Dirhodium(II)-catalyzed C-H amination reaction of (S)-3-(tert- butyldimethylsilyloxy)-2-methylpropyl carbamate: A facile preparation of optically active monoprotected 2-amino-2-methyl-1,3-propanediol

Article abstract of DOI:10.1248/cpb.55.1385

Dirhodium(II)-catalyzed C-H amination reaction of (S)-3-(tert- butyldimethylsilyloxy)-2-methylpropyl carbamate, which was easily prepared from methyl (S)-2-methyl-3-hydroxypropanoate, proceeded more smoothly than those of their 2-(methoxycarbonyl)propyl d

Full text of DOI:10.1248/cpb.55.1385

September 2007
Notes
Chem. Pharm. Bull. 55(9) 1385—1389 (2007)
1385
Dirhodium(II)-Catalyzed C–H Amination Reaction of (S)-3-(tert-
Butyldimethylsilyloxy)-2-methylpropyl Carbamate: A Facile Preparation
of Optically Active Monoprotected 2-Amino-2-methyl-1,3-propanediol
Takayuki YAKURA,* Yuya YOSHIMOTO, and Chisaki ISHIDA
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama; Sugitani, Toyama 930–0194, Japan.
Received March 22, 2007; accepted June 13, 2007; published online June 15, 2007
Dirhodium(II)-catalyzed C–H amination reaction of (S)-3-(tert-butyldimethylsilyloxy)-2-methylpropyl car-
bamate, which was easily prepared from methyl (S)-2-methyl-3-hydroxypropanoate, proceeded more smoothly
than those of their 2-(methoxycarbonyl)propyl derivative to give the corresponding oxazolidinone in excellent
yield. The resulting oxazolidinone was converted efficiently into both (R)-monoprotected and (S)-monoprotected
2-amino-2-methyl-1,3-propanediols.
Key words dirhodium(II); C–H amination; 3-silyloxy-2-methylpropyl carbamate; 2-amino-2-methyl-1,3-propanediol mono-
ether; oxazolidinone
The direct amination of chiral substrates in a stereoselec- of our studies on dirhodium(II)-catalyzed reactions,14—23)
tive manner is a simple and straightforward approach for the we have been interested in the study and development of
synthesis of optically active nitrogen-containing compounds. a more efficient route to a-methylserine derivatives using
Metal catalyzed C–H amination1—4) of carbamates and sul- dirhodium(II)-catalyzed C–H amination reaction of carba-
fonamides demonstrated by Du Bois’ group and the other mate.
groups have become a powerful tool for this purpose in re-
The unsatisfactory result in the reaction of 2 probably re-
cent synthetic organic chemistry. In our recently reported sults from the low reactivity of C–H bond a to the electron-
stereoselective total synthesis of an immunomodulator (ꢀ)- deficient ester group.1,2,24) We anticipated that the C–H ami-
conagenin,5,6) we applied dirhodium(II)-catalyzed C–H ami- nation reaction can proceed more smoothly if carbamate has
nation reaction of carbamate (2) derived from optically active a protected hydroxymethyl group as an alternative to the
methyl 2-methyl-3-hydroxypropanoate (1) to prepare its a- ester group. The expected resultant oxazolidinone (7) should
methylserine moiety (4) (Chart 1). This method has proved to be converted easily into optically active monoprotected 2-
be a convenient procedure for synthesis of a-methylserine it- amino-2-methyl-1,3-propanediol (8), which has proved to be
self because of the short steps and ready availability of the a useful intermediate of a-methyl-a-amino acids.25—28) Al-
starting material. Chiral a-methylserines have attracted much though dirhodium(II)-catalyzed C–H amination reaction of
attention also as important synthetic intermediates of a- simple alkyl carbamates and carbamates derived from cy-
methyl-a-amino acids,7—12) which are an important class of cloalkanols bearing alkoxy groups29—31) has been well inves-
non-proteinogenic amino acids used to increase conforma- tigated, little information is available concerning influences
tional restrictions in peptides and thereby change their bio- of protecting groups of hydroxy group in acyclic system. For
logical activity and stability.13) For intermediate synthesis of those reasons, we examined dirhodium(II)-catalyzed C–H
a-methyl-a-amino acids, however, the procedure is not satis- amination reaction of 3-hydroxy-2-methylpropyl carbamates
factory because of the only moderate yield of C–H amina- having typical protecting groups (6) (Chart 2).
tion reaction of carbamate (2). In this context and as a part
The starting carbamates (6a—d) were easily prepared
using the usual protocol6) from known alcohols (5a—
d),32—34) which were all obtainable from (S)-1. The results of
dirhodium(II)-catalyzed C–H amination reactions of 6a—d
are summarized in Table 1. Thus, according to our reported
prodcedure,6) treatment of 6a with 10 mol% of dirhodium(II)
Chart 2
Chart 1
∗ To whom correspondence should be addressed. e-mail: yakura@pha.u-toyama.ac.jp
© 2007 Pharmaceutical Society of Japan

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Vol. 55, No. 9
Table 1. Dirhodium(II)-Catalyzed C–H Amination of Carbamates (6)a)
Yield of
7 (%)
Recovery of
Yield based on
comsumed 6 (%)
Entry
6
Rh(II)
Solvent
6 (%)
1
2
3
a
b
c
d
c
c
c
c
c
c
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(oct)4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
(CH2Cl)2
CH2Cl2
CH2Cl2
CH2Cl2
28
32
63
24
59
20
35
54
57
67
22
26
31
57
16
20
0
30
22
2
36
43
91
56
70
25
35
77
73
69
4
5b)
6
7
8
9
10
Rh2(tpa)4
Rh2(esp)2
a) The reaction was carried out using 10 mol% of Rh(II) catalyst, 4.2 eq of PhI(OAc)2, and 6.9 eq of MgO under reflux for 17 h. b) The reaction was heated for 40 h.
