Osmium-catalyzed vicinal oxyamination of alkenes by N-(4- toluenesulfonyloxy)carbamates

Article abstract of DOI:10.1021/jo301372y

N-(4-Toluenesulfonyloxy)carbamates based on a range of common amine protecting groups serve as preformed nitrogen sources in the intermolecular osmium-catalyzed oxyamination reaction of a variety of mono-, di-, and trisubstituted alkenes. The reactions occur with low catalyst loadings and good yields and afford high regioselectivity for unsymmetrically substituted alkenes.

Full text of DOI:10.1021/jo301372y

Article
pubs.acs.org/joc
Osmium-Catalyzed Vicinal Oxyamination of Alkenes by
N‑(4‑Toluenesulfonyloxy)carbamates
Masruri,†,‡ Anthony C. Willis,† and Malcolm D. McLeod*,†
†Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia
‡Department of Chemistry, University of Brawijaya, Malang, Indonesia
S
* Supporting Information
ABSTRACT: N-(4-Toluenesulfonyloxy)carbamates based on a range
of common amine protecting groups serve as preformed nitrogen
sources in the intermolecular osmium-catalyzed oxyamination reaction
of a variety of mono-, di-, and trisubstituted alkenes. The reactions occur
with low catalyst loadings and good yields and afford high
regioselectivity for unsymmetrically substituted alkenes.
diastereoselectivity. Furthermore, competition reactions reveal
significant variation in the relative rate of addition to alkenes
with different substitution patterns. However, preliminary
investigations highlight that these nitrogen sources cannot be
substituted for the N-chlorocarbamates in the Sharpless AA
reaction.
INTRODUCTION
■
The vicinal amino alcohol is a commonly occurring functional
array in natural products and other synthetic targets such as
therapeutic agents and chiral auxiliaries. The prevalence of this
motif has inspired the development of numerous synthetic
approaches to this structural unit and its derivatives.1 Among
the most powerful and general methods of synthesis is the
direct oxyamination of alkenes,2 which is typified by catalytic
asymmetric aminohydroxylation (AA) reaction developed by
Sharpless and co-workers.3,4 Despite the success of this process,
the reaction suffers from problems with regioselectivity, and the
preferred in situ generation of the N-chlorocarbamate nitrogen
source can lead to chlorination of substrates.5,6 The catalytic
tethered aminohydroxylation (TA) developed by Donohoe et
al.7 addressed both of these concerns, albeit in nonasymmetric
form. Tethering the reactive carbamate to an adjacent
functionality leads to a secure regiochemical outcome. More
recently, the introduction of N-(sulfonyloxy)carbamates6 or N-
(acyloxy)carbamates8 as preformed nitrogen sources has
improved the efficiency of this process and allowed extension
of this method to the synthesis of cyclic amides.9 Related
preformed nitrogen sources have recently been employed in the
intermolecular oxyamination reaction of N-(acyloxy)-
carbamates10,11 and amides.12 The recently reported reaction
of N-(4-chlorobenzoyloxy)carbamates is notable in proceeding
under nonbasic conditions and with good enantioselectivity
controlled by cinchona alkaloid-derived chiral ligands for
mono- and disubstituted alkenes.10,11 These findings prompted
us to report the results of our investigations on the application
of nontethered N-(sulfonyloxy)carbamates as preformed nitro-
gen sources in the osmium-catalyzed oxyamination reaction.
We find that a range of these preformed nitrogen sources react
readily in the vicinal oxyamination reaction. The reactions
occur with low catalyst loadings and afford good regioselectivity
for unsymmetrically substituted alkenes. The reactions of allylic
alcohol derivatives proceed with moderate substrate-derived
RESULTS AND DISCUSSION
■
The synthesis of preformed nitrogen sources 1−6 with different
N-acyloxy and N-sulfonyloxy leaving groups was conducted
from tert-butyl hydroxycarbamate 7 (Table 1).13−16 Single-
crystal X-ray analysis confirmed the identity of compound 1.
The ability of these nitrogen sources to serve as oxidant in the
oxyamination reaction was investigated by reaction with trans-
stilbene 8 and potassium osmate and hydroquinidine 1,4-
phthalazinediyl diether, (DHQD)2PHAL, in aqueous propanol.
The nitrogen sources afforded the oxyamination product 9a in
varying yields. However, despite the presence of chiral ligand
(DHQD)2PHAL commonly used in the Sharpless asymmetric
dihydroxylation (AD) and asymmetric aminohydroxylation
(AA) reactions, the product was afforded in racemic form as
judged by HPLC analysis. This absence of asymmetric
induction is a feature shared with nitrogen sources in the
intramolecular TA reaction, which has been proposed to
operate in the secondary catalytic cycle that impedes ligand
binding.7 Alternately, the absence of asymmetric induction
could also be explained by the low pH of these reactions. The
oxyamination reactions reported here occur at moderately low
pH due to the liberation of 1 equiv of sulfonic or carboxylic
acid. In contrast, the Sharpless AA and AD and closely related
reactions are conducted under high pH, which has been
reported to be essential for high enantioselectivity.17−19
Received: July 1, 2012
© XXXX American Chemical Society
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Table 1. Synthesis and Reaction of Preformed Nitrogen
Sources 1−6
Scheme 1. Preparation of N-(Tosyloxy)carbamates 4a−e
yields (%)
a
b
c
entry
R1
step 1
step 2
1
2
3
4
5
6
C6F5CO, 1
ClCH2CO, 2
Ms, 3
67
86
93
71
58
46
71
29
75
59
78
62
a
Table 2. Optimizing the Oxyamination Reaction
Ts, 4
MesSO2, 5
p-NO2C6H4SO2, 6
a
b
Ms = methanesulfonyl; Ts = tosyl; Mes = mesityl. Conditions: tert-
butyl hydroxycarbamate 7, R1Cl, Et3N or i-Pr2NEt, CH2Cl2, 0 °C to rt.
c
Conditions: trans-stilbene 8 (1.0 equiv), nitrogen source 1−6 (2.0
equiv), K2OsO2(OH)4 (4.0 mol %), (DHQD)2PHAL (5 mol %),
nitrogen source
(equiv)
catalyst loading
(mol %)
yield
(%)
time
(h)
n‑PrOH/H2O (3:1), 0 °C to rt.
entry
1
2
3
4
5
2.0
1.0
1.0
1.0
1.0
4.0
4.0
2.0
1.0
0.10
81
71
71
88
55
4
5
To further explore the potential of this oxyamination
reaction, the N-(tosyloxy)carbamate 4 was selected for further
examination due to its ready availability and chemical stability.
This choice was also inspired by the reported application of N-
(sulfonyloxy)carbamates in a range of oxidation chemistry
including the TA reaction, C−H insertion reactions,20−24
sulfinamide25 and aziridine formation.26−39 The related N-
(methanesulfonyloxy)carbamate reagent 3 proved moderately
unstable to long-term 6-month storage in our hands.13
The preparation of N-(tosyloxy)carbamates 4a−e, corre-
sponding to commonly used carbamate protecting groups,
including the tert-butyl- (a), ethyl- (b), 2,2,2-trichloroethyl-
(TCE, c), 2-(trimethylsilyl)ethyl- (TMSE, d), and benzyl- (e)
carbamate derivatives, was conducted (Scheme 1).15,24,40,41
Single-crystal X-ray analysis confirmed the identity of
compound 4e.
The optimization of a number of oxyamination reaction
variables was conducted with benzyl N-(tosyloxy)carbamate 4e,
trans-stilbene 8, and potassium osmate(VI) dihydrate (Table
2). The reactions proceeded in homogeneous tert-butanol,
propanol, and acetonitrile/water mixtures, with the highest
yield of product 9e afforded in 3:1 acetonitrile/water. An
attempt to use a biphasic dichloromethane/water solvent
mixture gave no conversion after 96 h.
9
14
96
a
Conditions: trans-stilbene 8 (1.0 equiv), benzyl N-(tosyloxy)-
carbamate 4e (see table), K2OsO2(OH)4 (see table), MeCN/H2O
(3:1), 0 °C to rt.
N-sulfonyloxy and N-acyloxy preformed nitrogen sources
employed in the TA reaction.6,8,9
To investigate the substrate scope of the oxyamination
protocol, the reaction of a range of different alkenes 8 and 10−
24 were explored (Table 3). The substrates included alkenes of
different electron demand and also different substitution
patterns. In the cases noted, aqueous tert-butanol was employed
to improve the solubility of nitrogen source or substrate.
All nitrogen sources were effective in the reaction to afford
oxyamination products 9, 25−34, 36, 38, and 39, with
unsymmetrical alkenes also affording the minor oxyamination
products 40−44. The tert-butyl- (4a), 2,2,2-trichloroethyl-
(TCE; 4c), and benzyl- (4e) substituted nitrogen sources
generally affording higher yields than the ethyl (4b) or 2-
(trimethylsilyl)ethyl (TMSE; 4d) variants. Alkene substitution
patterns were observed to influence the transformation in two
ways. The reactions with mono- and disubstituted alkenes were
complete within 48 h, but in some instances the reactions of
trisubstituted alkenes required longer reaction times (entries 10
and 13). Furthermore, despite a number of attempts the
nitrogen sources could not be successfully employed for the
oxyamination of tetrasubstituted alkenes (entry 14). The lower
reactivity associated with higher levels of alkene substitution has
Changes to nitrogen source stoichiometry and osmium
catalyst loading were also investigated (Table 2). Using 1 equiv
of nitrogen source 4e and 1.0 mol % potassium osmate
dihydrate afforded the oxyamination product in 88% yield after
14 h. Lower (0.10 mol %) osmium catalyst loadings resulted in
slower conversion to product and lower yield. The low catalyst
loadings indicated a similar high level of efficiency to reported
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a
Table 3. Oxyamination of Alkenes 8 and 10−24
a
Conditions: alkene (1.0 equiv), nitrogen source 4a−e (0.8−2.5 equiv), K2OsO2(OH)4 (1−4 mol %), MeCN/H2O (3:1), 0 °C to rt. TCE = 2,2,2-
trichloroethyl; TMSE = 2-(trimethylsilyl)ethyl; PNP = p-nitrophenyl. bt-BuOH/H2O (3:1). cRatio of major regioisomer to minor regioisomer. dX-ray
analysis proved the identity of both the major 25c and minor 40c regioisomers. eX-ray analysis proved the identity of the products 9c and 28c. fNo
g
h
reaction. Affords a 2.4:1 mixture of anti:syn diastereomers. Affords a 2.6:1 mixture of anti:syn diastereomers.
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also been recently highlighted for N-(4-chlorobenzoyloxy)-
carbamates in the intermolecular oxyamination reaction.11 In
the case of the intramolecular TA variants involving preformed
nitrogen sources, the proximity effects largely override this
lower reactivity.6,8,9
and the trisubstituted alkene 3-methylbut-2-en-1-ol 18 afforded
only the product from the monosubstituted alkene (entry 3).
This result suggested that either the allylic alcohol functionality
or, consistent with the trends observed above (Table 3), the
higher level of alkene substitution dramatically slowed addition
of the osmium catalyst to this substrate. In a final experiment,
the competition reaction of 3-methylbut-3-en-2-ol 23 and its
acetate derivative 24 was performed. Oxyamination of this
substrate pair slightly favored addition to the allylic alcohol 23
over the acetate ester 24, suggesting that the presence of an
unprotected allylic alcohol did not in itself slow the rate of
osmium catalyst addition (Table 4, cf. entries 1−3 with entry
4). However, this reaction was also relatively slow and
proceeded in moderate yield. In this respect the competition
reaction correlated with the reactivity of other allylic alcohol
substrates that also gave slow conversion and moderate yields
(Table 3, entries 10 and 15) but not the higher reactivity of
protected allylic or homoallylic alcohols (Table 3, entries 4 and
16). Together these results suggest that allylic alcohols may
serve to retard catalyst turnover through slower hydrolysis or
reoxidation steps. Slow catalytic turnover was recently reported
for the racemic oxyamination of functionalized substrates
including allylic and homoallylic alcohols using N-(4-
chlorobenzoyloxy)carbamate-derived nitrogen sources, the
effects of which could be ameliorated by the use of increased
catalyst loading or heating of the reaction mixture.11 These
competition reactions also highlight the potential for the
selective partial oxyamination of appropriately substituted
polyene substrates.
