High performance of N -alkoxycarbonyl-imines in triethylborane-mediated tin-free radical addition

Article abstract of DOI:10.1021/jo2025042

Triethylborane-mediated tin-free radical alkylation of N-alkoxycarbonyl- imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, proceeded smoothly at a low temperature (-78 to -20 °C) to give the corresponding adducts in high yield. Although the formation of isocyanate was the major unfavorable reaction at room temperature, a one-pot conversion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.

Full text of DOI:10.1021/jo2025042

Article
pubs.acs.org/joc
High Performance of N-Alkoxycarbonyl-imines in Triethylborane-
Mediated Tin-Free Radical Addition
Ken-ichi Yamada,*,† Takehito Konishi,† Mayu Nakano,† Shintaro Fujii,† Romain Cadou,†
Yasutomo Yamamoto,‡ and Kiyoshi Tomioka*,‡
†Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Kyoto 606-8501, Japan
‡Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kodo, Kyotanabe 610-0395, Japan
S
* Supporting Information
ABSTRACT: Triethylborane-mediated tin-free radical alkylation of N-
alkoxycarbonyl-imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, pro-
ceeded smoothly at a low temperature (−78 to −20 °C) to give the
corresponding adducts in high yield. Although the formation of isocyanate
was the major unfavorable reaction at room temperature, a one-pot conver-
sion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the
corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-
imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl
radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.
Scheme 2. Pivaloyloxymethylation of N-Ts- and N-PMP-o-
tolualdimine 2d and 2e
INTRODUCTION
■
The addition reaction of carbon nucleophiles to imines is one
of the most versatile methodologies available for obtaining
amines of chemical and/or biologic importance.1,2 The
selection of an N-activating−protecting group of imines,
guaranteeing satisfactory reactivity and easy removal, is key to
successful reactions. Among our approaches toward these types
of reactions, we recently achieved radical acyloxymethylation
of imines to obtain amino alcohols.3 With iodomethyl
pivalate (1), imines 2a−c, bearing a Ts (tosyl), a PMP (4-
methoxyphenyl), and a Dpp (diphenylphosphinoyl) group as
an N-activating−protecting group, underwent pivaloyloxyme-
thylation in the presence of triethylborane−air in dichloro-
methane at room temperature to give 3a−c in 96, 89, and 80%
yield, respectively (Scheme 1).3 The removal of a Ts and a
Scheme 1. Previously Reported Pivaloyloxymethylation of
Benzaldimines 2a−c
adduct 3d only in 33%, and dipivalate 4d (R = Ts) was
obtained in 12% yield. The production of 4d is rationalized by
the reaction of pivaloyloxymethyl radical (8)5 and benzyl
radical 7, formed via 1,5-hydrogen shift of aminyl radical 5,
which indicates the slow conversion of 5 to borylamine 6 (R = Ts).
Although the reaction of N-PMP-benzaldimine 2b was faster
than that of N-Ts analogue 2a (Scheme 1), the reaction of N-
PMP-o-tolualdimine 2e was also sluggish, and adduct 3e (R =
PMP) was obtained in 58% yield after 23 h (Scheme 2).
Importantly, dipivalate 4e (R = PMP) was not detected in the
products, although other unidentified byproducts were
produced. These results suggest that the conversion of N-
PMP-aminyl radical to N-boryl-N-PMP-amine with triethylbor-
ane is sufficiently fast, but the radical accepting ability of
PMP group, however, usually requires rather harsh reductive
and oxidative conditions, respectively.4 Although a Dpp group
is removable under mildly acidic conditions, its performance in
pivaloyloxymethylation was moderate, and 20 equiv of
triethylborane and 48 h were required for completion of the
reaction. Besides, we met difficulty when we applied this
reaction to sterically hindered o-tolualdimines (Scheme 2). The
reactions of N-Ts-o-tolualdimine 2d produced the corresponding
Received: December 6, 2011
Published: December 30, 2011
© 2011 American Chemical Society
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a
Table 1. Production of 10 and 11 in the Reaction of 1 and 9
b
entry
9
R
solvent
time/h
10/%
11/%
10d/%
1
2
3
4
5
9a
9b
9c
9c
9d
t-Bu
CH2Cl2
CH2Cl2
CH2Cl2
PhCF3
12
8
10a/42
10b/42
10c/40
10c/24
18
32
33
0
9
7
(CH2)2TMS
Me
Me
Et
8
16
73
c
9, 36
d
toluene
7, 3
0
85
a
b
c
d
After initial addition of Et3B (3 equiv), Et3B (1 equiv each) was added every 2 h. Based on 1H NMR of the crude materials. At 100 °C. Under
reflux after addition of EtOH (17 equiv).
N-PMP-imine is unsatisfactory to overcome the steric
hindrance of the ortho-methyl group in the addition of 8.
