H NMR (270 MHz,
;
CDCl3) ꢀ 7.6–7.1 (15H, m), 4.4–4.1 (1H, m), 3.02 (1H, dd, J ¼
13:5, 6.8 Hz), 2.81 (1H, dd, J ¼ 13:5, 6.5 Hz), 1.28 (3H, d, J ¼
6:2 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 142.86, 142.62, 142.36,
142.12, 138.24, 130.33, 130.24, 130.02, 129.91, 129.50, 128.91,

K. Masutani et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006) 1113
128.81, 128.12, 128.04, 127.94, 126.09, 78.26 (d, J ¼ 20:6 Hz),
44.91 (d, J ¼ 5:6 Hz), 22.00 (d, J ¼ 5:0 Hz); HRMS (EI positive)
Found: m=z 320.1315. Calcd for C21H21OP: 320.1330.
0.14; HRMS (EI positive) Found: m=z 512.2296. Calcd for
C32H37O2PSi: 512.2300.
4-(t-Butyldiphenylsilyloxy)butan-2-yl Isocyanide (18c): Col-
orless oil; IR (ATR) 3070, 2955, 2933, 2858, 2139, 1589, 1471,
1427, 1388, 1360, 1348, 1261, 1227, 1187, 1107, 1088, 995,
1-Phenylpropan-2-yl Isocyanide (15c):
Colorless oil; IR
(ATR) 3030, 2986, 2928, 2140, 1603, 1494, 1453, 1381, 1347,
1277, 1206, 1090, 1076, 1032, 909, 738, 699 cmꢁ1; 1H NMR (270
MHz, CDCl3) ꢀ 7.4–7.1 (5H, m), 3.9–3.7 (1H, m), 3.0–2.7 (2H,
m), 1.37 (3H, dt, J ¼ 6:5, 2.2 Hz); 13C NMR (68 MHz, CDCl3)
ꢀ 154.99 (t, J ¼ 5:0 Hz), 135.89, 128.96, 128.24, 126.84, 51.31
(t, J ¼ 5:0 Hz), 42.77, 21.05.
983, 937, 902, 874, 821, 765, 735, 700, 689 cmꢁ1 1H NMR
;
(270 MHz, CDCl3) ꢀ 7.7–7.6 (4H, m), 7.5–7.3 (6H, m), 4.0–3.6
(3H, m), 2.8–2.7 (2H, m), 1.37 (3H, dt, J ¼ 6:5, 2.2 Hz), 1.03
(9H, s); 13C NMR (68 MHz, CDCl3) ꢀ 154.46 (t, J ¼ 5:0 Hz),
135.33, 135.28, 133.21, 133.01, 129.63, 129.61, 127.62, 127.59,
56.69, 46.95 (t, J ¼ 5:6 Hz), 39.47, 26.84, 21.71, 19.23.
1-Phenylpentan-3-yl Diphenylphosphinite (16b): Colorless
oil; IR (ATR) 3057, 3026, 2962, 2933, 2874, 1949, 1734, 1602,
1494, 1479, 1454, 1434, 1360, 1304, 1232, 1179, 1094, 1066,
1024, 963, 940, 828, 739, 694 cmꢁ1; 1H NMR (270 MHz, CDCl3)
ꢀ 7.6–7.0 (15H, m), 4.0–3.8 (1H, m), 2.7–2.4 (2H, m), 2.0–1.5
(4H, m), 0.87 (3H, t, J ¼ 7:3 Hz); 13C NMR (68 MHz, CDCl3) ꢀ
143.08 (d, J ¼ 6:1 Hz), 142.84 (d, J ¼ 6:7 Hz), 142.05, 130.55,
130.24, 130.22, 129.92, 129.03, 128.83, 128.18, 128.17, 128.10,
128.08, 128.00, 125.58, 82.47 (d, J ¼ 19:0 Hz), 37.31 (d, J ¼
5:0 Hz), 31.71, 28.84 (d, J ¼ 5:6 Hz), 9.86; HRMS (EI positive)
Found: m=z 348.1657 Calcd for C23H25OP: 348.1643.
4-(Benzo[b]furan-2-yl)butan-2-yl Diphenylphosphinite (19b):
Colorless oil; IR (ATR) 3054, 2968, 2926, 1600, 1587, 1478,
1454, 1434, 1376, 1349, 1305, 1252, 1194, 1169, 1127, 1096,
1063, 1005, 959, 935, 890, 822, 798, 736, 694 cmꢁ1 1H NMR
;
(270 MHz, CDCl3) ꢀ 7.6–7.0 (14H, m), 6.20 (1H, m), 4.2–4.0
(1H, m), 2.9–2.6 (2H, m), 2.2–1.9 (2H, m), 1.32 (3H, d, J ¼ 6:2
Hz); 13C NMR (68 MHz, CDCl3) ꢀ 158.87, 154.45, 142.84 (d,
J ¼ 16:2 Hz), 142.37 (d, J ¼ 16:7 Hz), 130.64, 130.32, 130.11,
129.79, 129.17, 128.86, 128.75, 128.23, 128.13, 128.04, 123.00,
122.27, 120.10, 110.60, 102.02, 76.37 (d, J ¼ 20:7 Hz), 36.12 (d,
J ¼ 6:1 Hz), 24.68, 22.32 (d, J ¼ 5:0 Hz); HRMS (EI positive)
Found: m=z 374.1420. Calcd for C24H23O2P: 374.1436.