Chart 3
Chart 4
tetraacetate, 4.2 eq of phenyliodine(III) diacetate, and 6.9 eq
of magnesium oxide in dichloromethane under reflux for 17 h
gave the corresponding C–H amination product 7a in 28%
yield along with 22% of recovered 6a and a complicated
mixture (entry 1). A similar reaction of 6b gave 7b in 32%
yield with 26% of 6b (entry 2). However, reaction of
TBDMS ether (6c) afforded 63% of 7c along with 31% of 6c
(91% yield based on the consumed 6c, entry 3). Reaction of
TBDPS ether (6d) proceeded slowly to provide 7d in 24%
yield (entry 4). Because the TBDMS group is the most suit-
able protecting group among the examined groups, we next
sought to optimize the reaction conditions. Unfortunately, we
Chart 5
observed no better result than that shown in entry 3, although
the starting 6c was not completely consumed. Consequently,
longer reaction time was ineffective (entry 5). Reactions at shown in Chart 4.2) Carbamate (6) is first oxidized with
higher temperatures decreased the yield of 7c and recovery PhI(OAc)2 to form iodonium ylide (A), which is transformed
of 6c (entries 6, 7). Slightly lower yields were obtained in the to rhodium nitrenoid (B) with elimination of iodobenzene.
reactions using dirhodium(II) tetraoctanoate [Rh2(oct)4] and The nitrogen atom is inserted stereospecifically to the me-
dirhodium(II) tetrakis(triphenylacetate) [Rh2(tpa)4] (entries 8, thine C–H bond with release of Rh(II) species, which can be
9). When 6c was reacted with dirhodium(II) bis(a,a,aꢁ,aꢁ- reused to form B, to give oxazolidinone (7). The electron-do-
tetramethyl-1,3-benzenedipropanoate) [Rh2(esp)2],35) which nating silyloxymethyl group in 6c would enhance the reactiv-
gave the best result in the reaction of ester 2,6) 7c was ob- ity of C–H bond at its a-position against the electrophilic
tained in the highest yield (67%). However, recovery of the rhodium nitrenoid, on the other hand, the electron-deficient
starting 6c was only 2%; therefore, the yield based on the ester group of 2 would decrease the reactivity of a C–H
consumed 6c was calculated as 69% (entry 10).
bond.1,2,24) In the reactions of PMB and benzyl ethers (6a, b),
37—40)
Alternatively, we examined the C–H amination of tosyl- oxidations of PMB and benzyl groups by PhI(OAc)2
oxycarbamate (9), which was prepared from 5c according to might occur as side reactions to produce complex mixtures
Lebel’s procedure36) (Chart 3). The C–H amination reaction and to give low yields of oxazolidinones (7a, b). The bulky
proceeded more smoothly than that of ester derivative (10)6) TBDPS group might decrease the reactivity of C–H group by
when 9 was treated with Rh2(tpa)4 in the presence of potas- steric hindrance to cause low yield.
sium carbonate in dichloromethane at room temperature to
give oxazolidinone (7c) in 54% yield (29% for 10). In this re- monoprotected 2-amino-2-methyl-1,3-propanediol was in-
action, the starting 9 was consumed completely. vestigated (Chart 5). The NH group of oxazolidinone (7c)
A possible reaction mechanism for C–H amination of 6 is was protected with tert-butoxycarbonyl (Boc) group in 90%
Application to the preparation of the optically active

September 2007
1387
(R)-3-(tert-Butyldimethylsilyloxy)-2-methylpropyl Carbamate (6c)
According to the general procedure, 5c34) (491 mg, 2.4 mmol) was treated
with trichloroacetyl isocyanate (542 mg, 2.88 mmol) in dichloromethane
(20 ml) and crude material was chromatographed on silica gel (40% EtOAc
in hexane) to give 6c (593 mg, quant) as a colorless oil. [a]D281 ꢀ4.03°
yield, followed by oxazolidinone ring opening by treatment
with cesium carbonate in methanol41) to give optically active
(S)-2-(Boc)amino-2-methyl-3-TBDMSoxypropanol (8c) in
77% yield. Dess–Martin oxidation of 8c proceeded smoothly
to provide the corresponding aldehyde (11) in 73% yield. (cꢃ0.99, CHCl3). IR (neat) cmꢂ1: 3352, 1715, 1603, 1472, 1408. H-NMR
(270 MHz, CDCl3) d: 0.04 (6H, s), 0.89 (9H, s), 0.93 (3H, d, Jꢃ6.9 Hz),
1.96 (1H, octet, Jꢃ6.4 Hz), 3.52 (2H, d, Jꢃ5.9 Hz), 3.97 (1H, dd, Jꢃ10.6,
6.3 Hz), 4.05 (1H, dd, Jꢃ10.6, 6.3 Hz), 4.64 (2H, br s). 13C-NMR
(67.5 MHz, CDCl3) d: ꢂ5.5 (2), 13.6, 18.3, 25.9 (3), 35.6, 64.7, 67.0, 157.1.
HR-MS m/z: 190.08899 (Calcd for C7H16NO3Si (MꢀꢂtBu): 190.08995).
