Catalytic asymmetric henry reaction of nitroalkanes and aldehydes catalyzed by a chiral N, N '-dioxide/Cu(I) complex

Article abstract of DOI:10.1021/jo5027832

An easily available N,N'-dioxide/Cu(I) complex has been developed for the catalytic asymmetric nitroaldol (Henry) reaction of aldehydes with nitroethane. Under mild reaction conditions, a series of substituted aromatic, heteroaromatic and α,β-unsaturated

Full text of DOI:10.1021/jo5027832

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Article
Catalytic Asymmetric Henry Reaction of Nitroalkanes and
Aldehydes Catalyzed by a Chiral N,N'-Dioxide/Cu(I) Complex
Hongjiang Mei, Xiao Xiao, Xiaohu Zhao, Bing Fang, Xiaohua Liu, Lili Lin, and Xiaoming Feng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo5027832 • Publication Date (Web): 30 Jan 2015
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Catalytic Asymmetric Henry Reaction of Nitroalkanes and Aldehydes Catalyzed
by a Chiral N,N′-Dioxide/Cu(I) Complex
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Hongjiang Mei,a Xiao Xiao,a Xiaohu Zhao,a Bing Fang,a Xiaohua Liu,a Lili Lina* and Xiaoming
Fenga,b*
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a Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry,
Sichuan University, Chengdu 610064, People′s Republic of China.
b Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)
*Eꢀmail: lililin@scu.edu.cn.; xmfeng@scu.edu.cn;
ABSTRACT: An easily available N,N′ꢀdioxide/Cu(I) complex has been developed for the
catalytic asymmetric nitroaldol (Henry) reaction of aldehydes with nitroethane. Under mild
reaction conditions, a series of substituted aromatic, hetero aromatic and α,βꢀunsaturated
aldehydes, are transformed to the corresponding antiꢀβꢀnitroalcohols in good to excellent yields
(up to 99%) with moderate to good dr (up to 16.7:1 anti/syn) and high ee values (up to 97%).
Besides nitroethane, nitromethane and 1ꢀnitropropane were also employed as nucleophiles and
good enantioselectivities were obtained.
INTRODUCTION
Henry reaction is a powerful and efficient method for the construction of carbonꢀcarbon bond.1 The
resulting products, βꢀnitroalcohols, can be easily transformed into 2ꢀhydroxycarboxylic acids,2 2ꢀnitro
ketones,3 nitro alkenes4 and βꢀamino alcohols.5 As we know, βꢀamino alcohol is a very important
structure in various biologically active natural products,6 pharmaceuticals7 and chiral ligands.8 Thus,
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the catalytic asymmetric protocols for Henry reaction have gained particular attention.9,10 Comparing
with the well developed Henry reaction of aldehydes with nitromethane,9c,h,i the Henry reaction of
aldehydes with other nitroalkanes is more challenging for often suffering from low reactivity and poor
stereoselectivity. An alternative approach is the application of trimethylsilyl nitronates.10a,b Taking into
account the atom economy, the direct reactions of aldehydes with nitroalkanes are more attractive.
After several years, impressive progress in asymmetric Henry reaction of aldehydes with nitroethane
has been achieved.10eꢀj Ooi’s tetraaminophosphonium saltꢀmediated catalyst10c and Shibasaki’s
heterobimetallic complexes1i,j,10pꢀr are quite efficient for the Henry reaction of nitroethane with different
types of aldehydes. Although great progress has been achieved, developing new catalysts for the
diastereoselective and enantioselective Henry reaction of aldehydes with nitroethane is still necessary.
In our group, N,N′ꢀdioxide/metal complexes have been used to catalyze a number of enantioselective
reactions.11 And, they were also proved to be efficient for the enantioselective Henry reaction of
nitromethane with aromatic aldehydes and alkyl substituted αꢀketoesters, giving the corresponding
products in moderate to excellent yields with good to excellent ee values.12 As a matter of course, we
want to know whether N,N′ꢀdioxide/metal complexes can also be efficient for the Henry reaction about
nitroethane. Herein, we present our intensive study of applying the N,N′ꢀdioxide/metal catalysts to the
diastereoꢀ and enantioselective Henry reaction of nitroalkanes with aldehydes.
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RESULTS AND DISCUSSION
In the initial study, benzaldehyde (1a) and nitroethane were chosen as the model substrate and
nucleophilic reagent. Firstly, the reaction was performed in THF at 0 oC using 5 mol% of N,N′ꢀdioxide
L-PicP in combination with various metal salts. When the complexes of NiBr2, Cu(OTf)2 and Zn(OTf)2
were applied as the catalysts, no or trace amount of products were detected (Table 1, entries 1 to 3).
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Delightedly, when using the complex of CuOTf•(C7H8)0.5 as catalyst, the corresponding 2a was
obtained in 65% yield with 66/34 anti/syn and 51%/63% ee (Table 1, entry 4). The quite different
behavior between Cu(OTf)2 and CuOTf•(C7H8)0.5 might be caused by their different coordination
nature. Cu(OTf)2 can coordinate with the four oxygen atoms of N,N′ꢀdioxides,13 thus next only either
aldehyde or nitroethane can be activated, which can not promote the reaction. Meanwhile,
CuOTf•(C7H8)0.5 can coordinate with two or three oxygen atoms of the ligand,10n and next active both
the aldehyde and nitroethane, and nitroethane is deprotonated by the counterion of Cu(I) to generate the
active nucleophile through a possible complex of nitronate, which attack aldehyde to yield
corresponding adduct. Then, the counterion of Cu(I) was screened. When CuBr and [Cu(CH3CN)4]PF6
were used, the reactivity and enantioselectivity of the reaction decreased dramatically (Table 1, entries
5 and 6). Next, the efficiency of CuOTf•(C7H8)0.5 with other N,N′ꢀdioxide ligands was explored (Figure
1), which showed that the reactivity and enantioselectivity were closely dependent on both the
substituent R1 of the amide moiety and the chiral backbone. As shown in Table 1, when the substituent
R1 was 2,6ꢀdiisopropylphenyl group, trace amount of product 2a was detected (Table 1, entry 7), while
alkyl cyclohexyl subunit could promote the reaction in 65%/60% ee and 69/31 anti/syn albeit with 17%
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yield (Table 1, entry 8). When different backbones were investigated, it was found that Lꢀpipecolic acid
derived L-PicH was much superior to Lꢀprolineꢀderived L-PrcH and Lꢀramiprilꢀderived L-RacH in
enantioselectivity but inferior in reactivity (Table 1, entry 8 vs entries 9 and 10).
Figure 1. Ligands screened in this work.
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Table 1. Screen of Lewis acids and N,N′ꢀdioxide ligands
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Yield
(%)b
n.r.d
Trace
n.r.d
65
Anti/syn
(%)c
Entrya
Metal
Ligand
Ee (%)c
1
2
NiBr2
L-PicP
L-PicP
L-PicP
L-PicP
L-PicP
L-PicP
L-PiPr2
L-PicH
L-PrcH
L-RacH
–
–
Cu(OTf)2
n.d.e
n.d.e
3
Zn(OTf)2
–
–
4
CuOTf•(C7H8)0.5
CuBr
66/34
62/38
58/42
n.d.e
69/31
67/33
64/36
51/63
6/ꢀ2
5
36
6
[Cu(CH3CN)4]PF6
CuOTf•(C7H8)0.5
CuOTf•(C7H8)0.5
CuOTf•(C7H8)0.5
CuOTf•(C7H8)0.5
10
11/ꢀ12
n.d.e
65/60
6/ꢀ11
5/10
7
Trace
17
8
9
78
10
66
aUnless otherwise noted, all reactions were performed with L/Metal (1:1, 5
mol %), 1a (0.2 mmol, 20 ꢁL), nitroethane (10 equiv, 142 ꢁL) in THF (0.5
mL) under N2 at 0 oC for 3 days. bIsolated yield. cDetermined by chiral HPLC
analysis (Chiralcel ADꢀH). dn.r. = no reaction. en.d. = not determined.
In order to improve the reactivity of L-PicH/CuOTf•(C7H8)0.5 complex catalysis, Brønsted bases
were designed to add in the catalytic system to achieve the goal by helping to generate the nitronate
and hence enhancing the nucleophilic capability. As expected, when the bases were added, the yield of
the nitroaldol product was improved dramatically and in most cases nearly quantitative yields were
obtained (Table 2, entries 1–6). However, the enantioselectivity and diastereoselectivity of the reaction
were decreased in varying degrees. The N,Nꢀdiisopropylethylamine (DIPEA) decreased the dr to 58/42
and the ee to 57%/68% (Table 2, entry 1). Other bases, such as DBU, DABCO, DMAP, pyridine and
Cs2CO3, decreased the enantioselectivity of the reaction more seriously (Table 2, entries 2–6). The base
might not only affect the generation of the nitronate, but also inhibit the formation of beneficial
catalytic species in varying degrees depending on their structures in this catalytic system.