These limitations prompted us to search for a more reactive
and easily removable N-activating group. We speculated that a
more electron-accepting N-activating group should make the
addition of radical faster but the following aminyl radical trap
slower. On the basis of pKa values of the corresponding N−H
(PhSO2NH2 16.1,6a EtOCONH2 24.2,6b PhNH2 30.66c), N-
alkoxycarbonyl-imines are expected to have moderate electron-
accepting ability between those of N-Ts and N-PMP analogues,
and thus both the addition step and the radical trap step might
be sufficiently fast. We describe herein the high performance of
N-alkoxycarbonyl-imines in the addition of alkyl radicals. Although
oxime ethers,7 hydrazones,8 N-aryl-imines,9 and N-sulfonyl-
imines10 were utilized as a radical accepting CN compound,
application of N-alkoxycarbonyl-imines,11 such as N-Boc-, N-Cbz-,
and N-(2-trimethylsilylethoxy)carbonyl (Teoc)-imines, in radical
addition is rarely reported,1,12 despite their easy removal.4
Scheme 3. Possible Pathway to 10−11 from 9
Prevention of the Isocyanate Formation. The above
speculation was confirmed by the one-pot conversion of 9c to
10d in 73% yield (Table 1, entry 4). Thus, the addition reaction
of 9c with 1 was conducted at room temperature for 9 h in
trifluoromethylbenzene and heated at 100 °C for 36 h, and 10d
was obtained in 73% yield along with 10c in 24% yield without
any residue of isocyanate 11, indicating complete conversion of
11 to 10d. N-Ethoxycarbonyl-imine 9d was a useful imine;
although the reaction in toluene at room temperature gave an
almost 1:1 mixture of N-ethoxycarbonylamine 10d and
isocyanate 11 after 7 h, 10d was obtained in 85% yield when
the reaction mixture was heated for 3 h under reflux in the
presence of ethanol (17 equiv) after the radical addition
reaction was completed (Table 1, entry 5). This addition−
elimination−addition sequence from 9 to 11 and then 10d is
applicable for preparing isocyanate, as the efficient conversion
of N-ethoxycarbonylamine to isocyanate is documented.16
Scheme 3 also indicates that the protonation of 13 should
prevent the elimination to 11 and selectively give 10. Indeed,
the reaction of 9a with 1 at room temperature in the presence
of 1 equiv of methanol and tert-butanol gave 10a with improved
yields of 60 and 73%, respectively (Table 2, entries 1 and 3). It
RESULTS AND DISCUSSION
■
Isocyanate Formation in the Pivaloyloxymethylation
of N-Alkoxycarbonyl-imines. The reaction of iodomethyl
pivalate (1) and N-Boc-benzaldimine 9a (R = t-Bu) was
conducted under the conditions3 for N-Ts-imine 2a; a 1.0 M
hexane solution of triethylborane (3 mL, 3 mmol) was added to
a solution of 1 (3 mmol) and 9a (1 mmol) in dichloromethane
(1 mL). The mixture was stirred at room temperature under
normal atmosphere, and triethylborane (1 mL, 1 mmol) was
added every 2 h. After a total addition of 8 equiv triethylborane,
the mixture was stirred for another 2 h to give the expected
adduct 10a in 42% yield along with unexpected isocyanate 11
in 18% yield as well as ethyl carbamate 10d in 9% yield (Table 1,
entry 1). The use of dimethylzinc in hexane13−15 in place of
triethylborane produced a complex mixture, and no product
could be identified. The reaction of N-Teoc-imine 9b (R =
(CH2)2TMS) and N-methoxycarbonyl-imine 9c (R = Me)
resulted in the similar formation of 10 as a major product in 42
and 40% yields and 10d (7 and 16%), while isocyanate 11 was
obtained in higher yields of 32 and 33%, respectively (Table 1,
entries 2 and 3).
a
Table 2. Effect of Alkanol in the Reaction of 9a and 1
b
entry
additive/equiv
time/h
10a/%
11/%
10d/%
15/%
1
2
3
4
MeOH/1.0
t-BuOH/0.5
t-BuOH/1.0
t-BuOH/1.5
10
10
8
60
65
73
43
0
0
0
0
0
0
0
0
4
4
11
7
10
a
The unexpected production of isocyanate 11 is rationalized
by the elimination of alkoxyborane 14 from N-Boc-borylamine
13 (Scheme 3).16 The increasing tendency toward the
formation of 11 by the reaction of 9b and 9c, having alkoxy
groups with better leaving group ability than that of 9a,
supported this speculation. Isocyanate 11 then reacted with
ethanol or ethoxyl, generated by the reaction of triethylborane
or 14 with air,17 to give ethoxycarbonylamine 10d.
After initial addition of Et3B (3 equiv), Et3B (1 equiv each) was
b
added every 2 h. Isolated yield after silica gel column chromatography
with partial hydrolysis.
is noteworthy that neither isocyanate 11 nor ethoxycarbonyl-
amine 10d was produced, while gem-diamine 15 was formed by
the reaction of 9a and tert-butyl carbamate, generated by
alcoholysis of 9a. Indeed, almost complete conversion of 9a and
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tert-butyl carbamate (0.5 mmol each) into 15 was observed by
1H NMR in CD2Cl2 (0.6 mL) at room temperature for 15 min
in the absence of any additives.18
Decreasing the temperature also effectively suppressed the
elimination; the reaction at 0 °C provided 10a in 67% yield
(Table 3, entry 2). The reaction at −20 °C gave 10a in 81%
gave 10f in high 94% yield, and the bromo moiety was intact
under the reaction conditions (Table 4, entry 4). Imine 9g,
bearing an electron-donating 4-methoxy substituent, reacted at
0 °C to give 10g in 89% yield without the production of
isocyanate and ethoxycarbonylamine (Table 4, entry 5).
Similarly, 9h reacted at −20 °C to give 10h in 86% yield
(Table 4, entry 6). The reaction of sterically hindered o-
tolualdimine 9i produced 10i also in high yield (Table 4, entry 7),
strikingly contrasting with poor results of N-Ts and N-PMP
analogues in Scheme 2. Aliphatic imine 9j reacted smoothly to
give 10j in 92% yield (Table 4, entry 8).
Table 3. Temperature Dependence in the Reaction of 9a
a
and 1
N-Boc-imine also performed well in a typical triethylborane-
mediated addition reaction of an alkyl radical10 (Scheme 4).
b
entry
solvent
temp/°C
time/h
10a/%
11/%
10d/%
1
2
3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
rt
0
12
12
6
42
67
81
95
95
97
18
13
0
9
11
0
Scheme 4. Et3B-Mediated Alkylation of 9a
−20
−20
−78
−20
c
4
6
0
0
c
5
10
10
0
0
c
6
0
0
a
After initial addition of Et3B (3 equiv), Et3B (1 equiv each) was
b
c
1
added every 2 h. Based on H NMR of the crude materials. Air was
introduced into the reaction mixture at 10 mL/h.
yield without the formation of 11 and 10d (Table 3, entry 3).
These results clearly show that elimination of 14 from 13
requires a higher temperature, between −20 and 0 °C, than the
radical addition and the following trap of 12 by triethylborane
to give 13. Air bubbling improved the yield of 10a (Table 3,
entry 4). The reaction proceeded even at −78 °C with the same
level of efficiency (Table 3, entry 5). Toluene was also a good
solvent to give 10a in 97% yield (Table 3, entry 6). The high
yield of the reactions at lower temperature sharply contrasted
with the low yield at room temperature.
Scope of the Reaction of N-Alkoxycarbonyl-imines.
The established conditions were successfully applied to
pivaloyloxymethylation of other N-alkoxycarbonyl-imines at
−20 or 0 °C (Table 4). N-Teoc-imine 9b and N-Cbz-imine 9e
were also good acceptors to give the corresponding adducts in
high yield (Table 4, entries 2 and 3). Interestingly, in the
reaction of 9e, isocyanate 11 was formed in 16% yield along
with 10e in 72% yield even at −40 °C, probably because of a
higher ability of a benzyloxy group as a leaving group (pKa in
DMSO: BnOH 26.93,19 EtOH 29.8, t-BuOH 32.220). N-Boc-
imine 9f, having an electron-withdrawing 4-bromo substituent,
The reactions of 9a with and without 2-iodopropane (3 equiv)
at −50 °C quantitatively afforded N-Boc isopropyl adduct 16a
and ethyl adduct 16b, respectively. Isopropylation was much
faster than ethylation and pivaloyloxymethylation probably
because of the higher nucleophilicity of the isopropyl radical.