1-Phenylpentan-3-yl Isocyanide (16c):
(ATR) 3028, 2970, 2935, 2136, 1603, 1495, 1454, 1384, 1355,
1179, 1114, 1059, 1029, 990, 917, 883, 847, 806, 749, 699 cmꢁ1
Colorless oil; IR
.
4-(Benzo[b]furan-2-yl)butan-2-yl Isocyanide (19c): Color-
less oil; IR (ATR) 2985, 2939, 2137, 1725, 1602, 1588, 1453,
1383, 1347, 1252, 1194, 1169, 1130, 1104, 1067, 1008, 941,
1H NMR (270 MHz, CDCl3) ꢀ 7.4–7.1 (5H, m), 3.5–3.3 (1H, m),
3.0–2.6 (2H, m), 2.0–1.7 (2H, m), 1.7–1.5 (2H, m), 1.03 (3H, t,
J ¼ 7:3 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 155.14 (t, J ¼ 5:6 Hz),
140.11, 128.38, 128.23, 126.09, 55.82 (t, J ¼ 5:6 Hz), 36.25,
31.95, 28.18, 10.12.
1
880, 854, 805, 747 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.6–7.3
(2H, m), 7.3–7.1 (2H, m), 6.44 (1H, s), 3.8–3.5 (1H, m), 3.1–
2.8 (2H, m), 2.1–1.9 (2H, m), 1.38 (3H, dt, J ¼ 6:8, 2.2 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 155.11 (t, J ¼ 4:5 Hz), 154.50,
128.42, 123.35, 122.47, 120.22, 110.63, 102.87, 49.43 (t, J ¼
5:6 Hz), 34.60, 24.89, 21.59.
4-(1-Methylindol-2-yl)butan-2-yl Diphenylphosphinite (20b):
Colorless oil; IR (ATR) 3051, 2965, 2927, 1545, 1468, 1433,
1402, 1375, 1343, 1312, 1233, 1125, 1095, 1059, 1026, 1013, 955,
940, 888, 847, 770, 736, 695 cmꢁ1; 1H NMR (270 MHz, CDCl3) ꢀ
7.6–7.0 (14H, m), 6.16 (1H, m), 4.3–4.1 (1H, m), 3.49 (3H, m),
2.9–2.6 (2H, m), 2.2–1.9 (2H, m), 1.37 (3H, d, J ¼ 6:2 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 142.81 (d, J ¼ 16:2 Hz), 142.44
(d, J ¼ 16:2 Hz), 140.44, 137.10, 130.78, 130.46, 129.98, 129.67,
129.24, 128.82, 128.13, 128.04, 127.66, 120.39, 119.59, 119.06,
108.56, 98.43, 76.96 (d, J ¼ 21:2 Hz), 37.01 (d, J ¼ 5:6 Hz),
22.99, 22.48 (d, J ¼ 4:5 Hz); HRMS (EI positive) Found: m=z
387.1763. Calcd for C25H26NOP: 387.1752.
4-(4-Methoxybenzyloxy)butan-2-yl Diphenylphosphinite
(17b): Colorless oil; IR (ATR) 3053, 2963, 2931, 2860, 1611,
1586, 1512, 1478, 1457, 1435, 1373, 1362, 1301, 1245, 1207,
1174, 1091, 1032, 971, 936, 883, 819, 738, 695 cmꢁ1
;
1H NMR
(270 MHz, CDCl3) ꢀ 7.5–7.3 (10H, m), 7.19 (2H, d, J ¼ 8:6 Hz),
6.84 (2H, d, J ¼ 8:6 Hz), 4.26 (3H, s), 3.79 (3H, s), 3.46 (2H, d,
J ¼ 6:2 Hz), 2.0–1.7 (2H, m), 1.27 (3H, d, J ¼ 5:7 Hz); 13C NMR
(68 MHz, CDCl3) ꢀ 158.87, 143.00 (d, J ¼ 16:7 Hz), 142.50 (d,
J ¼ 16:7 Hz), 130.61, 130.39, 130.28, 130.08, 129.76, 129.16,
129.04, 128.77, 128.14, 128.09, 128.04, 128.00, 113.60, 74.78 (d,
J ¼ 21:2 Hz), 72.57, 66.54, 55.26, 38.43 (d, J ¼ 5:6 Hz), 22.66 (d,
J ¼ 5:0 Hz); HRMS (EI positive) Found: m=z 394.1711. Calcd for
C24H27O3P: 394.1698.
4-(4-Methoxybenzyloxy)butan-2-yl Isocyanide (17c): Col-
orless oil; IR (ATR) 2937, 2865, 2139, 1612, 1586, 1512, 1460,
1365, 1301, 1245, 1174, 1091, 1032, 816, 755, 708 cmꢁ1
;
4-(1-Methylindol-2-yl)butan-2-yl Isocyanide (20c): Color-
less oil; IR (ATR) 3052, 2982, 2936, 2137, 1611, 1546, 1467,
1341, 1313, 1233, 1206, 1165, 1128, 1098, 1062, 1011, 921, 843,
1H NMR (270 MHz, CDCl3) ꢀ 7.25 (2H, d, J ¼ 8:4 Hz), 6.88 (2H,
d, J ¼ 8:6 Hz), 4.46 (1H, d, J ¼ 11:3 Hz), 4.41 (1H, d, J ¼ 11:3
Hz), 4.0–3.8 (1H, m), 3.79 (3H, s), 3.7–3.5 (2H, m), 1.9–1.7
(2H, m), 1.36 (3H, dt, J ¼ 6:8, 2.2 Hz); 13C NMR (68 MHz,
CDCl3) ꢀ 159.01, 154.28 (t, J ¼ 5:0 Hz), 129.87, 129.12, 113.65,
72.85, 65.60, 55.19, 47.31 (t, J ¼ 5:6 Hz), 36.91, 21.63.