Table 2. Screen of additive.
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Entrya
Base
Yield (%)b
Anti/syn (%)c
58/42
Ee (%)c
57/68
14/4
1
2
3
4
5
6
DIPEAd
DBUe
99
99
99
93
96
99
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60/40
DABCOf
DMAPg
Pyridine
Cs2CO3
41/59
2/ꢀ32
57/43
17/ꢀ16
43/25
36/40
59/41
63/37
aUnless otherwise noted, all reactions were performed with
L-PicH/CuOTf•(C7H8)0.5 (1:1, 5 mol %), 1a (0.2 mmol, 20 ꢁL), nitroethane
(10 equiv, 142 ꢁL) and base (5 mol %) in THF (0.5 mL) under N2 at 0 oC for
3 days. bIsolated yield. Determined by chiral HPLC analysis (Chiralcel
c
ADꢀH). DIPEA = N,NꢀDiisopropenyl ethylamine. eDBU = 1,8ꢀDiazabicycloꢀ
d
[5.4.0]undecꢀ7ꢀene. fDABCO = 1,4ꢀDiazabicyclo[2.2.2]octane. gDMAP =
4ꢀDimethylaminopyridine.
The effect of solvents was also examined (Table 3, entries 1–5). Aprotic solvents toluene, acetonitrile,
and THF (Table 3, entries 1–3) gave better enantioselectivity than halogenated solvent dichloromethane
(Table 3, entry 4) and protic solvent isopropanol (Table 3, entry 5). And THF was shown to be suitable
solvent for this reaction in terms of the yield and enantioselectivity (Table 3, entry 1). When the ratio of
ligand L-PicH to CuOTf•(C7H8)0.5 was invastigated from 0.5:1 to 2:1 (Table 3, entries 7–10). The
results suggested that the better ratio of ligand L-PicH/CuOTf•(C7H8)0.5 was 1.1:1, and the ee of the
product 2a was improved to 60%/74% without decreasing the anti/syn ratio, albeit with a slightly
decreased reactivity (Table 3, entry 8).
Table 3. Screen of solvents and the ratio of ligand to metal.
Entrya Solvent Ratio (L/M) Yield (%)b Anti/syn (%)c
Ee (%)c
57/68
26/15
33/50
1
2
3
THF
1:1
1:1
1:1
99
86
93
58/42
60/40
57/43
toluene
CH3CN
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CH2Cl2
iꢀPrOH
THF
1:1
1:1
85
99
92
89
93
92
53/47
61/39
60/40
57/43
55/45
56/44
16/13
4/ꢀ18
37/13
60/74
55/73
52/64
0.5:1
1.1:1
1.5:1
2:1
THF
THF
THF
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aUnless otherwise noted, all reactions were performed with
L-PicH/CuOTf•(C7H8)0.5 (ratio, 5 mol %), 1a (0.2 mmol, 20 ꢁL), nitroethane
(10 equiv, 142 ꢁL) and DIPEA (5 mol %) in solvent (0.5 mL) under N2 at 0
oC for
3
days. bIsolated yield. cDetermined by chiral HPLC analysis
(Chiralcel ADꢀH).
o
When the reaction temperature was lowered to ꢀ20 C, the enantioselectivity was increased to
84%/85% (Table 4, entry 2). Encouraged by the hopeful results obtained, the loading of DIPEA was
o
surveyed under ꢀ20 C. When the loading of DIPEA was increased from 5 mol % to 30 mol %, the
yield was increased sharply from 72% to 99% with dr and ee maintained (Table 4, entries 2–5). The dr
and ee was further improved to 78/22 and 93%/89% when the reaction temperature was further lowered
o
to ꢀ30 C (Table 4, entry 6). When 30 mg 3 Å MS were employed, the enantioselectivity improved
substantially to 96%/94% ee. According our previous work,14 the molecular sieves might help to form
the benificial catalytic species in the catalytic system.
Table 4. Screen of reaction temperature and the loading of DIPEA
.
Entrya
T/oC
0
x (mol %)
Yield (%)b
Anti/syn (%)c
57/43
Ee (%)c
60/74
84/85
86/85
83/84
86/84
93/89
96/94
1
2
5
89
72
99
99
99
89
93
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ30
ꢀ30
5
67/33
3
10
20
30
30
30
69/31
4
65/35
5
69/31
6
78/22
7d
71/29
aUnless otherwise noted, all reactions were performed with
L-PicH/CuOTf•(C7H8)0.5 (1.1:1, 5 mol %), 1a (0.2 mmol, 20 ꢁL), nitroethane
(10 equiv, 142 ꢁL) and DIPEA (5 mol %) in solvent (0.5 mL) under N2 at 0
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oC for 3 days. bIsolated yield. cDetermined by chiral HPLC analysis. d30 mg 3
4
5
Å molecular sieves were added.
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Thus the optimal reaction conditions were determined to be 5 mol % of L-PicH/Cu(I) (1.1:1), 30
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mol % of DIPEA, 10 equiv of nitroethane, 30 mg 3 Å MS at ꢀ30 oC in THF.
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Table 5. Substrate scope of aldehydes and nitroalkanes in the asymmetric Henry reaction.
Entrya
1
Aldehyde (Ar)
Ph(1a)
Nitroalkanes (R)
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Product
2a
Yield (%)b
93
93
91
80
99
99
86
88
96
99
99
99
96
98
88
91
90
93
82
80
93
86
66
93
46
77
93
85
95
95
95
Anti/syn (%)c
2.6:1
3.0:1
3.0:1
3.2:1
2.8:1
16.7:1
10.0:1
2.9:1
11.1:1
7.1:1
3.7:1
14.3:1
3.2:1
3.9:1
2.7:1
3.6:1
2.5:1
10.0:1
3.3:1
3.0:1
11.1:1
2.9:1
2.9:1
3.0:1
2.1:1
4.8:1
2.4:1
3.7:1
2.7:1
1.3:1
1.0:1
Ee (%)d
96(1R,2S)/94(1S,2S)
94/90
2
2ꢀFC6H4(1b)
2b
2c
3
3ꢀFC6H4(1c)
92/82
4
4ꢀFC6H4(1d)
94/84
2d
2e
5
2,6ꢀdiFC6H3(1e)
2ꢀClC6H4(1f)
93/97
6
90/n.d.e
2f
7
3ꢀClC6H4(1g)
4ꢀClC6H4(1h)
2,4ꢀdiClC6H3(1i)
2,6ꢀdiClC6H3(1j)
3,4ꢀdiClC6H3(1k)
2ꢀBrC6H4(1l)
2g
94/58
8
90/84
2h
2i
9
90/ n.d.e
10
11
12
13
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15
16
17
18
19
20
21
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23
24
25
26
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28
29
30
31
95/98
2j
89/77
2k
2l
95/ n.d.e
3ꢀBrC6H4(1m)
4ꢀBrC6H4(1n)
2ꢀF3CC6H4(1o)
4ꢀF3CC6H4(1p)
4ꢀO2NC6H4(1q)
2ꢀMeC6H4(1r)
3ꢀMeC6H4(1s)
4ꢀMeC6H4(1t)
2ꢀMeOC6H4(1u)
3ꢀMeOC6H4(1v)
4ꢀMeOC6H4(1w)
3ꢀPhOC6H4(1x)
4ꢀBnC6H4(1y)
4ꢀFꢀ3ꢀPhOC6H3(1z)
4ꢀPhC6H4(1aa)
1ꢀNaphyl(1ab)
2ꢀNaphyl(1ac)
PhC≡C(1ad)
2m
2n
2o
93/85
92/82
91/76
92/83
2p
2q
2r
85/76
92/ n.d.e
90/92
2s
90/86
2t
94/ n.d.e
2u
2v
97/95
93/92
2w
2x
96/92
94/95
2y
93/79
2z
2aa
2ab
2ac
2ad
2ae
93/89
93/84
94/95
81/79
2ꢀfuryl(1ae)
96/96
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3ꢀfuryl(1af)
2ꢀthiophenyl(1ag)
3ꢀthiophenyl(1ah)
Ph(1a)
CH3
CH3
90
81
94
83
35
1.7:1
1.1:1
1.9:1
ꢀꢀ
96/90
90/90
96/93
90(R)
84/56
2af
2ag
2ah
2ai
CH3
H
Ph(1a)
CH3CH2
2aj
1.8:1
9
aReactions were carried out on a 0.2 mmol scale of aldehyde with 10 equiv of nitroalkane in 0.5 mL THF in the presence of
L-PicH/CuOTf•(C7H8)0.5 (1.1:1, 5 mol %), 30 mol % DIPEA, and 30 mg 3 Å MS at ꢀ30 oC for 3 days. bIsolated yield.
cDetermined by 1H NMR spectroscopy analysis. dDetermined by chiral HPLC analysis. en.d. = not determined.
