Conversion of tertiary alcohols to tert-alkyl azides by way of quinone-mediated oxidation-reduction condensation using alkyl diphenylphosphinites

Article abstract of DOI:10.1016/j.tet.2007.03.176

A novel method for the preparation of alkyl azides from alcohols by way of oxidation-reduction condensation is described. In this reaction, the sterically-hindered tert-alkyl phosphinites that are prepared from the corresponding alcohols are converted int

Full text of DOI:10.1016/j.tet.2007.03.176

Tetrahedron 63 (2007) 6358–6364
Conversion of tertiary alcohols to tert-alkyl azides by way of
quinone-mediated oxidation–reduction condensation
using alkyl diphenylphosphinites
b,c,
Kiichi Kuroda,a Yujiro Hayashia, and Teruaki Mukaiyama
*
*
aDepartment of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science,
Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
bCenter for Basic Research, The Kitasato Institute, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003, Japan
cKitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
Received 27 January 2007; revised 30 March 2007; accepted 30 March 2007
Available online 6 April 2007
Abstract—A novel method for the preparation of alkyl azides from alcohols by way of oxidation–reduction condensation is described. In this
reaction, the sterically-hindered tert-alkyl phosphinites that are prepared from the corresponding alcohols are converted into tert-alkyl azides
with almost complete inversion of their stereochemistry: the obtained alkyl azides are then successfully reduced to afford the corresponding
amines on treatment with LiAlH4, thus, a versatile method for the preparation of chiral amines from the corresponding chiral alcohols is
established.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
our laboratory,11 where almost complete stereochemical in-
version was observed even in the case of bulky tert-alkyl
phosphinites. This method was then successfully applied
to the preparation of ethers,12 sulfides,13 cyanides10b,14 or
isocyanides,14 and to the alkylation of HC(CO2Et)3.15
Also, C–N bond forming reactions of alkyl phosphinites
using phthalimide16 or nitrobenzenesulfonamide17 as a nitro-
gen nucleophile were reported. In the cases of tert-alkyl
phosphinites, however, the yield of the corresponding N-
alkyl phthalimides or N-alkyl sulfonamides was poor. There-
fore, it was desired to develop a new and efficient method
for the stereospecific conversion of tert-alkyl alcohols into
the corresponding amine derivatives. Since the bulkiness
of N-nucleophile is considered to retard the nucleophilic
substitution to tert-alkyl phosphinites, less sterically de-
manding N-nucleophile should be required in order to
perform this process. Therefore, an azide anion (Nꢀ3 ) was
chosen as a small nucleophile. Treatment of the azide anion
with phosphinites in the presence of quinone derivatives
gives the zwitterionic intermediate A as shown in Scheme
1. This intermediate reacts with the azide anion to afford
the inverted azide 2 together with the phosphinate 3.
Since an azide1 is frequently used for introducing an amino
group and the construction of a heterocyclic skeleton, con-
version of an alcohol to its corresponding azide is one of
the most important functional group transformations in or-
ganic synthesis.2 The most fundamental method for azida-
tion is the Mitsunobu reaction,3 using hydrogen azide as
an azide source.4 There are some more alternative methods
using diphenyl phosphorazidate (DPPA),5 zinc azide/bis-
pyridine complex,6 DPPA/DBU,7 and so forth.8 These
methods are widely applied to primary and secondary alco-
hols, in which the reactions proceed via SN2 manner and
afford azides with complete inversion of their stereochemis-
tries. However, only a few examples8d,9 have been reported
on the conversion of sterically-hindered tertiary alcohols to
the corresponding azides, much less the azidation of chiral
tertiary alcohols with inversion in their configurations.
Recently, a new type of oxidation–reduction condensation10
of carboxylic acids with alkyl phosphinites that were readily
prepared from the corresponding alcohols in the presence of
2,6-dimethyl-1,4-benzoquinone (DMBQ) was reported from
Recently, a novel method for a preparation of the tert-alkyl
azides based on the oxidation–reduction condensation using
a quinone derivative and trimethylsilyl azide (TMSN3) as an
azide source was reported from our laboratory.18 In this
paper, we would like to report our further study on this reac-
tion to examine the scope and limitation.
Keywords: Oxidation–reduction condensation; Alkyl diphenylphosphinite;
Quinone; Trimethylsilyl azide.
* Corresponding authors. Tel.: +81 339113138; fax: +81 339113482;
e-mail: mukaiyam@abeam.ocn.ne.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.176

K. Kuroda et al. / Tetrahedron 63 (2007) 6358–6364
6359
Table 2. Effect of quinone derivatives on azidation of 1a
MN3
R
R
O
TMSN3 (2.4 equiv.)
Quinone (1.1 equiv.)