1
809, 776, 745, 681 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.6–7.5
(1H, m), 7.3–7.0 (3H, m), 6.25 (1H, s), 3.8–3.6 (1H, m), 3.64
(3H, s), 3.0–2.8 (2H, m), 2.1–1.8 (2H, m), 1.40 (3H, dt, J ¼ 7:0,
1.9 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 155.01 (t, J ¼ 5:6 Hz),
138.40, 137.19, 127.46, 120.78, 119.68, 119.29, 108.73, 99.0,
49.53 (t, J ¼ 5:6 Hz), 35.45, 29.44, 22.99, 21.66.
4-(t-Butyldiphenylsilyloxy)butan-2-yl Diphenylphosphinite
(18b): Colorless oil; IR (ATR) 3070, 3051, 2959, 2930, 2857,
1889, 1588, 1472, 1429, 1378, 1360, 1305, 1263, 1231, 1186,
1-Phenylethyl Diphenylphosphinite (21b): Colorless oil; IR
(ATR) 3055, 2973, 2882, 1953, 1586, 1492, 1480, 1449, 1434,
1370, 1357, 1326, 1304, 1285, 1206, 1157, 1091, 1063, 1027,
1010, 995, 924, 780, 738, 693 cmꢁ1; 1H NMR (270 MHz, CDCl3)
ꢀ 7.7–7.2 (15H, m), 5.1–4.9 (1H, m), 1.59 (3H, d, J ¼ 6:5 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 143.83, 143.77, 142.41 (d, J ¼
17:8 Hz), 141.94 (d, J ¼ 16:2 Hz), 130.39, 130.34, 130.07,
130.02, 129.06, 128.89, 128.22, 128.17, 128.12, 128.05, 127.95,
127.35, 125.96, 78.50 (d, J ¼ 20:7 Hz), 25.12 (d, J ¼ 5:6 Hz);
1104, 1088, 1026, 994, 974, 932, 893, 822, 766, 737, 696 cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.7–7.2 (20H, m), 4.4–4.2 (1H, m),
3.8–3.6 (2H, m), 2.0–1.7 (2H, m), 1.28 (3H, d, J ¼ 6:2 Hz), 1.01
(9H, s); 13C NMR (68 MHz, CDCl3) ꢀ 143.62 (d, J ¼ 17:3 Hz),
142.55 (d, J ¼ 16:2 Hz), 135.42, 135.39, 133.81, 133.71, 130.41,
130.17, 130.08, 129.85, 129.42, 129.38, 128.89, 128.79, 128.13,
128.09, 128.03, 128.00, 127.49, 127.47, 77.20, 74.63 (d, J ¼
21:2 Hz), 60.60, 41.23 (d, J ¼ 5:6 Hz), 26.90, 22.68, 19.26,

1114 Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006)
Cyanation of Alcohols
HRMS (EI positive) Found: m=z 306.1188. Calcd for C20H19OP:
306.1174.
preparation of tertiary alkyl diphenylphosphinites was done by a
similar method as for the secondary alkyl diphenylphosphinites
except for the purification step. After concentration of the filtrate,
it was subjected to basic silica-gel column chromatography and
subsequent filtration through a pad of alumina and Celite to afford
the desired phosphinites. The purification step was important for
the reproducibility of the reaction.
Typical Experimental Procedure for Cyanation of Tertiary
Alkyl Diphenylphosphinites. To a stirred mixture of alkyl di-
phenylphosphinite (0.75 mmol) and diethyl cyanophosphonate
(0.50 mmol) was added a dichloromethane solution (0.50 mL) of
2,6-dimethyl-1,4-benzoquinone (1.0 mmol) at room temperature
under an argon atmosphere. After 12 h, the reaction mixture was
quenched with saturated aqueous NaHCO3 solution and the aque-
ous layer was extracted with dichloromethane. The combined or-
ganic layer was washed with saturated aqueous NaHCO3 solution
and with brine, and then dried over anhydrous Na2SO4. After fil-
tration and evaporation, the resulting residue was purified by prep-
arative TLC to afford the corresponding isocyanide.
1-Phenylethyl Isocyanide (21c):33 Colorless oil; IR (ATR)
3034, 2989, 2938, 2139, 1603, 1496, 1451, 1378, 1349, 1279,
1
1202, 1075, 1029, 993, 913, 856, 756, 696 cmꢁ1; H NMR (270
MHz, CDCl3) ꢀ 7.5–7.2 (5H, m), 4.9–4.7 (1H, m), 1.68 (3H, dt,
J ¼ 6:8, 2.2 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 156.02 (t, J ¼
5:6 Hz), 138.37, 128.80, 128.14, 125.26, 53.81 (t, J ¼ 6:7 Hz),
25.20.