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With the optimized conditions in hand, the substrate scope of the reaction was evaluated and the
results were summarized in Table 5. Various substituted benzaldehydes proceeded smoothly to provide
the corresponding products in moderate to excellent yields (up to 99%) with moderate to good dr (up to
16.7:1 anti/syn) and high ee values (up to 97%). Generally, the reaction of orthoꢀsubstituted
benzaldehydes provided much higher diastereoselectivity than those with metaꢀ or paraꢀsubstituted
benzaldehydes. For example, the reaction of orthoꢀbromobenzaldehyde 1l afforded the corresponding
product 2l with 14.3:1 anti/syn, while the metaꢀ or paraꢀbromobenzaldehyde 1m and 1n gave a ratio of
3.2:1 and 3.9:1, respectively (Table 5, entry 12 vs entries 13 and 14). Besides, electronꢀdonating
substituents on the paraꢀposition of the phenyl ring had a negative influence on the reactivity. 1w and
1y with a paraꢀelectronꢀdonating substitutent gave the corresponding adduct 2w only in 66% yield and
2y in 46% yield (Table 5, entries 23 and 25). 1ꢀNaphthaldehyde 1ab and 2ꢀnaphthaldehyde 1ac
proceeded also well to afford the nitroaldol products in 85% and 95% yields with moderate anti/syn
ratios (3.7:1 and 2.7:1) and high ee values (93%/84% and 94%/95%), respectively (Table 5, entries 28
and 29). α,βꢀUnsaturated aldehyde 1ad afforded the corresponding product in 95% yield with 1.3:1
anti/syn ratio and 81%/79% ee values (Table 5, entry 30). Finally, heteroaromatic aldehydes 1ae–1ah
were also tested, giving the optically active nitroaldol adducts in 81%–95% yields with 1.0:1–1.9:1
anti/syn selectivities and 90%–96% ee values (Table 5, entries 31–34). Besides, nitromethane and
1ꢀnitropropane were also employed as nucleophiles to react with benzaldehyde. The corresponding
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products 2ai was obtained in 83% yield and 90% ee (Table 5, entry 35), while 2aj was obtained in 35%
yield with 84%/56% ee and 1.8:1 anti/syn (Table 5, entry 36). The poor reactivity of 1ꢀnitropropane
was caused by its steric hindrance. The absolute configuration of major antiꢀisomer of 2a was
determined to be (1R, 2S)10b,15aꢀg and that of 2ai was determined to be R12 by comparison of the HPLC
with literature data.
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In summary, a highly efficient catalytic asymmetric Henry reaction of aldehydes with
nitroalkanes has been realized by using a N,N′ꢀdioxide/Cu(I) complex. Various βꢀnitro alcohols were
obtained in moderate to high yields with high to excellent enantioselectivities and moderate to good
diastereoselectivities.
EXPERIMENTAL SECTION
General remarks:
Reactions were carried out using commercial available reagents in overꢀdried apparatus. THF was dried over Na and distilled
prior to use. Nitroalkanes were dried over anhydrous CaCl2 and distilled prior to use. Aldehydes were obtained from commercial
sources and were distilled or recrystallized before use. Enantiomeric excesses (ee) were determined by HPLC analysis using the
corresponding commercial chiral column as stated in the experimental procedures at 23 oC with UV detector at 210 nm. The ratio
1
of anti/syn was determined by 1H NMR spectroscopy analysis. H NMR spectra were recorded on commercial instruments (400
MHz). Chemical shifts were reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (CDCl3, δ
= 7.26 ppm). Spectra were reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, br = broad), coupling constants (Hz), integration and assignment. 13C NMR spectra were collected on
commercial instruments (100 MHz) with complete proton decoupling. Chemical shifts are reported in ppm from the
tetramethylsilane with the solvent resonance as internal standard (CDCl3, δ = 77.16 ppm).
General procedure for the catalytic asymmetric Henry reaction:
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A dry reaction tube was charged with CuOTf•(C7H8)0.5 (2.6 mg, 0.01 mmol), L-PicH (5.4 mg, 0.011 mmol) and 30 mg 3 Å MS
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under an N2 atmosphere. Then, THF (0.5 mL) was added and the mixture was stirred at 35 C for 0.5 h. Next, substrate 1 (0.2
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mmol) was added and the mixture was stirred at 35 oC for 0.5 h. Finally, 30 mol % DIPEA (10.5 ꢁL, 0.06 mmol) and 10 equiv
nitroalkanes (2.0 mmol) were added with being stirred at the indicated temperature. The mixture was stirred at the indicated
temperature for 3 days. The residue was purified by flash chromatography (petroleum ether/AcOEt, 9:1 to 3:1) on silica gel to
afford the products. The enantiomeric excesses (ee) were determined by high–performance liquid chromatography (HPLC). The
ratio of anti/syn was determined by 1H NMR spectroscopy analysis.
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2-Nitro-1-phenylpropan-1-ol (2a):10g,l,m,15aꢀg C9H11NO3. Yellow oil in 93% yield, 33.7 mg. Enantiomeric excesses
(96% for anti, 94% for syn) HPLC (DAICEL CHIRALPAK ADꢀH, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection
at 210 nm): (1S, 2R) tR (anti minor) = 15.74 min, (1R, 2S) tR (anti major) = 17.31 min, (1S, 2S) tR (syn minor) = 20.15 min, (1R,
2R) tR (syn major) = 22.17 min. Absolute configuration of major antiꢀisomer was determined to be (1R, 2S) by comparison of the
retention time with literature data. Diastereomeric ratio (anti/syn = 2.6:1, Table 5, entry 1) was determined by 1H NMR.1H NMR
(400 MHz, CDCl3, 25 oC, TMS): δ = 7.32ꢀ7.30 (m, 5H, anti+syn), 5.32 (s, 0.72H, anti), 4.94 (q, 0.28H, syn), 4.73ꢀ4.66 (m, 0.28H,
syn), 4.65ꢀ4.59 (m, 0.72H, anti), 2.66 (s, 0.72H, anti), 2.55 (s, 0.28H, syn), 1.43 (d, 2.16H, J = 6.8 Hz, anti), 1.24 (d, 0.84H, J =
7.6 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 138.6, 128.9, 128.7, 126.1, 87.6, 74.0, 12.2.
1-(2-Fluorophenyl)-2-nitropropan-1-ol (2b):10m,15g C9H10FNO3. Yellow oil in 93% yield, 37.0 mg.
Enantiomeric excesses (94% for anti, 90% for syn) HPLC (DAICEL CHIRALPAK IA, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti minor) = 6.30 min, tR (anti major) = 7.03 min, tR (syn minor) = 8.34 min, tR (syn major) =
9.36 min. Diastereomeric ratio (anti/syn = 3.0:1, Table 5, entry 2) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
oC, TMS): δ = 7.58ꢀ7.54 (m, 0.75H, anti), 7.48ꢀ7.45 (m,0.25H, syn), 7.39ꢀ7.31 (m, 1H, anti+syn), 7.23ꢀ7.19 (m, 1H, anti+syn),
7.12ꢀ7.04 (m, 1H, anti+syn), 5.73 (s, 0.75H, anti), 5.40 (q, 0.25H, syn), 4.88ꢀ4.78 (m, 1H, anti+syn), 2.95 (d, 0.75H, J = 3.6 Hz,
anti), 2.82 (d, 0.25H, J = 4.8 Hz, syn), 1.48 (d, 2.25H, J = 6.8 Hz, anti), 1.41 (d, 0.75H, J = 7.6 Hz, syn). 13C NMR (100 MHz,
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CDCl3, 25 oC): (anti) δ =160.5, 158.0, 130.3, 130.2, 128.0, 127.9, 125.7, 125.5, 124.8, 124.7, 115.6, 115.4, 85.3, 85.3, 68.4, 68.4,
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1-(3-Fluorophenyl)-2-nitropropan-1-ol (2c):10m C9H10FNO3. Yellow oil in 91% yield, 36.2 mg. Enantiomeric
excesses (92% for anti, 82% for syn) HPLC (DAICEL CHIRALPAK ID, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti major) = 6.54 min, tR (anti minor) = 6.95 min, tR (syn minor) = 8.58 min, tR (syn major) = 10.54
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min. Diastereomeric ratio (anti/syn = 3.0:1, Table 5, entry 3) was determined by H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
TMS): δ = 7.33ꢀ7.19 (m, 1H, anti+syn), 7.07ꢀ6.93 (m, 3H, anti+syn), 5.34 (s, 0.75H, anti), 4.96 (d, 0.25H, J = 8.8 Hz, syn),
4.69ꢀ4.57 (m, 1H, anti+syn), 2.81 (br, 0.75H, anti), 2.74 (br, 0.25H, syn), 1.41 (d, 2.25H, J = 6.8 Hz, anti), 1.271 (d, 0.75H, J =
7.6 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 164.4, 161.9, 141.2, 141.1, 130.5, 130.5, 121.7, 121.6, 115.7, 115.5,
113.4, 113.2, 87.3, 73.2, 73.3, 12.0.