The regioselectivity of the oxyamination reaction was
strongly influenced by alkene substitution. Unsymmetrical
mono- (entries 1, 3, and 4), 1,1-di- (entries 5, 15, and 16)
and trisubstituted (entries 10, 11, and 13) alkenes gave high
regioselectivity that favored addition of the nitrogen to the less
substituted alkene carbon. In unsymmetrically substituted cis-
1,2- (entry 9) and trans-1,2-disubstituted (entries 6 and 7)
alkenes, low regioselectivity was observed. These trends in
regioselectivity are in common with other intermolecular
osmium-catalyzed oxyamination protocols based on N-
(acyloxy)carbamates10,11 and are also observed to exert
considerable influence on the Sharpless AA reaction.4 No
significant trend in reactivity was evident upon the introduction
of electron-withdrawing carbonyl groups (entries 3, 6−8, and
13). In the case of 3-methylcyclohexenone 21, the adjacent
ketone facilitated the dehydration of the expected oxyamination
product to give enone 36, a reaction presumably promoted by
the mildly acidic reaction conditions (entry 13). The
oxyamination of chiral allylic alcohol derivatives 23 and 24
afforded moderate diastereoselectivity favoring the anti-
substituted product, consistent with Kishi’s empirical rule for
the osmium-catalyzed dihydroxylation reaction (entries 15 and
16).42,43
To provide further insight into the reaction, a series of
competition experiments were performed by reacting 1 equiv of
nitrogen source with 1 equiv each of two different alkenes
(Table 4). Under these conditions, the relative yield of product
Finally, we investigated the potential of N-(tosyloxy)-
carbamates to serve as nitrogen source in the Sharpless
asymmetric aminohydroxylation (AA). The use of preformed
nitrogen sources eliminates the presence of potentially
problematic chlorinating agents in the reaction.5,6 Conducting
the reaction under conditions typical for the Sharpless AA
protocol, but using benzyl N-(tosyloxy)carbamate 4e in place of
benzyl carbamate and tert-butyl hypochlorite, gave benzyl
carbamate 45 as the major product in 81% yield (Scheme 2).
a
Table 4. Competition Experiments
Scheme 2. Attempted Asymmetric Aminohydroxylation
Reaction
a
Conditions: alkene A (1.0 equiv), alkene B (1.0 equiv),
BnOCONHOTs 4e (1.0 equiv), K2OsO2(OH)4 (4.0 mol %),
MeCN/H2O (3:1), rt. bOne regioisomer was afforded. cTwo
d
regioisomers were afforded. Two diastereomers were afforded.
No amino alcohol product was isolated from the reaction.
Styrene 10 was observed at the conclusion of the reaction by
thin-layer chromatography (TLC) but was not isolated. The
formation of carbamate byproducts has previously been
observed for N-(acyloxy)carbamates in both the intra- and
intermolecular variants of the oxyamination reaction.8,11 The
result stands in marked contrast to the successful intermo-
lecular asymmetric aminohydroxylation of mono- and disub-
derived from each alkene correlates to the relative rate of
addition of the catalytically active imidoosmium species to the
alkenes. Competition between monosubstituted alkene styrene
10 and the 1,2-disubstituted alkenes trans-stilbene 8 and indene
17 indicated a similar rate of addition to the two alkene classes
(entries 1 and 2). In contrast, competition between styrene 10
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tert-Butyl N-(Methanesulfonyloxy)carbamate 3.13 General proce-
dure 1 was followed with minor modifications, with tert-butyl N-
hydroxycarbamate 7 (1.0 g, 7.51 mmol), methanesulfonyl chloride
(946.4 mg, 8.26 mmol), and triethylamine (836.0 mg, 8.26 mmol) to
afford the title compound as a white solid (1.47 g, 93%), mp 75−76
°C (lit.13 83−85 °C). Rf 0.31 (40% ethyl acetate/n-hexane). IR (thin
stituted10 but not trisubstituted alkenes11 mediated by the
recently reported N-(4-chlorobenzoyloxy)carbamate reagents
and hints at a subtle interplay of addition, hydrolysis, and
reoxidation steps within the catalytic cycle to afford products
with high enantioselectivity.4,7
1
film, cm−1) νmax 3292 (N−H), 1741 (CO). H NMR (300 MHz,
CONCLUSION
CDCl3) δ 7.92 (1H, s), 3.17 (3H, s), 1.51 (9H, s). LRMS (EI+) m/z
196 ([M − CH3]+, 15%). HRMS (EI+) [M − CH3]+ calcd for
C5H10NO5S 196.0280, found 196.0276. The 13C NMR data matched
the literature.13
■
In conclusion, we have developed a range of preformed N-
(sulfonyloxy)carbamate nitrogen sources that are suitable for
the intramolecular vicinal oxyamination reaction of a wide
variety of mono-, di-, and trisubstituted alkenes. These
reactions proceed with low catalyst loadings comparable with
leading osmium-catalyzed oxyamination protocols6,8−11 and
afford good regioselectivity for unsymmetrically substituted
alkenes. Competition reactions reveal similar rates of catalyst
addition to mono- and disubstituted alkenes but much slower
addition to more highly substituted substrates, highlighting the
potential selective partial oxyamination of appropriately
substituted polyene substrates. The reactions of allylic alcohol
derivatives proceed with moderate substrate-derived diaster-
eoselectivity. However, preliminary investigations highlight that
these nitrogen sources cannot be substituted for the N-
chlorocarbamates in the enantioselective Sharpless AA reaction
procedure. This study provides a range of new preformed
nitrogen sources for the intramolecular osmium-catalyzed
oxyamination reaction but also serves to highlight the ongoing
challenge associated with developing new and general nitrogen
sources for the asymmetric aminohydroxylation reaction.10,11
tert-Butyl N-(Tosyloxy)carbamate 4a.15,45 General procedure 1
was followed with minor modifications, with tert-butyl N-hydrox-
ycarbamate 7 (1.96 g, 14.7 mmol), toluenesulfonyl chloride (3.09 g,
16.2 mmol) and triethylamine (1.64 g, 16.2 mmol). Purification by
flash chromatography with 25% ethyl acetate/n-hexane afforded the
title compound as a white solid (3.01 g, 71%), mp 91−93 °C (lit.15 97
°C). Rf 0.18 (25% ethyl acetate/n-hexane). IR (thin film, cm−1) νmax
3289 (N−H), 3071, 2982, 2934 (C−H), 1768, 1730, 1709 (CO),
1597. LRMS (ESI+) m/z 310 ([M + Na]+, 25%). HRMS (ESI+) [M +
Na]+ calcd for C12H17NO5SNa 310.0725, found 310.0719. The 1H and
13C NMR data matched the literature.45
tert-Butyl N-(Mesitylsulfonyloxy)carbamate 5.14 General proce-
dure 1 was followed with minor modifications, with tert-butyl N-
hydroxycarbamate 7 (399.4 mg, 3.00 mmol), mesitylsulfonyl chloride
(722.0 mg, 3.06 mmol), and triethylamine (309.6 mg, 3.06 mmol).
Purification by flash chromatography with 20% ethyl acetate/n-hexane
provided the title compound as a white solid (550.8 mg, 58%), mp
110−113 °C (lit.14 104−105.5 °C). Rf 0.24 (20% ethyl acetate/n-
hexane). IR (thin film, cm−1) νmax 3292 (N−H), 1768, 1732, 1705
1
(CO), 1603. H NMR (300 MHz, CDCl3) δ 7.77 (1H, s), 6.98
(2H, s), 2.66 (6H, s), 2.31 (3H, s), 1.30 (9H, s). 13C NMR (75 MHz,
CDCl3) δ 154.5, 144.7, 142.2, 131.9, 128.7, 84.1, 27.9, 23.4, 21.4.
tert-Butyl N-(p-Nitrophenylsulfonyloxy)carbamate 6.16 General
procedure 1 was followed with minor modifications, with tert-butyl N-
hydroxycarbamate 7 (0.798 g, 6.00 mmol), diethyl ether (60 mL), p-
nitrophenylsulfonyl chloride (1.46 g, 6.60 mmol), and triethylamine
(0.618 g, 6.11 mmol). Purification by flash chromatography with 25%
ethyl acetate/n-hexane provided the title compound as a white-yellow
solid (0.881 g, 46%), mp 86−91 °C (lit.16 91−92 °C). Rf 0.58 (50%
ethyl acetate/n-hexane). IR (thin film, cm−1) νmax 3306 (N−H), 3109,
1733 (CO). 13C NMR (75 MHz, acetone-d6) δ 154.7, 151.8, 139.7,
131.4, 124.5, 83.1, 27.3. LRMS (ESI+) m/z 341 ([M + Na]+, 50%).
EXPERIMENTAL SECTION
■
General Procedure 1 for Synthesis of tert-Butyl Carbamate-
Based Preformed Nitrogen Sources. To a solution of tert-butyl N-
hydroxycarbamate 744 in dichloromethane cooled to 0 °C was added
carboxylic acid chloride or sulfonyl chloride. To this mixture was
added triethylamine, and the mixture was stirred at room temperature
until the reaction was complete. The mixture was quenched with water
and separated. The aqueous layer was extracted with dichloromethane,
and the combined dichloromethane layers were washed with brine,
dried (MgSO4), and concentrated under reduced pressure to afford
crude product. Purification was conducted by flash chromatography
with the specified solvents.
16
1
The H NMR data matched the literature.
Assay of tert-Butyl Carbamate-Based Preformed Nitrogen
Sources in the Oxyamination Reaction. To a mixture of trans-
stilbene 8 (1.0 equiv), (DHQD)2PHAL (5.0 mol %), and potassium
osmate dihydrate (4.0 mol %) in n-propanol/water (3:1) cooled to 0
°C was added nitrogen source (2.0 equiv). This mixture was stirred at
room temperature until the reaction was complete. Water was added,
and the mixture was extracted with ethyl acetate (5.0 mL). The
aqueous layer was further extracted with ethyl acetate (3 × 10 mL).
Combined ethyl acetate layers were washed with brine, dried
(MgSO4), and evaporated under reduced pressure. Purification was
performed by flash chromatography (1:9:5 ethyl acetate/dichloro-
methane/n-hexane) to afford tert-butyl (1R*,2R*)-2-hydroxy-1,2-
diphenylethylcarbamate 9a46 as a white solid (Table 2). The reaction
product was analyzed by HPLC (chiral column OD-H in 7.5% 2-
propanol/n-hexane; flow rate 1.0 mL·min−1). The enantiomeric excess
(ee) was calculated from the relative peak area of the two peaks,
retention times 10.0 and 11.4 min. The products were racemic.
General Procedure 2 for Synthesis of N-(Tosyloxy)-
carbamate Preformed Nitrogen Sources.40 To a solution of
alkyl N-hydroxycarbamate in diethyl ether at 0 °C was added
toluenesulfonyl chloride. Triethylamine was added dropwise over 30
min and the reaction was stirred at room temperature until complete.
The mixture was filtered, and the filtrate was extracted with diethyl
ether, washed with brine, dried (MgSO4), and concentrated under
reduced pressure to afford crude product. Purification was conducted
by flash chromatography with the specified solvents.
tert-Butyl N-(Pentafluorobenzoyloxy)carbamate 1. General pro-
cedure 1 was followed with tert-butyl N-hydroxycarbamate 7 (665.7
mg, 5.0 mmol), pentafluorobenzoyl chloride (1.15 g, 5.0 mmol), and
triethylamine (505.9 mg, 5.0 mmol). Purification by flash chromatog-
raphy with 15% ethyl acetate/n-hexane afforded the title compound as
a white solid (1.10 g, 67%), mp 70−73 °C. Rf 0.53 (40% ethyl acetate/
n-hexane). IR (thin film, cm−1) νmax 3276 (N−H), 2985, 2938 (C−H),
1
1783, 1741 (CO). H NMR (300 MHz, CDCl3) δ 8.13 (1H, s),
1.51 (9H, s). 13C NMR (75 MHz, CDCl3) δ 158.9, 155.3, 146.1 (d, J =
267 Hz), 144.3 (d, J = 261 Hz), 138.1 (d, J = 257 Hz), 105.4, 84.3,
28.0. LRMS (ESI+) m/z 350 ([M + Na]+, 8%). HRMS (ESI+) [M +
Na]+ calcd for C12H10F5NO4Na 350.0428, found 350.0427.
tert-Butyl N-(2-Chloroacetoxy)carbamate 2. General procedure 1
was followed with minor modifications, with tert-butyl N-hydrox-
ycarbamate 7 (100 mg, 0.751 mmol), chloroacetyl chloride (56.6 mg,
0.50 mmol), and N,N-diisopropylethylamine (64.7 mg, 0.50 mmol).