(R)-3-(tert-Butyldiphenylsilyloxy)-2-methylpropyl Carbamate (6d)
According to the general procedure, 5d34) (447 mg, 1.36 mmol) was treated
with trichloroacetyl isocyanate (307 mg, 1.63 mmol) in dichloromethane
(14 ml) and crude material was chromatographed on silica gel (30% EtOAc
in hexane) to give 6d (506 mg, quant) as a colorless oil. [a]D28 ꢂ1.28°
(cꢃ0.70, CHCl3). IR (neat) cmꢂ1: 3456, 3342, 1717. 1H-NMR (270 MHz,
CDCl3) d: 0.96 (3H, d, Jꢃ6.9 Hz), 1.05 (9H, s), 2.02 (1H, octet, Jꢃ6.3 Hz),
3.58 (2H, d, Jꢃ5.3 Hz), 4.04 (1H, dd, Jꢃ10.6, 6.3 Hz), 4.11 (1H, dd,
Jꢃ10.6, 6.6 Hz), 4.66 (2H, br s), 7.32—7.45 (6H, m), 7.60—7.72 (4H, m).
13C-NMR (67.5 MHz, CDCl3) d: 13.6, 19.3, 26.8 (3), 35.5, 65.2, 66.8, 127.6
(4), 129.6 (2), 133.7 (2), 135.6 (4), 157.1. HR-MS m/z: 314.12079 (Calcd
for C17H20NO3Si (MꢀꢂtBu): 314.12125).
On the other hand, 8c was acylated with pivaloyl chloride
and desilylated to afford the known (R)-2-(Boc)amino-2-
methyl-3-pivaloyloxypropanol (12),42) [a]D28 ꢂ8.71°(cꢃ1.26,
CHCl3) {lit.42) [a]D25 ꢂ8.6° (cꢃ0.90, CHCl3)}. Optical purity
of 12 was determined to be 92.4% ee by chiral HPLC
analysis using Daicel Chiralpak OF (hexane/iPrOH, 70/30,
0.4 ml/min). This result reveals that the dirhodium(II)-cat-
alyzed C–H amination of 6c proceeded with retention of the
configuration.1,6)
In summary, we showed that dirhodium(II)-catalyzed C–H
amination reaction of 3-(TBDMSoxy)-2-methylpropyl carba-
mate (6c) proceeded more smoothly than those of ester deriv-
ative (2) to give the corresponding oxazolidinone (7c) in ex-
cellent yield. The resulting oxazolidinone was converted effi-
ciently into the optically active monoprotected 2-amino-2-
methyl-1,3-propanediols (8c, 12).
Dirhodium(II)-Catalyzed C–H Amination of Compound 6a. General
Procedure A suspension of 6a (51 mg, 0.20 mmol), PhI(OAc)2 (273 mg,
0.84 mmol), MgO (57 mg, 1.38 mmol), and Rh2(OAc)4 (9 mg, 0.02 mmol) in
dichloromethane (1.5 ml) was refluxed for 17 h. After the mixture was
cooled to room temperature, it was passed through a short Celite pad and the
Experimental
Melting points are uncorrected. IR spectra were recorded using JASCO filtrate was concentrated. The residue was chromatographed on silica gel
1
FT/IR-460 Plus spectrophotometer. H-NMR spectra were determined with (30% EtOAc in hexane) to give 7a (14 mg, 28%) and recovered 6a (11 mg,
Varian Gemini 300 (300 MHz) and JEOL JNM-FX270 (270 MHz) spec-
22%). (R)-4-(p-Methoxybenzyloxymethyl)-4-methyloxazolidin-2-one (7a)
trometers, tetramethylsilane as an internal standard. 13C-NMR spectra were was obtained as a colorless oil. [a]D26 ꢀ14.3° (cꢃ1.04, CHCl3). IR (neat)
determined with Varian Gemini 300 (75 MHz) and JEOL JNM-FX270
(67.5 MHz) spectrometers. All 13C-NMR spectra were determined with com-
plete proton decoupling. High resolution MS were determined with JEOL
JMS-GCmate and JEOL JMS-AX505HAD instruments. Optical rotations
cmꢂ1: 3282, 1754, 1612, 1514. 1H-NMR (300 MHz, CDCl3) d: 1.34 (3H, s),
3.33 (2H, s), 3.80 (3H, s), 4.00 (1H, d, Jꢃ8.5 Hz), 4.23 (1H, d, Jꢃ8.5 Hz),
4.47 (2H, s), 5.96 (1H, br s), 6.88 (2H, d, Jꢃ8.8 Hz), 7.22 (2H, d, Jꢃ8.8 Hz).
13C-NMR (75 MHz, CDCl3) d: 23.2, 55.3, 57.7, 73.1, 73.4, 74.6, 113.8 (2),
were measured with JASCO DIP-1000 polarimeter. Column chromatogra- 129.2 (2), 129.4, 159.0, 159.2. HR-MS m/z: 251.11318 (Calcd for
phy was performed on Silica Gel 60 PF254 (Nacalai Tesque) under pressure. C13H17NO4 (Mꢀ): 251.11576).
Methyl (S)-3-hydroxy-2-methylpropanoate [(S)-1] was provided by Mit-
subishi Rayon Co., Ltd. The known alcohols (5a,32) 5b,33) 5c,34) 5d34)) were general procedure, 6b (100 mg, 0.45 mmol) was treated with PhI(OAc)2
prepared from (S)-1 according to the reported procedures.