1-(4-Fluorophenyl)-2-nitropropan-1-ol (2d):10m C9H10FNO3. Yellow oil in 80% yield, 31.8 mg. Enantiomeric
excesses (94% for anti, 84% for syn) HPLC (DAICEL CHIRALPAK IE, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti major) = 6.88 min, tR (anti minor) = 7.74 min, tR (syn minor) = 10.21 min, tR (syn major) = 11.18
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min. Diastereomeric ratio (anti/syn = 3.2:1, Table 5, entry 4) was determined by H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
TMS): δ = 7.28ꢀ7.19 (m, 2H, anti+syn), 7.04ꢀ6.98 (m, 2H, anti+syn), 5.29 (s, 0.76H, anti), 4.95 (d, 0.24H, J = 9.2 Hz, syn),
4.69ꢀ4.58 (m, 1H, anti+syn), 2.77ꢀ2.68 (m, 1H, anti+syn), 1.43 (d, 2.28H, J = 6.4 Hz, syn), 1.24 (d, 0.72H, J = 6.4 Hz, anti). 13
C
NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 163.0, 160.6, 133.3, 126.9, 126.9, 115.0, 114.7, 86.6, 72.5, 11.3.
1-(2,6-Difluorophenyl)-2-nitropropan-1-ol (2e):15 C9H10F2NO3. Yellow oil in 99% yield, 43.0 mg.
Enantiomeric excesses (93% for anti, 97% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (syn major) = 5.20 min, tR (syn minor) = 5.56 min, tR (anti minor) = 10.63 min, tR (anti major) =
11.72 min. Diastereomeric ratio (anti/syn = 2.8:1, Table 5, entry 5) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
oC, TMS): δ = 7.32ꢀ7.20 (m, 1H, anti+syn), 6.92ꢀ6.83 (m, 2H, anti+syn), 5.47ꢀ5.40 (m, 1H, anti+syn), 5.10ꢀ5.02 (m, 0.74H, anti),
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4.96ꢀ4.89 (m, 0.26H, syn), 2.81 (s, 1H, anti+syn), 1.66 (d, 1.22H, J = 6.8 Hz, syn), 1.31 (d, 1.78H, J = 7.8 Hz, anti). 13C NMR
(100 MHz, CDCl3, 25 oC): (anti) δ = 161.2, 161.1, 158.7, 158.6, 130.2, 130.1, 130.0, 111.3, 111.1, 85.4, 66.7, 15.3. HRMS
(ESIꢀTOF) calcd for C9H918.9984F2NNaO3+ ([M+Na+]) = 240.0450, found 240.0448.
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1-(2-Chlorophenyl)-2-nitropropan-1-ol (2f):10m C9H10ClNO3 Yellow oil in 99% yield, 42.7 mg. Enantiomeric
excesses (90% for anti, n.d. for syn) HPLC (DAICEL CHIRALPAK ID, hexane/ 2ꢀpropanol = 95/5, flow rate 1.0 mL/min,
detection at 210 nm) tR (anti minor) = 8.70 min, tR (anti major) = 9.04 min, tR (syn minor) = 12.07 min, tR (syn major) = 14.69
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min. Diastereomeric ratio (anti/syn = 16.7:1, Table 5, entry 6) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
TMS): δ = 7.57 (d, 0.93H, J = 7.6 Hz, anti), 7.43 (d, 0.07H, J = 7.2 Hz, syn), 7.31ꢀ7.19 (m, 3H, anti+syn), 5.77 (s, 0.94H, anti),
5.53 (q, 0.06H, J = 4.8 Hz, syn), 4.84ꢀ4.78 (m, 1H, anti+syn), 2.89ꢀ2.80 (m, 1H, ant+syn), 1.38ꢀ1.36 (m, 3H, anti+syn). 13C NMR
(100 MHz, CDCl3, 25 oC): (anti) δ = 135.9, 131.6, 129.8, 129.8, 128.3, 127.4, 84.2, 70.6, 11.3.
1-(3-Chlorophenyl)-2-nitropropan-1-ol (2g):10l C9H10ClNO3. Yellow oil in 86% yield, 37.1 mg. Enantiomeric
excesses (94% for anti, 58% for syn) HPLC (DAICEL CHIRALPAK ADꢀH, hexane/ 2ꢀpropanol = 90/10, flow rate 0.5 mL/min,
detection at 210 nm): (1S, 2R) tR (anti minor) = 13.22 min, (1R, 2S) tR (anti major) = 15.57 min, (1S, 2S) tR (syn minor) = 19.81
min, (1R, 2R) tR (syn major) = 25,53 min. Diastereomeric ratio (anti/syn = 10:1, Table 5, entry 7) was determined by 1H NMR.1H
o
NMR (400 MHz, CDCl3, 25 C, TMS): δ = 7.58ꢀ7.56 (m, 0.91H, anti), 7.44ꢀ7.42 (m,0.09H, syn), 7.34ꢀ7.19 (m, 3H, anti+syn),
5.77 (s,0.91H, anti), 5.52 (q, 0.09H, J = 3.2 Hz, syn), 4.84ꢀ4.75 (m, 1H, anti+syn), 2.88 (br, 0.91H, anti), 2.82 (br, 0.09H, syn),
1.37ꢀ1.36 (m, 3H, anti+syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ =135.9, 131.6, 129.8, 129.7, 128.2, 127.4, 84.2, 70.6,
11.3.
1-(4-Chlorophenyl)-2-nitropropan-1-ol (2h):10l,15d,h C9H10ClNO3. Yellow oil in 88% yield, 37.9 mg.
Enantiomeric excesses (90% for anti, 84% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti minor) = 5.71 min, tR (anti major) = 6.77 min, tR (syn minor) = 9.79 min, tR (syn major) =
11.65 min Diastereomeric ratio (anti/syn = 2.9:1, Table 5, entry 8) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
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oC, TMS): δ = 7.40ꢀ7.31 (m, 4H, anti+syn), 5.38 (t, 0.74H, J = 3.6 Hz, anti), 5.02 (q, 0.26H, J = 4.0 Hz, syn), 4.76ꢀ4.71 (m,
0.26H, syn), 4.69ꢀ4.63 (m, 0.74H, anti), 2.79ꢀ2.78 (m, 0.74H, anti), 2.67ꢀ2.66 (m, 0.26H, syn), 1.49 (d, 2.25H, J = 6.8 Hz, anti),
1.33 (d, 0.75H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 137.0, 134.5, 129.1, 127.5, 87.3, 73.3, 12.2.
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1-(2,4-Dichlorophenyl)-2-nitropropan-1-ol (2i):15 C9H10Cl2NO3. Yellow oil in 96% yield, 48.0 mg.
Enantiomeric excesses (91% for anti, n.d. for syn) HPLC (DAICEL CHIRALPAK ID, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti major) = 5.72 min, tR (anti minor) = 6.87 min, tR (syn minor) = 8.53 min, tR (syn major) =
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8.72 min. Diastereomeric ratio (anti/syn = 11.1:1, Table 5, entry 9) was determined by H NMR. 1H NMR (400 MHz, CDCl3,
25oC, TMS): δ = 7.60ꢀ7.58 (m, 1H, anti+syn), 7.40ꢀ7.33 (m, 2H, anti+ syn), 5.79 (s, 0.92H, anti), 5.56ꢀ5.54 (m, 0.08H, syn),
4.84ꢀ4.83 (m, 1H, anti+syn), 3.05 (s, 1H, anti+syn), 1.44ꢀ1.42 (m, 3H, ant+syni). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ =
135.1, 134.6, 132.2, 129.6, 129.3, 127.8, 83.9, 70.2, 11.2.
1-(2,6-Dichlorophenyl)-2-nitropropan-1-ol (2j):15 C9H10Cl2NO3. Yellow oil in 99% yield, 49.5 mg.
Enantiomeric excesses (95% for anti, 98% for syn) HPLC (DAICEL CHIRALPAK IE, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (syn minor) =6.49 min, tR (syn major) = 7.87 min, tR (anti minor) = 11.53 min, tR (anti major) =
12.88 min. Diastereomeric ratio (anti/syn = 7.1:1, Table 5, entry 10) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
oC, TMS): δ = 7.39ꢀ7.33 (m, 2H, anti+syn), 7.28ꢀ7.20 (m, 1H, anti+syn), 6.01ꢀ5.97 (m, 0.88H, anti), 5.81ꢀ5.77 (m, 0.12H, syn),
5.52ꢀ5.35 (m, 1H, anti+syn), 3.61ꢀ3.24 (m, 1H, anti+syn), 1.80 (d, 0.87H, J = 6.8 Hz, syn), 1.37 (d, 2.13H, J = 6.8 Hz, anti). 13
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NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 135.1, 132.7, 130.7, 130.5, 129.9, 86.0, 70.9, 16.1. HRMS (ESIꢀTOF) calcd for
C9H934.9689Cl2KNO3+ ([M+K+]) = 287.9589, found 287.9597; C9H936.9659Cl2KNO3+ ([M+K+]) = 291.9538, found 291.9585.
