Ni-catalyzed homoallylation of polyhydroxy N,O- Acetals with conjugated dienes promoted by triethylborane

Article abstract of DOI:10.3390/molecules19079288

In the presence of Ni-catalyst and triethylborane, N,O- Acetals prepared from glycolaldehyde and glyceraldehyde with primary amines in situ underwent homoallylation with conjugated dienes to provide 2- Amino-5-hexenols in high regio- And stereoselectivity

Full text of DOI:10.3390/molecules19079288

Molecules 2014, 19, 9288-9306; doi:10.3390/molecules19079288
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Ni-Catalyzed Homoallylation of Polyhydroxy N,O-Acetals with
Conjugated Dienes Promoted by Triethylborane
Takamichi Mori, Yusuke Akioka, Gen Onodera and Masanari Kimura *
Graduate School of Engineering, Nagasaki University, 1-14, Bunkyo machi, Nagasaki 852-8521, Japan
* Author to whom correspondence should be addressed; E-Mail: manasari@nagasaki-u.ac.jp;
Tel./Fax: +81-95-819-2677.
Received: 4 April 2014; in revised form: 13 June 2014 / Accepted: 23 June 2014 /
Published: 2 July 2014
Abstract: In the presence of Ni-catalyst and triethylborane, N,O-acetals prepared from
glycolaldehyde and glyceraldehyde with primary amines in situ underwent homoallylation
with conjugated dienes to provide 2-amino-5-hexenols in high regio- and stereoselectivity.
Under similar reaction conditions, N,O-acetals from carbohydrates with primary amines
provided the corresponding polyhydroxy-bishomoallylamines in good to reasonable yields.
Keywords: nickel; homoallylation; N,O-acetal; carbohydrate; conjugated diene;
triethylborane; reductive coupling
1. Introduction
Ni-catalyzed C-C bond formation is a useful strategy for organic syntheses [1]. Cross-coupling of
organometallic compounds with aromatic halides, as well as allylation and vinylation of carbonyls, is
widely utilized for the synthesis of physiologically active molecules and fine chemicals [2]. Compared
to catalytically C-C bond transformations involving allylation and vinylation, homoallylation of
carbonyls providing bis-homoallyl alcohols have serious limitations, which may be due to the
unavailability and low stability of homoallyl anion species that can react with electrophiles [3,4].
Recently, a Ni catalyst was developed that could promote the homoallylation of benzaldehyde with
a wide variety of 1,3-dienes in the presence of triethylborane to afford bis-homoallyl alcohols
(Equation (1)) [5,6]. For these processes, isoprene reacts at the C1 position with an aromatic aldehyde
to give 3-methyl-4-penten-1-ol with excellent 1,3-anti stereoselectivity. A similar homoallylation to
produce aliphatic aldehydes and ketones was successful using diethylzinc instead of triethylborane [7].

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Results indicated that diethylzinc functions as a more effective promoter than triethylborane for the
homoallylation of aliphatic aldehydes and ketones. In contrast, triethylborane is compatible with water
and alcohols, and even promotes homoallylation of aqueous aldehyde (e.g., glutaraldehyde) and
ω-hydroxyaldehyde (lactol) with conjugated dienes to afford ω-hydroxyhomoallyl alcohols
(Equation (2)) [8]. Thus, triethylborane and diethylzinc can be used in a complementary manner to
accelerate homoallyation of carbonyl compounds.
In addition, Ni-catalyzed homoallylation of aldimines prepared from aldehydes and primary amines
in situ with conjugated dienes provided bis-homoallylamines in high regio- and stereoselectivity
(Equation (3)) [9]. Thus, the C1 position of isoprene reacts with aldimines to afford 3-methyl-4-
pentenylamines with excellent 1,3-syn stereoselectivity, compared to 1,3-anti stereoselectivity when
using aldehydes.
(1)
(2)
(3)
This report describes a similar reaction system involving a Ni catalyst and triethylborane that was
extended successfully to the homoallylation of N,O-acetals prepared from cyclic hemiacetals and
primary amines to provide ω-hydroxybishomoallylamines in high regio- and moderate stereoselectivity
(Equation (4)). In similar catalytic reaction systems, N,O-acetals from carbohydrates with primary
amines gave the polyhydroxybishomoallylamines in good to reasonable yields.
(4)
2. Results and Discussion
Results of reactions of isoprene with N,O-acetals prepared from cyclic hemiacetals and
p-methoxyaniline are summarized in Table 1 (Equation (5), see, experimental section and
supporting information). Reactions were conducted at room temperature using isoprene, Ni(cod)2
catalyst, triethylborane, and N,O-acetals under nitrogen atmosphere. Isoprene reacted at the C1
position with N,O-acetals and underwent homoallylation to provide hydroxybishomoallylamines.
2-Hydroxytetrahydrofuran provided 1-(3-hydroxypropyl)-3-methyl-4-pentenylamine 1a in reasonable
yield along with a mixture of diastereomers in a 5:1 ratio (Table 1, entry 1). 5-Naphthyl-2-
hydroxytetrahydrofuran provided the desired product 1b in 71% yield along with two diastereomers in
a 2:1 ratio (Table 1, entry 2). 5-Methyl-5-n-hexyl-2-hydroxytetrahydrofuran participated in the

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homoallylation to afford hydroxylamine 1c, which possessed a tertiary alcohol moiety (Table 1, entry 3).
Six-membered cyclic hemiacetals could be used for homoallylation to form amino alcohols 1d and 1e
in 6:1 and 4:1 ratios, respectively (Table 1, entries 4 and 5). 2-Hydroxychroman served as an
N,O-acetal precursor by treatment with a primary amine to provide o-aminoalkyl phenol 1f (Table 1,
entry 6). N-Boc-2-hydroxypiperidine acted as an aldimine in the presence of p-methoxyaniline to
participate in the coupling reaction with isoprene to provide 2-butenylaminobishomoallylamine 1g
(Table 1, entry 7). Seven-membered cyclic hemiacetal underwent a similar homoallylation to provide
1-(5-hydroxypentyl)-3-methyl-4-pentenylamine 1h in reasonable yield (Table 1, entry 8).
(5)
Table 1. Ni-Catalyzed homoallylation of N,O-acetals with isoprene a.
Entry
Hemiacetal
Product
Yield (%) [Ratio]
1
1a: 58% [5:1]
2
3
1b: 71% [2:1]
1c: 59% [3:1]
4
5
1d: 91% [6:1]
1e: 69% [4:1]
6
1f: 66% [7:1]
7
8
1g: 41% [3:1]
1h: 58% [4:1]
a
N,O-Acetals were prepared from cyclic hemiacetals (1 mmol) and amines (2 mmol) stirring in THF
(2 mmol). A solution of isoprene (4 mmol), Ni(cod)2 (0.1 mmol) in THF (2 mL) and Et3B (3.6 mmol) were
introduced to the N,O-acetals, and the reaction mixture was stirred at room temperature for 24 h under N2.
Glycolaldehyde dimer is a two-carbon monosaccharide (diose) that is an important component of
biologically active molecules [10,11]. The reaction of glycolaldehyde dimer as an N,O-acetal precursor

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with conjugated dienes to furnish 1-hydroxymethyl-4-pentenylamines also was examined. Results using
various conjugated dienes and N,O-acetals prepared from primary amines and glycolaldehyde dimer
are summarized in Table 2 (Equation (6)). 1,3-Butadiene reacted with N,O-acetal prepared from
p-methoxyaniline to yield 47% of 1-hydroxymethyl-4-pentenylamine 1i along with 23% of the internal
olefin isomer 1i’ (Table 2, entry 1). N,O-Acetal from aniline underwent homoallylation with isoprene
to provide 1-hydroxymethyl-3-methyl-4-pentenylamine 1j in reasonable yield with a diastereomeric
mixture in a 8:1 ratio (Table 2, entry 2). o-Methoxy and p-methoxyaniline participated in similar
homoallylations to provide hydroxyamines 1k and 1l, respectively, with high stereoselectivity in an 8:1
ratio and as a single isomer, respectively (Table 2, entries 3 and 4). p-Bromoaniline underwent
homoallylation effectively to afford the desired hydroxylamine 1m as the sole product (Table 2, entry 5).
Benzylamine yielded an intractable mixture; the expected reaction was not observed (Table 2, entry 6).
Myrcene also participated in homoallylation with N,O-acetal to produce the corresponding
hydroxylamine 1n as a single product (Table 2, entry 7).
(6)
Table 2. Homoallylation of N,O-acetals prepared from glycolaldehyde dimer a.
Entry
Diene: R
Amine: R’
p-methoxyphenyl
phenyl
Product, Yield (%) [Ratio]
1i: 47% b
1
2
3
4
5
6
7
H
Me
1j: 64% [8:1]
Me
o-methoxyphenyl
p-methoxyphenyl
p-bromophenyl
benzyl
1k: 64% [8:1]
Me
1l: 59% [single]
1m: 50% [single]
intractable mixture
1n: 49% [single]
Me
Me
-(CH2)2CH=CMe2
p-methoxyphenyl
a
N,O-Acetals were prepared from glycolaldehyde dimer (1 mmol) and amines (4 mmol) stirring in THF
(2 mmol). A solution of conjugated diene (8 mmol), Ni(cod)2 (0.1 mmol) in THF (2 mL) and Et3B (6 mmol)
were introduced to the N,O-acetals, and the reaction mixture was stirred at room temperature for 48 h under
N2. b Internal olefin isomer 1i’ was obtained in 23%.
Glyceraldehyde is a triose monosaccharide generally used for the enzymatic synthesis of D-fructose
and L-sorbose with aldolases [12]. The glyceraldehyde can serve as an important electrophilic component
for coupling reactions to form a physiologically active molecules. The Ni-catalyzed homoallylation of
glyceraldehyde dimer was accomplished using primary amines and conjugated dienes in the presence
of triethylborane (Table 3, Equation (7)). In this reaction, N,O-acetals prepared from glyceraldehyde
dimer and primary amines in DMF via azeotropic distillation underwent homoallylation with
conjugated dienes to furnish dihydroxybishomoallylamines. 1,3-Butadiene reacted with N,O-acetal from
p-methoxyaniline to provide 1-(1,2-dihydroxyethyl)-4-pentenylamine 1o in 56% yield along with the
internal olefin isomer 1o’ in 17% yield (Table 3, entry 1). N,O-Acetal from aniline participated in
homoallylation with isoprene to provide 1-(1,2-dihydroxyethyl)-3-methyl-4-pentenylamine 1p in 62%
yield in a 2:1 ratio of diastereomers (Table 3, entry 2). p-Methoxyaniline gave a similar homoallylation
product 1q with a mixture of diastereoisomers in a 2:1 ratio (Table 3, entry 3). Benzylamine provided an