M
O
O
O
OPPh2
N3
OPPh2
O
Ph2P
R1
R3
R1
Ph
Ph
CHCl3 (0.5 M)
R2
1
R3
2a
1a (1.0 equiv.)
45 °C to rt, 3 17 h
R2
N3
Entry
1
Quinone
Yield/% Entry
Quinone
Yield/%
62
A
R2
OMe
OMe
R
O
Ph2P
R1
R3
+
O
OTMS
O
O
O
63
61
37
5
6
7
O
O
O
O
N3
2
(MBQ)
OMe
OMe
3
'' Inversion''
Scheme 1.
2
3
O
NDb
O
MeO
F
2. Results and discussion
2.1. Optimization of reaction conditions
Me
F
O
F
<7b
O
O
F
(DMBQ)
Me
According to the above mentioned considerations, the
reaction of tert-alkyl phosphinite 1a, derived from 2-methyl-
4-phenylbutan-2-ol, with tetrabutylammonium azide
(Bu4NN3) in the presence of methoxybenzoquinone (MBQ)
was examined first (Table 1, Entry 1) and the desired azide
2a was produced in 22% yield. Since trapping of the anionic
oxygen atom of intermediate A (Scheme 1) was considered
necessary, addition of 1.1 equiv of tetraisopropyl orthotita-
nate (Ti(OiPr)4) was examined next: the reaction of 1a with
t
Cl
O
Cl
Bu
31a,b
8
NDb
O
4
O
O
(DBBQ)
t
NC
CN
Bu
a
The reaction was carried out for 17 h.
Reaction performed from 0 ꢁC to rt.
b
19
Bu4NN3 in the presence of MBQ and Ti(OiPr)4 gave 2a
as DMBQ and DBBQ afforded the desired product in low
yield (Entries 3 and 4). 2,6-Dimethoxy-1,4-benzoquinone
gave a better result (Entry 5) while electron-withdrawing
substituents retarded the reaction (Entries 7 and 8). When
2,5-dimethoxy-1,4-benzoquinone was used, the desired
product was not detected (Entry 6).
in 22% yield (Entry 2). When trimethylsilyl azide (TMSN3)
was employed in place of Bu4NN3, the yield of 2a increased
to 61% (Entry 3). Since TMSN3 was found to be an effi-
cient azidation reagent, the effect of several Lewis acids
was examined next (Entries 4–7). Whereas the reaction
employing Yb(OiPr)3 afforded 2a in a slightly better yield
than other Lewis acids (Entry 5), the yield of 2a remained
almost the same in the reaction without any additives
(63%, Entry 8).
In the next stage, the effect of the solvent was examined at
0 ꢁC (see Table 3). Whereas polar solvents such as THF or
CH3CN lowered the yield of the desired azide (Entries 1
and 2), toluene or halogenated solvents gave better results
(Entries 3–5). As for the effect of concentration, no substan-
tial increase in the yield was observed (Entries 5–7).
The effect of the substituent(s) on various 1,4-benzoquinone
derivatives was examined (Table 2). The reaction of phos-
phinite 1a in the presence of 1,4-benzoquinone gave the cor-
responding azide (2a) in 61% yield (Entry 2). The reaction
with 2,6-disubstituted-1,4-benzoquinone derivatives such
Further, the molar ratio of 1a, MBQ and TMSN3 was exam-
ined (see Table 4). As the amount of TMSN3 increased, the
yield of 2a became slightly better (Entries 1–4). It is noted
Table 1. Additive effect
MN3 (2.4 equiv.)
OMe
Table 3. Effect of solvent
N3
OPPh2
(MBQ)
O
O
TMSN3 (2.4 equiv.)
MBQ (1.1 equiv.)
(1.1 equiv.)
OPPh2
N3
Ph
Ph
Additive (1.1 equiv.)
Ph
1a (1.0 equiv.)
Ph
2a
Solvent (0.5 M)
0 °C to rt, 3 h
1a (1.0 equiv.)
CHCl3
45 °C to rt
2a
Entry
Solvent
Yield/%
Entry
MN3
Additive
Yield/%
1
2
3
4
5
6
7
THF
30
21
55
51
1
2
3
4
5
6
7
8
Bu4NN3
None
22
22
61
51
68
55
53
63
Ti(OiPr)4
Ti(OiPr)4
Y(OiPr)3
Yb(OiPr)3
Yb(OTf)3
TMSOTf
None
CH3CN
Toluene
CH2Cl2
CHCl3 (0.5 M)
CHCl3 (0.2 M)
CHCl3 (1.0 M)
TMSN3
58 (63)a
58
56
a
Reaction performed form ꢀ45 ꢁC to rt.