1-(3,4-Dichlorophenyl)-2-nitropropan-1-ol (2k):15h C9H10Cl2NO3. Yellow oil in 99% yield, 49.5 mg.
Enantiomeric excesses (89% for anti, 76% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti major) = 5.64 min, tR (anti minor) = 6.43 min, tR (syn minor) = 8.49 min, tR (syn major) =
10.61 min. Diastereomeric ratio (anti/syn = 3.7:1, Table 5, entry 11) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
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oC, TMS): δ = 7.52ꢀ7.46 (m, 2H, anti +syn), 7.23ꢀ7.20 (m, 1H, anti+syn), 5.39 (t, 1H, J = 3.2 Hz, anti), 5.02 (q, 0.27H, J = 3.6
Hz, anti), 2.92ꢀ2.91 (m, 0.73H, anti), 2.84 (m, 0.27H, syn), 1.48 (d, 2.19H, J = 7.2 Hz, anti), 1.36 (d, 0.81H, J = 6.8 Hz, syn). 13C
NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 138.7, 133.2, 132.8, 130.9, 128.2, 125.4, 87.1, 72.7, 12.0.
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1-(2-Bromophenyl)-2-nitropropan-1-ol (2l):15g C9H10BrNO3. Yellow oil in 99% yield, 51.5 mg. Enantiomeric
excesses (95% for anti, n.d. for syn) HPLC (DAICEL CHIRALPAK IA, hexane/ 2ꢀpropanol = 95/5, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti minor) = 6.42 min, tR (anti major) = 7.31 min, tR (syn minor) = 9.07 min, tR (syn major) = 11.09
min. Diastereomeric ratio (anti/syn = 14.3:1, Table 5, entry 12) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 oC,
TMS):δ = 7.64ꢀ7.62 (m, 1H, anti+syn), 7.60ꢀ7.55 (m, 1H, anti+syn), 7.40 (t, 1H, J = 7.6 Hz, anti+syn), 7.26ꢀ7.20 (m, 1H,
anti+syn), 5.80 (s, 0.93H, anti), 5.58 (d, 0.07H, J = 8.4 Hz, syn), 4.93ꢀ4.85 (m, 1H, ant+syn), 3.52ꢀ3.51 (m, 0.07H, syn), 3.01 (m,
0.93H, anti), 1.47ꢀ1.43 (m, 3H, anti+syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 137.4, 133.1, 130.1, 128.6, 128.0,
121.6, 84.1, 72.6, 11.1.
1-(3-Bromophenyl)-2-nitropropan-1-ol (2m):15i C9H10BrNO3. Yellow oil in 96% yield, 49.9 mg. Enantiomeric
excesses (93% for anti, 85% for syn) HPLC (DAICEL CHIRALPAK ADꢀH, hexane/ 2ꢀpropanol = 90/10, flow rate 0.5 mL/min,
detection at 210 nm): (1S, 2R) tR (anti minor) = 15.00 min, (1R, 2S) tR (anti major) = 16.92 min, (1S, 2S) tR (syn minor) = 18.97
min, (1R, 2R) tR (syn major) = 27.41 min. Diastereomeric ratio (anti/syn = 3.2:1, Table 5, entry 13) was determined by 1H NMR.
1H NMR (400 MHz, CDCl3, 25 C, TMS): δ = 7.49ꢀ7.38 (m, 2H, anti+syn), 7.24ꢀ7.17 (m, 2H, anti+ syn), 5.32 (d, 0.75H, J =
o
2.8Hz, anti), 4.93 (d, 0.25H, J = 9.2 Hz, anti), 4.69ꢀ4.63 (m, 0.25H, syn), 4.62ꢀ4.56 (m, 0.75H, anti), 2.82ꢀ2.75 (m, 1H, anti+syn),
o
1.41 (d, 2.25H, J = 7.8 Hz, anti), 1.27 (d, 0.75H, J = 7.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 140.8, 131.7,
130.4, 129.2, 124.7, 123.0, 87.2, 73.1, 12.0.
1-(4-Bromophenyl)-2-nitropropan-1-ol (2n):10g,l C9H10BrNO3. Yellow oil in 98% yield, 51.4 mg. Enantiomeric
excesses (92% for anti, 82% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti major) = 5.98 min, tR (anti minor) = 7.15 min, tR (syn minor) = 10.48 min, tR (syn major) = 12.61
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min. Diastereomeric ratio (anti/syn = 3.9:1, Table 5, entry 14) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
TMS): δ = 7.48ꢀ7.44 (m, 2H, anti +syn), 7.20ꢀ7.17 (m, 2H, anti+syn), 5.29 (t, 0.79H, J = 3.6 Hz, anti), 4.93 (q, 0.21H, J = 3.6
Hz, syn), 4.68ꢀ4.62 (m, 0.21H, syn), 4.51ꢀ4.55 (m, 0.79H, anti), 2.77 (d, 0.79H, J = 3.6Hz, anti), 2.68 (d, 0.21H, J = 4.0 Hz, syn),
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1.41 (d, 2.37H, J = 7.6 Hz, anti), 1.25 (d, 0.63H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 137.5, 132.0,
127.8, 122.5, 87.2, 73.3, 12.1.
2-Nitro-1-(2-(trifluoromethyl)phenyl)propan-1-ol (2o):15 C10H10F3NO3. Yellow oil in 88% yield, 43.8 mg.
Enantiomeric excesses (91% for anti, 74% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti major) = 4.59 min, tR (anti minor) = 5.20 min, tR (syn major) = 6.80 min, tR (syn minor) =
7.92 min. Diastereomeric ratio (anti/syn = 2.7:1, Table 5, entry 15) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
oC, TMS): δ = 7.87ꢀ7.62 (m, 3H, anti+syn), 7.52ꢀ7.46 (m, 1H, anti+syn), 5.90 (s, 0.73H, anti), 5.54 (d, 0.27H, J = 8.8 Hz, syn),
4.95ꢀ4.87 (m, 0.27H, syn), 4.75ꢀ4.70 (m, 0.73H, anti), 2.99 (d, 0.73H, J = 3.2 Hz, anti), 2.87 (d, 0.27H, J = 3.2 Hz, syn), 1.54 (d,
2.19H, J = 6.8 Hz, anti), 1.31 (d, 0.81H, J = 6.4 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 136.9, 132.4, 128.9,
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128.6, 126.4, 126.3, 85.7, 69.3, 69.3, 11.5. HRMS (ESIꢀTOF) calcd for C10H1018.9984F3KNO3+ ([M+K+]) = 288.0259, found
288.0250.
2-Nitro-1-(4-(trifluoromethyl)phenyl)propan-1-ol (2p):15j C10H10F3NO3. Yellow oil in 88% yield, 43.8 mg.
Enantiomeric excesses (92% for anti, 83% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti major) = 4.59 min, tR (anti minor) = 5.20 min, tR (syn minor) = 6.80 min, tR (syn major) =
7.92 min. Diastereomeric ratio (anti/syn = 3.6:1, Table 5, entry 16) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
oC, TMS): δ = 7.59ꢀ7.57 (m, 2H, anti+syn), 7.46ꢀ7.44 (m, 2H, anti+syn), 5.42 (d, 0.78H, J = 1.6 Hz, anti), 5.03 (d, 0.22H, J =
8.4 Hz, syn), 4.72ꢀ4.59 (m, 1H, anti+syn), 2.94 (br, 1H, anti+syn), 1.40 (d, 2.34H, J = 6.8 Hz, anti), 1.27 (d, 0.66H, J = 6.8 Hz,
syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 142.5, 127.5, 126.5, 125.9, 125.8, 87.2, 73.3, 11.9.
2-Nitro-1-(4-nitrophenyl)propan-1-ol (2q):10l,15d,f,g C9H10N2O5. White solid in 90% yield, 40.7 mg.
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Enantiomeric excesses (91% for anti, 74% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti major) = 10.08 min, tR (anti minor) = 11.92 min, tR (syn minor) = 16.38 min, tR (syn major)
= 17.96 min. Diastereomeric ratio (anti/syn = 2.5:1, Table 5, entry 17) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3,
25 oC, TMS): δ = 8.27ꢀ8.24 (m, 2H, anti+syn), 7.62ꢀ7.58 (m, 2H, anti+syn), 5.57 (d, 0.71H, J = 2.8 Hz, anti), 5.20 (d, 0.29H, J =
8.4 Hz, syn), 4.81ꢀ4.70 (m, 1H, anti+syn), 3.16 (br, 1H, anti+syn), 1.49 (d, 2.13H, J = 6.8 Hz, anti), 1.39 (d, 0.87H, J = 6.4 Hz,
syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 148.0, 145.7, 127.1, 124.1, 86.9, 73.0, 12.0.