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intractable mixture in the same way as the result of glycolaldehyde with aliphatic amine (Table 3, entry 4).
Myrcene underwent homoallylation with N,O-acetal to produce the corresponding hydroxylamine 1r
in reasonable yield with diastereomers in a 2:1 ratio, as well as isoprene (Table 3, entry 5).
(7)
Table 3. Ni-Catalyzed homoallylation of N,O-acetals prepared from glyceraldehyde dimer a.
Entry
Diene: R
Amine: R’
p-methoxyphenyl
phenyl
Product, Yield (%) [Ratio]
1o: 56% [3:1] b
1
2
3
4
5
H
Me
1p: 62% [2:1]
Me
Me
p-methoxyphenyl
benzyl
1q: 69% [2:1]
intractable mixture
1r: 64% [2:1]
-(CH2)2CH=CMe2
p-methoxyphenyl
a
N,O-Acetals were prepared from glyceraldehyde dimer (1 mmol) and amines (4 mmol) in DMF (2 mmol)
via azeotropic distillation. A solution of conjugated diene (8 mmol), Ni(cod)2 (0.1 mmol) in THF (2 mL)
and Et3B (6 mmol) were introduced to the residual oil of N,O-acetals, and then the reaction mixture was
b
stirred at room temperature for 48 h under N2. Internal olefin isomer 1o’ was obtained in 17% with 3:1
diastereoisomeric ratio.
Next, homoallylation of N,O-acetals from carbohydrates, such as 2-deoxy-D-ribose, D-ribose, and
2-deoxy-D-glucose, was investigated. Various N,O-acetals prepared from 2-deoxy-D-ribose and aromatic
amines underwent homoallylation with conjugated dienes in one pot to provide polyhydroxyamines
(Table 4, Equation (8)). 1,3-Butadiene reacted with N,O-acetal from 2-deoxy-D-ribose and
p-methoxyaniline to afford the homoallylation product 1s in moderate yield along with the allylation
product as a diastereoisomeric mixture of internal olefin isomers 1s’ (Table 4, entry 1). Isoprene
reacted with high regioselectivity at the C1 position with N,O-acetals derived from 2-deoxy-D-ribose
and various aromatic amines to provide the desired polyhydroxyamines 1t–1x as mixtures of two
diastereomers in a nearly 2:1 ratio (Table 4, entries 2–6). Myrcene also participated in homoallylation
as a conjugated diene and afforded the desired product 1y in 56% in a 1:1 ratio (Table 4, entry 7).
These consecutive homoallylations of N,O-acetals from 2-deoxy-D-ribose and primary amines provided
bishomoallylamines as two diastereomers in 1:1 to 2:1 ratios, in spite of possible formation of four
diastereoisomers. Since D-ribose and 2-deoxy-D-glucose are insoluble in THF, a series of N,O-acetals
with D-ribose and 2-deoxy-D-glucose were prepared from amines in DMF via azeotropic distillation,
and were used for homoallylation with isoprene to produce the expected polyhydroxyamines 2 and 3,
respectively (Equations (9) and (10)).
(8)

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Table 4. Homoallylation of N,O-acetals prepared from 2-deoxy-D-ribose and amine a.
9293
Entry Conjugated Diene: R
Amine: R’
p-methoxyphenyl
p-methoxyphenyl
o-methoxyphenyl
3,4-dimethoxyphenyl
phenyl
Product, Yield (%) [Ratio]
1s: 27% [1:1] b
1t: 74% [2:1]
1
2
3
4
5
6
7
H
Me
Me
1u: 80% [2:1]
Me
1v: 58% [2:1]
Me
Me
1w: 75% [2:1]
p-chlorophenyl
p-methoxyphenyl
1x: 30% [2:1]
-(CH2)2CH=CMe2
1y: 56% [1:1]
a
N,O-Acetals were prepared from 2-deoxy-D-ribose (1 mmol) and amines (2 mmol) in THF (5 mmol) via
azeotropic distillation. A solution of conjugated diene (8 mmol), Ni(cod)2 (0.1 mmol) in THF (2 mL) and
Et3B (6 mmol) were introduced to the N,O-acetals, and the reaction mixture was stirred at room temperature
for 48 h under N2. b Internal olefin isomer 1s’ was obtained in 32% with 3:1 diastereoisomeric ratio.
(9)
(10)
Although all product absolute configurations have not been determined yet, a plausible reaction
mechanism might be assumed based on the results of the homoallylation of aldimines prepared from
aldehydes and primary amines with conjugated dienes [9]. N,O-Acetals were readily prepared from
cyclic hemiacetals with primary amines in situ, and the low concentration of ω-hydroxyimine tautomers
in equilibrium with the N,O-acetals appeared to promote reaction with conjugated dienes (Scheme 1).
As triethylborane coordinates to the nitrogen atom of N,O-acetals as a Lewis acid, the formation of
ω-hydroxyimine tautomers might predominate over N,O-acetals. An azanickelacycle intermediate via
oxidative cyclization of conjugated dienes and ω-hydroxyimine with Ni(0) catalyst followed by σ-bond
metathesis with triethylborane would result in the formation of ω-hydrox-bishomoallylamines.
Scheme 1. Equilibrium between cyclic N,O-acetal and ω-hydroxyamine.

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3. Experimental
3.1. General
Distillation were carried out in a Kugelrohr apparatus (GTO-350RG glass tube oven, SIBATA,
Soka (Saitama, Japan). Boiling points are meant to refer to the oven temperature (±1 °C).
Microanalyses were performed by the Instrumental Analysis Center of Nagasaki University. Analysis
agreed with the calculated values within ±0.4%. High resolution mass spectra (HRMS) were measured
with a JEOL JMSDX303 instrument (JEOL, Akishima (Tokyo), Japan). Infrared spectra were recorded
with a JASCO A-100 (Hachioji, Tokyo, Japan) or Shimadzu FTIR-8700 (Kyoto, Japan) infrared
spectrophotometer. 1H (400 MHz) and 13C-NMR spectra (100 MHz) were measured on JEOL-GX400
instrument with tetramethylsilane as an internal standard. Chemical shift values were given in ppm
downfield from the internal standard.
Tetrahydrofuran, toluene, and diethyl ether were dried and distilled from benzophenone-sodium
immediately prior to use under nitrogen atmosphere. DMF was distilled over calcium chloride.
Triethylborane (1 M THF, KANTO Kagaku, Tokyo, Japan), Ni(cod)2 (KANTO Kagaku, Tokyo, Japan)
were used without further purification. Isoprene, myrcene, glycolaldehyde dimmer, glyceraldehyde
dimer, 2-deoxy-D-ribose, D-ribose, 2-deoxy-D-glucose, aniline, p-methoxyaniline, o-methoxyaniline,
p-bromoaniline, benzylamine were purchased and used without purification. 1,3-Butadiene was
purchased (Tokyo Kasei Kogyo Co., Ltd., Tokyo, Japan), and was liquefied by cooling at −78 °C (dry
ice/isopropanol) prior to use under argon atmosphere. 1,3-Butadiene could be measured by syringe
kept cool in the freezer well beforehand, and then was introduced into the reaction mixture at room
temperature. Tetrahydrofuran-2-ol, tetrahydro-2H-pyran-2-ol, oxepane-2-ol, 5-(naphthalen-2-yl)
tetrahydrofuran-2-ol, and all of the substrates in Table 1 were prepared according to the literature [13–16].
3.2. Typical Procedure for Ni-catalyzed Homoallylation of N,O-acetal with Isoprene (Entry 4, Table 1)
A solution of tetrahydro-2H-pyran-2-ol (102 mg, 1 mmol) and p-anisidine (246 mg, 2 mmol) in dry
THF (2 mL) was stirred overnight under nitrogen. A mixture of Ni(cod)2 (27.5 mg, 0.1 mmol) and
isoprene (400 μL, 4 mmol) dissolved in THF (2 mL) and triethylborane (3.6 mmol, 1.0 M THF
solution) were successively added to the N,O-acetal solution. The reaction mixture was stirred at room
temperature for 24 h. The reaction mixture was diluted with 30 mL of EtOAc and washed with sat.
NaHCO3, and brine. The organic phase was dried (MgSO4) and concentrated in vacuo to give a
colorless oil, which was subjected to column chromatography over silica gel (hexane/EtOAc = 2/1 v/v)
to give 1d (258 mg, 91%) in a 6:1 ratio. Rf = 0.30 (hexane/EtOAc = 4/1 v/v).
(4S,6S)-4-(4-Methoxyphenylamino)-6-methyloct-7-en-1-ol (1a). (a mixture of major and minor isomers
in a ratio of 5:1): IR (neat) 3310 (s), 3071 (s), 2924 (s), 1643 (m), 1458 (s), 1065 (s), 910 (s), 741 (s) cm−1;
1H-NMR (CDCl3, major-isomer) δ 0.99 (d, J = 6.7 Hz, 3 H), 1.60–1.69 (m, 6 H), 2.35 (qm, J = 6.7 Hz,
1 H), 2.52 (br, 1H), 3.32 (m, 1 H), 3.60 (t, J = 6.1 Hz, 2 H), 3.73 (s, 3 H), 4.92 (dm, J = 10.7 Hz, 1 H),
4.93 (dd, J = 16.9, 1.0 Hz, 1 H), 5.65 (ddd, J = 16.9, 10.7, 8.0 Hz, 1 H), 6.54 (dd, J = 6.6, 2.2 Hz, 2 H),
13
6.75 (m, 2 H); C-NMR (CDCl3, major-isomer) δ 21.0, 29.3, 32.0, 35.0, 42.5, 54.0, 55.8, 62.9, 63.0,
113.2, 114.9, 115.0, 115.4, 141.5, 141.8, 144.3; 1H-NMR (CDCl3, minor-isomer) δ 0.99 (d, J = 6.7 Hz,