6360
K. Kuroda et al. / Tetrahedron 63 (2007) 6358–6364
Table 4. Optimization of the reaction conditions
and a catalytic amount of 4-(dimethylamino)pyridine
(DMAP) according to the reported procedure.13b The
reactions of the obtained secondary and tertiary alkyl phos-
phinites were next examined under the optimized conditions
(Table 5). The reaction of secondary phosphinite 1b afforded
the azide 2b in high yield (Entry 1). tert-Alkyl phosphinite 1c
bearing tert-butyldiphenylsilyl group or cyclic phosphinite
1d was successfully converted into the corresponding azides
in good yields (Entries 2 and 3). Next, azidation of a chiral
tertiary alkyl phosphinite 1e that was prepared from (S)-3-
methyl-1-phenylpentan-3-ol was carried out and the inverted
product 2e was obtained in high yield with almost complete
inversion of stereochemistry. This suggests that the reaction
proceeded basically via SN2 mechanism. Further, the reac-
tion of a chiral benzylic phosphinite 1f gave the correspond-
ing azide 2f in good yield with slight lowering of the optical
purity (Entry 5). It is considered that this reaction proceeded
partially via SN1 mechanism because the benzylic cation was
generated more easily in this case. This reaction was also
applicable to phosphinite 1g bearing ester part (Entry 6).
TMSN3
OPPh2
N3
MBQ
Ph
Ph
CHCl3, 3 h
–45 °C to rt
1a
2a
Entry
1a/equiv
TMSN3/equiv
MBQ/equiv
Yield/%
1
2
3
4
5
6
7
1.0
1.0
1.0
1.0
1.0
1.0
1.6
1.8
2.4
3.0
5.0
2.4
2.4
1.0
1.1
1.1
1.1
1.1
1.1
1.1
1.6
56
63
60
65
53a
20b
90c
a
MBQ was slowly added to the reaction mixture for 1 h at rt.
Compound 1a was slowly added to the reaction mixture for 3.5 h.
Yield based on TMSN3.
b
c
that substantial amounts of elimination products, 4-phenyl-
2-methylbut-2-ene and 4-phenyl-2-methylbut-1-ene were
formed14c under these conditions. In order to suppress the
formation of alkenes, slow addition of either MBQ (Entry
5) or TMSN3 (Entry 6) was further examined. However, no
substantial effect on the formation of alkenes was observed
irrespective of the rates of addition: i.e., 2a was obtained
in 53 and 20% yield, respectively. Finally, 2a was obtained
in 90% yield when 1.6 M amount of 1a was used (Entry 7).
The chiral azides (2e or 2f) obtained were converted into the
corresponding chiral amine 4e or 4f in high yield by treating
lithium aluminumhydride (LiAlH4) in ether (Scheme 2). The
chiral amine 4f was shown dextrorotatory as reported in the
literature20 and thus the azide 2f could be hypothesized to
be (R)-configurated. The alleged stereospecificity of this
azidation is thus also indicative of an inverted configuration
for the azide 2e. To the best of our knowledge, this is the
first example of the stereospecific synthesis of an inverted
chiral tertiary azide from a chiral tertiary alcohol via SN2
displacement.
2.2. Generality of the azidation by TMSN3
Alkyl diphenylphosphinites were prepared from the
corresponding alcohols on treatment with chlorodiphenyl-
phosphine (ClPPh2) in the presence of triethylamine (Et3N)
Table 5. Condensation of alcohols with TMSN3
TMSN3 (1.0 equiv.)
MBQ (1.6 equiv.)
ClPPh2, Et3N
cat. DMAP
ROPPh2
1 (1.6 equiv.)
R N3
2
ROH
CHCl3
45 °C to rt, 3 12 h
THF, rt, 2 h
Entry
1
Alcohol
OH
Yield/%
Product
N3
Yield/%
Inversiond
—
1b (quant)
2b (92)a
Ph
Ph
OH
N3
2
3
1c (98%)
1d (87%)
2c (67)b
2d (79)b
—
—
TBDPSO
Ph
TBDPSO
Ph
N3
Et N3
HO
Et OH
(80% ee)
4
5
1e (99%)
2e (88)b
94%
Ph
Ph
(75% ee)c
Et N3
Et OH
Ph
1f (96%)
1g (99%)
2f (77)b
2g (52)b
60%
—
Ph
(59% ee)c
(98% ee)
Ph OH
MeO2C
Ph N3
MeO2C
6
a
Compound 1 of 1.0 equiv, 2.4 equiv of TMSN3, and 1.1 equiv of MBQ was used.
Yield based on TMSN3.
b
c
d
The enantiomeric ratio was determined by HPLC analysis after reducing the azide to amine with LiAlH4.
Inversion (%) was defined as (% ee of 2)/(% ee of SM).