(606 mg, 1.88 mmol), MgO (125 mg, 3.09 mmol), and Rh2(OAc)4 (20 mg,
General Procedure for the Preparation of Carbamates (6a—d) 0.044 mmol) in refluxing dichloromethane (3.5 ml) and crude material was
Trichloroacetyl isocyanate (1.1—1.2 eq) was added to a solution of alcohol
chromatographed on silica gel (40% EtOAc in hexane) to give 7b (32 mg,
Dirhodium(II)-Catalyzed C–H Amination of 6b Following to the
(5) (1.0 eq) in dichloromethane at room temperature under a nitrogen atmo- 32%) and recovered 6b (26 mg, 26%). (R)-4-Benzyloxymethyl-4-methyloxa-
sphere and the mixture was stirred for 1 h. Then a mixture was passed zolidin-2-one (7b) was obtained as a colorless oil. [a]D26 ꢀ13.5° (cꢃ0.93,
1
through a short neutral Al2O3 column with ethyl acetate and the mixture was CHCl3). IR (neat) cmꢂ1: 3277, 1753. H-NMR (270 MHz, CDCl3) d: 1.37
concentrated. The residue was chromatographed on silica gel to give pure 6.
The following compounds were thus obtained.
(S)-3-(p-Methoxybenzyloxy)-2-methylpropyl Carbamate (6a) Accord-
ing to the general procedure, 5a32) (99 mg, 0.47 mmol) was treated with tri-
chloroacetyl isocyanate (107 mg, 0.55 mmol) in dichloromethane (5 ml) and
(3H, s), 3.37 (2H, s), 4.01 (1H, d, Jꢃ8.9 Hz), 4.24 (1H, d, Jꢃ8.6 Hz), 4.55
(2H, s), 5.76 (1H, br s), 7.24—7.41 (5H, m). 13C-NMR (67.5 MHz, CDCl3)
d: 23.1, 57.7, 73.3, 73.5, 75.0, 127.6 (2), 127.9, 128.5 (2), 137.4, 159.0. HR-
MS m/z: 221.10376 (Calcd for C12H15NO3 (Mꢀ): 221.10520).
Dirhodium(II)-Catalyzed C–H Amination of 6c Following to the gen-
crude material was chromatographed on silica gel (30% EtOAc in hexane) eral procedure, 6c (51 mg, 0.21 mmol) was treated with PhI(OAc)2 (279 mg,
to give 6a (111 mg, 94%) as colorless crystals, mp 47—49 °C
0.86 mmol), MgO (58 mg, 1.42 mmol), and Rh2(OAc)4 (9 mg, 0.021 mmol)
(EtOAc–hexane). [a]D28 ꢀ2.19°(cꢃ0.97, CHCl3). IR (KBr) cmꢂ1: 3411, in refluxing dichloromethane (1.6 ml) and crude material was chro-
1
1688, 1612, 1513. H-NMR (270 MHz, CDCl3) d: 0.96 (3H, d, Jꢃ6.6 Hz),
matographed on silica gel (10% EtOAc in hexane) to give 7c (32 mg, 63%)
2.10 (1H, octet, Jꢃ6.4 Hz), 3.31 (1H, dd, Jꢃ9.2, 5.9 Hz), 3.37 (1H, dd, and recovered 6c (16 mg, 31%). (S)-4-(tert-Butyldimethylsilyloxymethyl)-4-
Jꢃ9.2, 6.6 Hz), 3.80 (3H, s), 3.98 (1H, dd, Jꢃ10.5, 6.3 Hz), 4.07 (1H, dd, methyloxazolidin-2-one (7c) was obtained as colorless crystals, mp 75—
Jꢃ10.6, 5.9 Hz), 4.42 (2H, s), 4.78 (2H, br s), 6.86 (2H, d, Jꢃ8.6 Hz), 7.25
78 °C. [a]D28 ꢀ11.4° (cꢃ1.04, CHCl3). IR (KBr) cmꢂ1: 3347, 1720. 1H-
(2H, d, Jꢃ8.6 Hz). 13C-NMR (67.5 MHz, CDCl3) d: 14.0, 33.6, 55.2, 67.2, NMR (270 MHz, CDCl3) d: 0.08 (6H, s), 0.91 (9H, s), 1.34 (3H, s), 3.51
71.8, 72.7, 113.7 (2), 129.1 (2), 130.5, 157.1, 159.1. Anal. Calcd for (2H, s), 4.01 (1H, d, Jꢃ8.6 Hz), 4.27 (1H, d, Jꢃ8.2 Hz), 5.95 (1H, br s). 13C-
C13H19NO4: C, 61.64; H, 7.56; N, 5.53. Found: C, 61.73; H, 7.67; N, 5.57.