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3 H), 1.60–1.69 (m, 6 H), 2.35 (qm, J = 6.7 Hz, 1 H), 2.52 (br, 1H), 3.32 (m, 1 H), 3.60 (t, J = 6.1 Hz,
2 H), 3.73 (s, 3 H), 4.93 (dd, J = 16.9, 1.0 Hz, 1 H), 4.98 (dm, J = 17.1 Hz, 1 H), 5.65 (ddd, J = 16.9,
10.7, 8.0 Hz, 1 H), 6.54 (dd, J = 6.6, 2.2 Hz, 2 H), 6.75 (m, 2 H); 13C-NMR (CDCl3, minor-isomer) δ
20.8, 29.2, 32.0, 35.0, 45.3, 54.0, 55.8, 62.9, 63.0, 113.2, 114.8, 115.0, 115.4, 141.6, 141.8, 144.1;
HRMS, calcd for C16H25NO2: 263.1885. Found m/z (relative intensity): 264.1882 (M++1, 18),
263.1850 (M+, 97), 205.1411 (15), 204.1394 (100).
(4S,6S)-4-(4-Methoxyphenylamino)-6-methyl-1-(naphthalenyl) octen-7-ol (1b). (a mixture of major
and minor isomers in a ratio of 2:1): IR (neat) 3366 (s), 2930 (s), 2359 (m), 1506 (s), 1238 (s), 1040
(s), 820 (s), 750 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 0.95 (d, J = 6.8 Hz, 3 H), 1.38–1.94 (m, 6
H), 2.29 (qm, J = 6.8 Hz, 1 H), 3.11 (br, 1 H), 3.32 (br q, J = 5.9 Hz, 1 H), 3.71 (s, 3 H), 4.78–4.82 (m, 1
H), 4.88 (dd, J = 18.3, 1.9 Hz, 1 H), 4.89 (dd, J = 10.8, 1.9 Hz, 1 H), 5.59 (ddd, J = 18.3, 10.8, 8.3 Hz, 1
13
H), 6.53 (d, J = 8.9 Hz, 2 H), 6.70 (dd, J = 8.9, 1.0 Hz, 2 H), 7.39–7.82 (m, 7 H); C-NMR (CDCl3,
major-isomer) δ 20.9, 31.7, 35.0, 35.5, 42.3, 53.0, 55.7, 74.5, 113.2, 114.8, 115.3, 123.9, 124.4, 125.6,
1
125.7, 125.9, 126.0, 127.5, 128.0, 132.8, 133.1, 141.9, 144.1, 152.2; H-NMR (CDCl3, minor-isomer)
δ 0.92 (d, J = 6.8 Hz, 3 H), 1.38–1.94 (m, 6 H), 2.29 (qm, J = 6.8 Hz, 1 H), 3.11 (br, 1 H), 3.32 (br q,
J = 5.9 Hz, 1 H), 3.72 (s, 3 H), 4.83 (dm, J = 18.3 Hz, 1 H), 4.88 (dd, J = 18.3, 1.9 Hz, 1 H), 4.89
(dd, J = 10.8, 1.9 Hz, 1 H), 5.58–5.66 (m, 1 H), 6.53 (d, J = 8.9 Hz, 2 H), 6.70 (dd, J = 8.9, 1.0 Hz,
2 H), 7.39–7.82 (m, 7 H); 13C-NMR (minor-isomer) δ 20.9, 31.2, 34.9, 35.7, 42.3, 52.7, 55.7,
74.4, 113.2, 114.8, 115.2, 124.0, 124.4, 125.6, 125.7, 125.9, 126.0, 127.5, 128.1, 132.6, 133.1, 141.3,
144.1, 152.1; HRMS, calcd for C26H31NO2: 389.2355. Found m/z (relative intensity): 389.2340
(M+, 100).
10-(4-Methoxyphenylamino)-7,12-dimethyl-13-tetradecen-7-ol (1c). (a mixture of major and minor
isomers in a ratio of 3:1): IR (neat) 3379 (s), 2932 (s), 2359 (m), 1639 (s), 1514 (s), 1238 (s), 1043 (s),
912 (s), 818 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 0.88 (t, J = 6.4 Hz, 3 H), 0.96 (d, J = 6.8 Hz,
3 H), 1.12 –1.26 (m, 8 H), 1.42 (br, 3 H), 1.49–1.69 (m, 8 H), 2.29 (qm, J = 6.8 Hz, 1 H), 3.25–3.33
(m, 1 H), 3.74 (s, 3 H), 4.91 (dd, J = 10.7, 1.5 Hz, 1 H), 4.92 (dd, J = 17.5, 1.5 Hz, 1 H), 5.63 (ddd,
13
J = 17.5, 10.7, 8.0 Hz, 1 H), 6.69–6.72 (m, 2 H), 6.75 (d, J = 9.3 Hz, 2 H); C-NMR (CDCl3,
major-isomer) δ 14.1, 20.7, 20.9, 22.6, 26.9, 27.6, 29.8, 31.8, 35.0, 37.4, 37.6, 41.9, 55.6, 55.7, 72.6,
113.3, 114.0, 116.8, 143.4, 143.9, 144.0; 1H-NMR (CDCl3, minor-isomer) δ 0.88 (t, J = 6.4 Hz, 3 H),
0.97 (d, J = 6.8 Hz, 3 H), 1.12 –1.26 (m, 8 H), 1.42 (br, 3 H), 1.49–1.69 (m, 8 H), 2.29 (qm, J = 6.8 Hz,
1 H), 3.25–3.33 (m, 1 H), 3.74 (s, 3 H), 4.91 (dd, J = 10.7, 1.5 Hz, 1 H), 4.92 (dd, J = 17.5, 1.5 Hz,
1 H), 5.63 (ddd, J = 17.5, 10.7, 8.0 Hz, 1 H), 6.69–6.72 (m, 2 H), 6.75 (d, J = 9.0 Hz, 2 H); 13C-NMR
(CDCl3, minor-isomer) δ 14.1, 20.8, 20.9, 22.6, 26.8, 27.6, 29.8, 31.8, 35.0, 37.4, 37.6, 41.9, 55.6,
55.7, 72.7, 113.4, 114.0, 116.7, 143.5, 143.9, 144.0; HRMS, calcd for C23H39NO2: 361.2981. Found
m/z (relative intensity): 361.2969 (M+, 100).
5-[(4-Methoxyphenyl)amino]-7-methylnon-8-en-1-ol (1d) (a mixture of major and minor isomers in a
ratio of 6:1): IR (neat) 3368 (s), 2934 (s), 1514 (m), 1458 (s), 1236 (s), 1040 (s), 820 (s) cm−1; 1H-NMR
(CDCl3, major-isomer) δ 1.00 (d, J = 6.6 Hz, 3 H), 1.37–1.58, (m, 8 H), 2.33 – 2.38 (m, 1 H), 3.31 (m, 1
H), 3.62 (t, J = 6.3 Hz, 2 H), 3.73 (s, 3 H), 4.92 (dd, J = 10.4, 1.1 Hz, 1 H), 4.93 (dd, J = 17.0, 1.1 Hz,

Molecules 2014, 19
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1 H), 5.65 (ddd, J = 17.0, 10.4, 8.1 Hz, 1 H), 6.52 (d, J = 8.9 Hz, 2 H), 6.74 (d, J = 8.9 Hz, 2 H);
13C-NMR (CDCl3, major-isomer) δ 21.1, 22.0, 32.8, 35.0, 35.2, 42.5, 52.1, 55.8, 62.8, 113.2, 114.4,
1
114.9, 142.1, 144.3, 151.6; H-NMR (CDCl3, minor-isomer) δ 0.98 (d, J = 6.8 Hz, 3 H), 1.37–1.58,
(m, 8 H), 2.33–2.38 (m, 1 H), 3.31 (m, 1 H), 3.61 (t, J = 6.5 Hz, 2 H), 3.74 (s, 3 H), 4.92 (dd, J = 10.4,
1.1 Hz, 1 H), 4.93 (dd, J = 17.0, 1.1 Hz, 1 H), 5.65 (ddd, J = 17.0, 10.4, 8.1 Hz, 1 H), 6.52 (d, J = 8.9 Hz,
13
2 H), 6.74 (d, J = 8.9 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 21.1, 21.9, 32.8, 35.0, 35.2, 42.1,
52.1, 55.8, 62.8, 113.2, 114.2, 114.8, 142.1, 144.3, 151.6; HRMS, calcd for C17H27 NO2: 277.2018.
Found m/z (relative intensity): 278.2001 (M++1, 1), 277.2014 (M+, 2), 260.1983 (13), 204.1406 (100).
(5S,7S)-5-(4-Methoxyphenylamino)-3,3,7-trimethylnonen-8-ol (1e). (a mixture of major and minor
isomers in a ratio of 4:1): IR (neat) 3373 (s), 2932 (s), 2359 (m), 1732 (s), 1514 (s), 1234 (s), 1042 (s),
818 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 0.94 (s, 6 H), 0.97 (d, J = 6.8 Hz, 3 H), 1.21–1.70(m,
6 H), 2.28 (qm, J = 6.8 Hz, 1 H), 3.02 (br, 1 H),3.34 (m, 1 H), 3.69 (s, 3 H), 3.66–3.76 (m, 2 H), 4.98
(dd, J = 17.7, 1.8 Hz, 1 H), 4.99 (dd, J = 10.0, 1.8 Hz, 1 H), 5.67 (ddd, J = 17.7, 10.0, 8.3 Hz, 1 H),
6.55 (br, 2 H), 6.75 (br d, J = 8.3 Hz, 2 H); 13C-NMR (CDCl3, major-isomer) δ 20.1, 21.6, 28.4, 28.5,
1
32.7, 44.5, 47.5, 47.9, 49.3, 55.0, 59.6, 113.6, 114.9, 115.0, 144.1, 144.7, 152.0; H-NMR (CDCl3,
minor-isomer) δ 0.95 (s, 6 H), 0.99 (d, J = 6.6 Hz, 3 H), 1.21–1.70 (m, 6 H), 2.28 (qm, J = 6.8 Hz, 1
H), 3.02 (br, 1 H),3.34 (m, 1 H), 3.67 (s, 3 H), 3.66–3.76 (m, 2 H), 4.92 (dd, J = 10.2, 0.8 Hz, 1 H),
4.95 (dd, J = 16.9, 0.8 Hz, 1 H), 5.67 (ddd, J = 17.7, 10.0, 8.3 Hz, 1 H), 6.55 (br, 2 H), 6.75 (br d,
13
J = 8.3 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 20.1, 21.6, 28.4, 28.5, 32.6, 44.3, 47.5, 47.9,
49.3, 55.0, 59.6, 113.6, 114.8, 115.0, 144.1, 144.7, 152.0; HRMS, calcd for C19H31NO2: 305.2355.
Found m/z (relative intensity): 306.2373 (M++1, 9), 305.2337 (M+, 44), 237.1655 (18), 236.1608 (100),
235.1535 (19).
2-((3S,5S)-3-(4-Methoxyphenylamino)-5-methyl-6-heptenyl)phenol (1f). (a mixture of major and minor
isomers in a ratio of 7:1): IR (neat) 3308 (s), 2930 (s), 1583 (m), 1506 (s), 1236 (s), 1040 (s), 822 (s),
1
754 (s) cm−1; H-NMR (CDCl3, major-isomer) δ 0.84 (d, J = 6.8 Hz, 3 H), 1.11–1.68 (m, 4 H), 2.20
(qm, J = 6.8 Hz, 1 H), 2.65–2.71 (m, 2 H), 2.88–2.95 (m, 1 H), 3.13–3.29 (m, 1 H), 3.75 (s, 3 H), 4.86
(dd, J = 10.8, 0.8 Hz, 1 H), 4.87 (dd, J = 16.7, 0.8 Hz, 1 H), 5.57 (ddd, J = 16.7, 10.8, 7.8 Hz, 1 H),
6.78 (d, J = 8.6 Hz, 2 H), 6.84 (d, J = 8.6 Hz, 2 H), 6.73–6.92 (m, 2 H), 7.06–7.12 (m, 2 H); 13C-NMR
(CDCl3, major-isomer) δ 20.2, 26.2, 34.8, 35.3, 40.0, 53.3, 55.6, 55.7, 112.9, 114.8, 116.3, 120.3,
127.2, 127.3, 127.4, 129.9, 130.0, 144.3, 154.8; 1H-NMR (CDCl3, minor-isomer) δ 0.89 (d, J = 6.3 Hz,
3 H), 1.11–1.68 (m, 4 H), 2.20 (qm, J = 6.8 Hz, 1 H), 2.65–2.71 (m, 2 H), 2.88–2.95 (m, 1 H),
3.13–3.29 (m, 1 H), 3.75 (s, 3 H), 4.86 (dd, J = 10.8, 0.8 Hz, 1 H), 4.87 (dd, J = 16.7, 0.8 Hz, 1 H),
5.57 (ddd, J = 16.7, 10.8, 7.8 Hz, 1 H), 6.78 (d, J = 8.6 Hz, 2 H), 6.84 (d, J = 8.6 Hz, 2 H), 6.73–6.92
13
(m, 2 H), 7.06–7.12 (m, 2 H); C-NMR (CDCl3, minor-isomer) δ 20.2, 26.2, 34.8, 35.3, 40.0, 53.3,
55.6, 55.7, 112.9, 114.6, 116.3, 120.6, 127.2, 127.3, 127.4, 129.9, 130.1, 144.3, 154.8; HRMS, calcd
for C21H27NO2: 325.2042. Found m/z (relative intensity): 326.2086 (M++1, 18), 325.2045 (M+, 78),
257.1349 (18), 256.1329 (100).
Tert-Butyl(5S,7S)-5-(4-methoxyphenylamino)-7-methylnon-8-enylcarbamate (1g). (a mixture of major
and minor isomers in a ratio of 3:1):IR (neat) 2864 (s), 2359 (m), 1682 (s), 1539 (s), 1251 (s), 1173 (s),