(R)-4-Phenylbutan-2-yl Diphenylphosphinite (23): White
17
solid; mp 53–54 ꢂC; ½ꢁꢃD ¼ ꢁ40:9 (c 1.0, CHCl3); IR (ATR)
3069, 2961, 2933, 2869, 1602, 1492, 1479, 1453, 1434, 1373,
1349, 1312, 1191, 1124, 1097, 1080, 1049, 1017, 938, 912, 886,
1
791, 742, 723, 697 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.7–7.0
(15H, m), 4.2–4.0 (1H, m), 2.8–2.5 (2H, m), 2.1–1.7 (2H, m), 1.31
(3H, d, J ¼ 6:2 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 143.03 (d,
J ¼ 16:7 Hz), 142.57 (d, J ¼ 16:1 Hz), 141.90, 130.59, 130.26,
130.12, 129.81, 129.08, 128.81, 128.27, 128.20, 128.14, 128.10,
128.04, 125.62, 76.96 (d, J ¼ 20:6 Hz), 40.12 (d, J ¼ 6:2 Hz),
31.89, 22.41 (d, J ¼ 5:6 Hz); HRMS (EI positive) Found: m=z
334.1498. Calcd for C22H23OP: 334.1487.
2-Methyl-4-phenylbutan-2-yl Diphenylphosphinite (27b):
Colorless oil; IR (ATR) 3055, 3026, 2969, 2932, 2863, 1948,
1603, 1494, 1479, 1454, 1434, 1381, 1366, 1303, 1242, 1204,
1170, 1124, 1094, 1070, 1027, 981, 913, 846, 801, 739, 693
(S)-4-Phenylbutan-2-yl Isocyanide (24):
23
Colorless oil;
½ꢁꢃD ¼ þ97:9 (c 1.0, CHCl3), 96% ee; IR (ATR) 3028, 2984,
2937, 2862, 2137, 1727, 1603, 1495, 1453, 1382, 1347, 1185,
1
cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.6–7.4 (4H, m), 7.4–7.0
;
1129, 1052, 1031, 918, 858, 775, 743, 698 cmꢁ1; H NMR (270
(11H, m), 2.7–2.6 (2H, m), 2.1–1.9 (2H, m), 1.43 (6H, s);
13C NMR (68 MHz, CDCl3) ꢀ 143.56 (d, J ¼ 13:8 Hz), 142.40,
130.10, 129.77, 128.64, 128.21 (d, J ¼ 1:2 Hz), 128.06 (d, J ¼
7:3 Hz), 125.55, 78.44 (d, J ¼ 11:7 Hz), 45.13 (d, J ¼ 5:6 Hz),
30.76, 28.11 (d, J ¼ 9:5 Hz); HRMS (EI positive) Found: m=z
348.1632 Calcd for C23H25OP: 348.1643.
MHz, CDCl3) ꢀ 7.4–7.1 (5H, m), 3.6–3.5 (1H, m), 2.9–2.6
(2H, m), 2.0–1.7 (2H, m), 1.38 (3H, dt, J ¼ 6:8, 2.2 Hz); 13C NMR
(68 MHz, CDCl3) ꢀ 154.59 (t, J ¼ 5:0 Hz), 140.04, 128.43,
128.27, 126.16, 49.44 (t, J ¼ 5:6 Hz), 38.32, 31.96, 21.72; HPLC
analysis: DALCEL CHIRALCEL OJ-H (ꢂ4:6 ꢄ 250 mm),
hexane/isopropyl alcohol = 1000/1, flow rate: 1.0 mL minꢁ1
,
2-Methyl-4-phenylbutan-2-yl Isocyanide (27c): Colorless
oil; IR (ATR) 3028, 2984, 2937, 2866, 2131, 1604, 1496, 1468,
1454, 1391, 1372, 1283, 1218, 1170, 1134, 1074, 1030, 909,
Temp. 25 ꢂC, detector: 254 nm, (R)-4-Phenylbutan-2-yl Isocya-
nide (240) (tR ¼ 21:6 min), (S)-4-Phenylbutan-2-yl Isocyanide
(24) (tR ¼ 23:6 min).
1
881, 752, 697 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.4–7.1 (5H,
3-Phenylpropyl Isocyanide (26): Colorless oil; IR (ATR)
3062, 3027, 2930, 2861, 2147, 1735, 1603, 1496, 1452, 1350,
1243, 1178, 1084, 1030, 1006, 941, 912, 890, 853, 804, 744,
m), 2.9–2.7 (2H, m), 1.9–1.8 (2H, m), 1.47 (6H, t, J ¼ 1:9 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 153.34 (t, J ¼ 5:0 Hz), 140.69,
128.38, 128.18, 125.99, 57.24 (t, J ¼ 5:0 Hz), 44.32, 30.71, 29.00.
2-Methyl-4-phenylbut-1-ene (27d)34 and 3-Methyl-1-phenyl-
but-2-ene (27e):35 Mixture of stereoisomers; Colorless oil; IR
(ATR) 3063, 3027, 2970, 2916, 2857, 1649, 1604, 1494, 1451,
699 cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.4–7.1 (5H, m), 3.4–
;
3.3 (2H, m), 2.79 (2H, t, J ¼ 7:0 Hz), 2.1–1.9 (2H, m); 13C NMR
(68 MHz, CDCl3) ꢀ 155.86 (t, J ¼ 5:6 Hz), 139.54, 128.42,
128.24, 126.21, 40.60 (t, J ¼ 6:2 Hz), 32.10, 28.02.