NMR (67.5 MHz, CDCl3) d: ꢂ5.6 (2), 18.1, 22.5, 25.7 (3), 58.6, 68.4, 73.0,
159.3. Anal. Calcd for C11H23NO3Si: C, 53.84; H, 9.45; N, 5.71. Found: C,
(S)-3-Benzyloxy-2-methylpropyl Carbamate (6b) According to the
general procedure, 5b33) (769 mg, 4.26 mmol) was treated with tri- 53.73; H, 9.35; N, 5.68.
chloroacetyl isocyanate (963 mg, 5.12 mmol) in dichloromethane (25 ml)
Dirhodium(II)-Catalyzed C–H Amination of 6d Following to the gen-
and crude material was chromatographed on silica gel (40% EtOAc in eral procedure, 6d (70 mg, 0.19 mmol) was treated with PhI(OAc)2 (254 mg,
hexane) to give 6b (952 mg, quant) as colorless crystals, mp 39—41 °C
0.79 mmol), MgO (52 mg, 1.3 mmol), and Rh2(OAc)4 (8 mg, 0.019 mmol) in
(EtOAc–hexane). [a]D28 ꢀ3.37° (cꢃ1.17, CHCl3). IR (KBr) cmꢂ1: 3350, refluxing dichloromethane (1.4 ml) and crude material was chromatographed
1
1715, 1602, 1455. H-NMR (270 MHz, CDCl3) d: 0.98 (3H, d, Jꢃ6.6 Hz),
on silica gel (10% EtOAc in hexane) to give 7d (17 mg, 24%) and recovered
2.13 (1H, octet, Jꢃ6.5 Hz), 3.36 (1H, dd, Jꢃ9.2, 5.9 Hz), 3.41 (1H, dd, 6d (40 mg, 57%). (S)-4-(tert-Butyldiphenylsilyloxymethyl)-4-methyloxazo-
Jꢃ9.2, 6.6 Hz), 4.00 (1H, dd, Jꢃ10.6, 6.3 Hz), 4.09 (1H, dd, Jꢃ10.6,
lidin-2-one (7d) was obtained as colorless crystals, mp 103—105 °C. [a]D29
6.3 Hz), 4.50 (2H, s), 4.65 (2H, br s), 7.22—7.40 (5H, m). 13C-NMR ꢀ6.74° (cꢃ0.68, CHCl3). IR (KBr) cmꢂ1: 3855, 1725. H-NMR (270 MHz,
(67.5 MHz, CDCl3) d: 14.0, 33.6, 67.2, 72.2, 73.1, 127.5 (3), 128.3 (2), CDCl3) d: 1.06 (9H, s), 1.33 (3H, s), 3.32 (1H, d, Jꢃ10.3 Hz), 3.71 (1H, d,
138.5, 157.0. Anal. Calcd for C12H17NO3: C, 64.55; H, 7.67; N, 6.27. Found: Jꢃ10.3 Hz), 4.01 (1H, d, Jꢃ8.6 Hz), 4.26 (1H, d, Jꢃ8.6 Hz), 5.27 (1H, br s),
1
C, 64.36; H, 7.75; N, 6.16.
7.36—7.50 (6H, m), 7.60—7.70 (4H, m). 13C-NMR (67.5 MHz, CDCl3) d:

1388
Vol. 55, No. 9
19.2, 22.8, 26.8 (3), 58.7, 69.0, 73.0, 127.9 (4), 130.02, 130.05, 132.5 (2), methylpropanal (11)
A
mixture of 8c (30 mg, 0.094 mmol) and
135.52 (2), 135.59 (2), 158.8. HR-MS m/z: 312.10686 (Calcd for
Dess–Martin periodinane (68 mg, 0.16 mmol) in CH2Cl2 (1 ml) was stirred at
room temperature for 1 h. The mixturewas diluted with Et2O, the whole was
C17H18NO3Si (MꢀꢂtBu): 312.10560).
(R)-3-(tert-Butyldimethylsilyloxy)-2-methylpropyl p-Toluenesulfonyl- washed with saturated aqueous Na2S2O3, saturated aqueous NaHCO3, and
oxycarbamate (9) According to the reported procedures,36) 5c (240 mg,
brine, dried (MgSO4), and concentrated. The residue was chromatographed
1.17 mmol) was slowly added to a solution of 1,1ꢁ-carbonyldiimidazole on silica gel (30% EtOAc in hexane) to give 11 (22 mg, 73%) as a colorless
oil. [a]D27 ꢀ16.0° (cꢃ1.27, CHCl3). IR (neat) cmꢂ1: 3370, 1737, 1715. H-
1
(285 mg, 1.76 mmol) in THF (11 ml) and the resulting mixture was stirred at
room temperature for 2 h. The mixture was diluted with EtOAc. The solution NMR (300 MHz, CDCl3) d: 0.043 (3H, s), 0.048 (3H, s), 0.88 (9H, s), 1.34
was washed with saturated aqueous NH4Cl, water, and brine, dried (MgSO4) (3H, s), 1.45 (9H, s), 3.80 (2H, br s), 5.30 (1H, br s), 9.48 (1H, s). 13C-NMR
and concentrated. The product was dissolved in pyridine (6 ml), hydroxyl- (75 MHz, CDCl3) d: ꢂ5.47, ꢂ5.44, 17.2, 18.3, 25.8 (3), 28.4 (3), 63.6, 64.5,
amine hydrochloride (245 mg, 3.52 mmol) was added and the resulting mix-
ture was stirred at room temperature for 4 h. Most of the pyridine was re- 317.20224).