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2-Nitro-1-o-tolylpropan-1-ol (2r):10l,15d,g C10H13NO3. Yellow oil in 99% yield, 38.6 mg. Enantiomeric excesses (92%
for anti, n.d. for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection at 210 nm):
tR (anti major) = 6.11 min, tR (anti minor) = 7.12 min, tR (syn minor) = 11.86 min, tR (syn major) = 13.02 min. Diastereomeric
ratio (anti/syn = 10.0:1, Table 5, entry 18) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25oC, TMS):δ = 7.55ꢀ7.53
(m, 0.91H, anti), 7.40ꢀ7.38 (m, 0.09H, syn), 7.29ꢀ7.16 (m, 3H, anti+syn), 5.62 (t, 0.91H, J = 2.4 Hz, anti), 5.36 (q, 0.09H, J = 3.6
Hz, syn), 4.89ꢀ4.82 (m, 0.09H, syn), 4.67ꢀ4.61 (m, 0.91H, anti), 2.44 (s, 0.27H, syn), 2.37 (s, 2.73H, anti), 1.51 (d, 2.73H, J = 6.8
Hz, anti), 1.32 (d, 0.27H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 136.7, 134.4, 130.9, 128.5, 126.6,
126.1, 85.4, 71.0, 19.0, 11.7.
2-Nitro-1-m-tolylpropan-1-ol (2s):15k C10H13NO3. Yellow oil in 99% yield, 38.6 mg. Enantiomeric excesses (90%
for anti, 92% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection at 210
nm): tR (anti major) = 6.36 min, tR (anti minor) = 7.37 min, tR (syn minor) = 11.29 min, tR (syn major) = 12.75 min.
Diastereomeric ratio (anti/syn = 3.3:1, Table 5, entry 19) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 oC, TMS):
δ = 7.22ꢀ7.05 (m, 5H, anti+syn), 5.27 (t, 0.77H, J = 3.6 Hz, anti), 4.89 (q, 0.23H, J = 3.6 Hz, syn), 4.72ꢀ4.65 (m, 0.25H, syn),
2.67ꢀ2.66 (m, 0.75H, anti), 2.57ꢀ2.56 (m, 0.25H, syn), 2.30 (s, 0.71H, syn), 2.29 (s, 2.29H, anti), 1.42 (d, 2.30H, J = 6.8 Hz, anti),
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1.23 (d, 0.70H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 138.6, 138.6, 129.4, 128.8, 126.7, 123.1, 87.6,
74.1, 21.6, 12.2.
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2-Nitro-1-p-tolylpropan-1-ol (2t):10l C10H13NO3. Yellow oil in 62% yield, 24.2 mg. Enantiomeric excesses (90% for
anti, 86% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection at 210 nm):
tR (anti major) = 6.80 min, tR (anti minor) = 7.94 min, tR (syn minor) = 13.05 min, tR (syn major) = 15.45 min. Diastereomeric
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ratio (anti/syn = 3.0:1, Table 5, entry 20) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C, TMS): δ = 7.26ꢀ7.23
(m, 2H, anti+syn), 7.21ꢀ7.17 (m, 2H, anti+syn), 5.32 (d, 0.75H, J = 3.6 Hz, anti), 5.97 (d, 0.25H, J = 9.2 Hz, syn), 4.78ꢀ4.71 (m,
0.25H, syn), 4.70ꢀ4.64 (m, 0.75H, anti), 2.71 (br, 0.75H, anti), 2.59 (br, 0.25H, syn), 2.36 (s, 1H, syn), 2.35 (s, 3H, anti), 1.49 (d,
2.25H, J = 6.8 Hz, anti), 1.29 (d, 0.75H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 138.5, 135.6, 129.5,
o
126.0, 87.6, 74.0, 21.3, 12.3.
1-(2-Methoxyphenyl)-2-nitropropan-1-ol (2u):10m,l,15d,g C10H13NO4. Yellow oil in 93% yield, 39.2 mg.
Enantiomeric excesses (94% for anti, n.d. for syn) HPLC (DAICEL CHIRALPAK IE, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti minor) = 9.21 min, tR (anti major) = 9.95 min, tR (syn minor) = 18.43 min, tR (syn major) =
19.28 min. Diastereomeric ratio (anti/syn = 11.1:1, Table 5, entry 21) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3,
25 oC, TMS): δ = 7.43ꢀ7.41 (m, 1H, anti+syn), 7.33ꢀ7.29 (m, 1H, anti+syn), 7.00 (t, 1H, J = 3.6 Hz, anti+syn), 6.91 (q, 1H, J =
8.4 Hz, anti+syn), 5.53 (t, 0.92H, J = 4.4 Hz, anti), 5.13 (t, 0.08H, J = 8.8 Hz, syn), 5.04ꢀ4.97 (m, 0.08H, syn), 4.93ꢀ4.88 (m,
0.92H, anti), 3.89 (s, 0.23H, syn), 3.87 (s, 2.77H, anti), 3.31ꢀ3.29 (m, 0.08H, syn), 3.08ꢀ3.06 (m, 0.92H, anti), 1.48 (d, 2.78H, J =
6.8 Hz, anti), 1.33 (d, 0.22H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 155.9, 129.6, 127.8, 126.3, 121.1,
110.5, 85.1, 70.9, 55.5, 12.7.
1-(3-Methoxyphenyl)-2-nitropropan-1-ol (2v):10m C10H13NO4. Yellow oil in 86% yield, 36.3 mg. Enantiomeric
excesses (97% for anti, 95% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti major) = 8.99 min, tR (anti minor) = 10.54 min, tR (syn minor) = 15.24 min, tR (syn major) = 16.97
min. Diastereomeric ratio (anti/syn = 2.9:1, Table 5, entry 22) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
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TMS): δ = 7.33ꢀ7.26 (m, 1H, anti+syn), 6.94ꢀ6.85 (m, 3H, anti+syn), 5.38 (br, 0.75H, anti), 4.98 (d, 0.25H, J = 8.4 Hz, syn),
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4.79ꢀ4.74 (m, 0.25H, syn), 4.73ꢀ4.66 (m, 0.75H, anti), 3.82 (s, 0.77H, syn), 3.81 (s, 2.23H, anti), 2.77 (d, 0.75H, J = 2.8 Hz, anti),
2.67 (d, 0.25H, J = 2.4 Hz, syn), 1.49 (d, 2.25H, J = 6.8 Hz, anti), 1.32 (d, 0.75H, J = 6.8, syn). 13C NMR (100 MHz, CDCl3, 25
oC): (anti) δ = 160.0, 140.2, 130.0, 118.2, 114.0, 111.7, 87.5, 73.8, 55.4, 12.1.
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1-(4-Methoxyphenyl)-2-nitropropan-1-ol (2w):10g,l,15d,f C10H13NO4. Yellow oil in 66% yield, 27.8 mg.
Enantiomeric excesses (90% for anti, 86% for syn) HPLC (DAICEL CHIRALPAK ADꢀH, hexane/ 2ꢀpropanol = 90/10, flow rate
1.0 mL/min, detection at 210 nm): (1S, 2R)tR (anti minor) = 10.99 min, (1R, 2S) tR (anti major) = 12.32 min, (1S, 2S) tR (syn
minor) = 15.28 min, (1R, 2R) tR (syn major) = 17.36 min. Diastereomeric ratio (anti/syn = 2.9:1, Table 5, entry 23) was
determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 oC, TMS): δ = 7.24ꢀ7.19 (m, 2H, anti+syn), 6.87ꢀ6.83 (m, 2H, anti+syn),
5.24 (br, 0.75H, anti), 4.91 (q, 0.25H, J = 0.4 Hz, syn), 4.772ꢀ4.57 (m, 1H, anti+syn), 3.75 (s, 0.77H, syn), 3.74 (s, 2.23H, anti),
2.54 (d, 0.75H, J = 2.4 Hz, anti), 2.40 (d, 0.25H, J = 2.4 Hz, syn), 1.45 (d, 2.25H, J = 6.8 Hz, anti), 1.23 (d, 0.75H, J = 6.8 Hz,
syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 159.8, 130.5, 127.4, 114.3, 87.7, 73.9, 55.5, 12.6.