Molecules 2014, 19
9297
910 (s), 750 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 1.01 (d, J = 6.8 Hz, 3 H), 1.34–1.51 (m, 8 H),
1.44 (s, 9 H), 2.32 (dm, J = 7.4 Hz, 1 H), 3.11 (br, 2 H), 3.67 (br, 1 H), 4.93 (dd, J = 10.2, 1.1 Hz, 1 H),
5.01 (dd, J = 17.4, 1.1 Hz, 1 H), 5.77 (ddd, J = 17.4, 10.2, 7.4 Hz, 1 H); 13C-NMR (CDCl3, major-isomer)
1
δ 20.2, 22.6, 28.4, 30.1, 35.4, 37.2, 40.4, 44.5, 70.1, 79.0, 112.6, 114.9, 155.9; H-NMR (CDCl3,
minor-isomer) δ 0.98 (d, J = 6.6 Hz, 3 H), 1.34–1.51 (m, 8 H), 1.44 (s, 9 H), 2.32 (dm, J = 7.4 Hz, 1 H),
3.11 (br, 2 H), 3.67 (br, 1 H), 4.88 (dm, J = 11.2 Hz, 1 H), 5.01 (dd, J = 17.4, 1.1 Hz, 1 H), 5.77 (ddd,
13
J = 17.4, 10.2, 7.4 Hz, 1 H); C-NMR (CDCl3, minor-isomer) δ 19.8, 22.6, 28.4, 30.0, 35.4, 37.2,
40.4, 44.3, 69.8, 79.0, 112.0, 114.6, 155.9; HRMS, calcd for C15H29NO3: 271.2147. Found m/z
(relative intensity): 376.2731 (M+, 100).
(6S,8S)-6-(4-Methoxyphenylamino)-8-methyldec-9-en-1-ol (1h). (a mixture of major and minor isomers
in a ratio of 4:1): IR (neat) 3364 (s), 2934 (s), 1614 (m), 1514 (s), 1238 (s), 1038 (s), 822 (s) cm−1;
1H-NMR (CDCl3, major-isomer) δ 1.00 (d, J = 6.8 Hz, 3 H), 1.21–1.58, (m, 10 H), 2.34–2.38 (m, 1 H),
3.27–3.32 (m, 1 H), 3.61 (t, J = 6.6 Hz, 2 H), 3.74 (s, 3 H), 4.92 (dd, J = 10.2, 0.9 Hz, 1 H), 4.93 (dd,
J = 17.0, 0.9 Hz, 1 H), 5.65 (ddd, J = 17.0, 10.2, 8.1 Hz, 1 H), 6.63 (d, J = 9.1 Hz, 2 H), 6.74 (d,
J = 9.1 Hz, 2 H); 13C-NMR (CDCl3, major-isomer) δ 21.2, 25.6, 25.9, 32.8, 35.1, 35.3, 42.4, 55.8, 55.9,
62.9, 113.3, 114.9, 116.4, 139.8, 144.3, 152.8; 1H-NMR (CDCl3, minor-isomer) δ 0.97 (d, J = 6.8 Hz,
3 H), 1.21–1.58, (m, 10 H), 2.34–2.38 (m, 1 H), 3.27–3.32 (m, 1 H), 3.61 (t, J = 6.4 Hz, 2 H), 3.74 (s,
3 H), 4.92 (dd, J = 10.2, 0.9 Hz, 1 H), 4.93 (dd, J = 17.0, 0.9 Hz, 1 H), 5.65 (ddd, J = 17.0, 10.2, 8.1 Hz,
13
1 H), 6.63 (d, J = 9.1 Hz, 2 H), 6.74 (d, J = 9.1 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 21.2,
25.6, 25.9, 32.8, 35.1, 35.3, 42.4, 55.8, 55.9, 63.1, 113.3, 114.8, 116.4, 139.8, 144.3, 152.8; HRMS,
calcd for C18H29NO2: 291.2196. Found m/z (relative intensity): 292.2236 (M++1, 15), 291.2196 (M+,
65), 223.1501 (13), 222.1497 (100).
2-(4-Methoxyphenylamino)-5-hexenol (1i). IR (neat) 3375 (s), 3076 (m), 2936 (s), 1639 (s), 1514 (s),
1464 (s), 1238 (s), 1038 (s), 822 (s) cm−1; 1H-NMR (CDCl3) δ 1.42 (quin, J = 7.5 Hz, 2 H), 2.14 (br q,
J = 6.8 Hz, 1 H), 2.25 (br q, J = 6.4 Hz, 1 H), 2.69 (br, 1 H), 3.40 (m, 2 H), 3.49 (dd, J = 10.9, 6.1 Hz,
1 H), 3.51 (dd, J = 10.9, 6.1 Hz, 1 H), 3.74 (s, 3 H), 4.94 (dm, J = 9.7 Hz, 1 H), 5.00 (dt, J = 16.1,1.9 Hz,
1 H), 5.78 (ddt, J = 16.1, 9.7, 6.4 Hz, 1 H), 6.64 (dd, J = 6.6, 2.4 Hz, 2 H), 6.74 (dd, J = 6.6, 2.4 Hz, 2 H);
13C-NMR (CDCl3) δ 28.7, 30.4, 55.8, 56.3, 64.1, 114.8, 115.7, 116.4, 137.8, 139.8, 152.7; HRMS,
calcd for C13H19NO2: 221.1416. Found m/z (relative intensity): 222.1449 (M++1, 4), 221.1401 (M+,
28), 191.1235 (14), 190.1195 (100).
1
(E)-2-(4-Methoxyphenylamino)-4-hexenol (1i'). H-NMR (CDCl3) δ 1.64 (dm, J = 7.6 Hz, 3 H), 2.02
(m, 2 H), 3.40 (m, 2 H), 3.49 (dd, J = 10.9, 6.1 Hz, 1 H), 3.51 (dd, J = 10.9, 6.1 Hz, 1 H), 3.74 (s, 3 H),
5.40 (m, 1 H), 5.50 (m, 1 H), 6.64 (dd, J = 6.6, 2.4 Hz, 2 H), 6.74 (dd, J = 6.6, 2.4 Hz, 2 H); 13C-NMR
(CDCl3) δ 18.0, 33.3, 55.8, 56.5, 64.4, 114.9, 116.1, 125.7, 133.8, 139.8, 152.8.
(2R,4S)-4-Methyl-2-(phenylamino)-5-hexenol (1j). (a mixture of major and minor isomers in a ratio of
8:1): IR (neat) 3393 (s), 3078 (m), 2926 (s), 1601 (s), 1506 (s), 1317 (s), 1030 (s), 914 (m), 748 (s),
1
692 (s) cm−1; H-NMR (CDCl3, major-isomer) δ 1.03 (d, J = 6.8 Hz, 3 H), 1.52 (t, J = 5.7 Hz, 2 H),
2.32 (ddm, J = 7.7, 6.8 Hz, 1 H), 3.49 (dd, J = 10.5, 5.4 Hz, 1 H), 3.55 (tdm, J = 5.4, 4.1 Hz, 2 H), 3.71
(dd, J = 10.5, 4.1 Hz, 1 H), 4.89 (dd, J = 17.2, 0.9 Hz, 1 H), 4.92 (dd, J = 10.4, 0.9 Hz, 1 H), 5.64 (ddd,

Molecules 2014, 19
9298
J = 17.2, 10.4, 7.7 Hz, 1 H), 6.64 (dd, J = 8.6, 1.2 Hz, 2 H), 6.70 (t, J = 7.3 Hz, 1 H), 7.15 (dd, J = 8.6,
13
7.3 Hz, 2 H); C-NMR (CDCl3, major-isomer) δ 21.1, 35.0, 39.8, 53.5, 65.0, 113.7, 113.8, 117.8,
129.3, 143.7, 147.7; 1H-NMR (CDCl3, minor-isomer) δ 1.00 (d, J = 6.8 Hz, 3 H), 1.50 (t, J = 5.1 Hz, 2
H), 2.32 (ddm, J = 7.7, 6.8 Hz, 1 H), 3.49 (dd, J = 10.5, 5.4 Hz, 1 H), 3.55 (tdm, J = 5.4, 4.1 Hz, 2 H),
3.71 (dd, J = 10.5, 4.1 Hz, 1 H), 4.89 (dd, J = 17.2, 0.9 Hz, 1 H), 4.92 (dd, J = 10.4, 0.9 Hz, 1 H), 5.64
(ddd, J = 17.2, 10.4, 7.7 Hz, 1 H), 6.64 (dd, J = 8.6, 1.2 Hz, 2 H), 6.70 (t, J = 7.3 Hz, 1 H), 7.14 (dd,
13
J = 8.5, 7.3 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 21.1, 35.0, 39.8, 53.5, 65.0, 113.7, 113.8,
117.8, 129.3, 143.7, 147.7; HRMS, calcd for C13H19NO: 205.1467. Found m/z (relative intensity):
206.1505 (M++1, 4), 205.1463 (M+, 20), 175.1278 (16), 174.1268 (100).
(2R,4S)-2-(4-Methoxyphenylamino)-4-methyl-5-hexenol (1k). IR (neat) 3383 (s), 3078 (m), 2932 (s),
1
1618 (s), 1418 (s), 1238 (s), 1040 (s), 914 (m), 820 (s), 667 (m) cm−1; H-NMR (CDCl3) δ 1.01 (d,
J = 6.6 Hz, 3 H), 1.49 (t, J = 6.8 Hz, 2 H), 2.31 (qtm, J = 6.8, 6.6 Hz, 1 H), 3.45 (dd, J = 8.4, 3.2 Hz, 1
H), 3.46 (dd, J = 8.4, 5.5 Hz, 1 H), 3.71 (dm, J = 6.6 Hz, 1 H), 3.74 (s, 3 H), 4.89 (dd, J = 17.1, 1.2 Hz,
1 H), 4.92 (dd, J = 10.2, 1.2 Hz, 1 H), 5.63 (ddd, J = 17.1, 10.2, 8.1 Hz, 1 H), 6.64 (dd, J = 6.6, 2.2 Hz,
13
2 H), 6.76 (dd, J = 6.6, 2.2 Hz, 2 H); C-NMR (CDCl3) δ 21.0, 34.9, 39.6, 55.0, 55.7, 64.8, 113.6,
114.8, 115.4, 141.7, 143.7, 152.3; HRMS, calcd for C14H21NO2: 235.1572. Found m/z (relative
intensity): 236.1583 (M++1, 5), 235.1562 (M+, 28), 204.1378 (100).
(2R,4S)-2-(2-Methoxyphenylamino)-4-methyl-5-hexenol (1l). (a mixture of major and minor isomers in
a ratio of 8:1): IR (neat) 3414 (s), 3070 (m), 2932 (s), 2359 (s), 1601 (s), 1516 (s), 1456 (s), 1223 (s),
1
1030 (s), 914 (s), 737 (s) cm−1; H-NMR (CDCl3, major-isomer) δ 1.03 (d, J = 6.8 Hz, 3 H), 1.54 (t,
J = 6.6 Hz, 2 H), 2.31 (qm, J = 6.8 Hz, 1 H), 3.50 (dd, J = 10.4, 5.8 Hz, 1 H), 3.55 (tdm, J = 6.6, 3.9
Hz, 1 H), 3.72 (dd, J = 10.4, 3.9 Hz, 1 H), 3.85 (s, 3 H), 4.87 (dd, J = 17.8, 1.7 Hz, 1 H), 4.90 (dd,
J = 10.1, 1.7 Hz, 1 H), 5.64 (ddd, J = 17.8, 10.1, 8.0 Hz, 1 H), 6.68 (d, J = 7.6 Hz, 1 H), 6.69 (dd,
13
J = 7.6, 1.6 Hz, 1 H), 6.77 (dd, J = 7.6, 1.2 Hz, 1 H), 6.83 (dm, J = 7.6 Hz, 1 H); C-NMR (CDCl3,
major-isomer) δ 21.1, 34.9, 39.8, 53.4, 55.5, 65.1, 109.8, 111.2, 113.7, 116.9, 121.3, 137.4, 143.7,
147.0; 1H-NMR (CDCl3, minor-isomer) δ 0.99 (d, J = 6.8 Hz, 3 H), 1.54 (t, J = 6.6 Hz, 2 H), 2.31 (qm,
J = 6.8 Hz, 1 H), 3.50 (dd, J = 10.4, 5.8 Hz, 1 H), 3.55 (tdm, J = 6.6, 3.9 Hz, 1 H), 3.72 (dd, J = 10.4,
3.9 Hz, 1 H), 3.85 (s, 3 H), 4.87 (dd, J = 17.8, 1.7 Hz, 1 H), 4.90 (dd, J = 10.1, 1.7 Hz, 1 H), 5.64 (ddd,
J = 17.8, 10.1, 8.0 Hz, 1 H), 6.68 (d, J = 7.6 Hz, 1 H), 6.69 (dd, J = 7.6, 1.6 Hz, 1 H), 6.77 (dd, J = 7.6,
13
1.2 Hz, 1 H), 6.83 (dm, J = 7.6 Hz, 1 H); C-NMR (CDCl3, minor-isomer) δ 21.1, 35.0, 39.8, 53.4,
55.6, 65.1, 109.8, 111.2, 113.7, 116.9, 121.3, 137.4, 143.8, 147.0; HRMS, calcd for C14H21NO2:
235.1572. Found m/z (relative intensity): 235.1568 (M+, 29), 205.1415 (19), 204.1378 (100).
(2R,4S)-2-(4-Bromophenylamino)-4-methyl-5-hexenol (1m). IR (neat) 3400 (s), 2927 (s), 2868 (s),
1
2362 (m), 2345 (s), 1593 (s), 1496 (s), 1317 (s), 1074 (s), 916 (m), 812 (s) cm−1; H-NMR (CDCl3)
δ1.01 (d, J = 6.6 Hz, 3 H), 1.50 (m, 2 H), 2.02 (br, 1 H), 2.30 (m, 1 H), 3.48 (m, 2 H), 3.71 (dd,
J = 13 6.2 Hz, 1 H), 4.88 (dd, J = 23, 1.2 Hz, 1 H), 4.92 (dd, J = 16, 1.2 Hz, 1 H), 5.62 (ddd, J = 17.0,
10.2, 8.1 Hz, 1 H), 6.49 (d, J = 9.0 Hz, 2 H), 7.21 (d, J = 9.0 Hz, 2 H); 13C-NMR (CDCl3) δ 21.0, 34.9,
38.5, 53.4, 64.8, 109.0, 113.9, 115.0, 131.8, 143.5, 146.7; HRMS, calcd for C13H18BrNO: 283.0572.
Found m/z (relative intensity): 283.0562 (M+, 25), 254.0476 (100).