Purification by flash chromatography with 30% ethyl acetate/n-hexane
provided the title compound as a yellow oil (90.0 mg, 86%). Rf 0.33
(30% ethyl acetate/n-hexane). IR (thin film, cm−1) νmax 3271 (N−H),
1
2982 (C−H), 1795, 1737 (CO). H NMR (300 MHz, CDCl3) δ
8.14 (1H, s), 4.20 (2H, s), 1.47 (9H, s). 13C NMR (75 MHz, CDCl3)
δ 167.3, 155.2, 84.3, 38.9, 28.2. LRMS (EI+) m/z 212 ([M + H]+,
10%), 210 (8), 194 ([M − CH3]+, 80). HRMS (EI+) [M − CH3]+
calcd for C6H9NO435Cl 194.0220, found 194.0222; [M − CH3]+ calcd
for C6H9NO437Cl 196.0191, found 196.0193.
E
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Ethyl N-(Tosyloxy)carbamate 4b.40 General procedure 2 was
followed with ethyl N-hydroxycarbamate47 (400.0 mg, 3.81 mmol),
toluenesulfonyl chloride (725.6 mg, 3.81 mmol), and triethylamine
(385.1 mg, 3.81 mmol). Purification by flash chromatography with
30% ethyl acetate/n-hexane afforded the title compound as a colorless
solid (715.4 mg, 73%). Rf 0.22 (30% ethyl acetate/n-hexane). LRMS
(ESI+) m/z 282 ([M + Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd
afforded ethyl (R*)-2-hydroxy-2-phenylethylcarbamate 25b as a white
solid (46.7 mg, 73%), mp 85−86 °C (lit.52 85.5−87 °C). Rf 0.23 (40%
ethyl acetate/n-hexane). LRMS (ESI+) m/z 232 ([M + Na]+, 100%).
HRMS (ESI+) [M + Na]+ calcd for C11H15NO3Na 232.0950, found
232.0952. IR, 1H and 13C NMR data matched the literature.53
A
second fraction afforded ethyl (R*)-2-hydroxy-1-phenylethylcarbamate
40b as a colorless solid (2.3 mg, 3%), mp 61−63 °C (lit.52 62−63 °C).
Rf 0.13 (40% ethyl acetate/n-hexane). LRMS (ESI+) m/z 232 ([M +
Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for C11H15NO3Na
1
for C10H13NO5SNa 282.0412, found 282.0412. IR, H, and 13C NMR
data matched the literature.40
2,2,2-Trichloroethyl N-(Tosyloxy)carbamate 4c.24 General proce-
dure 2 was followed with 2,2,2-trichloroethyl N-hydroxycarbamate48
(900.0 mg, 4.32 mmol), toluenesulfonyl chloride (905.5 mg, 4.75
mmol), and triethylamine (436.9 mg, 4.32 mmol). Purification by flash
chromatography with 20% ethyl acetate/n-hexane afforded the title
compound as a white solid (1.37 g, 79%), mp 133−135 °C (lit.24 123
°C). Rf 0.25 (20% ethyl acetate/n-hexane). LRMS (ESI+) m/z 386
([M + Na]+, 100%), 384 ([M + Na]+, 98). HRMS (ESI+) [M + Na]+
1
232.0950, found 232.0951. IR, H and 13C NMR data matched the
literature.54
2,2,2-Trichloroethyl (R*)-2-Hydroxy-2-phenylethylcarbamate 25c
and 2,2,2-Trichloroethyl (R*)-2-Hydroxy-1-phenylethylcarbamate
40c. General procedure 3 was followed with styrene 10 (30.0 mg,
0.288 mmol), potassium osmate dihydrate (1.1 mg, 0.003 mmol), and
2,2,2-trichloroethyl N-(tosyloxy)carbamate 4c (125.3 mg, 0.346
mmol). Purification by flash chromatography with 30% ethyl
acetate/n-hexane afforded 2,2,2-trichloroethyl (R*)-2-hydroxy-2-phe-
nylethylcarbamate 25c as a white solid (82.1 mg, 91%), Rf 0.24 (30%
ethyl acetate/n-hexane). Recrystallization via slow evaporation from
chloroform/n-hexane provided white crystals, mp 116−118 °C. IR
(thin film, cm−1) νmax 3397 (O−H), 3317 (N−H), 3085, 3062, 2960,
calcd for C10H1035Cl3NO5SNa 383.9243, found 383.9238. IR, H, and
1
13C NMR data matched the literature.24
2-(Trimethylsilyl)ethyl N-(Tosyloxy)carbamate 4d. General proce-
dure 2 was followed with 2-(trimethylsilyl)ethyl N-hydroxycarba-
mate49 (761.0 mg, 4.29 mmol), toluenesulfonyl chloride (1.1 equiv,
900.2 mg, 4.72 mmol), and triethylamine (434.4 mg, 4.29 mmol).
Purification by flash chromatography with 20% ethyl acetate/n-hexane
afforded the title compound as a colorless oil (1.08 g, 76%). Rf 0.21
(20% ethyl acetate/n-hexane). IR (thin film, cm−1) νmax 3287 (N−H),
1741, 1711 (CO), 1597. 1H NMR (300 MHz, CDCl3) δ 8.29 (1H,
s), 7.87 (2H, d, J = 8.1 Hz), 7.36 (2H, d, J = 8.4 Hz), 4.08 (2H, m),
2.46 (3H, s), 0.84 (2H, m), 0.00 (9H, s). 13C NMR (75 MHz, CDCl3)
δ 157.5, 147.7, 131.9, 131.3, 131.2, 67.4, 23.4, 18.9, 0.0. LRMS (ESI+)
m/z 354 ([M + Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for
C13H21NO5SSiNa 354.0807, found 354.0804.
1
2894 (C−H), 1710 (CO). H NMR (400 MHz, CDCl3) δ 7.37−
7.28 (5H, m), 5.37 (1H, s), 4.87 (1H, m), 4.72 (2H, s), 3.61 (1H, ddd,
J = 14.0, 7.6, 4.0 Hz), 3.36 (1H, ddd, J = 13.2, 8.0, 4.8 Hz), 2.37 (1H,
d, J = 3.6 Hz). 13C NMR (100 MHz, CDCl3) δ 155.1, 141.1, 128.7,
128.2, 125.8, 77.2, 74.6, 73.4, 48.4. LRMS (ESI+) m/z 336 ([M +
Na]+, 95%), 334 (100). HRMS (ESI+) [M + Na]+ calcd for
C11H1235Cl3NO3Na 333.9780, found 333.9787; [M + Na]+ calcd for
C11H1235Cl237ClNO3Na 335.9751, found 335.9756. A second fraction
afforded 2,2,2-trichloroethyl (R*)-2-hydroxy-1-phenylethylcarbamate
40c as a white solid (8.0 mg, 9%), Rf 0.11 (30% ethyl acetate/n-
hexane). Recrystallization via slow evaporation from chloroform/n-
hexane afforded white crystals, mp 135−137 °C. IR (thin film, cm−1)
νmax 3322 (O−H), 3204 (N−H), 3052, 2951, 2927, 2853 (C−H),
Benzyl N-(Tosyloxy)carbamate 4e.41 General procedure 2 was
followed with benzyl N-hydroxycarbamate50 (936.3 mg, 5.60 mmol),
toluenesulfonyl chloride (1.28 g, 6.72 mmol), and triethylamine (680.0
mg, 6.72 mmol). Purification by flash chromatography provided the
title compound as a white solid (814.0 mg, 46%), mp 119−121 °C
(lit.41 120−123 °C). Rf 0.11 (80% dichloromethane/n-hexane). 13C
NMR (75 MHz, CDCl3) δ 155.5, 146.1, 134.5, 130.0, 129.7, 129.5,
128.7, 128.6, 128.3, 68.6, 21.8. LRMS (ESI+) m/z 344 ([M + Na]+,
100%). HRMS (ESI+) [M + Na]+ calcd for C15H15NO5SNa 344.0569,
1
1706 (CO), 1560. H NMR (400 MHz, CDCl3) δ 7.30−7.40 (5H,
m), 5.76 (1H, br s), 4.88 (1H, m), 4.73 (2H, s), 3.88−3.98 (2H, m),
1.82 (1H, s). 13C NMR (100 MHz, CDCl3) δ 154.4, 138.5, 128.9,
128.1, 126.5, 95.6, 74.7, 66.2, 57.1. LRMS (ESI+) m/z 336 ([M +
Na]+, 99%), 334 (100). HRMS (ESI+) [M + Na]+ calcd for
C11H1235Cl3NO3Na 333.9780, found 333.9782; [M + Na]+ calcd for
C11H1235Cl237ClNO3Na 335.9751, found 335.9749.
41
1
found 344.0568. IR and H NMR IR data matched the literature.
2-(Trimethylsilyl)ethyl (R*)-2-Hydroxy-2-phenylethylcarbamate
25d. General procedure 3 was followed with styrene 10 (35.0 mg,
0.336 mmol), potassium osmate dihydrate (4.9 mg, 0.013 mmol), and
2-(trimethylsilyl)ethyl N-(tosyloxy)carbamate 4d (136.5 mg, 0.412
mmol). Purification by flash chromatography with 2:2:6 ethyl acetate/
dichloromethane/n-hexane provided the title compound as a colorless
solid (37.1 mg, 39%), mp 75−77 °C. Rf 0.23 (2:2:6 ethyl acetate/
dichloromethane/n-hexane). IR (thin film, cm−1) νmax 3361 (O−H),
3266 (N−H), 3072, 2953, 2929, 2899 (C−H), 1679 (CO), 1554.
1H NMR (400 MHz, CDCl3) δ 7.27−7.37 (5H, m), 5.03 (1H, s), 4.84
(1H, m), 4.17 (2H, m), 3.54 (1H, m), 3.30 (1H, ddd, J = 14.0, 8.4, 5.6
Hz), 2.88 (1H, s), 0.98 (2H, m), 0.09 (9H, s). 13C NMR (100 MHz,
CDCl3) δ 159.2, 143.1, 130.1, 129.4, 127.3, 75.4, 64.9, 50.0, 19.2, 0.0.
LRMS (ESI+) m/z 304 ([M + Na]+, 100). HRMS (ESI+) [M + Na]+
calcd for C14H23NO3SiNa 304.1345, found 304.1345.
General Procedure 3 for Assay of N-(Tosyloxy)carbamate
Preformed Nitrogen Sources in the Oxyamination Reaction.
To a mixture of alkene and potassium osmate dihydrate in
acetonitrile/water (3:1) or the specified solvent was added the
nitrogen source at 0 °C. The mixture was stirred at room temperature
until the reaction was complete. The mixture was then extracted with
ethyl acetate (3 × 5 mL). The combined ethyl acetate fractions were
dried (Na2SO4) and concentrated under reduced pressure to afford
crude product. Purification was performed by flash chromatography
with the indicated solvents.
(2R*)-tert-Butyl 2-Hydroxy-2-phenylethylcarbamate 25a.51 Gen-
eral procedure 3 was followed with styrene 10 (40.0 mg, 0.384 mmol),
tert-butyl N-(tosyloxy)carbamate 4a (132.4 mg, 0.461 mmol), and
potassium osmate dihydrate (4.0 mol %, 5.7 mg, 0.015 mmol) in tert-
butanol/water (3:1). Purification by flash chromatography with 2:2:6
ethyl acetate/dichloromethane/n-hexane afforded the title compound
as a white solid (75.6 mg, 83%), mp 120−121 °C (lit.51 120−121 °C).