Isopropylation also proceeded smoothly even at −78 °C to give
16a in 92% yield after 2 h. These results clearly show the
general applicability of N-Boc-imine as an excellent acceptor in
triethylborane-mediated radical addition reactions at a low tem-
perature. The reaction with and without 2-iodopropane at −20 °C
provided the corresponding isocyanates in 27 and 10% yield with
16a and 16b in 68 and 73% yield, respectively. Thus, isopro-
pylation and ethylation required a lower temperature than pivaloyl-
oxymethylation to prevent isocyanate formation, suggesting that
the pivaloyloxy functionality stabilizes the N-boryl intermediate 13.
Comparison with the Reactions of N-Ts-imines and N-
PMP-imines. N-Boc-imines have apparently high reactivity
toward triethylborane-mediated radical addition; the addition
to N-Boc-imine 9a proceeded smoothly at −78 °C (Table 3,
entry 5). The result shows that both the addition of
a
Table 4. Radical Pivaloyloxymethylation of N-Boc-imines 9
entry
9
R1
R2
Et3B/equiv
temp/°C
time/h
10
yield/%
1
2
3
4
5
6
7
8
9a
9b
9e
9f
t-Bu
Ph
Ph
Ph
5
6
5
5
7
5
5
4
−20
−20
−60
−20
0
6
8
10a
10b
10e
10f
10g
10h
10i
95
89
96
94
89
86
92
92
TMS(CH2)2
Bn
6
t-Bu
4-BrC6H4
6
9g
9h
9i
t-Bu
4-MeOC6H4
4-MeC6H4
2-MeC6H4
Ph(CH2)2
10
6
t-Bu
−20
−20
−20
t-Bu
6
9j
t-Bu
4
10j
a
The reaction was conducted in a 20-mL 2-necked round-bottom flask with a NaOH drying tube. After initial addition of Et3B (3 equiv), Et3B (1
equiv each) was added every 2 h.
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pivaloyloxymethyl radical (8) to 9a and the trap of aminyl
radical 12 by triethylborane (Scheme 3) are sufficiently fast
even at −78 °C. In contrast, the reaction of N-Ts-benzaldimine
2a under the same conditions gave the corresponding adduct
3a in only 41% yield, along with 17a in 8% yield, after 10 h
(Scheme 5). The production of 17a is probably due to the
Scheme 6. Selective Deprotection of 10a
Scheme 5. Reactions of N-Ts-benzaldimine 2a and N-PMP-
benzaldimine 2b at −78 °C
N HCl in refluxing dioxane for 3 h,22 and phenylglycinol (22)
was directly obtained in 69% yield.
CONCLUSION
■
N-Alkoxycarbonyl-imines showed high performance in triethylborane−
air-initiated tin-free radical alkylation. This high performance
is likely due to mildly electron-withdrawing character of
alkoxycarbonyl groups that keeps both the radical addition step
and the aminyl radical trapping step sufficiently fast. The con-
trasting low performance at room temperature was attributed to
isocyanate formation, which could account for the reported low
efficiency of this class of imines.12b Not only the simple adduct but
also the addition−elimination−addition sequence product was
prepared in one pot. Because only mild conditions are required for
removal of N-Boc, N-Cbz, and N-Teoc groups, the present finding
that N-alkoxycarbonyl-imines are excellent radical acceptors
expands the synthetic utility of radical reactions.
reaction of aminyl radical 18a (R = Ts) with pivaloyloxymethyl
radical (8),21 indicating the slow conversion of 18a to N-Ts-
borylamine 19a (R = Ts), as previously illustrated in Scheme 2.
The formation of 17a by the ionic nucleophilic substitution of
19a with 1 could be excluded because 17a was not produced at
room temperature. The reaction of N-PMP-benzaldimine 2b
was also so inefficient at −78 °C that adduct 3b was obtained in
only 27% yield after 10 h with many unidentified byproducts,
although no production of 17b was observed (Scheme 5). This
result indicates that the formation of borylamine 19b from
aminyl radical 18b (R = PMP) and triethylborane is sufficiently
fast, but 2b is a poor radical acceptor at −78 °C due to less
strong electron-withdrawing character of the PMP group.
Importantly, N-Boc-o-tolualdimine 9i, the counterpart of 2d
and 2e (Scheme 2), reacted smoothly at −20 °C to give 10i in
92% yield without forming the product corresponding to 4d
(Table 4, entry 7). This result also confirms that both the
addition step and the aminyl radical trapping step are fast with
N-Boc-imines.
EXPERIMENTAL SECTION
■
General Methods. Imines 2a,23 2b,24 2d,25 2e,26 9a,27 9b,28 9c,29
9d,30 9e,31 9f−i,27 and 9j32 were prepared according to the literature.
PivOCH2I (1) was prepared by the reported procedure33 and
decolorized by being passed through Al2O3 prior to use. Anhydrous
CH2Cl2, toluene, and PhCF3, and hexane solutions of Me2Zn and Et3B
were purchased and used as received. MeOH, EtOH, and t-BuOH
were distilled from sodium prior to use. Column chromatography was
1
performed using silica gel. All melting points are uncorrected. H and
13C NMR spectra were recorded in CDCl3 at 500 and 125 MHz,
1
respectively. H NMR spectra were measured at 55 or 58 °C in the
Comparing the reaction of p-anisaldimine 9g (Table 4, entry 5)
with that of the N-Ts analogue, superiority of N-Boc-imine was
further indicated. As previously reported,3 the reaction of N-Ts-
p-anisaldimine requires 9 equiv of triethylborane and 3 equiv of
boron trifluoride to give the corresponding product in 94%
yield within 22 h. Without boron trifluoride, the reaction failed
to complete even after 60 h, and the yield of the product was
decreased to 41%. In contrast, adduct 10g was obtained in good
yield at 0 °C after 10 h in the absence of boron trifluoride
(Table 4, entry 5). These results seem to indicate that not only
the aminyl radical trap but also the radical addition step of
N-Boc-imines is faster than that of N-Ts-imines.