Molecules 2014, 19
9299
(2R,4S)-2-(4-Methoxyphenylamino)-8-methyl-4-vinylnon-7-enol (1n). IR (neat) 3368 (s), 3078 (m),
1
2916 (s), 1607 (m), 1514 (s), 1375 (s), 1240 (s), 1042 (s), 914 (s), 820 (s) cm−1; H-NMR (CDCl3) δ
1.33 (m, 2 H), 1.46 (dd, J = 10.1, 4.4 Hz, 2 H), 1.56 (s, 3 H), 1.67 (s, 3 H), 1.94 (m, 2 H), 2.15 (dm,
J = 4.4 Hz, 1 H), 3.44 (dd, J = 10.0, 7.4 Hz, 1 H), 3.46 (dd, J = 10.0, 5.8 Hz, 1 H), 3.69 (m, 2 H), 3.74
(s, 3 H), 4.84 (dd, J = 17.0, 2.0 Hz, 1 H), 4.99 (dd, J = 10.2, 2.0 Hz, 1 H), 5.05 (tt, J = 5.6, 1.4 Hz, 1
H), 5.49 (ddd, J = 17.0, 10.2, 9.0 Hz, 1 H), 6.65 (dd, J = 6.6, 2.3 Hz, 2 H), 6.75 (dd, J = 6.6, 2.3 Hz, 2
13
H); C-NMR (CDCl3) δ 17.7, 25.6, 25.7, 35.5, 38.1, 40.5, 55.7, 65.0, 114.8, 115.5, 115.8, 124.1,
131.4, 141.2, 142.2, 152.7; HRMS, calcd for C19H29NO2: 303.2198. Found m/z (relative intensity):
304.2201 (M++1, 11), 303.2183 (M+, 48), 273.2022 (19), 272.2000 (100).
3-(4-Methoxyphenylamino)-6-hexene-1,2-diol (1o). (a mixture of major and minor isomers in a ratio of
3:1): IR (neat) 3356 (s), 3074 (m), 2934 (s), 1666 (s), 1441 (s), 1236 (s), 1038 (s), 822 (s) cm−1;
1H-NMR (CDCl3, major-isomer) δ 1.62 (td, J = 8.7, 5.9 Hz, 2 H), 2.00–2.33 (m, 2 H), 2.60–3.00 (m, 1
H), 3.35–3.47 (m, 1 H), 3.68–3.80 (m, 2 H), 3.74 (s, 3 H), 4.95 (dd, J = 9.9, 1.5 Hz, 1 H), 4.96 (dd,
J = 17.8, 1.5 Hz, 1 H), 5.76 (ddt, J = 17.8, 9.9, 6.7 Hz, 1 H), 6.65 (dt, J = 9.3, 2.5 Hz, 2 H), 6.76 (dt,
13
J = 9.3, 2.5 Hz, 2 H); C-NMR (CDCl3, major-isomer) δ 30.3, 30.8, 55.7, 57.8, 64.0, 72.7, 114.9,
1
115.2, 115.6, 137.7, 141.1, 152.6; H-NMR (CDCl3, minor-isomer) δ 1.62 (td, J = 8.7, 5.9 Hz, 2 H),
2.00–2.33 (m, 2 H), 2.60–3.00 (m, 1 H), 3.35–3.47 (m, 1 H), 3.68–3.80 (m, 2 H), 3.74 (s, 3 H), 4.95
(dd, J = 9.9, 1.5 Hz, 1 H), 4.96 (dd, J = 17.8, 1.5 Hz, 1 H), 5.76 (ddt, J = 17.8, 9.9, 6.7 Hz, 1 H), 6.65
13
(dt, J = 9.3, 2.5 Hz, 2 H), 6.76 (dt, J = 9.3, 2.5 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 30.2,
30.8, 55.7, 57.8, 64.2, 72.6, 114.8, 115.2, 115.6, 137.7, 141.2, 152.6; HRMS, calcd for C14H21NO3:
251.1521. Found m/z (relative intensity): 252.1614 (M++1, 4), 251.1512 (M+, 30), 220.1334 (6),
191.1258 (14), 190.1187 (100).
(E)-3-(4-Methoxyphenylamino)-5-hexene-1,2-diol (1o'). (a mixture of major and minor isomers in a
ratio of 3:1): 1H-NMR (CDCl3, major-isomer) δ 1.72 (d, J = 6.8 Hz, 3 H), 2.00–2.33 (m, 2 H), 2.60–3.00
(m, 1 H), 3.35–3.47 (m, 1 H), 3.68–3.80 (m, 2 H), 3.74 (s, 3 H), 5.36–5.43 (m, 1 H), 5.48–5.55, (m, 1
H), 6.65 (dt, J = 9.3, 2.5 Hz, 2 H), 6.76 (dt, J = 9.3, 2.5 Hz, 2 H); 13C-NMR (CDCl3, major-isomer) δ
1
18.0, 33.8, 55.7, 57.4, 64.8, 72.2, 114.9, 115.2, 126.5, 128.8, 141.5, 152.8; H-NMR (CDCl3, minor-
isomer) δ 1.72 (d, J = 6.8 Hz, 3 H), 2.00–2.33 (m, 2 H), 2.60–3.00 (m, 1 H), 3.35–3.47 (m, 1 H),
3.68–3.80 (m, 2 H), 3.74 (s, 3 H), 5.36–5.43 (m, 1 H), 5.48–5.55, (m, 1 H), 6.65 (dt, J = 9.3, 2.5 Hz, 2
13
H), 6.76 (dt, J = 9.3, 2.5 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 18.0, 33.8, 55.7, 57.4, 64.7,
72.2, 114.8, 115.2, 126.5, 128.8, 141.5, 152.8.
(3R,5S)-5-Methyl-3-(phenylamino)-6-heptene-1,2-diol (1p). (a mixture of major and minor isomers in
a ratio of 2:1): IR (neat) 3281 (s), 2961 (s), 1603 (s), 1512 (s), 1325 (s), 1024 (s), 748 (s), 692 (s) cm−1;
1H-NMR (CDCl3, major-isomer) δ 1.01 (d, J = 6.8 Hz, 3 H), 1.54–1.63 (m, 2 H), 2.23–2.33 (qm,
J = 6.8 Hz, 1 H), 3.54–3.77 (m, 4 H), 4.94 (dd, J = 10.3, 1.5 Hz, 1 H), 4.98 (dd, J = 17.1, 1.5 Hz, 1 H),
5.59 (ddd, J = 17.1, 10.3, 8.3 Hz, 1 H), 6.65 (td, J = 8.5, 1.0 Hz, 2 H), 6.70–6.74 (m, 1 H), 7.15 (dt,
13
J = 8.5, 7.6 Hz, 2 H); C-NMR (CDCl3, major-isomer) δ 21.4, 34.9, 39.0, 54.3, 64.0, 73.5, 113.7,
1
117.8, 118.1, 129.2, 143.4, 147.6; H-NMR (CDCl3, minor-isomer) δ 0.97 (d, J = 6.6 Hz, 3 H), 1.47
(ddd, J = 14.0, 9.8, 4.2 Hz, 2 H), 2.23–2.33 (qm, J = 6.8 Hz, 1 H), 3.54–3.77 (m, 4 H), 4.82 (dd,