Rf 0.20 (2:2:6 ethyl acetate/dichloromethane/n-hexane). LRMS (ESI
+) m/z 260 ([M + Na]+, 100%). HRMS (ESI+) [M + H]+ calcd for
C13H20NO3 238.1443, found 238.1448; [M + Na]+ calcd for
C13H19NO3Na 260.1263, found 260.1266. IR, 1H and 13C NMR
data matched the literature.51
Benzyl (R*)-2-Hydroxy-2-phenylethylcarbamate 25e10,52 and
Benzyl (R*)-2-Hydroxy-1-phenylethylcarbamate 40e.10,52 General
procedure 3 was followed with styrene 10 (30.0 mg, 0.288 mmol),
potassium osmate dihydrate (1.1 mg, 0.003 mmol), and benzyl N-
(tosyloxy)carbamate 4e (111.1 mg, 0.346 mmol). Purification by flash
chromatography with 2:3:5 ethyl acetate/dichloromethane/n-hexane
provided (R*)-benzyl 2-hydroxy-2-phenylethylcarbamate 25e as a
white solid (61.7 mg, 80%), mp 109−111 °C (lit.52 114−115 °C). Rf
0.25 (2:3:5 ethyl acetate/dichloromethane/n-hexane). LRMS (ESI+)
m/z 294 ([M + Na]+, 100). HRMS (ESI+) [M + Na]+ calcd for
Ethyl (R*)-2-Hydroxy-2-phenylethylcarbamate 25b52,53 and
Ethyl (R*)-2-Hydroxy-1-phenylethylcarbamate 40b.52,54 General
procedure 3 was followed with styrene 10 (40.0 mg, 0.384 mmol),
potassium osmate dihydrate (1.4 mg, 0.004 mmol), and ethyl N-
(tosyloxy)carbamate 4b (79.7 mg, 0.307 mmol). Purification by flash
chromatography with 2:3:5 ethyl acetate/dichloromethane/n-hexane
1
C16H17NO3Na 294.1106, found 294.1108. IR, H and 13C NMR data
matched the literature.10 A second fraction afforded (R*)-benzyl 2-
hydroxy-1-phenylethylcarbamate 40e as a white solid (4.2 mg, 5%),
F
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The Journal of Organic Chemistry
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mp 81−82 °C (lit.52 83−84.5 °C). Rf 0.16 (2:3:5 ethyl acetate/
dichloromethane/n-hexane). 13C NMR (100 MHz, CDCl3) δ 156.4,
139.0, 136.2, 128.9, 128.5, 128.2, 127.9, 126.5, 125.8, 67.0, 66.6, 57.1.
LRMS (ESI+) m/z 294 ([M + Na]+, 100%). HRMS (ESI+) [M +
Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for C20H27NO3SiNa
380.1658, found 380.1659.
Benzyl (1R*,2R*)2-Hydroxy-1,2-diphenylethylcarbamate 9e.10,55
General procedure 3 was followed with trans-stilbene 8 (100.0 mg,
0.555 mmol), potassium osmate dihydrate (4.0 mol %, 8.2 mg, 0.022
mmol), and benzyl N-(tosyloxy)carbamate 4e (356.6 mg, 1.11 mmol)
in tert-butanol/water (3:1). Purification by flash chromatography with
10% ethyl acetate/dichloromethane afforded the title compound as a
white solid (116.3 mg, 61%), mp 148−150 °C (lit.55 149−151 °C). Rf
0.22 (20% ethyl acetate/dichloromethane). 13C NMR (75 MHz,
CDCl3) δ 156.3, 140.5, 136.3, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0,
127.9, 127.7, 126.9, 126.2, 67.0, 66.9, 61.0. LRMS (ESI+) m/z 370
([M + Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for
C22H21NO3Na 370.1419, found 370.1420. IR and 1H NMR data
matched the literature.10
1
Na]+ calcd for C16H17NO3Na 294.1106, found 294.1107. IR and H
NMR data matched the literature.10
tert-Butyl (1R*,2R*)-2-Hydroxy-1,2-diphenylethylcarbamate
9a.46 General procedure 3 was followed with trans-stilbene 8 (60.0
mg, 0.333 mmol), potassium osmate dihydrate (4.0 mol %, 4.9 mg,
0.013 mmol), and tert-butyl N-(tosyloxy)carbamate 4a (191.3 mg,
0.666 mmol) in tert-butanol/water (3:1). Purification by flash
chromatography with 1:9:5 ethyl acetate/dichloromethane/n-hexane
afforded the title compound as a white solid (89.9 mg, 86%), mp 130−
131 °C (lit.46 137−138 °C). Rf 0.15 (1:9:5 of ethyl acetate/
dichloromethane/n-hexane). IR (thin film, cm−1) νmax 3415 (O−H,
N−H), 3088, 3064, 3031, 3006, 2977, 2929 (C−H), 1691 (CO),
1604, 1586. 1H NMR (300 MHz, CDCl3) δ 7.23−7.31 (10H, m), 5.48
(1H, s), 4.89 (2H, s), 2.94 (1H, s), 1.34 (9H, s). 13C NMR (75 MHz,
CDCl3) δ 156.1, 140.8, 139.9, 128.5, 128.2, 127.7, 127.5, 126.9, 126.3,
79.8, 77.4, 60.7, 28.2. LRMS (ESI+) m/z 336 ([M + Na]+, 100%).
HRMS (ESI+) [M + Na]+ calcd for C19H23NO3Na 336.1576, found
336.1572.
Methyl (S*)-3-(Benzyloxycarbonylamino)-2-hydroxypropanoate
26e.56 General procedure 3 was followed with methyl acrylate 11
(31.4 mg, 0.365 mmol), potassium osmate dihydrate (1.3 mg, 0.004
mmol), and benzyl N-(tosyloxy)carbamate 4e (135.3 mg, 0.421
mmol). Purification by flash chromatography (3:2:5 ethyl acetate/
dichloromethane/n-hexane) provided the title compound as a
colorless oil (60.2 mg, 65%). Rf 0.11 (3:2:5 ethyl acetate/dichloro-
methane/n-hexane). 13C NMR (75 MHz, CDCl3) δ 173.4, 156.7,
136.3, 128.5, 128.2, 128.1, 70.1, 67.0, 52.8, 44.2. LRMS (ESI+) m/z
276 ([M + Na]+, 100%), 254 ([M + H]+, 20). HRMS (ESI+) [M +
H]+ calcd for C12H16NO5 254.1028, found 254.1029; [M + Na]+ calcd
Ethyl (1R*,2R*)-2-Hydroxy-1,2-diphenylethylcarbamate 9b.46
General procedure 3 was followed with trans-stilbene 8 (30.0 mg,
0.166 mmol), potassium osmate dihydrate (4.0 mol %, 2.5 mg, 0.007
mmol), and ethyl N-(tosyloxy)carbamate 4b (86.3 mg, 0.333 mmol) in
tert-butanol/water (3:1). Purification by flash chromatography with
10% dichloromethane/n-hexane provided the title compound as a
white solid (20.1 mg, 42%), mp 120−122 °C (lit.46 122−123.5 °C). Rf
0.23 (20% ethyl acetate/n-hexane). IR (thin film, cm−1) νmax 3346 (br,
O−H, N−H), 3062, 3032, 2978, 2922 (C−H), 1686 (CO), 1533.
1H NMR (300 MHz, CDCl3) δ 7.28−7.31 (10H, m), 5.64 (1H, d, J =
1
for C12H15NO5Na 276.0848, found 276.0855. IR and H NMR data
matched the literature.56
2-(Trimethylsilyl)ethyl (S*)-2-Hydroxy-4-(4-nitrophenoxy)-
butylcarbamate 27d57 and 2-(Trimethylsilyl)ethyl (S*)-1-Hydroxy-
4-(4-nitrophenoxy)butan-2-ylcarbamate 41d.57 General procedure
3 was followed with 1-(but-3-enyloxy)-4-nitrobenzene 1258 (65.0 mg,
0.336 mmol), potassium osmate dihydrate (4.0 mol %, 4.9 mg, 0.014
mmol), and 2-(trimethylsilyl)ethyl N-(tosyloxy)carbamate 4d (133.8
mg, 0.404 mmol). Purification by flash chromatography with 50% ethyl
acetate/n-hexane afforded 2-(trimethylsilyl)ethyl (S*)-2-hydroxy-4-(4-
nitrophenoxy)butylcarbamate 27d as a colorless oil (88.8 mg, 71%), Rf
0.5 (70% ethyl acetate/n-hexane). LRMS (ESI+) m/z 393 ([M +
Na]+, 100%), 371 ([M + H]+, 10). HRMS (ESI+) [M + Na]+ calcd for
6.9 Hz), 4.91 (2H, s), 4.00 (2H, s), 2.74 (1H, s), 1.56 (3H, s). 13C
NMR (75 MHz, CDCl3) δ 156.6, 140.7, 139.9, 128.5, 128.3, 127.8,
127.6, 126.9, 126.2, 76.9, 61.1, 61.0, 14.5. LRMS (ESI+) m/z 308 ([M
+ Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for C17H19NO3Na
308.1263, found 308.1258.
2,2,2-Trichloroethyl (1R*,2R*)-2-Hydroxy-1,2-diphenylethylcar-
bamate 9c. General procedure 3 was followed with trans-stilbene 8
(50.0 mg, 0.277 mmol), potassium osmate dihydrate (4.0 mol %, 4.1
mg, 0.011 mmol), and 2,2,2-trichloroethyl N-(tosyloxy)carbamate 4c
(201.2 mg, 0.555 mmol) in tert-butanol/water (3:1). Purification by
flash chromatography with 1:3:6 ethyl acetate/dichloromethane/n-
hexane provided the title compound as a white solid (85.4 mg, 80%),
mp 118−121 °C. Rf 0.20 (1:3:6 ethyl acetate/dichloromethane/n-
hexane). IR (thin film, cm−1) νmax 3423 (br, O−H, N−H), 3088, 3063,
1
C16H26N2O6SiNa 393.1458, found 393.1452. IR, H, and 13C NMR
data matched the literature.57 A second fraction afforded 2-
(trimethylsilyl)ethyl (S*)-1-hydroxy-4-(4-nitrophenoxy)butan-2-ylcar-
bamate 41d as a colorless oil (11.9 mg, 10%), Rf 0.36 (70% ethyl
acetate/n-hexane). LRMS (ESI+) m/z 393 ([M + Na]+, 100). HRMS
(ESI+) [M + Na]+ calcd for C16H26N2O6SiNa 393.1458, found
57
1
393.1456. IR, H, and 13C NMR data matched the literature.
(R*)-tert-Butyl 2-Hydroxy-2-phenylpropylcarbamate 28a. Gen-
eral procedure 3 was followed with α-methyl styrene 13 (45.0 mg,
0.381 mmol), potassium osmate dihydrate (4 mol %, 5.6 mg, 0.015
mmol), and tert-butyl N-(tosyloxy)carbamate 4a (131.3 mg, 0.457
mmol) in tert-butanol/water (3:1). Purification by flash chromatog-
raphy with 2:2:6 ethyl acetate/dichloromethane/n-hexane afforded the
title compound as a colorless solid (65.1 mg, 68%), mp 122−124 °C.
Rf 0.22 (2:2:6 ethyl acetate/dichloromethane/n-hexane). IR (thin film,
cm−1) νmax 3354 (N−H, O−H), 2974, 2925 (C−H), 1691 (CO),
1
3031, 3006, 2953, 2925 (C−H), 1720 (CO), 1603, 1586, 1509. H
NMR (300 MHz, CDCl3) δ 7.28−7.38 (10H, m), 5.93 (1H, d, J = 6.3
Hz), 4.99−5.04 (2H, m), 4.57−4.67 (2H, m), 2.19 (1H, d, J = 2.7 Hz).
13C NMR (75 MHz, CDCl3) δ 154.4, 140.3, 139.4, 128.7, 128.4, 128.0,
127.8, 126.8, 126.1, 110.0, 95.4, 74.4, 61.0. LRMS (ESI+) m/z 414
([M + Na]+, 32%), 412 (94), 410 (100). HRMS (ESI+) [M + Na]+
calcd for C17H1635Cl3NO3Na 410.0093, found 410.0090; [M + Na]+
calcd for C17H1635Cl237ClNO3Na 412.0064, found 412.0060; [M +
Na]+ calcd for C17H1635Cl37Cl2NO3Na 414.0034, found 414.0040.