1376, 1102, 1073, 1029, 982, 886, 854, 773, 737, 696 cmꢁ1
;
(S)-4-Phenylbutan-2-ylamine (25).23
To a cooled (0 ꢂC)
1H NMR (270 MHz, CDCl3) 27d: ꢀ 7.3–7.1 (5H, m), 4.74 (1H,
s), 4.71 (1H, s), 2.75 (2H, t, J ¼ 7:8 Hz), 2.31 (2H, t, J ¼ 8:9
Hz), 1.77 (3H, s); 27e: ꢀ 7.3–7.1 (5H, m), 5.33 (1H, tt, J ¼ 1:4,
7.3 Hz), 3.34 (2H, d, J ¼ 7:6 Hz), 1.74 (3H, s), 1.72 (3H, s);
13C NMR (68 MHz, CDCl3) ꢀ 145.25, 142.07, 141.68, 132.38,
128.23, 128.20, 128.18, 128.17, 125.65, 125.58, 123.08, 110.11,
39.66, 34.41, 34.29, 25.83, 22.70, 17.90; HRMS (EI positive)
Found: m=z 146.1095 Calcd for C11H14: 146.1096.
solution of the isocyanide 24 (56.5 mg, 0.354 mmol) in MeOH
(2.5 mL) was added dropwise 2 M HCl in MeOH (6.0 mL). Water
(125 mL) was added and the resulting solution allowed to warm to
rt and stirred for an additional 1 h. The solvent was removed in
vacuo and 1 M aqueous NaOH solution was added. The mixture
was extracted with AcOEt and the combined organic extracts were
washed with water and brine, dried over anhydrous Na2SO4, fil-
tered, and then concentrated in vacuo. The resulting residue was
purified by preparative TLC (CHCl3/MeOH = 1/1) to afford 25
3-Methyl-1-phenylpentan-3-yl Diphenylphosphinite (28b):
Colorless oil; IR (ATR) 3055, 3024, 2966, 2935, 2877, 1951,
1602, 1587, 1494, 1478, 1454, 1434, 1374, 1333, 1300, 1182,
1156, 1130, 1094, 1069, 1026, 998, 931, 908, 842, 804, 739,
23
(16.2 mg, 31%) as a colorless oil. ½ꢁꢃD ¼ þ7:2 (c 0.49, CHCl3)
20
[Lit.23 ½ꢁꢃD ¼ þ6:4 (c 0.47, CHCl3), 98% ee]; IR (ATR) 3739,
3673, 3649, 3061, 3026, 2954, 2923, 2857, 1868, 1772, 1734,
1716, 1699, 1684, 1650, 1602, 1558, 1542, 1522, 1494, 1454,
1374, 1095, 1063, 1030, 838, 743, 697 cmꢁ1; 1H NMR (270 MHz,
CDCl3) ꢀ 7.3–7.1 (5H, m), 3.0–2.8 (1H, m), 2.8–2.5 (2H, m), 1.9–
1.7 (2H, m), 1.8–1.6 (2H, m), 1.12 (3H, d, J ¼ 6:5 Hz); 13C NMR
(68 MHz, CDCl3) ꢀ 142.06, 128.24, 128.21, 125.64, 46.65, 41.64,
32.83, 23.86; HRMS (EI positive) Found: m=z 149.1194. Calcd for
C10H15N: 149.1204.
693 cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.6–7.4 (4H, m), 7.4–
;
7.0 (11H, m), 2.7–2.5 (2H, m), 2.1–1.9 (2H, m), 1.81 (2H, q,
J ¼ 7:0 Hz), 1.38 (3H, s), 0.90 (3H, t, J ¼ 7:3 Hz); 13C NMR
(68 MHz, CDCl3) ꢀ 143.89, 143.85, 143.66, 143.61, 142.47,
130.19, 130.14, 129.85, 129.81, 128.64, 128.60, 128.19, 128.03
(d, J ¼ 7:3 Hz), 125.55, 80.97 (d, J ¼ 10:0 Hz), 42.18 (d, J ¼
6:2 Hz), 33.24 (d, J ¼ 7:3 Hz), 30.42, 25.34 (d, J ¼ 11:1 Hz),
8.74 (d, J ¼ 1:2 Hz); HRMS (EI positive) Found: m=z 362.1798.
Calcd for C24H27OP: 362.1800.
Preparation of Tertiary Alkyl Diphenylphosphinites. The

K. Masutani et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006) 1115
3-Methyl-1-phenylpentan-3-yl Isocyanide (28c): Colorless
oil; IR (ATR) 3028, 2976, 2939, 2883, 2129, 1603, 1496, 1456,
1383, 1295, 1193, 1157, 1075, 1030, 1005, 928, 904, 864, 824,
945, 878, 800, 748, 682 cmꢁ1; 1H NMR (270 MHz, CDCl3) ꢀ 7.6–
7.3 (2H, m), 7.3–7.1 (2H, m), 6.42 (1H, s), 3.0–2.9 (2H, m), 2.1–
1.9 (2H, m), 1.47 (6H, t, J ¼ 1:6 Hz); 13C NMR (68 MHz, CDCl3)
ꢀ 157.23, 154.45, 153.90 (t, J ¼ 4:5 Hz), 128.51, 123.30, 122.43,
120.23, 110.60, 102.29, 56.98 (t, J ¼ 5:0 Hz), 40.04, 28.93, 23.75.