Molecules 2014, 19
9300
J = 17.3, 1.7 Hz, 1 H), 4.92 (dd, J = 9.9, 1.7 Hz, 1 H), 5.72 (ddd, J = 17.3, 9.9, 7.4 Hz, 1 H), 6.65 (td,
J = 8.5, 1.0 Hz, 2 H), 6.70–6.74 (m, 1 H), 7.15 (dt, J = 8.5, 7.6 Hz, 2 H); 13C-NMR (CDCl3, minor-isomer)
δ 21.2, 34.5, 38.2, 54.6, 63.8, 72.7, 113.8, 117.8, 118.0, 129.3, 143.9, 147.4; HRMS, calcd for
C14H21NO2: 235.1572. Found m/z (relative intensity): 236.1596 (M++1, 3), 235.1554 (M+, 12),
175.1262 (13), 174.1240 (100).
(3R,5S)-3-(4-Methoxyphenylamino)-5-methyl-6-heptene-1,2-diol (1q). (a mixture of major and minor
isomers in a ratio of 2:1): IR (neat) 3366 (s), 3078 (m), 2932 (m), 2835 (m), 1655 (s), 1238 (s), 1036
1
(s), 822 (s) cm−1; H-NMR (CDCl3, major-isomer) δ 1.00 (d, J = 6.6 Hz, 3 H), 1.48 (ddd,
J = 14.0, 9.7, 4.2 Hz, 1 H), 1.55 (ddd, J = 14.0, 9.7, 4.2 Hz, 1 H), 2.03 (br, 2 H) 2.25 (m, 1 H),
3.44–3.54 (m, 1 H), 3.74 (s, 3 H), 3.66–3.8 (m, 4 H), 4.80 (dd, J = 17.1, 1.3 Hz, 1 H), 4.91 (dd,
J = 10.5, 1.3 Hz, 1 H), 5.57 (ddd, J = 17.1, 10.5, 8.3 Hz, 1 H), 6.68 (dd, j = 6.8, 2.3 Hz, 2 H), 6.76 (dd,
13
J = 6.8, 2.3 Hz, 2 H); C-NMR (CDCl3, major-isomer) δ 21.4, 35.0, 39.0, 55.8, 56.3, 64.1, 73.1,
114.2, 114.9, 115.9, 143.5, 143.7, 152.8; 1H-NMR (CDCl3, minor-isomer) δ 0.96 (d, J = 6.6 Hz, 3 H),
1.48 (ddd, J = 14.0, 9.7, 4.2 Hz, 1 H), 1.55 (ddd, J = 14.0, 9.7, 4.2 Hz, 1 H), 2.03 (br, 2 H) 2.25 (m, 1
H), 3.44–3.54 (m, 1 H), 3.74 (s, 3 H), 3.66–3.8 (m, 4 H), 4.80 (dd, J = 17.1, 1.3 Hz, 1 H), 4.97 (dd,
J = 17.4, 1.3 Hz, 1 H), 5.67 (ddd, J = 17.4, 10.2, 7.6 Hz, 1 H), 6.68 (dd, J = 6.8, 2.3 Hz, 2 H), 6.76 (dd,
13
J = 6.8, 2.3 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 20.4, 34.7, 39.0, 55.8, 56.3, 63.8, 73.1,
115.0, 114.9, 116.1, 143.5, 143.7, 152.8; HRMS, calcd for C15H23NO3: 265.1678. Found m/z (relative
intensity): 266.1678 (M++1, 3), 265.1659 (M+, 18), 205.1406 (15), 204.1406 (100).
(3R,5S)-3-(4-Methoxyphenylamino)-9-methyl-5-vinyl-8-decene-1,2-diol (1r). (a mixture of major and
minor isomers in a ratio of 2:1): IR (neat) 3358 (s), 3074 (s), 2916 (s), 2343 (m), 1666 (s), 1514 (s),
1238 (s), 1040 (s), 822 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 1.19–1.38 (m, 4 H), 1.55 (s, 3 H),
1.67 (s, 3 H), 1.79–1.98 (dm, J = 7.5 Hz, 1 H), 2.00–2.17 (m, 2 H), 3.47 (dd, J = 12.0, 5.9 Hz, 1 H),
3.54 (dd, J = 12.0, 6.9 Hz, 1 H), 3.69–3.80 (m, 3 H), 3.74 (s, 3 H), 4.74 (dd, J = 18.6, 2.0 Hz, 1 H),
4.94–5.05 (m, 1 H), 4.98 (dd, J = 10.0, 2.0 Hz, 1 H), 5.46 (ddd, J = 18.6, 10.0, 7.5 Hz, 1 H), 6.69 (d,
J = 6.6 Hz, 2 H), 6.75–6.78 (m, 2 H); 13C-NMR (CDCl3, major-isomer) δ 17.7, 25.4, 25.6, 35.2, 35.4,
1
40.5, 55.6, 55.7, 64.0, 73.1, 114.9, 115.3, 116.2, 124.1, 124.3, 131.5, 131.6, 141.9; H-NMR (CDCl3,
minor-isomer) δ 1.19–1.38 (m, 4 H), 1.54 (s, 3 H), 1.64 (s, 3 H), 1.79–1.98 (dm, J = 7.5 Hz, 1 H),
2.00–2.17 (m, 2 H), 3.47 (dd, J = 12.0, 5.9 Hz, 1 H), 3.54 (dd, J = 12.0, 6.9 Hz, 1 H), 3.69–3.80 (m, 3
H), 3.75 (s, 3 H), 4.74 (dd, J = 18.6, 2.0 Hz, 1 H), 4.94–5.05 (m, 1 H), 4.98 (dd, J = 10.0, 2.0 Hz, 1 H),
13
5.46 (ddd, J = 18.6, 10.0, 7.5 Hz, 1 H), 6.69 (d, J = 6.6 Hz, 2 H), 6.75–6.78 (m, 2 H); C-NMR
(CDCl3, minor-isomer) δ 17.7, 25.4, 25.6, 35.2, 35.4, 40.4, 55.6, 55.7, 64.0, 73.1, 114.8, 115.3, 116.3,
124.1, 124.3, 131.4, 131.6, 141.8; HRMS, calcd for C20H31NO3: 333.2304. Found m/z (relative
intensity): 334.2348 (M++1, 7), 333.2312 (M+, 33), 302.2102 (4), 273.2012 (20), 272.2004 (100).
(2S, 3S, 5S)-5-(4-Methoxyphenylamino)-8-nonen-1,2,3-triol (1s). (a mixture of major and minor
isomers in a ratio of 1:1): IR (neat) 3277 (m), 2932 (s), 2839 (s), 1732 (s), 1514 (s), 1456 (s), 1441 (s),
1
1238 (s), 1040 (s), 970 (s), 912 (m), 824 (s) cm−1; H-NMR (CDCl3, major-isomer) δ 1.43 (m, 2 H),
1.87 (dt, J = 11.5, 3.2 Hz, 2 H), 2.15–2.30 (br d, J = 6.8 Hz, 2 H), 3.51–3.62 (m, 4 H), 3.61 (br t,
J = 3.2 Hz, 1 H), 3.74 (s, 3 H), 3.93–4.01 (m, 1 H), 4.95 (dd, J = 11.2, 1.6 Hz, 1 H), 4.98 (dd, J = 18.1,

Molecules 2014, 19
9301
1.6 Hz, 1 H), 5.78 (ddd, J = 18.1, 11.2, 6.8 Hz, 1 H), 6.70 (d, J = 8.8 Hz, 2 H), 6.77 (d, J = 8.8 Hz, 2 H);
13C-NMR (CDCl3, major-isomer) δ 28.7, 32.7, 36.5, 55.7, 56.8, 63.7, 71.3, 74.6, 114.5, 114.8, 118.3,
138.5, 141.1, 153.2; 1H-NMR (CDCl3, minor-isomer) δ 1.43 (m, 2 H), 1.87 (dt, J = 11.5, 3.2 Hz, 2 H),
2.15–2.30 (br d, J = 6.8 Hz, 2 H), 3.51–3.62 (m, 4 H), 3.61 (br t, J = 3.2 Hz, 1 H), 3.74 (s, 3 H), 3.93–4.01
(m, 1 H), 4.95 (dd, J = 11.2, 1.6 Hz, 1 H), 4.98 (dd, J = 18.1, 1.6 Hz, 1 H), 5.78 (ddd, J = 18.1, 11.2,
6.8 Hz, 1 H), 6.70 (d, J = 8.8 Hz, 2 H), 6.77 (d, J = 8.8 Hz, 2 H); 13C-NMR (CDCl3, minor-isomer) δ
28.7, 32.7, 36.1, 55.7, 56.8, 63.7, 71.3, 74.7, 114.6, 114.8, 118.5, 138.5, 141.1, 153.3; HRMS, calcd
for C16H25NO4: 295.1783. Found m/z (relative intensity): 296.1817 (M++1, 21), 295.1776 (M+, 100),
294.1700 (5).
(2S, 3S, 5S)-5-(4-Methoxyphenylamino)-7-nonen-1,2,3-triol (1s'). (a mixture of major and minor
isomers in a ratio of 3:1): 1H-NMR (CDCl3, major-isomer) δ 1.43 (m, 2 H), 1.87 (dt, J = 11.5, 3.2 Hz, 2 H),
2.15–2.30 (m, 2 H), 2.03 (d, J = 7.3 Hz, 3 H), 3.51–3.62 (m, 4 H), 3.61 (br t, J = 3.2 Hz, 1 H), 3.74 (s,
3 H), 3.93–4.01 (m, 1 H), 5.32 (dq, J = 14.6, 7.3 Hz, 1 H), 5.46 (dt, J = 14.6, 6.6 Hz, 1 H), 6.70 (d,
J = 8.8 Hz, 2 H), 6.77 (d, J = 8.8 Hz, 2 H); 13C-NMR (CDCl3, major-isomer) δ 18.0, 32.5, 37.7, 52.7,
1
55.7, 63.9, 71.1, 74.1, 114.9, 116.9, 125.5, 130.6, 140.8, 154.0; H-NMR (CDCl3, minor-isomer) δ
1.43 (m, 2 H), 1.87 (dt, J = 11.5, 3.2 Hz, 2 H), 2.15–2.30 (m, 2 H), 2.03 (d, J = 7.3 Hz, 3 H), 3.51–3.62
(m, 4 H), 3.61 (br t, J = 3.2 Hz, 1 H), 3.74 (s, 3 H), 3.93–4.01 (m, 1 H), 5.32 (dq, J = 14.6, 7.3 Hz, 1
13
H), 5.46 (dt, J = 14.6, 6.6 Hz, 1 H), 6.70 (d, J = 8.8 Hz, 2 H), 6.77 (d, J = 8.8 Hz, 2 H); C-NMR
(CDCl3, minor-isomer) δ 18.0, 32.5, 37.4, 52.7, 55.7, 63.9, 71.1, 74.3, 114.9, 117.0, 125.2, 130.7,
140.8, 154.0.
(2S, 3S, 5S, 7S)-5-(4-Methoxyphenylamino)-7-methyl-8-nonen-1,2,3-triol (1t). (a mixture of major and
minor isomers in a ratio of 2:1): IR (neat) 3267 (s), 2835 (s), 1639 (m), 1616 (m), 1417 (s), 1238 (s),
1180 (s), 1038 (s), 914 (s), 824 (s), 606 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 1.00 (d, J = 6.6 Hz,
3 H), 1.46–1.64 (m, 4 H), 1.88 (ddd, J = 14.4, 8.5, 3.4 Hz, 1 H), 2.26–2.33 (br-d, J = 7.3 Hz, 1 H),
3.48–3.80 (m, 3 H), 3.75 (s, 3 H), 3.97 (ddd, J = 11.5, 5.6, 2.9 Hz, 1 H), 4.89 (dd, J = 17.2, 1.0 Hz,
1 H), 4.91 (dd, J = 9.7, 1.7 Hz, 1 H), 5.65 (ddd, J = 17.2, 9.7, 7.3 Hz, 1 H), 6.66 (d, J = 9.0 Hz, 2 H),
13
6.77 (d, J = 9.0 Hz, 2 H); C-NMR (CDCl3, major-isomer) δ 20.7, 35.1, 37.4, 42.6, 51.2, 55.8, 63.9,
71.3, 74.0, 113.5, 114.9, 116.2, 141.0, 144.0, 153.0; 1H-NMR (CDCl3, minor-isomer) δ 0.94 (d, J = 6.8 Hz,
3 H), 1.46–1.64 (m, 4 H), 1.91 (ddd, J = 14.4, 8.5, 3.4 Hz, 1 H), 2.26–2.33 (br-d, J = 7.3 Hz, 1 H),
3.48–3.80 (m, 3 H), 3.75 (s, 3 H), 3.97 (ddd, J = 11.5, 5.6, 2.9 Hz, 1 H), 4.89 (dd, J = 17.2, 1.0 Hz,
1 H), 4.91 (dd, J = 9.7, 1.7 Hz, 1 H), 5.65 (ddd, J = 17.2, 9.7, 7.3 Hz, 1 H), 6.67 (d, J = 10.5 Hz, 2 H),
6.69 (d, J = 10.2 Hz, 2 H); 13C-NMR (CDCl3, minor-isomer) δ 20.7, 34.9, 37.2, 43.2, 51.6, 55.7, 63.8,
71.3, 74.2, 113.5, 114.9, 116.2, 141.0, 144.2, 153.0; HRMS, calcd for C17H27NO4: 309.1940. Found
m/z (relative intensity): 310.1951 (M++1, 19), 309.1932 (M+, 100), 248.1652 (12), 247.1566 (5).
(2S, 3S, 5S, 7S)-5-(2-Methoxyphenylamino)-7-methyl-8-nonen-1,2,3-triol (1u). (a mixture of major and
minor isomers in a ratio of 2:1): IR (neat) 3379 (s), 3071 (s), 2932 (s), 2360 (s), 1596 (s), 1512 (s),
1458 (s), 1227 (s), 1026 (s), 910 (s), 733 (s), 679 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 0.99 (d,
J = 6.6 Hz, 3 H), 1.42–1.52 (br d, J = 6.6 Hz, 4 H), 2.22–2.27 (br d, J = 6.6 Hz, 1 H), 3.42–3.43 (m,
1 H), 3.57–3.58 (m, 2 H), 3.76–3.78 (m, 3 H), 3.77 (s, 3 H), 4.01 (br, 3 H), 4.83 (d, J = 17.3 Hz, 1 H),