Selective Deprotection of the Adduct. Finally, we
demonstrated selective deprotection of the adduct (Scheme 6).
O-Deprotection of 10a was selectively realized by our reported
conditions (KOH, H2O/MeOH),3 and N-Boc-phenylglycinol
20 was obtained in 80% yield after 5 h. N-Deprotection was
achieved by TFA treatment for 30 min to give 21 exclusively in
90% yield. It was important to liberate free amine 21 from the
TFA salt using 10% NaOH at 0 °C to prevent undesired
migration of the pivaloyl group; an 89:11 mixture of O- and N-
pivaloyl-phenylglycinol was obtained at room temperature.
N,O-Dual-deprotection was also possible by treatment with 3
cases that peaks were broadened at rt. Chemical shifts and coupling
constants are presented in ppm δ relative to Me4Si and Hz,
respectively. Data are reported as follows: chemical shift, multiplicity
(s = singlet, d = doublet, t = triplet, q = quartet, br = broad, and m =
multiplet), coupling constants, integration, and assignment. 13C peak
multiplicity assignments were made on the basis of DEPT spectra. IR
spectroscopy of oil and solid samples were measured as neat liquid
films and KBr pellets, respectively. The wave numbers of maximum
absorption peaks of IR spectroscopy are presented in cm−1.
Typical Procedure (Table 4, Entry 1): 2-tert-Butoxycarbony-
lamino-2-phenylethyl pivalate (10a). A stirring bar and 9a (205
mg, 1.0 mmol) were placed in a dry 20-mL two-neck round-bottom
flask, which was filled with argon by three-time evacuation-and-refill
using an argon balloon. To the flask were added CH2Cl2 (1 mL),
iodomethyl pivalate (1) (0.50 mL, 3.0 mmol), and a hexane solution of
Et3B (1.0 M; 3.0 mL, 3.0 mmol) at −20 °C. After replacing the argon
balloon with a NaOH drying tube, air was introduced into the stirred
mixture through a syringe needle (10 mL/h), and the solution of Et3B
(1.0 mL, 1.0 mmol) was added every 2 h. After a total addition of 5.0
mmol Et3B, the mixture was stirred for another 2 h, and saturated
NaHCO3 was added. The whole was extracted three times with
EtOAc, and the combined organic layers were washed with 10%
Na2S2O3 and brine, dried over Na2SO4, and then concentrated in
vacuo. The resulting residue was purified by column chromatography
(hexane/EtOAc 19/1) to afford the title compound (305 mg, 95%)
1
as white solids of mp 107−108 °C (hexane): H NMR (55 °C) 1.15
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(s, 9H), 1.41 (s, 9H), 4.25 (dd, J = 5.0, 11.5, 1H), 4.32 (dd, J = 6.5, 11.5,
1H), 4.9−5.1 (br m, 2H), 7.24−7.35 (m, 5H); 13C NMR 27.0 (CH3),
28.2 (CH3), 38.7 (C), 53.8 (CH), 66.2 (CH2), 79.6 (C), 126.6 (CH),
127.7 (CH), 128.6 (CH), 139.0 (C), 155.2 (C), 178.4 (C); IR 3402,
1728, 1690, 1520, 1142; FABMS m/z 322 (M + H), 266 (M − t-Bu),
206 (M − PivOCH2), 150, 57 (t-Bu). Anal. Calcd. for C18H27NO4: C,
67.26; H, 8.47; N, 4.36. Found: C, 67.21; H, 8.35; N, 4.31.
156.4 (C), 178.4 (C); IR 3341, 2970, 1728, 1535; FABMS m/z 280
(M + H), 220 (M − CO2Me), 205 (M − NHCO2Me), 57 (t-Bu);
HRMS−FAB (m/z) [M + H]+ calcd for C15H22NO4 280.1543, found
280.1546.
2-Isocyanato-2-phenylethyl Pivalate (11). The yields were
1
calculated on the basis of integration area of the H NMR signals at
4.95 (CH of 11) and 4.22−4.26 (overlapping PivOCH2 of 10a and
10d) ppm of crude mixtures. After column chromatography (hexane/
EtOAc 19/1), the title compound was isolated with 20−90% loss of
N-(2-Methylbenzylidene)-p-anisidine (2e). Pale yellow blocks
1
of mp 50−51 °C (hexane): H NMR 2.58 (s, 3H), 3.84 (s, 3H), 6.94
1
(d, J = 9.0, 2H), 7.19−7.25 (m, 3H), 7.27−7.37 (m, 2H), 8.06 (dd, J =
1.5, 8.0, 1H), 8.77 (s, 1H); 13C NMR 19.4 (CH3), 55.5 (CH3), 114.3
(CH), 122.1 (CH), 126.3 (CH), 127.5 (CH), 130.7 (CH), 130.9
(CH), 134.3 (C), 138.3 (C), 145.6 (C), 157.1 (CH), 158.2 (C); IR
2908, 1597, 1504, 1242; EIMS m/z 225 (M+); HRMS−FAB (m/z)
[M + H]+ calcd for C15H16NO, 226.1226, found 226.1229.
the yield as colorless oil: H NMR 1.23 (s, 9H), 4.09 (dd, J = 9.0, 11.5,
1H), 4.35 (dd, J = 4.0, 11.5, 1H), 4.95 (dd, J = 4.0, 9.0, 1H), 7.32−7.43 (m,
5H); 13C NMR 27.0 (CH3), 38.9 (C), 57.9 (CH), 68.3 (CH2), 125.4 (C),
126.3 (CH), 128.6 (CH), 128.9 (CH), 136.7 (C), 178.1 (C); IR 2970,
2268, 1736, 1481; CIMS m/z 248 (M + H), 205 (M − NCO); HRMS−
CI (m/z) [M + H]+ calcd for C14H18NO3, 248.1281, found 248.1280.
2-Ethoxycarbonylamino-2-phenylethyl Pivalate (10d). Table 1,
Entry 5. The typical procedure was followed, except that toluene,
instead of CH2Cl2, was used as solvent at rt using 9d in place of 9a.
After a total addition of 6.0 mmol Et3B, the mixture was stirred for
another 1 h, and EtOH (1.0 mL, 17 mmol) was added. The mixture
was heated under reflux for 3 h, cooled to rt, and diluted with EtOAc.
