One-pot synthesis of trisubstituted 1,2-amino alcohols from deprotonated α-amino nitriles

Article abstract of DOI:10.1002/ejoc.200701205

A short synthesis of N,1,2-trisubstituted vicinal amino alcohols by 1,2-addition of deprotonated N-monosubstituted α-amino nitriles to aldehydes and subsequent one-pot reduction of the intermediates with borane-THF is described. This procedure leads to the predominant formation of the anti-configured products. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200701205

FULL PAPER
DOI: 10.1002/ejoc.200701205
One-Pot Synthesis of Trisubstituted 1,2-Amino Alcohols from Deprotonated
α-Amino Nitriles
Coralie Kison[a] and Till Opatz*[b]
Keywords: Amino alcohols / Umpolung / Amino nitriles / Reduction
A
short synthesis of N,1,2-trisubstituted vicinal amino
This procedure leads to the predominant formation of the
alcohols by 1,2-addition of deprotonated N-monosubstituted
anti-configured products.
α-amino nitriles to aldehydes and subsequent one-pot re- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
duction of the intermediates with borane–THF is described.
Germany, 2008)
nitriles and aldehydes that does not require protecting-
group manipulations. Owing to the anion-stabilizing effect
of the nitrile function, α-amino nitriles can serve as readily
accessible α-amino carbanion equivalents.[22] Stork et al.
used the addition of deprotonated Strecker products to al-
dehydes for the preparation of 1,2-amino alcohols.[23] In
this case, however, an N-acyl protecting group was used to
prevent the undesired elimination of HCN, that is, the retro-
Strecker reaction, during the deprotonation of the pronu-
cleophile.
Introduction
Vicinal amino alcohols are prominent members of the
large class of 1,2-difunctional compounds. They can be
found in nature where they play for instance a role as neuro-
transmitters, hormones or constituents of enzyme inhibi-
tors. Some synthetic 1,2-amino alcohols are used as antiret-
roviral or antimalarial[1] agents or as drugs that interfere
with noradrenergic signal transmission.[2] Moreover, they
can serve as useful synthetic intermediates for the prepara-
tion of heterocyclic compounds. Chiral vicinal amino
alcohols are used as ligands in asymmetric catalysis as well
as in the preparation of chiral auxiliaries.[3–5] Owing to their
versatility in a range of applications, miscellaneous methods
have been developed for the preparation of vicinal amino
alcohols,[6] including the reduction of amino acids,[7,8] α-
amino ketones[9–11] or nitro alcohols,[12] nucleophilic ad-
dition to α-amino aldehydes,[13] cyanohydrins[14] or α-hy-
droxyimines,[15] the opening of epoxides with nitrogen nu-
cleophiles[16,17] and many more.
Methods for the formation of the central C–C bond of a
1,2-amino alcohol are also known, the most important one
being the addition of nitronates to aldehydes.[18–20] This re-
action can also be conducted in an asymmetric fashion but
its scope is limited by the availability of suitably substituted
nitroalkanes.[21] An alternative route is the 1,2-addition of
α-metallated amines to aldehydes. In this case, however,
protection of the amine nitrogen is required if products with
a primary or secondary amino function are to be obtained.
Herein, we describe a short access to N,1,2-trisubstituted
vicinal amino alcohols from N-monosubstituted α-amino
Results and Discussion
We found that N-mono- and even N-unsubstituted α-
amino nitriles can be quantitatively deprotonated without
inducing the elimination of HCN if an aromatic, heteroaro-
matic or olefinic α-substituent is present. The resulting sta-
bilized α-amino carbanions readily undergo 1,4-additions
to α,β-unsaturated aldehydes, ketones and esters, whereas
their 1,2-addition to imines furnishes enediamines.[24–26]
The latter reaction can be understood by the intermediate
formation of an amide anion followed by intramolecular
elimination of HCN. In contrast, the addition of α-depro-
tonated Strecker products to non-enolizable aldehydes is
not immediately accompanied by the retro-Strecker reac-
tion. Presumably, the basicity of the resulting alkoxide is
not sufficient to effect abstraction of the vicinal N–H pro-
ton. The resulting intermediates 4 can be isolated but de-
compose slowly at ambient temperature. To convert them
to the 1,2-amino alcohols 5 without prior isolation
(Scheme 1), we tested several reduction methods. Although
the reductive decyanation of 4 with NaCNBH3 and acetic
acid, which gave the best results in other cases,[27] turned
out to be sluggish and inefficient, we found, in particular,
the borane–THF complex to be well suited for this purpose.
In accordance with a chelate model for the transition state
of the reduction of the α-hydroxyimine formed upon spon-
[a] Institut für Organische Chemie, Johannes Gutenberg Uni-
versität Mainz,
Duesbergweg 10–14, 55128 Mainz, Germany
[b] Institut für Organische Chemie, Universität Hamburg,
Martin-Luther-King Platz 6, 20146 Hamburg, Germany
Fax: +49-40-42838-3834
E-mail: opatz@chemie.uni-hamburg.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
2740
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2740–2745