4-(1-Methylindol-2-yl)-2-methylbutan-2-yl Diphenylphos-
phinite (32b): White solid; mp 81 ꢂC; IR (ATR) 3052, 2965,
1742, 1548, 1467, 1432, 1401, 1384, 1367, 1337, 1317, 1303,
1275, 1248, 1233, 1164, 1138, 1093, 1067, 1023, 1009, 937,
751, 700 cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.4–7.1 (5H, m),
;
2.9–2.7 (2H, m), 2.0–1.5 (4H, m), 1.40 (3H, t, J ¼ 1:6 Hz), 1.04
(3H, t, J ¼ 7:3 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 153.69 (t, J ¼
4:4 Hz), 140.80, 128.36, 128.15, 125.95, 60.87 (t, J ¼ 5:0 Hz),
42.40, 33.79, 30.35, 25.73, 8.23.
3-Ethyl-1-phenylpentan-3-yl Diphenylphosphinite (29b):
Colorless oil; IR (ATR) 3746, 3055, 3024, 2965, 2938, 2878,
1601, 1494, 1477, 1453, 1434, 1377, 1336, 1303, 1212, 1174,
1155, 1093, 1067, 1028, 995, 966, 923, 839, 820, 738, 694
912, 856, 838, 780, 740, 728, 696 cmꢁ1 1H NMR (270 MHz,
;
CDCl3) ꢀ 7.6–7.0 (14H, m), 6.20 (1H, s), 3.53 (3H, s), 2.9–2.7
(2H, m), 2.2–2.0 (2H, m), 1.48 (6H, s); 13C NMR (68 MHz,
CDCl3) ꢀ 143.36 (d, J ¼ 15:7 Hz), 140.98, 137.18, 130.15,
129.82, 128.76, 128.11 (d, J ¼ 7:3 Hz), 127.72, 120.39, 119.60,
119.08, 108.58, 98.30, 78.17 (d, J ¼ 11:7 Hz), 41.83 (d, J ¼ 5:6
Hz), 29.32, 28.12 (d, J ¼ 9:5 Hz), 21.66; HRMS (EI positive)
Found: m=z 401.1917. Calcd for C26H28NOP: 401.1909.
cmꢁ1 1H NMR (270 MHz, CDCl3) ꢀ 7.6–7.4 (4H, m), 7.3–6.9
;
(11H, m), 2.6–2.4 (2H, m), 2.0–1.9 (2H, m), 1.9–1.7 (4H, m),
0.84 (6H, t, J ¼ 7:6 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 143.80 (d,
J ¼ 15:6 Hz), 142.53, 130.24, 129.90, 128.63, 128.16, 128.02 (d,
J ¼ 7:3 Hz), 125.52, 83.42 (d, J ¼ 8:9 Hz), 39.54 (d, J ¼ 6:7 Hz),
29.99 (d, J ¼ 1:2 Hz), 29.79 (d, J ¼ 8:4 Hz), 8.27 (d, J ¼ 1:7 Hz);
HRMS (EI positive) Found: m=z 376.1965. Calcd for C25H29OP:
376.1956.
4-(1-Methylindol-2-yl)-2-methylbutan-2-yl Isocyanide (32c):
Yellow solid; mp 95–97 ꢂC; IR (ATR) 3055, 2986, 2947, 2132,
1936, 1600, 1541, 1466, 1436, 1410, 1391, 1372, 1355, 1334,
1311, 1280, 1222, 1180, 1143, 1130, 1098, 1007, 997, 928, 909,
3-Ethyl-1-phenylpentan-3-yl Isocyanide (29c):
Colorless
1
oil; IR (ATR) 3027, 2973, 2943, 2883, 2128, 1603, 1496, 1455,
1384, 1343, 1204, 1177, 1154, 1077, 1030, 998, 977, 907, 891,
876, 844, 788, 753, 700, 662 cmꢁ1; H NMR (270 MHz, CDCl3)
ꢀ 7.52 (1H, d, J ¼ 7:6 Hz), 7.26 (1H, d, J ¼ 8:1 Hz), 7.16 (1H,
dt, J ¼ 10:5, 1.4 Hz), 7.07 (1H, dt, J ¼ 7:6, 1.1 Hz), 6.24 (1H,
s), 3.67 (3H, s), 3.0–2.8 (2H, m), 2.1–1.9 (2H, m), 1.50 (6H, t,
J ¼ 1:9 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 153.94 (t, J ¼ 5:0
Hz), 139.10, 137.26, 127.57, 120.80, 119.74, 119.31, 108.75,
98.70, 57.17 (t, J ¼ 4:5 Hz), 41.12, 29.53, 29.06, 21.87.
1
828, 751, 700 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.4–7.1 (5H,
m), 2.8–2.6 (2H, m), 1.9–1.8 (2H, m), 1.8–1.6 (4H, m), 1.00
(6H, t, J ¼ 7:3 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 153.99 (t, J ¼
4:5 Hz), 140.93, 128.26, 128.18, 126.00, 64.36 (t, J ¼ 5:0 Hz),
39.15, 30.27, 30.05, 7.94.