2-(Trimethylsilyl)ethyl (1R*,2R*)-2-hydroxy-1,2-diphenylethylcar-
bamate 9d. General procedure 3 was followed with trans-stilbene 8
(95.0 mg, 0.527 mmol), potassium osmate dihydrate (7.7 mg, 0.021
mmol), and 2-(trimethylsilyl)ethyl N-(tosyloxy)carbamate 4d (174.7
mg, 0.527 mmol) in tert-butanol/water (3:1). Purification by flash
chromatography with 1:6:3 ethyl acetate/dichloromethane/n-hexane
provided the title compound as a white solid (93.3 mg, 50%), mp
134−135 °C. Rf 0.34 (1:7:2 ethyl acetate/dichloromethane/n-hexane).
IR (thin film, cm−1) νmax 3339 (br, O−H, N−H), 3063, 3029, 2954,
1
1533. H NMR (400 MHz, CDCl3) δ 7.45 (2H, m), 7.36 (2H, m),
7.28 (1H, m), 4.76 (1H, s), 3.52 (1H, dd, J = 14.4, 7.6 Hz), 3.32 (1H,
dd, J = 14.4, 5.6 Hz), 3.14 (1H, s), 1.54 (3H, s), 1.41 (9H, s). 13C
NMR (100 MHz, CDCl3) δ 157.3, 145.7, 128.3, 127.0, 125.0, 79.8,
75.0, 52.0, 28.3, 27.5. LRMS (ESI+) m/z 274 ([M + Na]+, 100%).
HRMS (ESI+) [M + Na]+ calcd for C14H21NO3Na 274.1419, found
274.1419.
(R*)-2,2,2-Trichloroethyl 2-Hydroxy-2-phenylpropylcarbamate
28c. General procedure 3 was followed with α-methyl styrene 13
(30.0 mg, 0.254 mmol), potassium osmate dihydrate (0.9 mg, 0.003
mmol), and 2,2,2-trichloroethyl N-(tosyloxy)carbamate 4c (110.5 mg,
0.305 mmol). Purification by flash chromatography with 25% ethyl
acetate/n-hexane provided the title compound as a colorless solid
(75.6 mg, 91%), Rf 0.22 (30% ethyl acetate/n-hexane). Recrystalliza-
tion via slow evaporation from chloroform/n-hexane solvent provided
1
2897 (C−H), 1689 (CO), 1602, 1586, 1537. H NMR (300 MHz,
CDCl3) δ 7.25−7.30 (10H, m), 5.61 (1H, d, J = 7.8 Hz), 4.93 (2H, s),
4.04 (2H, m), 2.72 (1H, s), 0.91 (2H, m), 0.00 (9H, s). 13C NMR
(100 MHz, CDCl3) δ 158.2, 142.2, 141.5, 130.0, 129.8, 129.3, 129.1,
128.4, 127.7, 78.5, 64.8, 62.5, 19.1, 0.0. LRMS (ESI+) m/z 380 ([M +
G
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colorless crystals, mp 132−133 °C. IR (thin film, cm−1) νmax 3422
(O−H), 3331 (N−H), 3062, 3002, 2935, 2851 (C−H), 1716 (C
O). 1H NMR (400 MHz, CDCl3) δ 7.45 (2H, m), 7.36 (2H, m), 7.26
(1H, m), 5.22 (1H, s), 4.72−4.65 (2H, m), 3.60 (1H, dd, J = 14.0, 6.8
Hz), 3.45 (1H, dd, J = 14.0, 5.6 Hz), 2.23 (1H, s), 1.53 (3H, s). 13C
NMR (100 MHz, CDCl3) δ 155.4, 145.0, 128.5, 127.3, 124.9, 77.2,
74.7, 74.5, 52.2, 27.5. LRMS (ESI+) m/z 350 ([M + Na]+, 100%).
HRMS (ESI+) [M + Na]+ calcd for C12H1435Cl3NO3Na 347.9937,
found 347.9941; [M + Na]+ calcd for C12H1435Cl237ClNO3Na
349.9907, found 349.9911.
N−H), 3066, 3020, 2955, 2855 (C−H), 1735 (CO), 1522. 13C
NMR (100 MHz, CDCl3) δ 173.0, 154.0, 138.3, 128.7, 128.1, 126.7,
95.4, 74.6, 73.2, 56.6, 53.2. LRMS (ESI+) m/z 396 ([M + Na]+, 18%),
394 (50), 392 (53). HRMS (ESI+) [M + Na]+ calcd for
C13H1435Cl3NO5Na 391.9835, found 391.9839; [M + Na]+ calcd for
C13H1435Cl237ClNO5Na 393.9806, found 393.9808; [M + Na]+ calcd
for C13H1435Cl37Cl2NO5Na 395.9776, found 395.9770; [M + Na]+
calcd for C13H1437Cl3NO5Na 397.9747, found 397.9747. The 1H NMR
data matched the literature.61 A second fraction (tR 10.22 min)
afforded methyl (2S*,3R*)-3-hydroxy-3-phenyl-2-[(2,2,2-
trichloroethoxy)carbonylamino]propanoate 29c as a colorless oil
(42.2 mg, 46%). IR (thin film, cm−1) νmax 3431 (O−H, N−H),
Methyl (2S*,3R*)-3-(tert-Butoxycarbonylamino)-2-hydroxy-3-
phenylpropanoate 42a59 and Methyl (2S*,3R*)-2-(tert-Butoxycar-
bonylamino)-3-hydroxy-3-phenylpropanoate 29a.60 General proce-
dure 3 was followed with trans-methyl cinnamate 14 (40.0 mg, 0.247
mmol), tert-butyl N-(tosyloxy)carbamate 4a (85.1 mg, 0.296 mmol),
and potassium osmate dihydrate (3.6 mg, 0.010 mmol) in tert-
butanol/water (3:1). The product was afforded as a mixture of two
regioisomers after purification by flash chromatography with 2:2:6
ethyl acetate/dichloromethane/n-hexane. Rf 0.23 (2:2:6 ethyl acetate/
dichloromethane/n-hexane). LRMS (ESI+) m/z 318 ([M + Na]+,
100%). HRMS (ESI+) [M + Na]+ calcd for C15H21NO5Na 318.1317,
found 318.1317. Further purification by preparative HPLC afforded
methyl (2S*,3R*)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenyl-
propanoate 42a as a white solid (17.5 mg, 24%) at tR 12.76 min
(2% 2-propanol/98% n-hexane, flow rate 10 mL·min−1). 13C NMR
(100 MHz, CDCl3) δ 173.4, 155.1, 139.1, 128.6, 127.7, 126.7, 79.9,
73.5, 56.0, 53.1, 28.2. IR and 1H NMR data matched the literature.59 A
second fraction (tR 21.00 min) afforded methyl (2S*,3R*)-2-(tert-
butoxycarbonylamino)-3-hydroxy-3-phenylpropanoate 29a as a color-
1
3065, 3029, 2955 (C−H), 1733 (CO), 1606, 1521. H NMR (400
MHz, CDCl3) δ 7.39−7.27 (5H, m), 5.85 (1H, d, J = 9.6 Hz), 5.35
(1H, t, J = 3.2 Hz), 4.66−4.61 (2H, m), 4.55 (1H, d, J = 12.0 Hz), 3.80
(3H, s), 2.67 (1H, d, J = 4.0 Hz). 13C NMR (100 MHz, CDCl3) δ
170.6, 154.5, 139.3, 128.5, 128.3, 125.8, 95.2, 74.6, 73.5, 59.9, 52.8.
LRMS (ESI+) m/z 396 ([M + Na]+, 32%), 394 (98), 392 (100).
HRMS (ESI+) [M + Na]+ calcd for C13H1435Cl3NO5Na 391.9835,
found 391.9835; [M + Na]+ calcd for C13H1435Cl237ClNO5Na
393.9806, found 393.9801; [M
+
Na]+ calcd for
C13H1435Cl37Cl2NO5Na 395.9776, found 395.9781; [M + Na]+ calcd
for C13H1437Cl3NO5Na 397.9747, found 397.9747.
Methyl (2S*,3R*)-2-Hydroxy-3-phenyl-3-{[2-(trimethylsilyl)-
ethoxy]carbonylamino}propanoate 42d and Methyl (2S*,3R*)-3-
Hydroxy-3-phenyl-2-{[2-(trimethylsilyl)ethoxy]carbonylamino}-
propanoate 29d.62 General procedure 3 was followed with trans-
methyl cinnamate 14 (56.0 mg, 0.345 mmol), potassium osmate
dihydrate (4.0 mol %, 5.0 mg, 0.014 mmol), and 2-(trimethylsilyl)ethyl
N-(tosyloxy)carbamate 4d (147.4 mg, 0.445 mmol). Purification by
flash chromatography with 2:2:6 ethyl acetate/dichloromethane/n-
hexane provided a mixture of both regioisomers, Rf 0.22 (2:2:6 ethyl
acetate/dichloromethane/n-hexane). Further separation by preparative
HPLC with 2% 2-propanol/98% n-hexane at a flow rate of 10
mL·min−1 afforded methyl (2S*,3R*)-2-hydroxy-3-phenyl-3-{[2-
(trimethylsilyl)ethoxy]carbonylamino}propanoate 42d (tR 12.24
min) as a colorless liquid (22.3 mg, 19%). IR (thin film, cm−1) νmax
3370 (br, O−H, N−H), 3067, 3021, 2953 (C−H), 1721, 1697 (C
1
less solid (29.7 mg, 41%). IR, H, and 13C NMR data matched the
literature.60
Methyl (2S*,3R*)-3-(Ethoxycarbonylamino)-2-hydroxy-3-phenyl-
propanoate 42b10,55 and Methyl (2S*,3R*)-2-(Ethoxycarbonylami-
no)-3-hydroxy-3-phenylpropanoate 29b. General procedure 3 was
followed with trans-methyl cinnamate 14 (40.0 mg, 0.247 mmol),
potassium osmate dihydrate (0.9 mg, 0.003 mmol), and ethyl N-
(tosyloxy)carbamate 4b (161.1 mg, 0.622 mmol). Purification by flash
chromatography with 40% ethyl acetate/n-hexane gave a mixture of
regioisomers, Rf 0.22 (40% ethyl acetate/n-hexane). Further separation
by preparative HPLC (solvent 2% 2-propanol/98% n-hexane, flow rate
10 mL·min−1) afforded methyl (2S*,3R*)-3-(ethoxycarbonylamino)-
2-hydroxy-3-phenylpropanoate 42b (tR 22.42 min) as a colorless solid
(20.4 mg, 31%). LRMS (ESI+) m/z 290 ([M + Na]+, 100). HRMS
(ESI+) [M + H]+ calcd for C13H18NO5 268.1185, found 268.1182; [M
+ Na]+ calcd for C13H17NO5Na 290.1004, found 290.1005. IR, 1H, and
13C NMR data matched the literature.10 A second fraction (tR 30.03
1
O), 1603, 1514. H NMR (400 MHz, CDCl3) δ 7.28−7.36 (5H, m),
5.51 (1H, d, J = 9.0 Hz), 5.25 (1H, d, J = 9.3 Hz), 4.49 (1H, m), 4.12
(2H, m), 3.85 (3H, s), 3.15 (1H, s), 0.96 (2H, m), 0.00 (9H, s). 13C
NMR (75 MHz, CDCl3) δ 174.8, 157.5, 140.5, 130.2, 129.4, 128.2,
74.9, 65.0, 57.8, 54.7, 19.1, 0.0. LRMS (ESI+) m/z 362 ([M + Na]+,
100%). HRMS (ESI+) [M + Na]+ calcd for C16H25NO5SiNa
362.1400, found 362.1402. A second fraction (tR 19.87 min) afforded
methyl (2S*,3R*)-3-hydroxy-3-phenyl-2-{[2-(trimethylsilyl)ethoxy]-
carbonylamino}propanoate 29d as a colorless liquid (34.9 mg, 30%).