K. Kuroda et al. / Tetrahedron 63 (2007) 6358–6364
6361
LiAlH4
uncorrected. Infrared (IR) spectra were recorded on a Shi-
madzu FT-IR 8900 spectrometer or a SensIR Technologies
TravelIR portable FT-IR spectrometer. 1H NMR spectra were
recorded in CDCl3 on a JEOL JNM-EX270L (270 MHz)
spectrometer; chemical shifts (d) 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 recorded on
a EX270L (68 MHz) spectrometer with complete proton
decoupling. Chemical shifts are reported in parts per million
relative to tetramethylsilane with the solvent resonance as
the internal standard (CDCl3; d¼77.0 ppm). Carbon–31P
coupling constants are reported when possible. High-
resolution mass spectral analysis (HRMS) was carried out
on a Bruker LC/ESI-TOF MS or a JEOL JMS-700V. The
optical rotations were measured with a JASCO P-1020
polarimeter. High-performance liquid chromatography
(HPLC) was carried out using a Hitachi LC-Organizer,
L-4000UV Detector, L-6200 Intelligent Pump, and D-2500
Chromato-Integrator. Analytical TLC was performed on
Et N3
Et NH2
(4.0 equiv.)
Ph
Ph
R
ether, reflux
2e
4e
95%
LiAlH4
(4.0 equiv.)
Et N3
Et NH2
Ph
Ph
R
ether, reflux
2f
4f
quant.
[α]D15 = + 8.5 (c 0.54, EtOH)
Lit.20 for 4f:
[α]D20= + 15.6 (c 0.50, EtOH, >95%ee)
Scheme 2.
The reaction mechanism is assumed21 as follows (Scheme
3): reaction of phosphinite 1 with MBQ gives a zwitterionic
intermediate A and following O-silylation by TMSN3 results
in the formation of intermediate B and azide anion (Nꢀ3 ).
Subsequent nucleophilic attack of Nꢀ3 to the phosphonium
part in an SN2 manner gives the phosphinate derivative 3
and the inverted azide 2. It is noted that since O-silylation
of the intermediate A is irreversible and is playing an impor-
tant role in carrying out this transformation, an electron-
donating substituent of the quinone derivative advantaged
the nucleophilicity of the intermediate A.
Merck preparative TLC plates (silica gel 60 GF254
,
0.25 mm). Preparative thin-layer chromatography (PTLC)
was carried out on silica gel Wakogel B-5F. All reactions
were carried out under an argon atmosphere in dried glass-
ware, unless otherwise noted. Dry solvents (CH2Cl2 and tol-
uene) were prepared by distilling over appropriate drying
agents. Dry solvents were purchased from Kanto (THF,
CHCl3, and Et2O) and Kokusan (CH3CN). Most organic
chemicals were purchased from Tokyo Kasei Kogyo (TCI)
unless otherwise noted. Lewis acids were purchased from
TCI and Koujyundo. LiAlH4 was purchased from Kanto.
TMSN3
OMe
OMe
O
O
OPPh2
O
O
Ph2P
R1
TMS N3
R3
R1
O
R2
1
R3
R2
4.2. Procedure for the preparation of tertiary alchohols
A
OMe
OTMS
(S)-3-Methyl-5-phenylpentan-3-ol (Ref. 14c) and methyl
a-phenyllactate (Ref. 13c) (Table 5, Entries 4 and 6) were
prepared following the literature procedure. (S)-2-Phenyl-
butan-2-ol (Table 5, Entry 5) was prepared according to
Walsh’s procedure.22,13c
R2
O
O
OMe
OTMS
R1
R3
Ph2P
R1
Ph2P
O
+
B
O
N3
2
R3
R2
3
N3
''Inversion''
4.2.1. 4-(tert-Butyldiphenylsiloxy)-2-methylbutan-2-ol
(Table 5, Entry 2). To a solution of 3-methylbutane-1,3-
diol (1.56 g, 15 mmol) in DMF (60 mL) were added
TBDPSCl (4.24 mL, 16.5 mmol) and imidazole (1.53 g,
22.5 mmol) at rt. After the reaction mixture was stirred for
2 days at rt, the reaction mixture was quenched with H2O
and diluted with ethyl acetate. It was extracted with ethyl
acetate, and the organic layer was washed with brine and
dried over anhydrous sodium sulfate. After evaporation of
the solvent under reduced pressure, the crude product was
purified by column chromatography to afford 4-(tert-butyl-
diphenylsiloxy)-2-methylbutan-2-ol (4.00 g, 78%). Color-
Scheme 3.