5-(t-Butyldiphenylsilyloxy)-2-methylpentan-2-yl Diphenyl-
phosphinite (30b): Colorless oil; IR (ATR) 3068, 3051, 2958,
2930, 2857, 1587, 1472, 1429, 1383, 1365, 1305, 1248, 1214,
1183, 1094, 1054, 1028, 998, 971, 931, 916, 822, 791, 738, 696
2-Phenylpropan-2-yl Diphenylphosphinite (33b): Colorless
oil; IR (ATR) 3061, 2981, 2968, 2923, 1739, 1599, 1493, 1476,
1460, 1446, 1431, 1380, 1363, 1303, 1261, 1192, 1144, 1097,
1067, 1027, 1000, 946, 901, 887, 757, 745, 694 cmꢁ1 1H NMR
;
cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.7–7.6 (4H, m), 7.5–7.2
(270 MHz, CDCl3) ꢀ 7.6–7.4 (6H, m), 7.4–7.2 (9H, m), 1.74 (6H,
d, J ¼ 1:9 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 147.32 (d, J ¼ 2:8
Hz), 143.17 (d, J ¼ 15:7 Hz), 130.29, 129.96, 128.69, 128.05 (d,
J ¼ 7:3 Hz), 126.85, 125.31 (d, J ¼ 1:6 Hz), 79.58 (d, J ¼ 13:9
Hz), 30.43 (d, J ¼ 10:0 Hz); HRMS (EI positive) Found: m=z
320.1315. Calcd for C21H21OP: 320.1330.
2-Phenylpropan-2-yl Isocyanide (33c):36 Colorless oil; IR
(ATR) 3064, 2988, 2937, 2133, 1603, 1497, 1447, 1390, 1369,
1257, 1167, 1107, 1079, 1030, 934, 912, 823, 762, 697 cmꢁ1
;
1H NMR (270 MHz, CDCl3) ꢀ 7.5–7.3 (5H, m), 1.79 (6H, t, J ¼
1:9 Hz); 13C NMR (68 MHz, CDCl3) ꢀ 154.84 (t, J ¼ 4:4 Hz),
141.98, 128.48, 127.55, 123.93 (d, J ¼ 1:7 Hz), 60.56 (t, J ¼
6:2 Hz), 31.92.
(16H, m), 3.62 (2H, t, J ¼ 6:5 Hz), 1.8–1.5 (4H, m), 1.35 (6H,
s), 1.04 (9H, s); 13C NMR (68 MHz, CDCl3) ꢀ 143.69 (d, J ¼
16:1 Hz), 135.44, 133.91, 130.04, 129.71, 129.39, 128.52, 127.99
(d, J ¼ 6:7 Hz), 127.48, 78.59 (d, J ¼ 11:7 Hz), 39.40 (d, J ¼ 6:1
Hz), 28.01 (d, J ¼ 10:0 Hz), 27.69, 26.94, 19.32; HRMS (Record-
ed on a micromass Q-Tof-2 instrument, ESI positive) Found: m=z
541.2684. Calcd for C34H41O2PSi + H: 541.2692.
5-(t-Butyldiphenylsilyloxy)-2-methylpentan-2-yl Isocyanide
(30c): Colorless oil; IR (ATR) 3071, 2934, 2859, 2132, 1589,
1470, 1427, 1389, 1371, 1222, 1179, 1103, 1009, 975, 939, 822,
804, 755, 740, 701, 689 cmꢁ1; 1H NMR (270 MHz, CDCl3) ꢀ 7.7–
7.6 (4H, m), 7.5–7.3 (6H, m), 3.70 (2H, t, J ¼ 5:4 Hz), 1.7–1.5
(4H, m), 1.38 (6H, s), 1.06 (9H, s); 13C NMR (68 MHz, CDCl3)
ꢀ 152.88 (t, J ¼ 3:9 Hz), 135.38, 133.57, 129.49, 127.52, 63.34,
57.16 (t, J ¼ 5:0 Hz), 38.90, 29.02, 27.45, 26.89, 19.24.
(S)-3-Methyl-1-phenylpentan-3-yl Diphenylphosphinite (35):
20
Colorless oil; ½ꢁꢃD ¼ þ3:8 (c 1.0, CHCl3); IR (ATR) 3056, 3025,
2967, 2935, 2878, 1603, 1587, 1495, 1479, 1454, 1434, 1375,
1333, 1301, 1182, 1157, 1131, 1095, 1067, 1026, 998, 931, 908,
4-(Benzo[b]furan-2-yl)-2-methylbutan-2-yl Diphenylphos-
phinite (31b): Colorless oil; IR (ATR) 3054, 2970, 2928, 1600,
1588, 1477, 1454, 1434, 1382, 1366, 1303, 1252, 1205, 1166,
1129, 1098, 1068, 1025, 1007, 933, 909, 846, 817, 797, 739,
1
842, 804, 739, 693 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.6–7.4
(4H, m), 7.4–7.0 (11H, m), 2.7–2.5 (2H, m), 2.1–1.9 (2H, m),
1.81 (2H, q, J ¼ 7:3 Hz), 1.38 (3H, s), 0.90 (3H, t, J ¼ 7:6 Hz);
13C NMR (68 MHz, CDCl3) ꢀ 143.87, 143.82, 143.63, 143.59,
142.48, 130.18, 130.13, 129.84, 129.80, 128.63, 128.60, 128.20,
128.04 (d, J ¼ 7:2 Hz), 125.54, 80.98 (d, J ¼ 10:6 Hz), 42.16 (d,
J ¼ 6:1 Hz), 33.22 (d, J ¼ 7:8 Hz), 30.42, 25.33 (d, J ¼ 11:2 Hz),
8.74 (d, J ¼ 1:2 Hz); HRMS (EI positive) Found: m=z 362.1806.
Calcd for C24H27OP: 362.1800.