IR (thin film, cm−1) νmax 3401 (O−H, N−H), 3065, 3029, 2953, 2898
(C−H), 1752, 1724, 1701 (CO), 1606, 1513. 1H NMR (400 MHz,
CDCl3) δ 7.26−7.38 (5H, m), 5.42 (1H, d, J = 8.4 Hz), 5.26 (1H, m),
4.58 (1H, d, J = 7.2 Hz), 4.06−4.03 (2H, m), 3.76 (3H, s) 2.76 (1H,
s), 0.91 (2H, t, J = 7.6 Hz), 0.00 (9H, s). 13C NMR (100 MHz,
CDCl3) δ 172.8, 158.1, 141.1, 130.0, 129.7, 127.4, 75.3, 65.2, 61.2,
54.2, 19.1, 0.0. LRMS (ESI+) m/z 362 ([M + Na]+, 100%). HRMS
(ESI+) [M + Na]+ calcd for C16H25NO5SiNa 362.1400, found
362.1400; [M + H]+ calcd for C16H26NO5Si 340.1580, found
340.1580.
min) afforded methyl (2S*,3R*)-2-(ethoxycarbonylamino)-3-hydroxy-
3-phenylpropanoate 29b (33.3 mg, 51%) as a colorless oil. IR (thin
film, cm−1) νmax 3401 (O−H, N−H), 3020, 2955, 2931, 2851 (C−H),
1
1720, 1701 (CO), 1622, 1516. H NMR (400 MHz, CDCl3) δ
7.34−7.36 (4H, m), 7.30 (1H, m), 5.48 (1H, d, J = 8.4 Hz), 5.25 (1H,
m), 4.57 (1H, d, J = 7.6 Hz), 4.00−4.01 (2H, m), 3.76 (3H, s), 2.81
(1H, s), 1.16 (3H, t, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3) δ
171.2, 156.5, 139.6, 128.4, 128.1, 125.9, 73.7, 61.3, 59.7, 52.6, 14.4.
LRMS (ESI+) m/z 290 ([M + Na]+, 95). HRMS (ESI+) [M + Na]+
calcd for C13H17NO5Na 290.1004, found 290.1004; [M + H]+ calcd
for C13H18NO5 268.1185, found 268.1184.
Ethyl (2S*,3R*)-3-(Benzyloxycarbonylamino)-2-hydroxy-3-phe-
nylpropanoate 43e63 and Ethyl (2S*,3R*)-2-(Benzyloxycarbonyla-
mino)-3-hydroxy-3-phenylpropanoate 30e.63 General procedure 3
was followed with trans-ethyl cinnamate 15 (50.0 mg, 0.284 mmol),
potassium osmate dihydrate (1.0 mol %, 1.1 mg, 0.003 mmol), and
benzyl N-(tosyloxy)carbamate 4e (109.9 mg, 0.341 mmol).
Purification by flash chromatography with 2:2:6 ethyl acetate/
dichloromethane/n-hexane afforded a mixture of two regioisomers,
Rf 0.33 (3:2:5 ethyl acetate/dichloromethane/n-hexane). Further
purification by preparative HPLC with 1% 2-propanol/99% n-hexane
at a flow rate of 10 mL·min−1 provided ethyl (2S*,3R*)-3-
(benzyloxycarbonylamino)-2-hydroxy-3-phenylpropanoate 43e (tR
9.20 min) as a white solid (34.5 mg, 35%), mp 86−88 °C. IR (thin
Methyl (2S*,3R*)-2-Hydroxy-3-phenyl-3-[(2,2,2-trichloroethoxy)-
carbonylamino]propanoate 42c61 and Methyl (2S*,3R*)-3-Hy-
droxy-3-phenyl-2-[(2,2,2-trichloroethoxy)carbonylamino]-
propanoate 29c. General procedure 3 was followed with trans-methyl
cinnamate 14 (40.0 mg, 0.247 mmol), potassium osmate dihydrate
(0.9 mg, 0.003 mmol), and 2,2,2-trichloroethyl N-(tosyloxy)carbamate
4c (107.3 mg, 0.296 mmol). Purification by flash chromatography with
25% ethyl acetate/n-hexane afforded a mixture of both regioisomers, Rf
0.22 (30% ethyl acetate/n-hexane). Further separation by preparative
HPLC with 4% 2-propano/96% n-hexane at a flow rate of 10
mL·min−1 provided methyl (2S*,3R*)-2-hydroxy-3-phenyl-3-[(2,2,2-
trichloroethoxy)carbonylamino]propanoate 42c (tR 7.82 min) as a
colorless oil (33.1 mg, 36%). IR (thin film, cm−1) νmax 3351 (O−H,
H
dx.doi.org/10.1021/jo301372y | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
film, cm−1) νmax 3367 (O−H, N−H), 3089, 3064, 2981, 2960, 2934,
of 8 mL·min−1 provided 2-(trimethylsilyl)ethyl (1R*,2S*)-1-hydroxy-
2,3-dihydro-1H-inden-2-yl carbamate 32d (tR 33.81 min) as an oil
(47.8 mg, 48%). IR (thin film, cm−1) νmax 3413 (O−H, N−H), 3071,
3046, 2952, 2897, (C−H), 1718, 1691 (CO), 1512. 1H NMR (400
MHz, CDCl3) δ 7.38 (1H, d, J = 6.8 Hz), 7.20−7.28 (3H, m), 5.25
(1H, s), 5.00 (1H, m), 4.38 (1H, m), 4.14 (2H, t, J = 8.4 Hz), 3.20
(1H, dd, J = 16.0, 7.6 Hz), 2.84 (1H, dd, J = 16.0, 7.6 Hz), 1.91 (1H,
s), 0.96 (2H, t, J = 8.4 Hz), 0.00 (9H, s). 13C NMR (100 MHz,
CDCl3) δ 158.4, 143.5, 142.5, 130.8, 128.8, 126.7, 126.6, 76.2, 64.7,
56.3, 38.3, 19.2, 0.0. LRMS (ESI+) m/z 316 ([M + Na]+, 100). HRMS
(ESI+) [M + Na]+ calcd for C15H23NO3SiNa 316.1345, found
316.1344. A second fraction (tR 41.53 min) afforded 2-(trimethylsilyl)-
ethyl (1R*,2S*)-2-hydroxy-2,3-dihydro-1H-inden-1-ylcarbamate 44d
as an oil (22.5 mg, 23%). IR (thin film, cm−1) νmax 3408 (O−H), 3323
(N−H), 3047, 2952, 2897 (C−H), 1720, 1694 (CO), 1609, 1518.
LRMS (ESI+) m/z 316 ([M + Na]+, 100). HRMS (ESI+) [M + Na]+
1
2851 (C−H), 1730 (CO), 1604, 1586, 1519. H NMR (400 MHz,
CDCl3) δ 7.28−7.40 (10H, m), 5.69 (1H, d, J = 9.2 Hz), 5.29 (1H, d, J
= 8.8 Hz), 5.12−5.03 (2H, m), 4.47 (1H, s), 4.29−4.23 (2H, m), 3.19
(1H, d, J = 4.0 Hz), 1.28 (3H, t, J = 6.8 Hz). 13C NMR (100 MHz,
CDCl3) δ 127.7, 155.6, 138.9, 136.3, 128.6, 128.5, 128.1, 128.1, 127.8,
126.7, 73.4, 67.0, 62.6, 56.4, 14.0. LRMS (ESI+) m/z 366 ([M + Na]+,
100%), 344 (5). HRMS (ESI+) [M + H]+ calcd for C19H22NO5
344.1498, found 344.1496; [M + Na]+ calcd for C19H21NO5Na
366.1317, found 366.1317. A second fraction afforded ethyl
(2S*,3R*)-2-(benzyloxycarbonylamino)-3-hydroxy-3-phenylpropa-
noate 30e (tR 14.68 min) as a white solid (45.7 mg, 47%), mp 78−80
°C. IR (thin film, cm−1) νmax 3423 (O−H, N−H), 3064, 3032, 2981,
1
2962, 2937(C−H), 1726 (CO), 1605, 1518. H NMR (400 MHz,
CDCl3) δ 7.27−7.37 (10H, m), 5.59 (1H, d, J = 8.8 Hz), 5.25 (1H, s),
5.01 (2H, s), 4.59 (1H, d, J = 6.8 Hz), 4.24−4.16 (2H, m), 2.73 (1H,
d, J = 3.2 Hz), 1.24 (3H, t, J = 6.8 Hz). 13C NMR (100 MHz, CDCl3)
δ 170.5, 156.3, 139.6, 136.2, 128.4, 128.2, 128.1 (2C), 127.9, 126.0,
73.8, 67.0, 61.8, 59.9, 14.0. LRMS (ESI+) m/z 366 ([M + Na]+,
100%), 344 (14). HRMS (ESI+) [M + H]+ calcd for C19H22NO5
344.1498, found 344.1498; [M + Na]+ calcd for C19H21NO5Na
366.1317, found 366.1317.
1
calcd for C15H23NO3SiNa 316.1345, found 316.1344. IR, H, and 13C
NMR data matched the literature.64
(S*)-tert-Butyl 1,3-Dihydroxy-3-methylbutan-2-ylcarbamate
33a.65 General procedure 3 was followed with 3-methyl-2-buten-1-ol
18 (34.7 mg, 0.406 mmol), tert-butyl N-(tosyloxy)carbamate 4a (140.1
mg, 0.488 mmol), and potassium osmate dihydrate (5.9 mg, 0.016
mmol) in tert-butanol/water (3:1). Purification by flash chromatog-
raphy with 5:2:3 ethyl acetate/dichloromethane/n-hexane afforded the
title compound as a yellow oil (47.8 mg, 54%). Rf 0.33 (60% ethyl
acetate/dichloromethane/n-hexane). LRMS (ESI+) m/z 242 ([M +
Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for C10H21NO4Na
Dimethyl (2S*,3S*)-2-(Benzyloxycarbonylamino)-3-hydroxysuc-
cinate 31e.10,55 General procedure 3 was followed with dimethyl
fumarate 16 (40.0 mg, 0.278 mmol), potassium osmate dihydrate (1.0
mg, 0.003 mmol), and benzyl N-(tosyloxy)carbamate 4e (107.8 mg,
0.335 mmol). Purification by flash chromatography with 40% ethyl
acetate/n-hexane provided the title compound as a white solid (74.6
mg, 86%), mp 124−126 °C (lit.55 129−130 °C). Rf 0.23 (50% ethyl
acetate/n-hexane). LRMS (ESI+) m/z 334 ([M + Na]+, 100%).
HRMS (ESI+) [M + Na]+ calcd for C14H17NO7Na 334.0903, found
1
242.1368; found 242.1366. IR, H, and 13C NMR data matched the
literature.65
Benzyl (R*)-(1,3-Dihydroxy-3-methylbutan-2-ylcarbamate 33e.66
General procedure 3 was followed with 3-methyl-2-buten-1-ol 18
(64.3 mg, 0.747 mmol), potassium osmate dihydrate (9.2 mg, 0.025
mmol), and benzyl N-(tosyloxy)carbamate 4e (200 mg, 0.622 mmol)
in acetonitrile/water (3:1). Purification by flash chromatography with
3:2:5 ethyl acetate/dichloromethane/n-hexane provided the title
compound as a yellow oil (101.0 mg, 64%). Rf 0.13 (3:2:5 ethyl
acetate/dichloromethane/n-hexane). LRMS (ESI+) m/z 276 ([M +
Na]+, 100%), 236 (20). HRMS (ESI+) [M + Na]+ calcd for
10
1
334.0903. IR, H, and 13C NMR data matched the literature.
2,2,2-Trichloroethyl (1R*,2S*)-2-Hydroxy-2,3-dihydro-1H-inden-
1-ylcarbamate 44c64 and 2,2,2-Trichloroethyl (1R*,2S*)-1-Hy-
droxy-2,3-dihydro-1H-inden-2-ylcarbamate 32c. General procedure
3 was followed with indene 17 (30.0 mg, 0.258 mmol), potassium
osmate dihydrate (0.9 mg, 0.003 mmol), and 2,2,2-trichloroethyl N-
(tosyloxy)carbamate 4c (110.1 mg, 0.304 mmol). Purification by flash
chromatography with 20% ethyl acetate/n-hexane provided 2,2,2-
trichloroethyl (1R*,2S*)-2-hydroxy-2,3-dihydro-1H-inden-1-ylcarba-
mate 44c as a colorless oil (17.5 mg, 21%). Rf 0.20 (30% ethyl
acetate/n-hexane). IR (thin film, cm−1) νmax 3411 (O−H), 3350 (N−
H), 3074, 3045, 3028, 2952, 2926, 2853 (C−H), 1717 (CO), 1599,
1514. LRMS (ESI+) m/z 348 (30%), 346 ([M + Na]+, 40). HRMS
(ESI+) [M + Na]+ calcd for C12H1235Cl3NO3Na 345.9780, found
345.9768; [M + Na]+ calcd for C12H1235Cl237ClNO3Na 347.9751,
1
C13H19NO4Na 276.1212, found 276.1212. IR, H, and 13C NMR data
matched the literature.66
Ethyl (1S*,2R*)-2-Hydroxy-2-methylcyclohexylcarbamate 34b.46
General procedure 3 was followed with 1-methylcyclohex-1-ene 19
(48.5 mg, 0.504 mmol), potassium osmate dihydrate (4.0 mol %, 7.43
mg, 0.020 mmol), and ethyl N-(tosyloxy)carbamate 4b (161.6 mg,
0.620 mmol). Purification by flash chromatography provided the title
compound as a brown oil (75.1 mg, 74%). Rf 0.22 (2:2:6 ethyl acetate/
dichloromethane/n-hexane). IR (thin film, cm−1) νmax 3436 (O−H),
64
1
found 347.9756. The H and 13C NMR data matched the literature.