The whole was washed with 10% Na2S2O3 and brine, dried over
Na2SO4, and then concentrated in vacuo. The resulting residue was
purified by column chromatography (hexane/EtOAc 9/1) to afford
the title compound (249 mg, 85%) as colorless oil: 1H NMR (55 °C)
1.14 (s, 9H), 1.22 (t, J = 7.0, 3H), 4.05−4.15 (m, 2H), 4.26 (dd, J =
5.5, 11.0, 1H), 4.36 (dd, J = 7.5, 11.0, 1H), 5.03 (ddd, J = 5.5, 6.0, 7.5,
1H), 5.13 (br m, 1H), 7.26−7.36 (m, 5H); 13C NMR 14.5 (CH3),
27.0 (CH3), 38.8 (C), 54.5 (CH), 61.1 (CH2), 66.2 (CH2), 126.7
(CH), 127.9 (CH), 128.7 (CH), 138.9 (C), 156.1 (C), 178.4 (C); IR
3387, 1720, 1512, 1157; FABMS m/z 294 (M + H), 278 (M − Me),
221 (M + H − CO2Et), 205 (M − NHCO2Et), 178 (M − PivOCH2),
57 (t-Bu); HRMS−FAB (m/z) [M + H]+ calcd for C16H24NO4,
294.1705, found 294.1710.
2-Benzyloxycarbonylamino-2-phenylethyl Pivalate (10e).
Purified by column chromatography (hexane/EtOAc 19/1). White
solids of mp 49−50 °C (hexane): 1H NMR (55 °C) 1.12 (s, 9H), 4.28
(dd, J = 11.5, 5.0, 1H), 4.36 (dd, J = 11.5, 7.5, 1H), 5.00−5.15 (m,
3H), 5.24 (br m, 1H), 7.25−7.40 (m, 10H); 13C NMR 26.8 (CH3),
38.5 (C), 54.2 (CH), 65.9 (CH2), 66.6 (CH2), 126.4 (CH), 127.6
(CH), 127.90 (CH), 127.94 (CH), 128.2 (CH), 128.4 (CH), 136.2
(C), 138.4 (C), 155.7 (C), 178.2 (C); IR 3379, 2955, 1697, 1528,
1234, 1157; FABMS m/z 356 (M + H), 254 (M − t-BuCO2), 240 (M −
t-BuCO2CH2), 221 (M + H − PhCH2OCO), 205 (M − PhCH2OCONH).
Anal. Calcd. for C21H25NO4: C, 70.96; H, 7.09; N, 3.94. Found: C,
70.84; H, 7.09; N, 3.92.
2-p-Toluenesulfonamido-2-o-tolylethyl Pivalate (3d) and 2-
(2-Pivaloyloxyethyl)phenyl-2-(p-toluenesulfonamido)ethyl
Pivalate (4d). The typical procedure at rt using 2d in place of 9a
followed by column chromatography (toluene/EtOAc 19/1 to 3/1)
afforded 3d as colorless prisms of mp 106−107 °C (EtOAc): 1H NMR
1.11 (s, 9H), 2.25 (s, 3H), 2.34 (s, 3H), 4.15 (d, J = 8.5, 2H), 4.93 (dt,
J = 8.5, 8.5, 1H), 5.25 (br m, 1H), 6.99−7.04 (m, 2H), 7.07−7.12 (m,
4H), 7.53 (d, J = 8.5, 2H); 13C NMR 19.0 (CH3), 21.3 (CH3), 27.0
(CH3), 38.7 (C), 53.0 (CH), 65.6 (CH2), 126.2 (CH), 126.4 (CH),
127.0 (CH), 127.8 (CH), 129.4 (CH), 130.5 (CH), 135.1 (C), 135.3
(C), 137.4 (C), 143.3 (C), 178.5 (C); IR 3279, 2978, 1728, 1597,
1458, 1327, 1281, 1165, 1088, 1034; EIMS m/z 274 (M − PivOCH2),
155 (Ts), 118, 91 (tolyl). Anal. Calcd. for C21H27NO4S: C, 64.75; H,
6.99; N, 3.60. Found: C, 64.49; H, 6.91; N, 3.59. 4d was also afforded
as colorless oil: 1H NMR 1.11 (s, 9H), 1.18 (s, 9H), 2.35 (s, 3H), 2.91
(m, 2H), 4.15−4.23 (m, 4H), 5.00 (dt, J = 6.5, 6.5, 1H), 5.35 (br m,
1H), 7.04−7.15 (m, 6H), 7.55 (d, J = 8.0, 2H); 13C NMR 21.3 (CH3),
26.9 (CH3), 27.0 (CH3), 31.4 (CH2), 38.6 (C), 38.7 (C), 52.6 (CH),
65.8 (CH2), 65.9 (CH2), 127.0 (CH), 127.0 (CH), 127.1 (CH), 127.9
(CH), 129.4 (CH), 130.0 (CH), 135.1 (C), 135.4 (C), 137.5 (C),
143.3 (C), 178.4 (C), 178.5 (C); IR 3279, 2970, 1728, 1481, 1350,
1288, 1157, 1088; FABMS m/z 504 (M + H), 402 (M − PivO), 388
(M − PivOCH2); HRMS−FAB (m/z) [M + H]+ calcd for
C27H38SNO6, 504.2420, found 504.2419.
2-p-Anisidino-2-o-tolylethyl Pivalate (3e). The typical proce-
dure at rt using 2e in place of 9a followed by column chromatography
(hexane/EtOAc 19/1) afforded the title compound as pale-yellow oil:
1H NMR 1.18 (s, 9H), 2.49 (s, 3H), 3.69 (s, 3H), 4.11 (br s, 1H), 4.16
(dd, J = 8.5, 11.5, 1H), 4.32 (dd, J = 4.5, 11.5, 1H), 4.78 (dd, J = 4.5,
8.5, 1H), 6.43 (d, J = 9.0, 2H), 6.69 (d, J = 9.0, 2H), 7.13−7.22
(m, 3H), 7.47 (m, 1H); 13C NMR 18.9 (CH3), 27.0 (CH3), 38.7 (C),
54.8 (CH), 55.4 (CH3), 66.2 (CH2), 114.3 (CH), 114.6 (CH), 126.0
(CH), 126.3 (CH), 127.3 (CH), 130.6 (CH), 135.2 (C), 137.3 (C),
141.3 (C), 152.1 (C), 178.4 (C); IR 3402, 2970, 1728, 1512, 1149;
FABMS m/z 342 (M + H), 341 (M+), 226 (M − PivOCH2), 219
(M − NHC6H4OMe), 57 (t-Bu); HRMS−FAB (m/z) [M + H]+ calcd
for C21H28NO3, 342.2064, found 342.2062.