80.0, 154.8, 200.5. HR-MS m/z: 317.20019 (Calcd for C15H31NO4Si (Mꢀ):
moved under reduced pressure and the residue was dissolved in EtOAc. The
mixture was washed with 10% aqueous HCl, saturated aqueous NaHCO3,
(S)-2-tert-Butoxycarbonylamino-3-(tert-butyldimethylsilyloxy)-2-
methylpropyl 2,2-Dimethylpropanoate mixture of 8c (65 mg,
A
water, and brine, dried (MgSO4) and concentrated. The residue was chro- 0.20 mmol), pivaloyl chloride (37 mg, 0.3 mmol), triethylamine (31 mg,
matographed on silica gel (15% EtOAc in hexane) to give N-hydroxycarba- 0.3 mmol), and DMAP (13 mg, 0.1 mmol) in CH2Cl2 (2 ml) was stirred at
mate (222 mg, 72%) as a colorless oil, which was used in the next step with- room temperature for 12 h. The mixture was diluted with EtOAc, the whole
out further purification. 1H-NMR (300 MHz, CDCl3) d: 0.04 (6H, s), 0.89 was washed with saturated aqueous Na2CO3, water, and brine, dried
(9H, s), 0.92 (3H, d, Jꢃ6.9 Hz), 1.65 (1H, br s), 1.92—2.05 (1H, m), 3.49 (MgSO4), and concentrated. The residue was chromatographed on silica gel
(1H, dd, Jꢃ9.9, 6.0 Hz), 3.53 (1H, dd, Jꢃ9.9, 5.5 Hz), 4.07 (1H, dd, Jꢃ10.4, (5% EtOAc in hexane) to give the titled compound (69 mg, 84%) as a color-
6.0 Hz), 4.16 (1H, dd, Jꢃ10.4, 6.3 Hz), 6.35 (1H, br s). p-Toluenesulfonyl less oil. [a]D27 ꢀ1.95° (cꢃ1.18, CHCl3). IR (neat) cmꢂ1: 3381, 1727, 1496.
chloride (370 mg, 1.94 mmol) was added to a solution of N-hydroxycarba- 1H-NMR (300 MHz, CDCl3) d: 0.05 (6H, s), 0.89 (9H, s), 1.21 (9H, s), 1.31
mate (465 mg, 1.76 mmol) in Et2O (18 ml) at 0 °C. Triethylamine (232 mg, (3H, s), 1.43 (9H, s), 3.54 (1H, d, Jꢃ9.6 Hz), 3.62 (1H, d, Jꢃ9.6 Hz), 4.10
2.29 mmol) was then added slowly and the resulting white suspension was (1H, d, Jꢃ10.7 Hz), 4.22 (1H, d, Jꢃ10.7 Hz), 4.77 (1H, s). 13C-NMR
stirred at room temperature for 12 h. The mixture was diluted with Et2O. The
(75 MHz, CDCl3) d: ꢂ5.4 (2), 18.3, 19.1, 25.9 (3), 27.3 (3), 28.5 (3), 38.9,
solution was washed with water, and brine, dried (MgSO4) and concentrated. 55.6, 65.2, 65.6, 79.2, 154.5, 177.8. HR-MS m/z: 404.28450 (Calcd for
The residue was chromatographed on silica gel (20% EtOAc in hexane) to C20H42NO5Si (MꢀꢀH): 404.28322).
give 9 (313 mg, 43%) as a colorless oil. [a]D26 ꢀ4.39° (cꢃ1.14, CHCl3). IR
(R)-2-tert-Butoxycarbonylamino-3-hydroxy-2-methylpropyl
2,2-Di-
1
(neat) cmꢂ1: 3278, 1742, 1598, 1471. H-NMR (300 MHz, CDCl3) d: 0.01 methylpropanoate (12) A ether solution of tetrabutylammonium fluoride
(6H, s), 0.81 (3H, d, Jꢃ6.9 Hz), 0.86 (9H, s), 1.84 (1H, octet, Jꢃ6.3 Hz),
2.44 (3H, s), 3.39 (1H, dd, Jꢃ9.9, 6.3 Hz), 3.45 (1H, dd, Jꢃ10.2, 5.2 Hz),
(1.0 mol/l, 0.1 ml, 0.1 mmol) was added to a solution of (S)-2-tert-butoxy-
carbonylamino-3-(tert-butyldimethylsilyloxy)-2-methylpropyl 2,2-dimethyl-
3.93 (1H, dd, Jꢃ10.4, 6.0 Hz), 4.03 (1H, dd, Jꢃ10.4, 6.0 Hz), 7.34 (2H, d, propanoate (30 mg, 0.074 mmol) in THF (1 ml) under a nitrogen atmosphere
Jꢃ8.0 Hz), 7.86 (2H, d, Jꢃ8.2 Hz), 8.11 (1H, br d, Jꢃ4.4 Hz). 13C-NMR
at 0 °C and the resulting mixture was stirred at the same temperature for
(75 MHz, CDCl3) d: ꢂ5.4 (2), 13.3, 18.3, 21.8, 25.9 (3), 35.3, 64.1, 68.8, 30 min. The mixture was diluted with EtOAc. The solution was washed with
129.3 (2), 129.6 (2), 130.2, 145.9, 155.6. HR-MS m/z: 418.17675 (Calcd for
saturated aqueous NH4Cl, water, and brine, dried (MgSO4) and concen-
trated. The residue was chromatographed on silica gel (25% EtOAc in
C18H32NO6SSi (MꢀꢀH): 418.17196).