2-Nitro-1-(3-phenoxyphenyl)propan-1-ol (2x):15 C15H15NO4. Yellow oil in 93% yield, 50.8 mg. Enantiomeric
excesses (95% for anti, 92% for syn) HPLC (DAICEL CHIRALPAK IE, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti minor) = 8.69 min, tR (anti major) = 9.50 min, tR (syn minor) = 12.12 min, tR (syn major) = 16.40
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min. Diastereomeric ratio (anti/syn = 3.0:1, Table 5, entry 24) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
TMS): δ = 7.38ꢀ7.32 (m, 3H, anti+syn), 7.17ꢀ6.94 (m, 6H, anti+syn), 5.37 (br, 0.75H, anti), 4.99 (q, 0.25H, J = 2.0 Hz, syn),
4.76ꢀ4.64 (m, 1H, anti+syn), 2.74 (d, 75H, J = 3.2 Hz, anti), 2.64 (d, 0.25H, J = 3.2 Hz, syn), 1.50 (d, 2.25H, J = 6.8 Hz, anti),
1.34 (d, 0.75H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 157.9, 156.8, 140.6, 130.3, 130.0, 123.8, 119.2,
116.1, 87.4, 73.6, 12.2. HRMS (ESIꢀTOF) calcd for C15H15NNaO4+ ([M+Na+]) = 296.0895, found 296.0899.
1-(4-Benzylphenyl)-2-nitropropan-1-ol (2y):15 C16H17NO3. White solid in 46% yield, 25.0 mg. Enantiomeric
excesses (96% for anti, 91% for syn) HPLC (DAICEL CHIRALPAK IB, hexane/ 2ꢀpropanol = 95/5, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti major) = 24.29 min, tR (anti minor) = 25.89 min, tR (syn major) = 29.21 min, tR (syn minor) = 31.13
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min. Diastereomeric ratio (anti/syn = 2.1:1, Table 5, entry 25) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
TMS): δ = 7.44ꢀ7.28 (m, 7H, anti +syn), 7.01ꢀ6.97 (m, 2H, anti+syn), 5.31 (d, 0.68H, J = 4.0 Hz, anti), 5.07ꢀ5.06 (m, 2H,
anti+syn), 4.98 (d, 0.32H, J = 5.2 Hz, syn), 4.78ꢀ4.71 (m, 0.32H, syn), 4.70ꢀ4.64 (m, 0.68H, anti), 2.59 (s, 0.68H, anti), 2.44 (s,
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0.32H, syn), 1.52 (d, 2.04H, J = 6.8 Hz, anti), 1.31 (d, 0.96H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ =
159.1, 130.8, 128.8, 128.3, 128.2, 127.6, 127.4, 115.2, 87.7, 73.9, 70.2, 12.6. HRMS (ESIꢀTOF) calcd for C16H17KNO3+ ([M+K+])
= 310.0846, found 310.0846.
1-(4-Fluoro-3-phenoxyphenyl)-2-nitropropan-1-ol (2z):15 C15H14FNO4. Yellow oil in 93% yield, 54.1 mg.
Enantiomeric excesses (93% for anti, 89% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0
mL/min, detection at 210 nm): tR (anti major) = 6.70 min, tR (anti minor) = 7.26 min, tR (syn minor) = 10.62 min, tR (syn major) =
12.77 min. Diastereomeric ratio (anti/syn = 4.8:1, Table 5, entry 26) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25
oC, TMS): δ = 7. 30ꢀ7.24 (m, 2H, anti+syn), 7.16ꢀ7.09 (m, 1H, anti+syn), 7.08ꢀ6.95 (m, 3H, anti+syn), 6.90ꢀ6.88 (m, 2H,
anti+syn), 5.23 (t, 0.82H, J = 3.2 Hz, anti), 4.88 (q, 0.18H, J = 4.0 Hz, anti), 4.62ꢀ4.51 (m, 1H, anti+syn), 2.70 (s, 0.82H, anti),
2.62 (s,0.18H, syn), 1.40 (d, 2.46H, J = 6.8 Hz, anti), 1.25 (d, 0.54H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti)
δ = 157.0, 155.4, 152.9, 144.3, 144.2, 135.3, 130.0, 123.6, 117.7, 117.6, 117.5, 117.4, 87.3, 73.1, 12.3. HRMS (ESIꢀTOF) calcd
for C15H1418.9984FNNaO4+ ([M+Na+]) = 314.0804, found 314.0805.
1-(Biphenyl-4-yl)-2-nitropropan-1-ol (2aa):10m C15H15NO3. White solid in 93% yield, 47.8 mg. Enantiomeric
excesses (93% for anti, 89% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): tR (anti major) = 8.09 min, tR (anti minor) = 9.96 min, tR (syn minor) = 15.42 min, tR (syn major) = 17.83
min. Diastereomeric ratio (anti/syn = 2.4:1, Table 5, entry 27) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
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TMS): δ = 7.62ꢀ7.56 (m, 4H, anti+syn), 7.46ꢀ7.41 (m, 4H, anti+syn), 7.39ꢀ7.34 (m, 1H, anti+syn), 5.43ꢀ5.42 (m, 0.70H, anti),
5.06ꢀ5.04 (m, 0.3H, syn), 4.83ꢀ4.76 (m, 0.30H, syn), 4.75ꢀ4.69 (m, 0.70H, anti), 2.80 (s, 1H, anti+syn), 2.59 (s, 0.25H, syn), 1.52
(d, 2.10H, J = 6.8 Hz, anti), 1.35 (d, 0.90H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 140.5, 140.4, 137.5,
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1-(Naphthalen-1-yl)-2-nitropropan-1-ol (2ab):10g C13H13NO3. Yellow oil in 85% yield, 32.3 mg. Enantiomeric
excesses (93% for anti, 84% for syn) HPLC (DAICEL CHIRALPAK ADꢀH, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): (1S, 2R) tR (anti minor) = 8.28 min, (1R, 2S) tR (anti major) = 9.82 min, (1S, 2S) tR (syn minor) = 13.20 min,
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(1R, 2R) tR (syn major) = 14.88 min. Diastereomeric ratio (anti/syn = 3.7:1, Table 5, entry 28) was determined by H NMR.1H
NMR (400 MHz, CDCl3, 25 oC, TMS): δ = 8.28 (d, 0.78H, J = 8.4 Hz, syn), 8.00 (d, 0.22H, J = 8.4 Hz, anti), 7.92ꢀ7.77 (m, 3H,
anti+syn), 6.27 (s, 0.78H, anti), 5.79 (d, 0.22H, J = 5.6 Hz, syn), 5.16ꢀ5.09 (m, 0.22H, syn), 4.94ꢀ4.88 (m, 0.78H, anti), 2.77 (br,
1H, anti+syn), 1.43 (d, 2.34H, J = 6.8 Hz, anti), 1.26 (d, 0.66H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ =
157.9, 156.8, 140.6, 130.3, 130.0, 123.8, 119.2, 116.1, 87.4, 73.6, 12.2.
1-(Naphthalen-2-yl)-2-nitropropan-1-ol (2ac):10g C13H13NO3. Yellow oil in 95% yield, 43.9 mg. Enantiomeric
excesses (95% for anti, 92% for syn) HPLC (DAICEL CHIRALPAK ADꢀH, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min,
detection at 210 nm): (1S, 2R) tR (anti minor) = 10.57 min, (1R, 2S) tR (anti major) = 12.24 min, (1S, 2S) tR (syn minor) = 16.32
min, (1R, 2R) tR (syn major) = 18.72 min. Diastereomeric ratio (anti/syn = 2.7:1, Table 5, entry 29) was determined by 1H NMR.
1H NMR (400 MHz, CDCl3, 25 oC, TMS): δ = 7.79ꢀ7.71 (m, 4H, anti+syn), 7.46ꢀ7.39 (m, 2H, anti+syn), 7.37ꢀ7.32 (m, 1H,
anti+syn), 5.45 (s, 0.73H, anti), 5.07 (q, 0.27H, J = 2.8 Hz, syn), 4.81ꢀ4.73 (m, 0.27H, syn), 4.73ꢀ4.66 (m, 73H, anti), 2.85 (br,
0.73H, anti), 2.75 (br, 0.27H, syn), 1.41 (d, 2.19H, J = 6.8 Hz, anti), 1.22 (d, 0.81H, J = 6.8 Hz, syn). 13C NMR (100 MHz,
CDCl3, 25 oC): (anti) δ = 135.9, 133.2, 128.8, 128.2, 127.8, 126.7, 126.6, 125.4, 123.4, 87.4, 74.1, 12.1.
4-Nitro-1-phenylpent-1-yn-3-ol (2ad):10c C11H11NO3. Yellow oil in 95% yield, 39.0 mg. Enantiomeric excesses (81%
for anti, 79% for syn) HPLC (DAICEL CHIRALPAK IE, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection at 210
nm): tR (anti major) = 19.31 min, tR (anti minor) = 20.13 min, tR (syn minor) = 23.90 min, tR (syn major) = 26.44 min.