2-(4-Bromophenyl)-2-tert-butoxycarbonylaminoethyl Piva-
late (10f). Purified by column chromatography (hexane/EtOAc 19/1).
1
Colorless needles of mp 92−93 °C (hexane): H NMR (55 °C) 1.15
(s, 9H), 1.41 (s, 9H), 4.22 (dd, J = 5.0, 11.5, 1H), 4.29 (dd, J = 7.0,
11.5, 1H), 4.92 (br m, 1H), 4.99 (br m, 1H), 7.17 (d, J = 8.5, 2H),
7.46 (d, J = 8.5, 2H); 13C NMR 27.0 (CH3), 28.2 (CH3), 38.7 (C),
53.4 (CH), 65.9 (CH2), 79.9 (C), 121.6 (C), 128.2 (CH), 131.6
(CH), 138.1 (C), 155.0 (C), 178.3 (C); IR 3348, 2978, 1728, 1681, 1535,
1157; FABMS m/z 402, 400 (M + H), 346, 344 (M − t-Bu), 302, 300,
285, 283 (M − NHBoc), 230, 228. Anal. Calcd. for C18H26BrNO4: C,
54.01; H, 6.55; N, 3.50. Found: C, 54.03; H, 6.56; N, 3.44.
2-Phenyl-2-(2-trimethylsilylethyl)carbonylaminoethyl Piva-
late (10b). Purified by column chromatography (hexane/EtOAc 9/1).
1
White solids of mp 59−61 °C (hexane): H NMR (55 °C) 0.02 (s,
9H), 0.96 (dd, J = 7.5, 9.5, 2H), 1.14 (s, 9H), 4.12−4.20 (m, 2H), 4.27
(dd, J = 5.0, 11.5, 1H), 4.35 (dd, J = 7.5, 11.0, 1H), 5.02 (ddd, J = 5.0,
7.5, 7.5, 1H), 5.13 (br m, 1H), 7.24−7.36 (m, 5H); 13C NMR −1.60
(CH3), 17.6 (CH2), 27.0 (CH3), 38.8 (C), 54.3 (CH), 63.3 (CH2),
66.2 (CH2), 126.6 (CH), 127.9 (CH), 128.7 (CH), 138.8 (C), 156.1
(C), 178.5 (C); IR 3348, 2955, 1728, 1528, 1250; FABMS m/z 366
(M + H), 250 (M − PivOCH2), 205 (M − NHCO2C2H4TMS), 57
(t-Bu). Anal. Calcd. for C19H31NO4Si: C, 62.43; H, 8.55; N, 3.83.
Found: C, 62.13; H, 8.25; N, 3.82.
2-tert-Butoxycarbonylamino-2-(4-methoxyphenyl)ethyl Piv-
alate (10g). Purified by column chromatography (hexane/EtOAc 19/1).
1
White solids of mp 76−76.5 °C (hexane): H NMR (55 °C) 1.15 (s,
9H), 1.41 (s, 9H), 3.77 (s, 3H), 4.22 (dd, J = 5.5, 11.5, 1H), 4.28 (dd,
J = 7.5, 11.5, 1H), 4.91 (br m, 1H), 5.06 (br d, J = 7.5, 1H), 6.86 (d,
J = 8.5, 2H), 7.21 (d, J = 8.5, 2H); 13C NMR 27.0 (CH3), 28.3 (CH3),
38.7 (C), 53.5 (CH), 55.2 (CH3), 66.2 (CH2), 79.5 (C), 114.1 (CH),
127.7 (CH), 131.3 (C), 155.1 (C), 159.2 (C), 178.2 (C); IR 3371, 2978,
1720, 1512, 1165; FABMS m/z 352 (M + H), 296 (M − t-Bu), 236
(M − PivOCH2), 235 (M − NHBoc), 180. Anal. Calcd. for C19H29NO5:
C, 64.93; H, 8.32; N, 3.99. Found: C, 64.77; H, 8.48; N, 4.06.
2-Methoxycarbonylamino-2-phenylethyl Pivalate (10c). Pu-
rified by column chromatography (hexane/EtOAc 9/1). Colorless oil:
1H NMR (58 °C) 1.14 (s, 9H), 3.66 (s, 3H), 4.27 (dd, J = 4.5, 11.5,
1H), 4.36 (dd, J = 7.5, 11.5, 1H), 5.02 (m, 1H), 5.15 (br m, 1H),
7.26−7.37 (m, 5H); 13C NMR 27.0 (CH3), 38.8 (C), 52.2 (CH3), 54.4
(CH), 66.1 (CH2), 126.5 (CH), 127.9 (CH), 128.6 (CH), 138.5 (C),
2-tert-Butoxycarbonylamino-2-p-tolylethyl Pivalate (10h).
Purified by column chromatography (hexane/EtOAc 19/1). Colorless
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Article
1
prisms of mp 75−75.5 °C (hexane): H NMR (55 °C) 1.15 (s, 9H),
afforded 3a3 (41%) along with 2a (24%), tosylamide (11%), and
17a (8%) as colorless oil: 1H NMR 1.05 (s, 9H), 1.06 (s, 9H), 2.44 (s,
3H), 4.29 (dd, J = 6.0, 11.5, 1H), 4.59 (dd, J = 8.5, 11.5, 1H), 5.10 (d,
J = 12.5, 1H), 5.39 (dd, J = 6.0, 8.5, 1H), 5.64 (d, J = 12.5, 1H), 7.13−
7.19 (m, 2H), 7.27−7.34 (m, 5H), 7.80 (d, J = 8.5, 2H); 13C NMR 21.5
(CH3), 26.8 (CH3), 26.9 (CH3), 38.5 (C), 38.6 (C), 58.3 (CH), 62.8
(CH2), 70.2 (CH2), 127.6 (CH), 128.0 (CH), 128.5 (CH), 128.7 (CH),
129.7 (CH), 134.9 (C), 137.6 (C), 144.0 (C), 177.4 (C), 177.9 (C); IR
2970, 1728, 1149; FABMS m/z 512 (M + Na), 388 (M − PivO), 374
(M − PivOCH2), 260, 205 (M − PivOCH2NTs); HRMS−FAB (m/z)
[M + Na]+ calcd for C26H35NO6SNa, 512.2077, found 512.2088.