3. Conclusion
Azidation of tert-alcohols by a new type of oxidation–
reduction condensation via alkyl diphenylphosphinites was
described. tert-Alkyl azides are synthesized under neutral
and mild conditions by treating tert-alkyl phosphinites
with TMSN3 in the presence of MBQ. It is also noted that
chiral tert-alkyl azides were formed from the corresponding
chiral tert-alcohols with almost complete inversion in con-
figuration. Thus, a concise method for preparation of chiral
amines from the corresponding alcohols was established.
1
less oil; IR (ATR, cmꢀ1) 3441, 1107, 1079, 737, 700; H
NMR (270 MHz, CDCl3) d 7.72–7.65 (m, 4H), 7.48–7.36
(m, 6H), 3.90 (t, J¼5.8 Hz, 2H), 3.82 (br, 1H), 1.75 (t,
J¼5.8 Hz, 2H), 1.27 (s, 6H), 1.05 (s, 9H); 13C NMR
(68 MHz, CDCl3) d 135.4, 132.6, 129.7, 127.7, 70.9, 62.0,
43.0, 29.4, 26.8, 19.1. Anal. Calcd for C21H30OSi: C,
73.63; H, 8.83%. Found: C, 73.42; H, 8.55%.
4. Experimental
4.1. General
4.2.2. 1-(3-Phenylethyl)cyclopentanol (Table 5, Entry 3).
To a solution of cyclopentanone (3.22 mL, 36.4 mmol) in
THF (15 mL) were added the Grignard reagent prepared
All melting points were determined on a Yanagimoto micro
melting point apparatus (Yanaco MP-S3) and remain

6362
K. Kuroda et al. / Tetrahedron 63 (2007) 6358–6364
from magnesium turnings (972 mg, 40.0 mmol) and 2-chlo-
roethylbenzene (4.78 mL, 36.4 mmol) in THF (15 mL) at
0 ꢁC. After the reaction mixture was stirred for 2 h at rt,
the reaction mixture was quenched with saturated aq ammo-
nium chloride and diluted with ethyl acetate. It was extracted
with ethyl acetate, and the organic layer was washed with
brine and dried over anhydrous sodium sulfate. After evap-
oration of the solvent under reduced pressure, the crude
product was purified by column chromatography to afford
1-(3-phenylethyl)cyclopentanol (0.88 g, 13%). Colorless
oil; IR (ATR, cmꢀ1) 740, 696; 1H NMR (270 MHz, CDCl3)
d 7.37–7.13 (m, 5H), 2.81–2.70 (m, 2H), 1.95–1.53 (m,
10H), 1.29 (br, 1H); 13C NMR (68 MHz, CDCl3) d 142.5,
128.3, 128.2, 125.6, 82.4, 43.5, 39.8, 31.3, 23.9. HRMS
(ESI+) Calcd for C13H18NaO: [M+Na]+ 213.1250. Found:
213.1242.
J¼7.3 Hz), 127.5, 77.8 (d, J¼12.2 Hz), 60.5, 45.5 (d, J¼
4.1 Hz), 28.5 (d, J¼9.5 Hz), 26.9, 19.2. HRMS (EI+) Calcd
for C33H39O2SiP: [M]+ 526.2457. Found: 526.2452.
4.3.4. 1-(3-Phenylethyl)cyclopentyl diphenylphosphinite
(1d). Colorless oil; IR (ATR, cmꢀ1) 908, 739, 694; 1H
NMR (270 MHz, CDCl3) d 7.58–7.25 (m, 4H), 7.56–7.22
(m, 6H), 7.22–7.05 (m, 3H), 6.93–6.85 (m, 2H), 2.63–2.52
(m, 2H), 2.25–1.98 (m, 4H), 1.80–1.50 (m, 6H); 13C NMR
(68 MHz, CDCl3) d 143.6 (d, J¼15.7 Hz), 142.5, 130.0 (d,
J¼22.9 Hz), 128.7, 128.1, 128.1, 128.0, 125.5, 90.4 (d,
J¼10.6 Hz), 42.3 (d, J¼8.4 Hz), 38.5 (d, J¼8.9 Hz), 31.3,
23.8. HRMS (ESI+) Calcd for C25H27NaOP: [M+Na]+
397.1692. Found: 397.1701.
4.3.5. (S)-3-Methyl-5-phenylpentan-3-yl diphenylphos-
phinite (1e). Spectral data were consistent with those of
the literature.14c Colorless oil; [a]D13 +4 (c 0.98, CHCl3);
IR (ATR, cmꢀ1) 908, 739, 693; 1H NMR (270 MHz,
CDCl3) d 7.58–7.47 (m, 4H), 7.32–7.02 (m, 11H), 2.63–
2.57 (m, 2H), 2.03–1.93 (m, 2H), 1.81 (q, J¼7.4 Hz, 2H),
1.37 (s, 3H), 0.90 (t, J¼7.4 Hz, 3H); 13C NMR (68 MHz,
CDCl3) d 143.8, 143.8, 143.6, 143.6, 142.5, 130.2,
130.1, 130.0, 130.0, 128.6, 128.6, 128.2, 128.1, 128.1,
128.0, 125.5, 81.0 (d, J¼10.6 Hz), 42.2 (d, J¼6.7 Hz),
33.2 (d, J¼7.3 Hz), 30.4, 25.3 (d, J¼11.2 Hz), 8.7 (d,
J¼1.1 Hz).