Dirhodium(II)-Catalyzed C–H Amination of 9 According to the re- hexane) to 12 (20 mg, 93%) as colorless crystals, mp: 108—109 °C (lit.42)
ported procedures,36) a white suspension of 9 (91 mg, 0.22 mmol), potassium
carbonate (90 mg, 0.65 mmol), and Rh2(tpa)4 (18 mg, 0.012 mmol) in
dichloromethane (2 ml) was stirred at room temperature for 5 h. The mixture
was filtered through a celite pad and the filtrate was concentrated. The
mp 106—107 °C). [a]D28 ꢂ8.71° (cꢃ1.26, CHCl3) {lit.42) [a]D25 ꢂ8.6°
1
(cꢃ0.90, CHCl3)}. IR (KBr) cmꢂ1: 3273, 1728, 1681. H-NMR (300 MHz,
CDCl3) d: 1.22 (9H, s), 1.26 (3H, s), 1.43 (9H, s), 3.55 (1H, dd, Jꢃ11.9,
7.1 Hz), 3.61 (1H, dd, Jꢃ11.9, 6.6 Hz), 3.90 (1H, br s), 4.20 (1H, d,
residue was chromatographed on silica gel (30% EtOAc in hexane) to give Jꢃ11.1 Hz), 4.25 (1H, d, Jꢃ11.1 Hz), 4.86 (1H, br s). 13C-NMR (75 MHz,
7c (29 mg, 54%), whose spectroscopic data were identical with those of the CDCl3) d: 20.2, 27.2 (3), 28.4 (3), 39.0, 56.4, 65.7, 67.1, 80.0, 155.5, 178.5.
sample prepared from 6c.
HPLC (Daicel Chiralpak OF (0.46ꢄ25 cm); hexane/iPrOH, 70/30; flow rate
3-tert-Butyl (S)-4-(tert-Butyldimethylsilyloxymethyl)-4-methyl-2-oxo- 0.4 ml/min; UV 220 nm): (S)-12: tR 10.30 min (3.8%); (R)-12, tR 11.83 min
oxazolidine-3-carboxylate A mixture of 7c (125 mg, 0.51 mmol), (Boc)2O (96.2%).
(223 mg, 1.02 mmol), triethylamine (181 mg, 1.78 mmol), and DMAP
(13 mg, 0.1 mmol) in THF (5 ml) was stirred at room temperature under a ni-
trogen atmosphere for 30 min. The mixture was diluted with Et2O. The solu-
tion was washed with saturated aqueous NH4Cl, water, and brine, dried
Acknowledgments We wish to thank Mitsubishi Rayon Co., Ltd. for
providing methyl (S)-3-hydroxy-2-methylpropanoate.
(MgSO4) and concentrated. The residue was chromatographed on silica gel References
(10% EtOAc in hexane) to give the titled compound (158 mg, 90%) as a col-
orless oil. [a]D28 ꢂ17.5° (cꢃ0.96, CHCl3). IR (neat) cmꢂ1: 1817, 1790, 1725.
1H-NMR (300 MHz, CDCl3) d: 0.05 (3H, s), 0.06 (3H, s), 0.88 (9H, s), 1.45
(3H, s), 1.55 (9H, s), 3.50 (1H, d, Jꢃ10.2 Hz), 3.86 (1H, d, Jꢃ8.2 Hz), 4.02
(1H, d, Jꢃ10.2 Hz), 4.31 (1H, d, Jꢃ8.2 Hz). 13C-NMR (75 MHz, CDCl3) d:
ꢂ5.5, ꢂ5.4, 18.1, 20.9, 25.7 (3), 28.1 (3), 62.4, 65.6, 70.9, 83.6, 149.5,
152.7. HR-MS m/z: 345.19706 (Calcd for C16H31NO5Si (Mꢀ): 345.19715).
(S)-2-(tert-Butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-2-
1) Espino C. G., Du Bois J., Angew. Chem. Int. Ed., 40, 598—600 (2001).
2) Review: Espino C. G., Du Bois J., “Modern Rhodium-Catalyzed Or-
ganic Reactions,” ed. by Evans P. A., Wiley-VCH, Weinheim, 2005,
pp. 379—416.
3) Review: Davies H. M. L., Long M. S., Angew. Chem. Int. Ed., 44,
3518—3520 (2005).
4) A recent application to natural product synthesis: Narina S. V., Kumar
T. S., George S., Sudalai A., Tetrahedron Lett., 48, 65—68 (2007), and
references cited therein.
methylpropanol (8c)
A
mixture of 3-tert-butyl (S)-4-(tert-butyl-
dimethylsilyloxymethyl)-4-methyl-2-oxooxazolidine-3-carboxylate (28 mg,
0.081 mmol) and Cs2CO3 (40 mg, 0.12 mmol) in MeOH (0.8 ml) was stirred
at room temperature for 12 h. The mixture was diluted with Et2O. The solu-
tion was washed with saturated aqueous NH4Cl, water, and brine, dried
(MgSO4) and concentrated. The residue was chromatographed on silica gel
(30% EtOAc in hexane) to give 8c (20 mg, 77%) as a colorless oil. [a]D27
ꢂ4.97° (cꢃ1.74, CHCl3). IR (neat) cmꢂ1: 3600—3300, 1719, 1697. 1H-
NMR (300 MHz, CDCl3) d: 0.08 (6H, s), 0.90 (9H, s), 1.18 (3H, s), 1.44
5) Yakura T., Yoshimoto Y., Ishida C., Mabuchi S., Synlett, 2006, 930—
932 (2006).
6) Yakura T., Yoshimoto Y., Ishida C., Mabuchi S., Tetrahedron, 63,
4429—4438 (2007).
7) Fuji K., Chem. Rev., 93, 2037—2066 (1993).
8) Ohfune Y., Horikawa M., J. Synth. Org. Chem., 55, 982—983 (1997).
9) Cativiela C., Díaz-de-Villegas M. D., Tetrahedron: Asymmetry, 9,
3517—3599 (1998).