2-(4-Methoxyphenyl)amino-2-phenylethyl Pivalate (3b). The
typical procedure at −78 °C using 2b in place of 9a followed by
column chromatography (hexane/EtOAc 9/1) afforded the title
compound3 in 27% yield.
1.40 (s, 9H), 2.30 (s, 3H), 4.23 (dd, J = 5.5, 11.5, 1H), 4.28 (dd, J =
7.5, 11.5, 1H), 4.94 (br m, 1H), 5.27 (br m, 1H), 7.11 (d, J = 8.0, 2H),
7.18 (d, J = 8.0, 2H); 13C NMR 20.7 (CH3), 26.9 (CH3), 28.2 (CH3),
38.6 (C), 53.8 (CH), 66.2 (CH2), 79.3 (C), 126.4 (CH), 129.0 (CH),
136.1 (C), 137.1 (C), 155.1 (C), 178.0 (C); IR 3363, 2978, 1736, 1681,
1528, 1150; FABMS m/z 336 (M + H), 280 (M − t-Bu), 236, 220 (M −
PivOCH2), 219 (M − NHBoc), 164. Anal. Calcd. for C19H29NO4: C,
68.03; H, 8.71; N, 4.18. Found: C, 67.92; H, 8.95; N, 4.14.
2-tert-Butoxycarbonylamino-2-o-tolylethyl Pivalate (10i).
Purified by column chromatography (hexane/EtOAc 19/1). Colorless
needles of mp 113−114 °C (hexane): 1H NMR (55 °C) 1.16 (s, 9H),
1.40 (s, 9H), 2.43 (s, 3H), 4.23 (d, J = 7.0, 2H), 4.97 (br d, J = 7.0,
1H), 5.22 (br m, 1H), 7.13−7.23 (m, 4H); 13C NMR 19.2 (CH3),
27.1 (CH3), 28.4 (CH3), 38.8 (C), 50.6 (CH), 65.6 (CH2), 79.7 (C),
125.6 (CH), 126.2 (CH), 127.6 (CH), 130.8 (CH), 135.9 (C), 137.3
(C), 155.1 (C), 178.4 (C); IR 3309, 2978, 1736, 1674, 1550, 1288,
1142; FABMS m/z 336 (M + H), 280 (M − t-Bu), 220 (M −
PivOCH2), 219 (M − NHBoc), 164. Anal. Calcd. for C19H29NO4: C,
68.03; H, 8.71; N, 4.18. Found: C, 68.00; H, 8.92; N, 4.12.
2-tert-Butoxycarbonylamino-4-phenylbutyl Pivalate (10j).
Purified by column chromatography (hexane/EtOAc 19/1). Colorless
needles of mp 69−70 °C (hexane): 1H NMR (55 °C) 1.20 (s, 9H), 1.45
(s, 9H), 1.69−1.78 (m, 1H), 1.78−1.88 (m, 1H), 2.62−2.77 (m, 2H),
3.89 (br m, 1H), 4.03 (dd, J = 4.5, 11.0, 1H), 4.11 (dd, J = 5.5, 11.0, 1H),
4.45 (br m, 1H), 7.14−7.20 (m, 3H), 7.25−7.30 (m, 2H); 13C NMR 26.9
(CH3), 28.1 (CH3), 31.9 (CH2), 33.5 (CH2), 38.5 (C), 49.2 (CH), 65.7
(CH2), 78.9 (C), 125.7 (CH), 128.1 (CH), 128.2 (CH), 141.1 (C), 155.2
(C), 178.0 (C); IR 3333, 2963, 1728, 1690, 1535, 1173; FABMS m/z 350
(M + H), 294 (M − t-Bu), 250. Anal. Calcd. for C20H31NO4: C, 68.74;
H, 8.94; N, 4.01. Found: C, 68.64; H, 8.94; N, 4.03.
tert-Butyl N-(2-Hydroxy-1-phenylethyl)carbamate (20). To a
solution of 10a (161 mg, 0.50 mmol) in MeOH (0.5 mL) was added 2
M KOH (0.5 mL) at rt, and the mixture was stirred for 5 h. The
mixture was diluted with water (5 mL) and extracted three times with
EtOAc. The combined organic layers were washed with brine, dried
over Na2SO4, and concentrated in vacuo. The resulting residue was
purified by chromatography (hexane/EtOAc 4/1) gave the title
compound (94.4 mg, 80%) as a white solid of mp 141−142 °C (lit.38
141−142 °C): IR 3310, 3225, 1674, 1558; FABMS (m/z) 238 (M + H),
1
206 (M − CH2OH), 182 (M − t-Bu), 136 (M − Boc). H and 13C
NMR were identical to those reported.39
2-Amino-2-phenylethyl Pivalate (21). To a solution of 10a
(161 mg, 0.50 mmol) in CH2Cl2 (2 mL) was added TFA (1 mL) at rt.
The mixture was stirred for 30 min and concentrated in vacuo. The
residual TFA was removed by three-time azeotropic distillation with
toluene. The residue, containing a TFA salt of the title compound, was
dissolved in Et2O (2 mL) and poured into stirred 10% NaOH cooled
in an ice−water bath. The whole was extracted three times with Et2O.
The combined organic layers were washed with brine, dried over
K2CO3, and concentrated in vacuo to give the title compound (99.6
Di-tert-butyl Benzylidenedicarbamate (15). The typical
procedure was followed in the presence of t-BuOH (1 equiv) at rt
to afford 10a (73%) along with the title compound (11%) as white
1
solids of mp 140−142 °C (EtOAc): H NMR (55 °C) 1.44 (s, 18H),
5.33 (br m, 2H), 6.09 (t, J = 7.5, 1H), 7.26−7.44 (m, 5H); 13C NMR
28.3 (CH3), 61.9 (CH), 80.1 (C), 125.8 (CH), 127.9 (CH), 128.5
(CH), 140.0 (C), 154.8 (C); IR 3317, 2978, 1697, 1504; FABMS m/z
345 (M + Na), 323 (M + H), 206 (M − NHBoc); HRMS−FAB (m/z)
[M + H]+ calcd for C17H27N2O4, 323.1965, found 323.1970.