4.3. General procedure for the preparation of alkyl
diphenylphosphinites
A typical procedure for the preparation of alkyl diphenyl-
phosphinites (1a–1g) is described for 1a. To a stirred solu-
tion of 2-methyl-4-phenylbutan-2-ol (1.64 g, 10 mmol) and
DMAP (244 mg, 2 mmol) in dry THF (20 mL) were added
Et3N (1.67 mL, 12 mmol) followed by ClPPh2 (2.02 mL,
11 mmol) under an argon atmosphere. After stirring at rt
for 2 h, the resulting white slurry was concentrated by a ro-
tatory evaporator. After dilution of the residue with hexane/
ethyl acetate (v/v¼9/1, ca. 100 mL, HPLC grade), the mix-
ture was filtered through a pad of alumina (activated, 300
mesh; purchased from Wako Pure Chemical Industries,
Ltd.) and Celite. The filtrate was concentrated under reduced
pressure to give the desired phosphinite 1a (3.48 g, quant),
which required no further purification.
4.3.6. (S)-2-Phenylbutan-2-yl diphenylphosphinite (1f).
Spectral data were consistent with those of the literature.13c
White solid; mp 78–80 ꢁC; [a]D16 ꢀ6 (c 0.95, CHCl3); IR
(ATR, cmꢀ1) 1053, 1017, 939, 746, 695; 1H NMR
(270 MHz, CDCl3) d 7.61–7.18 (m, 15H), 2.21–1.89 (m,
2H), 1.70 (s, 3H), 0.70 (t, J¼7.4 Hz, 3H); 13C NMR
(68 MHz, CDCl3) d 145.8, 145.8, 143.6, 143.4, 143.2, 130.4,
130.3, 130.0, 130.0, 128.7, 128.6, 128.1, 128.1, 128.0, 128.0,
127.9, 126.6, 125.8, 125.8, 82.6 (d, J¼12.9 Hz), 36.6 (d,
J¼6.2 Hz), 27.2 (d, J¼12.9 Hz), 8.8.
4.3.1. 2-Methyl-4-phenylbutan-2-yl diphenylphosphinite
(1a). Spectral data were consistent with those of the litera-
ture.13c,14c Colorless oil; IR (ATR, cmꢀ1) 913, 739, 694;
1H NMR (270 MHz, CDCl3) d 7.60–7.47 (m, 4H), 7.45–
7.05 (m, 11H), 2.74–2.62 (m, 2H), 2.03–1.94 (m, 2H),
1.43 (s, 6H); 13C NMR (68 MHz, CDCl3) d 143.6 (d,
J¼15.6 Hz), 142.4, 130.0 (d, J¼22.4 Hz), 128.6, 128.2,
128.2, 128.1 (d, J¼6.7 Hz), 128.0, 125.6, 78.4 (d,
J¼11.2 Hz), 45.1 (d, J¼5.6 Hz), 30.8, 28.1 (d, J¼9.5 Hz).
4.3.7. Methyl 2-(diphenylphosphinoxy)-2-phenylpropa-
noate (1g). Spectral data were consistent with those of the
literature.13c Colorless oil; IR (ATR, cmꢀ1) 1742, 1227,
1
1125, 1103, 692; H NMR (270 MHz, CDCl3) d 7.61–7.49
(m, 6H), 7.39–7.24 (m, 9H), 3.63 (s, 3H), 1.91 (s, 3H); 13C
NMR (68 MHz, CDCl3) d 173.2, 142.6, 142.4, 142.4, 142.2,
141.7, 141.7, 130.6, 130.4, 130.3, 130.1, 129.1, 128.8, 128.2,
128.2, 128.1, 128.1, 128.0, 127.9, 125.4, 82.8 (d, J¼
16.8 Hz), 52.4, 26.5 (d, J¼12.3 Hz).
4.3.2. 4-Phenylbutan-2-yl diphenylphosphinite (1b).