Diastereomeric ratio (anti/syn = 1.3:1, Table 5, entry 30) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 oC, TMS):
δ = 7.45ꢀ7.43 (m, 2H, anti+syn), 7.39ꢀ7.30 (m, 3H, anti+syn), 5.16ꢀ5.14 (m, 0.56H, anti), 5.03ꢀ4.99 (m, 0.44H, syn), 4.80ꢀ4.71
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(m, 1H, anti+syn), 4.75ꢀ4.70 (m, 1H, anti+syn), 2.90 (s, 0.56H, anti) 2.78 (s, 0.44H, syn), 1.73 (d, 1.69H, J = 6.8 Hz, anti), 1.71
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(d, 1.31H, J = 6.8 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 132.0, 129.3, 128.5, 121.4, 87.8, 85.5, 84.0, 64.3,
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1-(Furan-2-yl)-2-nitropropan-1-ol (2ae):15e,f C7H9NO4. Yellow oil in 95% yield, 32.5 mg. Enantiomeric excesses
(96% for anti, 97% for syn) HPLC (DAICEL CHIRALPAK ID, hexane/ 2ꢀpropanol = 95/5, flow rate 1.0 mL/min, detection at
210 nm): tR (syn minor) = 12.03 min, tR (syn major) = 13.19 min, tR (anti minor) = 19.04 min, tR (anti major) = 20.09 min.
Diastereomeric ratio (anti/syn = 1.0:1, Table 5, entry 31) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 oC, TMS):
δ = 7.36ꢀ7.33 (m, 1H, anti+syn), 6.35ꢀ6.31 (m, 2H, anti+syn), 5.28 (s, 0.50H, anti), 5.00ꢀ4.99 (m, 0.50H, syn), 4.94ꢀ4.86 (m,
0.50H, syn), 4.83ꢀ4.77 (m, 0.50H, anti), 2.72 (d, 0.50H, J = 4.0 Hz, anti), 2.63 (d, 50H, J = 4.0 Hz, syn), 1.54 (d, 1.50H, J = 6.8
Hz, anti), 1.33 (d, 1.50H, J = 6.4 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 150.3, 149.9, 142.5, 142.0, 109.8,
109.7, 108.5, 107.4, 85.4, 84.0, 68.7, 68.1, 15.4, 12.3.
1-(Furan-3-yl)-2-nitropropan-1-ol (2af):15e,f C7H9NO4. Yellow oil in 90% yield, 30.8 mg. Enantiomeric excesses
(96% for anti, 90% for syn) HPLC (DAICEL CHIRALPAK ID, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection at
210 nm): tR (anti minor) = 6.81 min, tR (anti major) = 7.51 min, tR (syn minor) = 7.93 min, tR (syn major) = 8.54 min.
Diastereomeric ratio (anti/syn = 1.7:1, Table 5, entry 32) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 oC, TMS):
δ = 7.50ꢀ7.43 (m, 2H, anti+syn), 6.42 (s, 0.40H, syn), 6.37 (s, 0.60H, anti), 5.31 (m, 0.60H, anti), 5.06ꢀ5.04 (m, 0.40H, syn),
4.80ꢀ4.72 (m, 0.40H, syn), 4.71ꢀ4.65 (m, 0.40H, anti), 2.71 (s, 0.60H, anti), 2.59 (s, 0.40H, syn), 1.58 (d, 1.80H, J = 6.8 Hz, anti),
1.43 (d, 1.20H, J = 6.4 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC): (anti) δ = 144.0, 140.4, 123.8, 108.1, 86.6, 68.3, 12.9.
2-Nitro-1-(thiophen-2-yl)propan-1-ol (2ag):15f C7H9NO3S. Yellow oil in 94% yield, 35.2 mg. Enantiomeric
excesses (92% for anti, 92% for syn) HPLC (DAICEL CHIRALPAK IE, hexane/ 2ꢀpropanol = 95/5, flow rate 0.8 mL/min,
detection at 210 nm): tR (syn major) =18.37 min, tR (syn minor) = 19.67 min, tR (anti minor) = 29.60 min, tR (anti major) = 34.25
o
min. Diastereomeric ratio (anti/syn = 1.1:1, Table 5, entry 33) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
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TMS): δ = 7.30ꢀ7.29 (d, 0.50H, J = 5.2 Hz, syn), 7.25ꢀ7.23 (q, 0.50H, J = 1.6 Hz, anti), 7.02ꢀ6.93 (m, 2H, anti+syn), 5.53 (d,
0.50H, J = 4.0 Hz, anti), 5.25 (m, 0.50H, J = 8.8 Hz, syn), 4.78ꢀ4.65 (m, 1H, anti+syn), 2.89ꢀ2.80 (m, 1H, anti+syn), 1.54 (d,
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1.50H, J = 6.8 Hz, anti), 1.33 (d, 1.50H, J = 6.4 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 141.4, 127.3, 127.2,
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126.8, 125.8, 87.5, 71.0, 13.0.
2-Nitro-1-(thiophen-3-yl)propan-1-ol (2ah):15f C7H9NO3S. Yellow oil in 94% yield, 35.1 mg. Enantiomeric
excesses (92% for anti, 92% for syn) HPLC (DAICEL CHIRALPAK IE, hexane/ 2ꢀpropanol = 95/5, flow rate 0.8 mL/min,
detection at 210 nm): tR (anti major) = 18.37 min, tR (anti minor) = 19.67 min, tR (syn minor) = 29.60 min, tR (syn major) = 34.25
min. Diastereomeric ratio (anti/syn = 1.9:1, Table 5, entry 34) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 C,
o
TMS): δ = 7.32ꢀ7.24 (m, 2H, anti+syn), 7.02 (q, 0.34H, J = 1.2 Hz, syn), 6.97 (q, 0.66H, J = 1.2 Hz, anti), 5.38 (d, 0.67H, J =
3.6 Hz, anti), 5.08 (m, 0.33H, syn), 4.76ꢀ4.70 (m, 0.33H, syn), 4.68ꢀ4.620 (m, 0.67H, anti), 2.74ꢀ2.63 (m, 1H, anti+syn), 1.46 (d,
2.01H, J = 6.8 Hz, anti), 1.309 (d, 0.99H, J = 6.4 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 C): (anti) δ = 139.9, 127.0, 125.1,
o
122.6, 86.9, 71.2, 12.6. HRMS (ESIꢀTOF) calcd for C7H9KNO331.9721S+ ([M+K+]) = 225.9901, found 225.9940.
2-Nitro-1-phenylethan-1-ol (2ai):12 C8H9NO3. Colorless oil in 83% yield, 27.7 mg (Table 5, entry 35). HPLC
(DAICEL CHIRALPAK ODꢀH, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection at 210 nm): major (R) tR = 14.33
min, minor (S) tR = 18.05 min. 1H NMR (400 MHz, CDCl3, 25 oC, TMS): δ = 7.42ꢀ7.34 (m, 5H), 5.48ꢀ5.42 (m, 1H), 4.59 (q, 1H,
J = 9.6 Hz), 4.50 (q, 1H, J = 2.8 Hz). 13C NMR (100 MHz, CDCl3, 25 oC): δ = 138.2, 129.2, 129.1, 126.1, 81.3, 71.1.
2-Nitro-1-phenylbutan-1-ol (2aj):15d C10H13NO3. Colorless oil in 35% yield, 13.7 mg. Enantiomeric excesses (84%
for anti, 56% for syn) HPLC (DAICEL CHIRALPAK IC, hexane/ 2ꢀpropanol = 90/10, flow rate 1.0 mL/min, detection at 210
nm): tR (anti major) = 5.51 min, tR (anti minor) = 6.73 min, tR (syn minor) = 11.78 min, tR (syn major) = 12.82 min.
Diastereomeric ratio (anti/syn = 1.8:1, Table 5, entry 36) was determined by 1H NMR. 1H NMR (400 MHz, CDCl3, 25 oC, TMS):
δ = 7.43ꢀ7.31 (m, 5H, anti+syn), 5.18 (q, 0.64H, J = 3.2 Hz, anti), 5.03 (q, 0.36H, J = 4.0 Hz, syn), 4.65ꢀ4.56 (m, 1H, anti+syn),
2.69 (d, 0.64H, J = 3.2 Hz, anti), 2.48 (d, 0.36H, J = 4.0 Hz, syn), 2.23ꢀ2.11 (m, 0.64H, anti), 1.96ꢀ1.80 (m, 1H, anti+syn),
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1.47ꢀ1.37 (m, 0.36H, syn), 0.94 (t, 1.92H, J = 7.6 Hz, anti), 0.87 (t, 1.08H, J = 7.6 Hz, syn). 13C NMR (100 MHz, CDCl3, 25 oC):
(anti) δ = 138.6, 129.2, 128.9, 126.3, 94.8, 74.4, 21.4, 10.5.
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ACKNOWLEDGMENTS
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We appreciate the National Natural Science Foundation of China (Nos. 21372162, 21321061 and 21432006) for financial
support. We also thank the State Key Laboratory of Biotherapy for HRMS analysis.
Supporting Information
HPLC data, 1H and 13C NMR spectra. This material is available free of charge via the Internet at http://pubs.acs.org.
References
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