1
mg, 90%) as pale orange oil: H NMR 1.19 (s, 9H), 1.59 (br s, 2H),
4.05 (dd, J = 7.5, 10.0, 1H), 4.23 (dd, J = 4.5, 10.0, 1H), 4.26 (dd, J =
4.5, 7.5, 1H), 7.27−7.42 (m, 5H); 13C NMR 27.0 (CH3), 38.6 (C),
54.5 (CH), 69.6 (CH2), 126.6 (CH), 127.5 (CH), 128.4 (CH), 141.6
(C), 178.0 (C); IR 3379, 2970, 1728, 1481; FABMS m/z 222 (M + H),
205 (M − NH2), 165 (M − t-Bu); HRMS−FAB (m/z) [M + H]+ calcd
for C13H20NO2, 222.1489, found 222.1488.
tert-Butyl 2-Methyl-1-phenylpropylcarbamate (16a). The
typical procedure at −50 °C using 2-iodopropane in place of 1
followed by column chromatography (hexane/EtOAc 19/1) afforded
the title compound in 99% yield as white solids of mp 107−107.5 °C
(lit.34 61 °C): FABMS m/z 250 (M + H), 206 (M − i-Pr), 194 (M −
Migration of a Pivaloyl Group: 2-Amino-2-phenylethyl
Pivalate. The above procedure was followed to obtain a TFA salt
of 21, to which was added 10% NaOH (5 mL). The whole was
extracted three times with Et2O. The combined organic layers were
washed with brine, dried over K2CO3 and concentrated in vacuo to
34
t-Bu). H and 13C NMR and IR were identical to those reported.
1
2-Methyl-1-phenylpropyl Isocyanate.35 Purified by column
1
chromatography (hexane/EtOAc 19/1). Colorless oil: H NMR 0.92
(d, J = 6.5, 3H), 0.94 (d, J = 6.5, 3H), 2.03 (dqq, J = 6.0, 6.5, 6.5, 1H),
4.42 (d, J = 6.0, 1H), 7.24−7.40 (m, 5H); 13C NMR 17.6 (CH3), 19.7
(CH3), 36.0 (CH), 65.5 (CH), 122.6 (C), 126.3 (CH), 127.7 (CH),
128.4 (CH), 140.3 (C); IR 2970, 2268, 1458; EIMS m/z 175 (M), 132
(M − i-Pr), 77 (Ph); HRMS−FAB (m/z) [M+] calcd for C11H13NO,
175.0997, found 175.1000.
1
give a mixture of 21 and the title compound (89:11 based on H
NMR) as orange oil. The oil was dissolved in Et2O (5 mL), and the
solution was extracted three times with 10% HCl. The combined
aqueous layers were washed three times with CHCl3, basified with
10% NaOH, and extracted three times with Et2O. The combined
organic layers were washed with brine, dried over Na2SO4, and
concentrated in vacuo to give the title compound (55.8 mg, 25%) as
white solids of mp 143−144 °C: IR 3271, 2962, 1627, 1535; FABMS
tert-Butyl 1-Phenylpropylcarbamate (16b). The typical
procedure at −50 °C without 1 followed by column chromatography
(hexane/EtOAc 19/1) afforded the title compound in 98% yield as
white solids of mp 91−92 °C (lit. 92−94 °C,12b 95 °C36): EIMS m/z
1
m/z 222 (M + H), 190 (M − CH2OH), 136 (M − Piv). H and 13C
234 (M − H), 206 (M − Et), 178 (M − t-Bu), 150, 106. H and 13
C
1
NMR were identical to those reported for the (S)-enantiomer.40
2-Amino-2-phenylethanol (22). To a solution of 10a (161 mg,
0.50 mmol) in dioxane (6 mL) was added 3 M HCl (12 mL). The
mixture was heated under reflux for 3 h, cooled to rt, basified with 10%
NaOH, and extracted three times with Et2O. The combined organic
layers were washed with brine, dried over Na2SO4, and concentrated in
vacuo. The resulting residue was purified by column chromatography
(EtOAc/EtOH 1/1) to afford the title compound (48.4 mg, 69%) as
white solids of mp 58−59 °C (lit.41 48.0−49.5 °C): IR 3333, 2870,
1605; FABMS m/z 138 (M + H). 1H and 13C NMR were identical to
those reported.42
NMR12b and IR36 were identical to those reported.
1-Phenylpropyl Isocyanate. Not isolated. The production was
confirmed on the basis of 1H NMR (identical signals to those
reported37), IR (2268 cm−1), and EIMS (m/z = 161 [M+]) of the
crude material. The yield was based on integration area of the H
NMR signals at 1.82 (CH2 of the title compound) and 1.77 (CH2 of
16b) ppm of the crude mixture.
2-Phenyl-2-(p-toluenesulfonamido)ethyl Pivalate (3a) and
2-Phenyl-2-(N-pivaloyloxymethyl-p-toluenesulfonamido)ethyl
Pivalate (17a). The typical procedure at −78 °C using 2a in place of
9a followed by column chromatography (hexane/EtOAc 9/1)
1
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Article
265. (b) Yamada, K.; Maekawa, M.; Yamamoto, Y.; Nakano, M.;
Akindele, T.; Tomioka, K. Tetrahedron Lett. 2009, 50, 6040.
(c) Yamada, K.; Maekawa, M.; Akindele, T.; Yamamoto, Y.; Nakano,
M.; Tomioka, K. Tetrahedron 2009, 65, 903. (d) Yamada, K.;
Maekawa, M.; Akindele, T.; Nakano, M.; Yamamoto, Y.; Tomioka, K.
J. Org. Chem. 2008, 73, 9535 and references therein.
(14) (a) Maury, J.; Feray, L.; Perfetti, P.; Bertrand, M. P. Org. Lett.
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Tetrahedron 2007, 63, 77 and references therein.
(15) (a) Akindele, T.; Yamada, K.; Tomioka, K. Acc. Chem. Res. 2009,
42, 345. (b) Bazin, S.; Feray, L.; Bertrand, M. P. Chimia 2006, 60, 260.
(16) (a) Valli, V. L. K.; Alper, H. J. Org. Chem. 1995, 60, 257.
(b) Butler, D. C. D.; Alper, H. Chem. Commun. 1998, 2575.
(17) Formation of ethylcarbamate from isocyanate in the presence of
Et3B and air: Yoshimitsu, T.; Matsuda, K.; Nagaoka, H.; Tsukamoto,
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ASSOCIATED CONTENT
* Supporting Information
NMR spectra of the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: yamak@pharm.kyoto-u.ac.jp; tomioka@pharm.kyoto-u.
ac.jp.
■
ACKNOWLEDGMENTS
We are grateful to JSPS and JST for financial support.
■
REFERENCES
■
(1) Reviews on radical addition to CN bonds: (a) Miyabe, H.;
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