Spectral data were consistent with those of the literature.14c
White solid; mp 33–35 ꢁC; IR (ATR, cmꢀ1) 940, 888, 741,
1
723, 695; H NMR (270 MHz, CDCl3) d 7.71–7.02 (m,
15H), 4.22–4.02 (m, 1H), 2.81–2.55 (m, 2H), 2.12–1.72
(m, 2H), 1.31 (d, J¼6.5 Hz, 3H); 13C NMR (68 MHz,
CDCl3) d 143.0 (d, J¼16.7 Hz), 142.5 (d, J¼16.1 Hz),
141.9, 130.6, 130.3, 130.1, 130.0, 129.2, 128.8, 128.2,
128.1, 128.1, 128.0, 125.6, 77.0 (d, J¼20.6 Hz), 40.1 (d,
J¼5.6 Hz), 31.9, 22.4 (d, J¼5.6 Hz).
4.4. General procedure for reaction of alkyl diphenyl-
phosphinites with TMSN3
A typical procedure for the preparation of azide (2a–2g) is
described for 2f. To a stirred solution of 1f (232 mg,
0.64 mmol) in dry CHCl3 (1.28 mL) were added MBQ
(88.4 mg, 0.64 mmol) followed by TMSN3 (54.6 mL,
0.40 mmol) at ꢀ45 ꢁC under an Ar atmosphere. The reaction
mixture was allowed to warm to rt and was stirred for 12 h.
Direct purification by preparative TLC afforded 2f (71.4 mg,
88%).
4.3.3. 4-(tert-Butyldiphenylsiloxy)-2-methylbutan-2-yl
diphenylphosphinite (1c). Colorless oil; IR (ATR, cmꢀ1
)
1
1090, 937, 910, 738, 696; H NMR (270 MHz, CDCl3)
d 7.63–7.60 (m, 4H), 7.43–7.20 (m, 16H), 3.84–3.78 (m,
2H), 2.05–1.98 (m, 2H), 1.35 (s, 6H), 1.04 (s, 9H); 13C
NMR (68 MHz, CDCl3) d 143.4 (d, J¼16.2 Hz), 135.4,
133.9, 130.0 (d, J¼22.4 Hz), 129.4, 128.6, 128.0 (d,
4.4.1. (3-Azido-3-methylbutyl)benzene (2a). Spectral
data were consistent with those of the literature.9d Pale

K. Kuroda et al. / Tetrahedron 63 (2007) 6358–6364
6363
yellow oil; IR (ATR, cmꢀ1) 2095, 1253, 743, 697; 1H NMR
(270 MHz, CDCl3) d 7.34–7.15 (m, 5H), 2.73–2.63 (m, 2H),
1.84–1.75 (m, 2H), 1.33 (s, 6H); 13C NMR (68 MHz, CDCl3)
d 141.7, 128.3, 128.2, 125.8, 61.4, 43.5, 30.8, 26.1.
was filtered through Celite and anhydrous sodium sulfate.
The filtrate was concentrated under reduced pressure to
give the desired amine 4 (39.6 mg, 95%). Pale yellow oil;
75% ee; the ee value was determined by chiral HPLC anal-
ysis (DAICEL CHIRALCEL OD-H column, hexane/
i-PrOH/Et2NH¼100/1/0.1, flow rate¼1.0 mL minꢀ1): tR¼
34.0 (S), 38.1 min (R); [a]1D6 +1 (c 1.19, EtOH); IR (ATR,
cmꢀ1) 754, 723, 697; 1H NMR (270 MHz, CDCl3) d 7.34–
7.12 (m, 5H), 2.68–2.55 (m, 2H), 1.68–1.57 (m, 2H), 1.45
(q, J¼7.4 Hz, 2H), 1.19 (br, 2H), 1.09 (s, 3H), 0.91 (t,
J¼7.4 Hz, 3H); 13C NMR (68 MHz, CDCl3) d 142.7, 128.1,
128.1, 125.4, 51.4, 44.3, 35.1, 30.5, 27.5, 8.3. HRMS (ESI+)
Calcd for C12H20N: [M+H]+ 178.1590. Found: 178.1596.
4.4.2. (3-Azido-butyl)benzene (2b). Spectral data were
consistent with those of the literature.9d Pale yellow oil; IR
1
(ATR, cmꢀ1) 2095, 1247, 744, 698; H NMR (270 MHz,
CDCl3) d 7.34–7.15 (m, 5H), 3.50–3.35 (m, 1H), 2.82–
2.58 (m, 2H), 1.90–1.67 (m, 2H), 1.28 (d, J¼6.4 Hz, 3H);
13C NMR (68 MHz, CDCl3) d 141.0, 128.4, 128.3, 126.0,
57.1, 37.9, 32.4, 19.5.