(9H, s), 3.55 (1H, dd, Jꢃ11.5, 8.5 Hz), 3.61 (1H, d, Jꢃ9.9 Hz), 3.70 (1H, dd, 10) Cativiela C., Díaz-de-Villegas M. D., Tetrahedron: Asymmetry, 11,
Jꢃ11.5, 4.4 Hz), 3.77 (1H, d, Jꢃ9.9 Hz), 4.04 (1H, br s), 5.14 (1H, br s). 645—732 (2000).
13C-NMR (75 MHz, CDCl3) d: ꢂ5.45, ꢂ5.40, 18.3, 19.6, 25.9 (3), 28.5 11) Wang M., Liu J., Wang D.-X., Zheng Q.-Y., Tetrahedron: Asymmetry,
(3), 56.6, 67.7, 69.2, 79.5, 155.7. HR-MS m/z: 320.22583 (Calcd for
16, 2409—2416 (2005).
12) Cativiela C., Díaz-de-Villegas M. D., Tetrahedron: Asymmetry, 18,
569—623 (2007), and references cited therein.
C15H34NO4Si (MꢀꢀH): 320.22571).
(R)-2-(tert-Butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-2-

September 2007
1389
13) Mossel E., Formaggio F., Crisma M., Toniolo C., Broxterman Q. B.,
Zurbanoa M. M., Tetrahedron: Asymmetry, 12, 949—957 (2001).
Boesten W. H. J., Kamphuis J., Quaedflieg P. J. L. M., Temussi P., 27) Tsuji T., Iio Y., Takemoto T., Nishi T., Tetrahedron: Asymmetry, 16,
Tetrahedron: Asymmetry, 8, 1305—1314 (1997), and references cited
therein.
14) Yakura T., Yoshida D., Ueki A., Nakao K., Ikeda M., Chem. Pharm.
Bull., 45, 651—658 (1997).
3139—3142 (2005).
28) Nakamura T., Tsuji T., Iio Y., Miyazaki S., Takemoto T., Nishi T.,
Tetrahedron: Asymmetry, 17, 2781—2792 (2006), and references cited
therein.
15) Yakura T., Yamada, S., Ueki A., Ikeda M., Synlett, 1997, 185—186 29) Trost B. M., Gunzner J. L., Dirat O., Rhee Y. H., J. Am. Chem. Soc.,
(1997). 124, 10396—10415 (2002).
16) Yakura T., Yamada S., Kunimune Y., Ueki A., Ikeda M., J. Chem. Soc., 30) Hinman A., Du Bois J., J. Am. Chem. Soc., 125, 11510—11511
Perkin Trans. 1, 1997, 3643—3649 (1997). (2003).
17) Yakura T., Ueki A., Morioka Y., Kurata T., Tanaka K., Ikeda M., 31) Huang H., Panek J. S., Org. Lett., 5, 1991—1993 (2003).
Chem. Pharm. Bull., 46, 1182—1183 (1997).
18) Yakura T., Yamada S., Azuma M., Ueki A., Ikeda M., Synthesis, 1998,
973—974 (1998).
32) Smith A. B., III, Beauchamp T. J., LaMarche M. J., Kaufman M. D.,
Qiu Y., Arimoto H., Jones D. R., Kobayashi K., J. Am. Chem. Soc.,
122, 8654—8664 (2000).
19) Yakura T., Ueki A., Kitamura T., Tanaka K., Nameki M., Ikeda M., 33) Chakraborty T. K., Goswami R. K., Tetrahedron Lett., 47, 4917—4919
Tetrahedron, 55, 7461—7470 (1999).
(2006).
20) Yakura T., Yakugaku Zasshi, 120, 1309—1322 (2000).
34) Tan Z., Negishi E., Angew. Chem. Int. Ed., 43, 2911—2914 (2004).
21) Yakura T., Tanaka T., Ikeda M., Uenishi J., Chem. Pharm. Bull., 51, 35) Espino C. G., Fiori K. W., Kim M., Du Bois J., J. Am. Chem. Soc., 126,
471—473 (2003). 15378—15379 (2004).
22) Yakura T., Muramatsu W., Uenishi J., Chem. Pharm. Bull., 53, 989— 36) Lebel H., Huard K., Lectard S., J. Am. Chem. Soc., 127, 14198—
994 (2005). 14199 (2005).
23) Yakura T., Sato S., Yoshimoto Y., Chem. Pharm. Bull., 55, 1284— 37) “Hypervalent Iodine in Organic Synthesis,” ed. by Varvoglis A., Acad-
1286 (2007).
emic Press, San Diego, 1997.
24) A similar influence was observed in the C–H insertion reaction of
38) Varvoglis A., Tetrahedron, 53, 1179—1255 (1997).
rhodium carbenoids, see: Stork G., Nakatani K., Tetrahedron Lett., 29, 39) Wirth T., Hirt U. H., Synthesis, 1999, 1271—1287 (1999).
2283—2286 (1988). 40) Zhdankin V. V., Stang P. J., Chem. Rev., 102, 2523—2584 (2002).
25) Avenoza A., Cativiela C., Corzana F., Peregrina J. M., Zurbanoa M. 41) Ishizuka T., Kunieda T., Tetrahedron Lett., 28, 4185—4188 (1987).
M., J. Org. Chem., 64, 8220—8225 (1999).
26) Avenoza A., Cativiela C., Corzana F., Peregrina J. M., Sucunzaa D.,
42) Hatakeyama S., Fukuyama H., Mukugi Y., Irie H., Tetrahedron Lett.,
37, 4047—4050 (1996).