Molecules 2014, 19
9302
4.86 (d, J = 10.0 Hz, 1 H), 5.62 (ddd, J = 17.3, 10.0, 7.5 Hz, 1 H), 6.56–6.64 (m, 1 H), 6.70–6.72 (m,
13
2 H), 6.78 (t, J = 7.6 Hz, 1 H); C-NMR (CDCl3, major-isomer) δ 20.5, 34.7, 38.4, 43.3, 48.4, 55.3,
63.1, 70.1, 74.5, 109.7, 110.8, 113.1, 116.2, 121.2, 137.6, 143.9, 146.6; 1H-NMR (CDCl3, minor-isomer)
δ 0.95 (d, J = 6.3 Hz, 3 H), 1.65–1.78 (m, 4 H), 2.22–2.27 (br d, J = 6.6 Hz, 1 H), 3.42–3.43 (m, 1 H),
3.57–3.58 (m, 2 H), 3.76–3.78 (m, 3 H), 3.77 (s, 3 H), 4.01 (br, 3 H), 4.83 (d, J = 17.3 Hz, 1 H), 4.86
(d, J = 10.0 Hz, 1 H), 5.62 (ddd, J = 17.3, 10.0, 7.5 Hz, 1 H), 6.56–6.64 (m, 1 H), 6.70–6.72 (m, 2 H),
13
6.78 (t, J = 7.6 Hz, 1 H); C-NMR (CDCl3, minor-isomer) δ 20.7, 34.6, 38.4, 43.3, 48.2, 55.3, 63.1,
70.1, 74.5, 109.7, 110.8, 113.2, 116.4, 121.2, 137.5, 143.9, 146.6; HRMS, calcd for C17H27NO4:
309.1940. Found m/z (relative intensity): 309.1922 (M+, 100).
(2S, 3S, 5S, 7S)-5-(3,4-Dimethoxyphenylamino)-7-methyl-8-nonen-1,2,3-triol (1v). (a mixture of major
and minor isomers in a ratio of 2:1):IR (neat) 3379 (s), 3078 (m), 2932 (s), 1705 (m), 1612 (s), 1458
(s), 1234 (s), 1026 (s), 918 (m), 733 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ 1.00 (d, J = 6.6 Hz, 3 H),
1.45–1.63 (m, 4 H), 1.86 (ddd, J = 14.2, 9.3, 3.2 Hz, 1 H), 2.20–2.40 (m, 1 H), 3.12 (br, 1 H), 3.56 (br
dd, J = 9.5, 5.4 Hz, 1 H), 3.75 (m, 2 H), 3.80 (s, 3 H), 3.82 (s, 3 H), 3.95 (ddd, J = 8.8, 5.4, 3.1 Hz, 1 H),
4.90 (d, J = 17.1 Hz, 1 H), 4.92 (d, J = 10.5 Hz, 1 H), 5.65 (ddd, J = 17.1, 10.5, 7.9 Hz, 1 H), 6.23 (dd,
J = 8.5, 2.4 Hz, 1 H), 6.32 (d, J = 2.4 Hz, 1 H), 6.72 (d, J = 8.5 Hz, 1 H); 13C-NMR (CDCl3, major-isomer)
δ 20.7, 35.0, 37.7, 42.7, 50.8, 55.8, 56.6, 56.8, 63.6, 70.9, 100.5, 105.7, 113.4, 122.3, 132.3, 141.7,
1
144.0, 149.9; H-NMR (CDCl3, minor-isomer) δ 0.96 (d, J = 6.8 Hz, 3 H), 1.45–1.63 (m, 4 H), 1.95
(ddd, J = 14.4, 8.8, 3.2 Hz, 1 H), 2.20–2.40 (m, 1 H), 3.12 (br, 1 H), 3.56 (br dd, J = 9.5, 5.4 Hz, 1 H),
3.75 (m, 2 H), 3.80 (s, 3 H), 3.82 (s, 3 H), 4.00 (m, 1 H), 4.88 (d, J = 18.8 Hz, 1 H), 4.98 (br d,
J = 10.8 Hz, 1 H), 5.58 (ddd, J = 18.8, 10.8, 8.0 Hz, 1 H), 6.29 (dt, J = 8.5, 2.4 Hz, 1 H), 6.34 (d,
J = 2.4 Hz, 1 H), 6.74 (d, J = 8.5 Hz, 1 H); 13C-NMR (CDCl3, minor-isomer) δ 20.7, 35.0, 37.7, 42.7,
50.8, 55.8, 56.6, 56.8, 63.6, 70.9, 100.5, 105.7, 113.4, 122.3, 132.3, 141.7, 144.0, 149.9; HRMS, calcd
for C18H29NO5: 339.2046. Found m/z (relative intensity): 340 (M++1, 24), 339.2039 (M+, 100),
324 (7), 321 (3).
(2S, 3S, 5S, 7S)-5-Phenylamino-7-methyl-8-nonen-1,2,3-triol (1w). (a mixture of major and minor
isomers in a ratio of 2:1): IR (neat) 3400 (s), 2870 (s), 1639 (s), 1602 (s), 1502 (s), 1259 (s), 1180 (s),
1
993 (s), 873 (s), 754 (s), 667 (s) cm−1; H-NMR (CDCl3, major-isomer) δ 1.01 (d, J = 6.8 Hz, 3 H),
1.52–1.58 (m, 4 H), 1.85 (ddd, J = 14.4, 9.3, 3.4 Hz, 2 H), 2.28–2.35 (br d, J = 7.2 Hz, 1 H), 3.55 (br d,
J = 9.3 Hz, 1 H), 3.77 (m, 3 H), 3.95 (ddd, J = 9.3, 5.4, 2.7 Hz, 1 H), 4.88 (dt, J = 17.4, 1.0 Hz, 1 H),
4.92 (dt, J = 9.9, 0.9 Hz, 1 H), 5.65 (ddd, J = 17.4, 9.9, 7.5 Hz, 1 H), 6.65 (dd, J = 8.5, 1.0 Hz, 2 H),
13
6.70 (dd, J = 8.5, 7.3 Hz, 1 H), 7.16 (dd, J = 8.5, 7.3 Hz, 2 H); C-NMR (CDCl3, major-isomer) δ
1
20.9, 35.1, 38.1, 43.1, 49.5, 63.7, 71.0, 74.1, 113.9, 114.5, 129.3, 144.0, 147.5; H-NMR (CDCl3,
minor-isomer) δ 0.97 (d, J = 6.8 Hz, 3 H), 1.52–1.58 (m, 4 H), 1.85 (ddd, J = 14.4, 9.3, 3.4 Hz, 2 H),
2.28–2.35 (br d, J = 7.2 Hz, 1 H), 3.55 (br d, J = 9.3 Hz, 1 H), 3.77 (m, 3 H), 3.95 (ddd, J = 9.3, 5.4,
2.7 Hz, 1 H), 4.88 (dt, J = 17.4, 1.0 Hz, 1 H), 4.92 (dt, J = 9.9, 0.9 Hz, 1 H), 5.59 (br dd, J = 9.6,
7.5 Hz, 1 H), 6.65 (dd, J = 8.5, 1.0 Hz, 2 H), 6.70 (dd, J = 7.6, 6.8 Hz, 1 H), 7.16 (dd, J = 8.5, 7.3 Hz, 2 H);
13C-NMR (CDCl3, minor-isomer) δ 20.9, 35.0, 38.1, 43.1, 49.5, 63.7, 71.0, 74.1, 113.6, 115.5, 129.3,
144.0, 147.5; HRMS, calcd for C16H25NO3: 279.1834. Found m/z (relative intensity): 280.1877 (M++1,
19), 279.1831 (M+, 100), 278.1753 (4), 248.1628 (6), 217.1507 (3).