1
694 cmꢁ1; H NMR (270 MHz, CDCl3) ꢀ 7.6–7.1 (14H, m), 6.28
(1H, m), 2.9–2.8 (2H, m), 2.2–2.1 (2H, m), 1.45 (6H, s). 13C NMR
(68 MHz, CDCl3) ꢀ 159.19, 154.43, 143.31 (d, J ¼ 15:7 Hz),
130.18, 129.85, 128.80, 128.73, 128.09 (d, J ¼ 6:7 Hz), 122.98,
122.28, 120.07, 110.57, 101.60, 78.00 (d, J ¼ 11:7 Hz), 40.81
(d, J ¼ 5:0 Hz), 27.95 (d, J ¼ 10:0 Hz), 23.55; HRMS (EI posi-
tive) Found: m=z 388.1575. Calcd for C25H25O2P: 388.1592.
4-(Benzo[b]furan-2-yl)-2-methylbutan-2-yl Isocyanide (31c):
Colorless oil; IR (ATR) 2984, 2932, 2131, 1650, 1601, 1590,
1453, 1391, 1372, 1253, 1219, 1170, 1141, 1121, 1105, 1008,
(R)-3-Methyl-1-phenylpentan-3-yl Isocyanide (36): Color-
22
less oil; ½ꢁꢃD ¼ þ14:7 (c 1.0, CHCl3), 78% ee; IR (ATR) 3027,
2976, 2940, 2883, 2128, 1603, 1496, 1456, 1383, 1294, 1193,
1157, 1075, 1030, 1004, 928, 904, 864, 825, 751, 700 cmꢁ1
;

1116 Bull. Chem. Soc. Jpn. Vol. 79, No. 7 (2006)
Cyanation of Alcohols
1H NMR (270 MHz, CDCl3) ꢀ 7.4–7.1 (5H, m), 2.9–2.7 (2H, m),
2.0–1.5 (4H, m), 1.41 (3H, t, J ¼ 1:9 Hz), 1.04 (3H, t, J ¼ 7:3
Hz); 13C NMR (68 MHz, CDCl3) ꢀ 153.58 (t, J ¼ 4:4 Hz), 140.77,
128.33, 128.12, 125.92, 60.84 (t, J ¼ 5:0 Hz), 42.36, 33.77, 30.31,
25.70, 8.19; HPLC analysis: DALCEL CHIRALCEL OD-H
(ꢂ4:6 ꢄ 250 mm), hexane/isopropyl alcohol = 500/1, flow rate:
1.0 mL minꢁ1, Temp. 25 ꢂC, detector: 254 nm, (R)-3-methyl-1-
phenylpentan-3-yl isocyanide (36) (tR ¼ 18:6 min), (S)-3-methyl-
1-phenylpentan-3-yl isocyanide (360) (tR ¼ 24:1 min).
This study was supported in part by the Grant of the 21st
Century COE Program, Ministry of Education, Culture, Sports,
Science and Technology (MEXT). We thank Dr. Shigeru
Nakajima, Dr. Hirokazu Ohsawa, Mr. Atsushi Hirano, Ms.
Ikuko Nishimura, and Ms. Chihiro Suzuki, Banyu Pharmaceut-
ical Company, for NMR analysis, high resolution mass spec-
trometry analysis, HPLC analysis, IR analysis, and optical
rotation analysis, respectively.
Preparation of (R)-5-Ethyl-5-methyltetrahydropyrrol-2-one
(37). To a cooled (0 ꢂC) solution of the isocyanide 36 (200.0 mg,
1.07 mmol) in MeOH (4.0 mL) was added dropwise 2 M HCl in
MeOH (8.0 mL). Water (200 mL) was added and the resulting solu-
tion was allowed to warm to rt and further stirred for 11 h. The sol-
vent was removed in vacuo and 1 M aqueous NaOH solution was
added. The mixture was extracted with AcOEt and the combined
organic extracts were washed with water and brine, dried over an-
hydrous Na2SO4, filtered, and then concentrated in vacuo to afford
(R)-3-methyl-1-phenylpentane-3-ylamine as a crude product.
To a stirred solution of the crude amine, DMAP (13.4 mg, 0.11
mmol), and Et3N (0.45 mL, 3.21 mmol) in THF (5.0 mL) was add-
ed di-t-butyl dicarbonate (0.49 mL, 2.14 mmol) dropwise at 0 ꢂC,
and the reaction mixture was heated at reflux for 5 h. The solvent
was evaporated in vacuo, and saturated aqueous NaHCO3 solution
was added. The mixture was extracted with diethyl ether and the
combined organic extracts were washed with water and brine,
dried over anhydrous Na2SO4, filtered, and then concentrated in
vacuo. The obtained crude product was purified by preparative
TLC (hexane/AcOEt = 5/1) to give (R)-3-methyl-1-phenylpen-
tan-3-ylcarbamic acid t-butyl ester (239 mg, 81%) as a colorless
Supporting Information
Experimental procedures, characterization data, and references
to known compounds for 9a, 10a, 16a–20a, 29a–32a, and 34. This
material is available free of charge on the web at http://www.
csj.jp/journals/bcsj/.
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oil. ½ꢁꢃD ¼ þ6:8 (c 1.0, CHCl3); IR (ATR) 3362, 3025, 2970,
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7.3–7.1 (5H, m), 4.36 (1H, brs), 2.55 (2H, t, J ¼ 9:5 Hz), 2.1–1.5
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29
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