1
A second fraction afforded 2,2,2-trichloroethyl (1R*,2S*)-1-hydroxy-
2,3-dihydro-1H-inden-2-ylcarbamate 32c as a colorless solid (18.3 mg,
22%), mp 112−115 °C. Rf 0.16 (30% ethyl acetate/n-hexane). IR (thin
film, cm−1) νmax 3404 (O−H), 3328 (N−H), 3072, 3026, 2925, 2849
3395 (N−H), 2931, 2855 (C−H), 1696 (CO), 1515. H NMR
(400 MHz, CDCl3) δ 5.01 (1H, d, J = 8.0 Hz), 4.10 (2H, q, J = 6.8
Hz), 3.40 (1H, m), 1.67−1.76 (4H, m), 1.53 (1H, s), 1.41−1.51 (4H,
m), 1.22−1.25 (6H, m). 13C NMR (100 MHz, CDCl3) δ 156.6, 71.4,
60.7, 56.0, 39.0, 29.1, 27.7, 24.8, 21.0, 14.6. LRMS (ESI+) m/z 224
([M + Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for
C10H19NO3Na 224.1263, found 224.1258.
1
(C−H), 1714 (CO), 1514. H NMR (300 MHz, CDCl3) δ 7.46−
7.38 (4H, m), 5.70 (1H, d, J = 8.1 Hz), 5.18 (1H, dd, J = 8.7, 5.1 Hz),
4.88 (1H, d, J = 11.7 Hz), 4.76 (1H, d, J = 12.3 Hz), 4.67 (1H, m),
3.19 (1H, dd, J = 16.5, 4.8 Hz), 2.96 (1H, d, J = 16.5 Hz), 1.90 (1H, d,
J = 4.2 Hz). 13C NMR (100 MHz, CDCl3) δ 155.0, 140.0, 139.5,
128.5, 127.4, 125.5, 124.5, 95.5, 74.7, 73.5, 59.3, 39.7. LRMS (ESI+)
m/z 348 ([M + Na]+, 24%), 346 ([M + Na]+, 25). HRMS (ESI+) [M
+ Na]+ calcd for C12H1235Cl3NO3Na 345.9780, found 345.9773; [M +
Na]+ calcd for C12H1235Cl237ClNO3Na 347.9751, found 347.9743.
2-(Trimethylsilyl)ethyl (1R*,2S*)-1-Hydroxy-2,3-dihydro-1H-
inden-2-ylcarbamate 32d and 2-(Trimethylsilyl)ethyl (1R*,2S*)-2-
Hydroxy-2,3-dihydro-1H-inden-1-ylcarbamate 44d.64 General pro-
cedure 3 was followed with indene 17 (39.2 mg, 0.338 mmol),
potassium osmate dihydrate (4.0 mol %, 4.9 mg, 0.014 mmol), and 2-
(trimethylsilyl)ethyl N-(tosyloxy)carbamate 4d (148.0 mg, 0.447
mmol). Purification by flash chromatography with 30% ethyl
acetate/n-hexane afforded a mixture of both regioisomers, Rf 0.38
(2:2:6 ethyl acetate/dichloromethane/n-hexane). Further separation
by preparative HPLC with 1% 2-propanol/99% n-hexane at a flow rate
Ethyl 2-Methyl-6-oxocyclohex-1-enylcarbamate 36b.67 General
procedure 3 was followed with 3-methylcyclohex-2-enone 21 (58.2
mg, 0.528 mmol), potassium osmate dihydrate (7.79 mg, 0.021
mmol), and ethyl N-(tosyloxy)carbamate 4b (165.9 mg, 0.640 mmol).
Purification by flash chromatography provided the title compound as a
brown viscous oil (37.4 mg, 36%). Rf 0.42 (60% ethyl acetate/n-
hexane). IR (thin film, cm−1) νmax 3317 (N−H), 2925, 2852 (C−H),
1727 (CO), 1672, 1639. 1H NMR (400 MHz, CDCl3) δ 6.42 (1H,
s), 4.13 (2H, q, J = 6.9 Hz), 2.49−2.44 (4H, m), 1.97 (2H, m), 1.94
(3H, s), 1.26 (3H, t, J = 7.0 Hz). 13C NMR (100 MHz, CDCl3) δ
194.8, 154.3, 151.7, 129.6, 61.4, 36.8, 32.2, 29.7, 21.3, 14.5. LRMS
(ESI+) m/z 220 ([M + Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd
for C10H15NO3Na 220.0950, found 220.0950. A second fraction
afforded recovered starting material 21 (23.2 mg, 40%).
Benzyl (2S*,3R*)-2,3-Dihydroxy-2-methylbutylcarbamate
(2S*,3R*)-38e and Benzyl (2R*,3R*)-2,3-Dihydroxy-2-methylbutyl-
I
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The Journal of Organic Chemistry
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carbamate (2R*,3R*)-38e. General procedure 3 was followed with 3-
methylbut-3-en-2-ol 23 (48.5 mg, 0.56 mmol), potassium osmate
dihydrate (8.30 mg, 0.02 mmol), and benzyl N-(tosyloxy)carbamate
4e (217 mg, 0.68 mmol). Purification by flash chromatography with
40% ethyl acetate/n-hexane afforded a mixture of two diastereomers as
a colorless oil (64.6 mg, 45%), Rf 0.27 (70% ethyl acetate/n-hexane).
(2R*,3R*)-4-(benzyloxycarbonylamino)-3-hydroxy-3-methylbutan-2-
yl acetate (2R*,3R*)-39e as a colorless oil (12.1 mg, 19%). Rf 0.09
(80% diethyl ether/n-hexane). IR (thin film, cm−1) νmax 3584 (O−H),
3419 (N−H), 3090, 3066, 3033, 2984, 2942 (C−H), 1722 (CO),
1
1529. H NMR (400 MHz, CDCl3) δ 7.29−7.38 (5H, m), 5.16 (1H,
s), 5.08−5.14 (2H, m), 4.89 (1H, q, J = 6.4 Hz), 3.34 (1H, dd, J =
13.6, 6.0 Hz), 3.17 (1H, dd, J = 14.0, 6.0 Hz), 2.09 (3H, s) 1.44 (1H,
s), 1.25 (3H, d, J = 6.4 Hz), 1.16 (3H, s). 13C NMR (100 MHz,
CDCl3) δ 170.8, 157.0, 136.3, 128.5, 128.2, 128.1, 74.3, 74.1, 67.0,
47.8, 30.3, 20.4, 14.8. LRMS (ESI+) m/z 318 ([M + Na]+, 100).
HRMS (ESI+) [M + H]+ calcd for C15H22NO5 296.1498; found
296.1498; [M + Na]+ calcd for C15H21NO5Na 318.1317, found
318.1317. The anti- and syn-diastereomeric structures were confirmed
by NOESY_1D analysis of their acetonide derivatives.
1
Integration of the NH signal of the 400 MHz H NMR spectrum
showed a 2.4:1 ratio of benzyl (2S*,3R*)-2,3-dihydroxy-2-methyl-
butylcarbamate (2S*,3R*)-38e and benzyl (2R*,3R*)-2,3-dihydroxy-
2-methylbutylcarbamate (2R*,3R*)-38e.
To a solution of (2R*,3S*)-4-(benzyloxycarbonylamino)-3-hy-
droxy-3-methylbutan-2-yl acetate (2S*,3R*)-39e (20.0 mg, 0.068
mmol) in methanol (0.5 mL) and dichloromethane (3.0 mL) was
added a freshly prepared solution of ammonia in methanol (2.0 mL,
10%). This mixture was stirred at room temperature until the reaction
was complete (9 h), quenched with aqueous hydrochloric acid (3.0
mL, 1.0 M), and extracted with dichloromethane (3 × 10 mL). The
combined dichloromethane extracts were washed with brine (5 mL),
dried over sodium sulfate, and concentrated under reduced pressure to
afford benzyl (2S*,3R*)-2,3-dihydroxy-2-methylbutylcarbamate
(2S*,3R*)-38e as a yellow oil (17.0 mg, 99%). Rf 0.35 (80% ethyl
acetate/n-hexane). IR (thin film, cm−1) νmax 3401 (O−H, N−H),
Benzyl [(4S*,5R*)-2,2,4,5-Tetramethyl-1,3-dioxolan-4-yl]-
methylcarbamate 46. To a stirred solution of benzyl (2S*,3R*)-
2,3-dihydroxy-2-methylbutylcarbamate (2S*,3R*)-38e (15.0 mg,
0.059 mmol) in 2,2-dimethoxypropane (67.0 mg, 0.64 mmol) and
dichloromethane (3.0 mL) were added camphorsulfonic acid (0.6 mg,
0.003 mmol) and p-toluenesulfonic acid (0.5 mg, 0.003 mmol). The
mixture was stirred until the reaction was complete, quenched with
aqueous sodium hydrogen carbonate (3.0 mL, 1.0 M), and extracted
with dichloromethane (3 × 5 mL). The combined organic extracts
were washed with brine (5 mL), dried over sodium sulfate, and
concentrated under reduced pressure. Purification by flash chromatog-
raphy with 20% ethyl acetate/n-hexane afforded the title compound 46
as a colorless oil (14.5 mg, 83%). Rf 0.18 (20% ethyl acetate/n-
hexane). IR (thin film, cm−1) νmax 3345 (N−H), 3036, 2983, 2933,
1
3066, 3033, 2925, 2854 (C−H), 1700 (CO), 1525. H NMR (400
MHz, CDCl3) δ 7.30−7.38 (5H, m), 5.28 (1H, s), 5.12 (2H, s), 3.68
(1H, q, J = 6.8 Hz), 3.50 (1H, dd, J = 14.8, 6.0 Hz), 3.12 (1H, dd, J =
14.4, 6.4 Hz), 2.29 (1H, m), 2.05 (1H, m), 1.19 (3H, d, J = 6.8 Hz),
1.13 (3H, s). 13C NMR (100 MHz, CDCl3) δ 158.07, 136.17, 128.55,
128.25, 128.13, 74.68, 71.34, 67.19, 47.09, 20.67, 16.66. LRMS (ESI+)
m/z 276 ([M + Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd for
C13H19NO4Na 276.1212, found 276.1213.