4.4.3. (3-Azido-3-methylbutoxy)tert-butyldiphenylsilane
(2c). Spectral data were consistent with those of the
literature.9d Pale yellow oil; IR (ATR, cmꢀ1) 2101, 1108,
4.4.9. (R)-2-Phenylbutan-2-ylamine (4f). Spectral data
were consistent with those of the literature.20 Pale yellow
oil; 59% ee; the ee value was determined by chiral HPLC
analysis (DAICEL CHIRALCEL OD-H column, hexane/
i-PrOH/Et2NH¼500/1/0.5, flow rate¼1.0 mL minꢀ1): tR¼
15.0 (R), 20.0 min (S); [a]1D5 +9 (c 0.54, EtOH); IR (ATR,
cmꢀ1) 760, 732, 699; 1H NMR (270 MHz, CDCl3) d 7.50–
7.39 (m, 2H), 7.39–7.16 (m, 3H), 1.90–1.62 (m, 2H), 1.53
(br, 2H), 1.45 (s, 3H), 0.74 (t, J¼7.4 Hz, 3H); 13C NMR
(68 MHz, CDCl3) d 148.6, 128.0, 125.9, 125.2, 55.2, 37.7,
30.7, 8.8.
1
905, 727, 704; H NMR (270 MHz, CDCl3) d 7.71–7.63
(m, 4H), 7.45–7.34 (m, 6H), 3.77 (t, J¼6.8 Hz, 2H), 1.79
(t, J¼6.8 Hz, 2H), 2.82–2.58 (m, 2H), 1.25 (s, 6H), 1.05
(s, 9H); 13C NMR (68 MHz, CDCl3) d 135.4, 133.6, 129.6,
127.6, 60.6, 60.3, 43.5, 26.9, 26.6, 19.2.
4.4.4. [3-(1-Azidocyclopentyl)propyl]benzene (2d). Pale
yellow oil; IR (ATR, cmꢀ1) 2093, 1254, 744, 698; 1H
NMR (270 MHz, CDCl3) d 7.32–7.13 (m, 5H), 2.77–2.68
(m, 2H), 1.98–1.50 (m, 10H); 13C NMR (68 MHz, CDCl3)
d 141.8, 128.3, 128.1, 125.8, 73.4, 41.2, 37.0, 31.7, 23.8.
Anal. Calcd for C13H17N3: C, 72.52; H, 7.96; N, 19.52%.
Found: C, 72.41; H, 7.90; N, 19.15%.
Acknowledgements
One of the present authors (K.K.) acknowledges useful dis-
cussions with Dr. H. Yamabe (The Kitasato Institute). This
study was supported in part by the Grant of the 21st Century
COE Program from Ministry of Education, Culture, Sports,
Science, and Technology (MEXT), Japan. K.K. was granted
a Research Fellowship of the Japan Society for the Promo-
tion of Science for Young Scientist.
4.4.5. (R)-(3-Azido-3-methylbutyl)benzene (2e). Colorless
oil; [a]1D2 +19 (c 1.10, CHCl3); IR (ATR, cmꢀ1) 2088, 1254,
754, 740, 697; 1H NMR (270 MHz, CDCl3) d 7.34–7.13 (m,
5H), 2.71–2.58 (m, 2H), 1.83–1.72 (m, 2H), 1.62 (q,
J¼7.5 Hz, 2H), 1.28 (s, 3H), 0.95 (t, J¼7.5 Hz, 3H); 13C
NMR (68 MHz, CDCl3) d 141.8, 128.3, 128.2, 125.8, 64.3,
41.1, 32.1, 30.5, 22.8, 8.4. Anal. Calcd for C12H17N3: C,
70.90; H, 8.43; N, 20.67%. Found: C, 70.69; H, 8.63; N,
20.26%.
References and notes
1. For reviews on organic azides, see: (a) Scriven, E. F. V.;
€
4.4.6. (R)-(1-Azido-1-methylpropyl)benzene (2f). Color-
less oil; [a]1D3 +46 (c 0.95, CHCl3); IR (ATR, cmꢀ1) 2092,
1248, 759, 697; H NMR (270 MHz, CDCl3) d 7.43–7.23
Turnbull, K. Chem. Rev. 1988, 88, 297; (b) Brase, S.; Gil, C.;
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1
(m, 5H), 1.97–1.77 (m, 2H), 1.66 (s, 3H), 0.79 (t,
J¼7.4 Hz, 3H); 13C NMR (68 MHz, CDCl3) d 143.2,
128.3, 127.1, 125.5, 67.3, 35.1, 25.2, 8.8. Anal. Calcd for
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4.4.7. Methyl 2-azido-2-phenylpropanoate (2g). Pale
yellow oil; IR (ATR, cmꢀ1) 2098, 1738, 1241, 1106, 697;
1H NMR (270 MHz, CDCl3) d 7.45–7.30 (m, 5H), 3.80 (s,
3H), 1.83 (s, 3H); 13C NMR (68 MHz, CDCl3) d 171.8,
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