Molecules 2014, 19
9303
(2S, 3S, 5S, 7S)-4-(4-Chlorophenylamino)-7-methyl-8-nonen-1,2,3-triol (1x). (a mixture of major and
minor isomers in a ratio of 2:1): IR (neat) 3364 (s), 3078 (s), 2924 (s), 2361 (s), 1705 (s), 1597 (s),
1504 (s), 1319 (s), 1258 (s), 1180 (s), 918 (s), 818 (s), 671 (s) cm−1; 1H-NMR (CDCl3, major-isomer) δ
0.91 (d, J = 6.6 Hz, 3 H), 1.38 (t, J = 6.6 Hz, 2 H), 1.18–1.60 (m, 2 H), 2.18 (br quint, d, J = 6.6 Hz, 1 H),
3.34–3.39 (m, 1 H), 3.49–3.57 (m, 3 H), 3.70–3.72 (m, 2 H), 3.78 (br, 3 H), 4.76 (d, J = 17.2 Hz, 1 H),
4.83 (d, J = 10.2 Hz, 1 H), 5.52 (ddd, J = 17.2, 10.2, 7.9 Hz, 1 H), 6.46 (d, J = 8.8 Hz, 2 H), 6.97 (d,
13
J = 8.8 Hz, 2 H); C-NMR (CDCl3, major-isomer) δ 20.0, 34.9, 38.4, 43.1, 49.2, 63.1, 70.2, 74.5,
113.6, 114.5, 121.6, 129.0, 143.9, 146.5; 1H-NMR (CDCl3, minor-isomer) δ 0.88 (d, J = 6.8 Hz, 3 H),
1.38 (t, J = 6.6 Hz, 2 H), 1.18–1.60 (m, 2 H), 2.18 (br quint, d, J = 6.6 Hz, 1 H), 3.34–3.39 (m, 1 H),
3.49–3.57 (m, 3 H), 3.70–3.72 (m, 2 H), 3.78 (br, 3 H), 4.76 (d, J = 17.2 Hz, 1 H), 4.83 (d, J = 10.2 Hz,
1 H), 5.52 (ddd, J = 17.2, 10.2, 7.9 Hz, 1 H), 6.51 (d, J = 8.8 Hz, 2 H), 7.02 (d, J = 8.8 Hz, 2 H);
13C-NMR (CDCl3, minor-isomer) δ 21.0, 34.8, 38.4, 42.7, 49.2, 63.1, 70.2, 74.4, 113.7, 114.5, 121.6,
129.1, 143.8, 146.5; HRMS, calcd for C16H24ClNO3: 313.1445. Found m/z (relative intensity):
314.1446 (M++1, 6), 313.1418 (M+, 29), 245.0748 (13), 244.0726 (100).
(2S, 3S, 5S, 7S)-5-(4-Methoxyphenylamino)-7-vinyl-11-dodecen-1,2,3-triol (1y). (a mixture of major
and minor isomers in a ratio of 1:1): IR (neat) 3300 (m), 2912 (s), 2835 (s), 1639 (s), 1618 (s), 1500
1
(s), 1456 (s), 1294 (s), 1238 (s), 1180 (s), 1039 (s), 916 (s), 821 (s), 748 (s) cm−1; H-NMR (CDCl3,
major-isomer) δ 1.18–1.36 (m, 2 H), 1.46–1.71 (m, 2 H), 1.56 (s, 3 H), 1.67 (s, 3 H), 1.82–2.00 (m, 2
H), 1.91 (ddd, J = 14.1, 9.2, 3.7 Hz, 2 H), 2.04–2.16 (m, 1 H), 3.53–3.59 (br dd, J = 9.2, 5.3 Hz, 1 H),
3.62–3.65 (br d, J = 3.7 Hz, 1 H), 3.71–3.85 (m, 2 H), 3.75 (s, 3 H), 3.95–4.00 (m, 1 H), 4.86 (dd,
J = 17.1, 1.7 Hz, 1 H), 4.99 (dd, J = 10.1, 1.7 Hz, 1 H), 5.02–5.06 (t m, J = 7.1 Hz, 1 H), 5.49 (ddd,
13
J = 17.1, 10.1, 7.1 Hz, 1 H), 6.67 (d, J = 8.9 Hz, 2 H), 6.76 (d, J = 8.9 Hz, 2 H); C-NMR (CDCl3,
major-isomer) δ 17.8, 25.6, 25.8, 35.4, 37.6, 40.7, 41.1, 51.6, 55.8, 63.8, 71.4, 74.1, 114.9, 115.5,
1
116.5, 124.2, 131.5, 142.6, 142.8, 153.2; H-NMR (CDCl3, minor-isomer) δ 1.18–1.36 (m, 2 H),
1.46–1.71 (m, 2 H), 1.56 (s, 3 H), 1.67 (s, 3 H), 1.82–2.00 (m, 2 H), 1.91 (ddd, J = 14.1, 9.2, 3.7 Hz,
2 H), 2.04–2.16 (m, 1 H), 3.53–3.59 (br dd, J = 9.2, 5.3 Hz, 1 H), 3.62–3.65 (br d, J = 3.7 Hz, 1 H),
3.71–3.85 (m, 2 H), 3.75 (s, 3 H), 3.95–4.00 (m, 1 H), 4.80 (dd, J = 17.6, 1.6 Hz, 1 H), 4.97 (dd,
J = 10.2, 1.6 Hz, 1 H), 5.02–5.06 (t m, J = 7.1 Hz, 1 H), 5.49 (ddd, J = 17.1, 10.1, 7.1 Hz, 1 H), 6.67
13
(d, J = 8.9 Hz, 2 H), 6.78 (d, J = 9.0 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 17.8, 25.4, 25.7,
35.4, 37.6, 40.7, 41.1, 51.6, 55.7, 63.8, 71.4, 74.2, 114.8, 115.5, 116.5, 124.2, 131.5, 142.6, 142.8,
153.8; HRMS, calcd for C22H35NO4: 377.2566. Found m/z (relative intensity): 377.2561 (M+, 100).
General procedure for the Ni-catalyzed homoallylation of N,O-acetals prepared from carbohydrate
and primary amines with dienes (entry 8, Table 4): A solution of D-ribose (150 mg, 1 mmol) and
p-anisidine (246 mg, 2 mmol) in dry DMF (5 mL) was refluxed for 120 min under nitrogen. The
solvent was removed by distillation under reduced pressure (azeotropic removal of water). A mixture
of Ni(cod)2 (27.5 mg, 0.1 mmol) and isoprene (800 μL, 8 mmol) dissolved in THF (2 mL) and
triethylborane (6.0 mmol, 1.0 M THF solution) were successively added to the flask containing N,O-acetal.
The reaction mixture was stirred at 50 °C for 48 h, and the reaction mixture was diluted with 30 mL of
EtOAc and washed with sat. NaHCO3, and brine. The organic phase was dried (MgSO4) and
concentrated in vacuo to give a colorless oil, which was subjected to column chromatography

Molecules 2014, 19
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over silica gel (hexane/EtOAc = 0/100 v/v) to give 2 (192 mg, 57%) in a 2:1 ratio. Rf = 0.30
(hexane/EtOAc = 0/100 v/v).
5-[(4-Methoxyphenyl)amino]-7-methylnon-8-ene-1,2,3,4-tetraol (2). (a mixture of major and minor
isomers in a ratio of 2:1): IR (neat) 3400 (m), 2930 (m), 1653 (s), 1539 (s), 1456 (s), 1231 (s), 1180 (s),
1
1038 (s), 916 (s), 829 (s), 735 (s), 667 (s) cm−1; H-NMR (CDCl3, major-isomer) δ 0.98 (d,
J = 6.6 Hz, 3 H), 1.48–1.57 (br d, J = 13.8 Hz, 2 H), 1.74 (ddd, J = 13.8, 10.4, 2.9 Hz, 1 H), 2.27–2.29
(br d, J = 7.7 Hz, 1 H), 3.61–3.69 (m, 2 H), 3.74 (s, 3 H), 3.76–3.90 (m, 3 H), 4.82 (d, J = 17.1 Hz, 1 H),
4.92 (dd, J = 10.2, 1.7 Hz, 1 H), 5.60 (ddd, J = 17.1, 10.2, 7.7 Hz, 1 H), 6.78 (d, J = 10.6 Hz, 2 H), 6.79
(d, J = 10.6 Hz, 2 H); 13C-NMR (CDCl3, major-isomer) δ 21.7, 35.2, 37.0, 55.9, 57.5, 63.6, 73.0, 73.4,
73.9, 114.4, 115.0, 117.4, 143.9, 153.9, 162.5; 1H-NMR (CDCl3, minor-isomer) δ 0.96 (d, J = 6.8 Hz,
3 H), 1.48–1.57 (br d, J = 13.8 Hz, 2 H), 1.74 (ddd, J = 13.8, 10.4, 2.9 Hz, 1 H), 2.27–2.29 (br d,
J = 7.7 Hz, 1 H), 3.61–3.69 (m, 2 H), 3.75 (s, 3 H), 3.76–3.90 (m, 3 H), 4.82 (d, J = 17.1 Hz, 1 H),
4.91 (d, J = 11.2 Hz, 1 H), 5.60 (ddd, J = 17.1, 10.2, 7.7 Hz, 1 H), 6.78 (d, J = 10.6 Hz, 2 H), 6.79 (d,
13
J = 10.6 Hz, 2 H); C-NMR (CDCl3, minor-isomer) δ 21.7, 34.9, 36.6, 55.9, 57.5, 63.6, 73.2, 73.7,
73.9, 114.4, 115.1, 117.8, 144.2, 153.9, 162.5; HRMS, calcd for C17H27NO5: 325.1889. Found m/z
(relative intensity): 326.1940 (M++1, 20), 325.1873 (M+, 100).
(2R, 3S, 4R, 6S, 8S)-6-(4-Methoxyphenylamino)-8-methyl-9-decen-1,2,3,4-tetraol (3). (a mixture of
major and minor isomers in a ratio of 1:1): IR (KBr) 3285 (s), 2937 (m), 2924 (m), 1514 (s), 1412 (m),
1240 (s), 1074 (s), 1040 (s), 822 (w), 640 (w) cm−1; 1H-NMR (CDCl3, major-isomer) δ 1.00 (d, J = 6.8 Hz,
3 H), 1.44–1.62 (m, 4 H), 2.04–2.11 (ddd, J = 5.1, 9.3, 12.7, 1 H), 2.26 (br d, J = 7.5 Hz, 1 H),
3.51–3.83 (m, 5 H), 3.74 (s, 3 H), 4.16–4.20 (m, 1 H), 4.89 (d, J = 18.0 Hz, 1 H), 4.92 (d, J = 10.5 Hz,
1 H), 5.63 (ddd, J = 17.1, 10.2, 7.8 Hz, 1 H), 6.73 (d, J = 9.0 Hz, 2 H), 6.77 (d, J = 9.0 Hz, 2 H);
13C-NMR (CDCl3, major-isomer) δ 20.8, 35.2, 37.9, 42.5, 51.7, 55.9, 64.0, 68.9, 72.9, 74.7, 113.7,
1
115.0, 116.7, 140.8, 144.1, 153.3; H-NMR (CDCl3, minor-isomer) δ 0.93 (d, J = 6.8 Hz, 3 H),
1.44–1.62 (m, 4 H), 2.04–2.11 (ddd, J = 5.1, 9.3, 12.7, 1 H), 2.26 (br d, J = 7.5 Hz, 1 H), 3.51–3.83 (m,
5 H), 3.76 (s, 3 H), 4.16–4.20 (m, 1 H), 4.88 (d, J = 17.3 Hz, 1 H), 4.97 (d, J = 9.3 Hz, 1 H), 5.63 (ddd,
J = 17.1, 10.2, 7.8 Hz, 1 H), 6.72 (d, J = 10.7 Hz, 2 H), 6.79 (d, J = 9.0 Hz, 2 H); 13C-NMR (CDCl3,
minor-isomer) δ 20.6, 35.0, 37.6, 42.9, 51.7, 55.5, 64.2, 68.9, 73.0, 74.3, 113.5, 115.0, 116.7, 140.8,
144.3, 153.3; HRMS, calcd for C18H29NO5: 339.2046. Found m/z (relative intensity): 340.2072 (M++1,
20), 339.2037 (M+, 100).
4. Conclusions
Homoallylation of N,O-acetals prepared from cyclic hemiacetals and primary amines provided
hydroxyhomoallylamines in the presence of a Ni-catalyst and triethylborane. N,O-Acetals prepared
from glycolaldehyde dimer and glyceraldehyde dimer with primary amines underwent homoallylation
with conjugated dienes to give 2-amino-5-hexenols. Under similar conditions, N,O-acetals from
carbohydrates with primary amines provided polyhydroxybishomoallylamines in good to reasonable
yields. These reactions can be applied to the efficient synthesis of physiologically active molecules,
such as polyhydroxyamines, terpenes, and neurotransmitters, from non-protected carbohydrates.

Molecules 2014, 19
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Supplementary Materials
Supplementary materials can be accessed at: : http://www.mdpi.com/1420-3049/19/7/9288/s1.
Acknowledgments
This work was supported by a Grant-in-Aid Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan (MEXT).
Author Contributions
TM, YA, GO, and MK designed research; TM and YA performed research and analyzed the data;
TM and MK wrote the paper. All authors read and approved the final manuscript.
Conflicts of Interest
The authors declare no conflict of interest.
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