1
2869 (C−H), 1724 (CO), 1513. H NMR (400 MHz, CDCl3) δ
7.30−7.37 (5H, m), 5.11 (2H, s), 5.06 (1H, d, J = 8.4 Hz), 4.00 (1H,
q, J = 6.4 Hz), 3.32 (1H, dd, J = 12.8, 8.8 Hz), 3.10 (1H, m), 1.41 (3H,
s), 1.35 (3H, s), 1.24 (3H, d, J = 6.4 Hz), 1.22 (3H, s). 13C NMR (100
MHz, CDCl3) δ 157.00, 142.92, 136.72, 128.66, 128.25, 107.47, 81.43,
78.70, 66.95, 45.24, 28.48, 26.71, 21.34, 12.99. LRMS (ESI+) m/z 316
([M + Na]+, 100%). HRMS (ESI+) [M + H]+ calcd for C16H24NO4
294.1705, found 294.1700; [M + Na]+ calcd for C16H23NO4Na
316.1525, found 316.1518.
To a solution of (2R*,3R*)-4-(benzyloxycarbonylamino)-3-hy-
droxy-3-methylbutan-2-yl acetate (2R*,3R*)-39e (20 mg, 0.07
mmol) in dichloromethane (3.0 mL) and methanol (0.5 mL) was
added a freshly prepared solution of ammonia in methanol (2.0 mL,
10%). This reaction mixture was stirred at room temperature,
quenched with aqueous hydrochloric acid (3.0 mL, 1.0 M), and
extracted with dichloromethane (3 × 5 mL). The combined
dichloromethane extracts were washed with brine (5 mL) and dried
over sodium sulfate. Purification by flash chromatography with 50%
ethyl acetate/n-hexane afforded benzyl (2R*,3R*)-2,3-dihydroxy-2-
methylbutylcarbamate (2R*,3R*)-38e as a colorless liquid (10.1 mg,
59%). Rf 0.33 (80% ethyl acetate/n-hexane). IR (thin film, cm−1) νmax
3368 (O−H, N−H), 3066, 3033, 2976, 2923, 2853 (C−H), 1700
Benzyl [(4R*,5R*)-2,2,4,5-Tetramethyl-1,3-dioxolan-4-yl)-
methylcarbamate 47. To a stirred solution of benzyl (2R*,3R*)-
2,3-dihydroxy-2-methylbutylcarbamate (2R*,3R*)-38e (15.0 mg,
0.059 mmol) in 2,2-dimethoxypropane (61.9 mg, 0.59 mmol) and
dichloromethane (3.0 mL) were added camphorsulfonic acid (0.600
mg, 0.002 mmol) and p-toluenesulfonic acid (0.500 mg, 0.003 mmol).
The mixture was stirred until the reaction was complete, quenched
with aqueous sodium hydrogen carbonate (3.0 mL, 1.0 M), and
extracted with dichloromethane (3 × 5 mL). The combined organic
extracts were washed with brine (5 mL), dried over sodium sulfate,
and concentrated under reduced pressure. The title compound 47 was
afforded without further purification as a colorless oil (14.5 mg, 83%).
IR (thin film, cm−1) νmax 3347 (N−H), 2978, 2926, 2862 (C−H),
1
(CO), 1649 (CC), 1538. H NMR (300 MHz, CDCl3) δ 7.32−
7.37 (5H, m), 5.12 (3H, br s), 3.67 (1H, q, J = 4.5 Hz), 3.40 (1H, dd, J
= 14.1, 7.2 Hz), 3.09 (1H, dd, J = 14.1, 5.7 Hz), 2.97 (1H, s), 2.62
(1H, s), 1.17 (3H, d, J = 6.6 Hz), 1.09 (3H, s). 13C NMR (75 MHz,
CDCl3) δ 157.79, 136.12, 128.59, 128.32, 128.16, 74.36, 69.90, 67.23,
48.63, 20.19, 16.61. LRMS (ESI+) m/z 276 ([M + Na]+, 25%). HRMS
(ESI+) [M + Na]+ calcd for C13H19NO4Na 276.1212, found 276.1214.
(2R*,3S*)-4-(Benzyloxycarbonylamino)-3-hydroxy-3-methylbu-
tan-2-yl Acetate (2R*,3S*)-39e and (2R*,3R*)-4-(Benzyloxycarbo-
nylamino)-3-hydroxy-3-methylbutan-2-yl Acetate (2R*,3R*)-39e.
General procedure 3 was followed with 3-methylbut-3-en-2-yl acetate
24 (27.1 mg, 0.21 mmol), potassium osmate dihydrate (3.10 mg,
0.0084 mmol), and benzyl N-(tosyloxy)carbamate 4e (81.6 mg, 0.25
mmol). Purification by flash chromatography with gradient elution by
60−100% diethyl ether/n-hexane afforded (2R*,3S*)-4-(benzyloxy-
carbonylamino)-3-hydroxy-3-methylbutan-2-yl acetate (2R*,3S*)-39e
as a colorless oil (30.4 mg, 49%). Rf 0.14 (80% diethyl ether/n-
hexane). IR (thin film, cm−1) νmax 3415 (N−H, O−H), 3090, 3066,
1
1717 (CO), 1537. H NMR (400 MHz, CDCl3) δ 7.30−7.36 (5H,
m), 5.06−5.16 (3H, m), 3.95 (1H, q, J = 6.0 Hz), 3.31 (1H, dd, J =
14.0, 6.8 Hz), 3.19 (1H, dd, J = 14.0, 5.2 Hz), 1.32 (3H, s), 1.26 (3H,
s), 1.21 (3H, d, J = 6.4 Hz), 1.08 (3H, s). 13C NMR (100 MHz,
CDCl3) δ 156.65, 136.46, 128.51, 128.14, 128.05, 106.95, 85.50, 82.13,
66.84, 46.14, 28.55, 26.67, 19.61, 14.13. LRMS (ESI+) m/z 316 ([M +
Na]+, 88%). HRMS (ESI+) [M + Na]+ calcd for C16H23NO4Na
316.1525, found 316.1523.
General Procedure 4 for Competition Reactions. To a mixture
of alkene A (1.0 equiv), alkene B (1.0 equiv), and potassium osmate
dihydrate (4.0 mol %) in acetonitrile (1.0 mL) and water (1.0 mL) was
added solution benzyl N-(tosyloxy)carbamate 4e (1.0 equiv) in
acetonitrile (2.0 mL). This mixture was stirred until the reaction was
complete, quenched with aqueous sodium hydrogen sulfite (5.0 mL,
0.05 M), and stirred for 30 min. The mixture was filtered through
Celite and extracted with ethyl acetate (3 × 10 mL). The combined
ethyl acetate extracts were washed with brine (10 mL), dried
(Na2SO4), and concentrated to afford the crude product. Purification
by flash chromatography afforded the target compounds.
1
3034, 2985, 2943 (C−H), 1724 (CO), 1532. H NMR (400 MHz,
CDCl3) δ 7.29−7.36 (5H, m), 5.31 (1H, br s), 5.07−5.15 (2H, m),
4.90 (1H, q, J = 6.4 Hz), 3.34 (1H, dd, J = 14.0, 7.2 Hz), 3.15 (1H, dd,
J = 14.4, 5.6 Hz), 2.50 (1H, s), 2.06 (3H, s), 1.25 (3H, d, J = 6.0 Hz),
1.16 (3H, s). 13C NMR (100 MHz, CDCl3) δ 170.8, 157.8, 136.3,
128.5, 128.2, 128.1, 73.8, 73.3, 67.1, 47.4, 21.2, 20.6, 14.3. LRMS (ESI
+) m/z 318 ([M + Na]+, 100%). HRMS (ESI+) [M + H]+ calcd for
C15H22NO5 296.1498, found 296.1499; [M + Na]+ calcd for
C15H21NO5Na 318.1317, found 318.1318. A second fraction afforded
J
dx.doi.org/10.1021/jo301372y | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Competition between trans-Stilbene 8 and Styrene 10. The
reaction was conducted according to general procedure 4 with trans-
stilbene 8 (70.5 mg, 0.39 mmol), styrene 10 (40.5 mg, 0.39 mmol),
potassium osmate dihydrate (5.4 mg, 0.015 mmol), and benzyl N-
(tosyloxy)carbamate 4e (125 mg, 0.39 mmol). Purification by flash
chromatography with 25% ethyl acetate/n-hexane afforded benzyl
(1R*,2R*)-2-hydroxy-1,2-diphenylethylcarbamate 9e as a white solid
(58.2 mg, 43%). A second fraction afforded benzyl (R*)-2-hydroxy-2-
phenylethylcarbamate 25e as a colorless oil (37.7 mg, 36%).
propanol (3.5 mL) was added, and the mixture was stirred at room
temperature (1 h) until TLC indicated the disappearance of the
nitrogen source. Aqueous sodium bisulfite (10 mL, 10% w/v) was
added and the reaction was stirred for 30 min. The mixture was filtered
through Celite, washed with ethyl acetate (5 mL), and extracted with
ethyl acetate (3 × 10 mL). The combined extracts were washed with
brine, dried (MgSO4), and concentrated to provide the crude product.
Purification by flash chromatography with 40% ethyl acetate/n-hexane
afforded benzyl carbamate 45 as a white solid (148.9 mg, 81%).
Competition between 1H-Indene 17 and Styrene 10. The
reaction was conducted according to general procedure 4 with 1H-
indene 17 (49.0 mg, 0.42 mmol), styrene 10 (43.9 mg, 0.42 mmol),
potassium osmate dihydrate (5.40 mg, 0.02 mmol), and benzyl N-
(tosyloxy)carbamate 4e (135.6 mg, 0.42 mmol). Purification by flash
chromatography with 20% ethyl acetate/n-hexane afforded an
inseparable mixture of two regioisomers from 1H-indene and one
regioisomer from styrene. Further separation by preparative HPLC
(SunFire prep silica 5 μm, 2% 2-propanol/98% n-hexane, flow rate 0.7
mL·min−1) afforded benzyl (1R*,2S*)-1-hydroxy-2,3-dihydro-1H-
inden-2-ylcarbamate68 32e as an orange oil (26.8 mg, 22%) at tR
8.57 min. LRMS (ESI+) m/z 306 ([M + Na]+, 85%). HRMS (ESI+)
[M + Na]+ calcd for C17H17NO3Na 306.1106, found 306.1105. IR, 1H,
and 13C NMR data matched the literature.68 A second fraction
afforded benzyl (1R*,2S*)-2-hydroxy-2,3-dihydro-1H-inden-1-ylcarba-
mate68 44e as an orange oil (20.1 mg, 17%) at tR 13.44 min. LRMS
(ESI+) m/z 306 ([M + Na]+, 100%). HRMS (ESI+) [M + Na]+ calcd
ASSOCIATED CONTENT
* Supporting Information
■
S
General experimental methods; CIFs and seven figures showing
anisotropic displacement ellipsoid plots derived from single-
crystal X-ray analyses for compounds 1, 4e, 9c, 25c, 28c, and
40c (CCDC nos. 885356−885361, respectively); H and 13C
1
NMR spectra; and proof of stereochemistry for compounds
38e and 39e. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail malcolm.mcleod@anu.edu.au.
Notes
■
1
for C17H17NO3Na 306.1106, found 306.1106. IR, H, and 13C NMR
The authors declare no competing financial interest.
data matched the literature.68 A third fraction afforded benzyl (R*)-2-
hydroxy-2-phenylethylcarbamate 25e as a colorless oil (33.6 mg, 29%)
at tR 17.90 min.
ACKNOWLEDGMENTS
■
Competition between 3-Methylbut-2-en-1-ol 18 and Styrene 10.
The reaction was conducted according to general procedure 4 with 3-
methylbut-2-en-1-ol 18 (39.1 mg, 0.44 mmol), styrene 10 (45.9 mg,
0.44 mmol), potassium osmate dihydrate (5.1 mg, 0.014 mmol), and
benzyl N-(tosyloxy)carbamate 4e (142 mg, 0.44 mmol). Purification
by flash chromatography with gradient elution from 25% to 50% ethyl
acetate/n-hexane afforded benzyl (R*)-2-hydroxy-2-phenylethylcarba-
mate 25e as a colorless solid (70.3 mg, 59%). A second fraction
afforded benzyl (R*)-2-hydroxy-1-phenylethylcarbamate 40e as a
colorless oil (6.8 mg, 5.7%).
We thank the Directorate General of Higher Education
Indonesia (DIKTI) for scholarship support and Tony Herlt
(ANU) for assistance with HPLC.
REFERENCES
■
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