1,2-Amino Alcohols from α-Amino Nitriles
Table 1. Preparation of amino alcohols from α-amino nitriles.
Nr.
Nitrile
R1
R2
Aldehyde
R3
Product
% Yield[a]
dr (anti/syn)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1c
1d
1d
1d
1e
Ph2CH
Ph2CH
Ph2CH
Ph2CH
Me
Me
Me
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
iPr
iPr
iPr
Ph
Ph
Ph
Ph
2-naphth
2-naphth
2-naphth
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3a
3b
3c
3a
3b
3c
3e
3a
3b
3c
3e
Ph
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
74
61
68
56
52
58
48
55
78
63
76
54
47
32
34
3.2:1
4.0:1
3.0:1
2.5:1
3.0:1
2.4:1
3.1:1
8.2:1
5.3:1
2.9:1
2.1:1
6.2:1
4.7:1
7.3:1
2.3:1
4-ClC6H4
3,4-(MeO)2C6H3
4-pyridyl
Ph
4-ClC6H4
3,4-(MeO)2C6H3
Ph
4-ClC6H4
3,4-(MeO)2C6H3
3-furyl
9
10
11
12
13
14
15
Ph
4-ClC6H4
3,4-(MeO)2C6H3
3-furyl
PhCH2
2-thienyl
[a] Yield after purification by chromatography or crystallization.
taneous or induced elimination of HCN, the anti-config-
ured products were predominantly formed (Scheme 2). The
results of the one-pot synthesis of amino alcohols 5 from
amino nitriles 1 are summarized in Table 1.
Figure 1. Crystal structure of anti-5h at 193 K (ORTEP). Thermal
ellipsoids are drawn at the 50% probability level.
Scheme 1. Mechanism of the reaction of α-amino nitriles to form
amino alcohols.
Remarkably, the presence of electron-donating substitu-
ents in the electrophile does not lead to a clear decrease in
the overall yield, which is in sharp contrast to the observa-
tions made in the 1,2-addition of carbanions 2 to N-arylim-
ines.[27] Although the reaction with pivalaldehyde led to low
yields due to steric hindrance, the addition to enolizable
aldehydes such as isobutyraldehyde was presumably ham-
pered by concurrent α-deprotonation.
In summary, we have developed a one-pot synthesis of
N,1,2-trisubstituted vicinal amino alcohols by the 1,2-ad-
dition of deprotonated N-monosubstituted α-amino nitriles
to aldehydes followed by reductive decyanation. As the pro-
nucleophiles can be readily obtained by the Strecker reac-
tion from an aldehyde and an amine, the reaction is amena-
ble to combinatorial variation of all three substituents.
Scheme 2. Chelate model for the reduction step.
1
The diastereomeric products show characteristic H and
13C NMR chemical shifts. The signals of the 1-H and 2-H
atoms of the anti compounds appear as comparatively
sharp doublets with a coupling constant of around 5–6 Hz,
whereas the corresponding signals of the syn isomers are
broader, have coupling constants of around 8–9 Hz and are
constantly found at a higher field. The C-1 and C-2 atoms
of the anti products resonate at a higher field than their
counterparts in the corresponding syn diastereomers. The
X-ray crystallographic analysis of the major isomer of com-
pound 5h proved the anti arrangement of the substituents.
Its crystal structure is shown in Figure 1.
Experimental Section
1
Methods: H and 13C NMR spectra were recorded with a Bruker
AC-300 or Avance II-400 spectrometer; chemical shifts were refer-
enced to the residual solvent signal (CDCl3: δH = 7.24 ppm, δC
=
Eur. J. Org. Chem. 2008, 2740–2745
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2741

C. Kison, T. Opatz
FULL PAPER
77.0 ppm). ESI-HRMS spectra were measured with a Waters Q-
TOF-Ultima 3 spectrometer equipped with a LockSpray interface
(NaO2CH or NaI/CsI as the external reference). IR spectra were
recorded with a Perkin–Elmer 1760X FTIR spectrometer. Elemen-
tal analyses were performed with a Vario Micro Cube (Elementar
Analysensysteme). The melting points were measured with a Dr.
Tottoli apparatus (Büchi) and are uncorrected. α-Amino nitriles
1a–e were synthesized by the Strecker reaction according to known
procedures.[26,28–30]
(75.5 MHz, CDCl3): δ = 143.8, 142.4, 139.1, 138.7, 133.3, 128.7–
127.1 (partly overlapping signals), 76.8 (C-1 syn), 76.3 (C-1 anti),
67.3 (C-2 syn), 65.7 (C-2 anti), 63.6 (Ph2CH syn), 63.3 (Ph2CH
anti) ppm. IR (NaCl, film): ν = 3430 (s), 3062 (m), 3028 (m), 2925
˜
(w), 2854 (w), 1600 (m), 1493 (vs), 1454 (s), 1266 (s), 1092 (s),
1029 (s), 1014 (s) cm–1. ESI-MS: m/z (%)
= 273.97 (90)
[Ph2CHNHCH2Ph + H]+, 414.09 (100) [M + H]+. C27H24ClNO
(413.94): calcd. C 78.34, H 5.84, N 3.38; found C 78.39, H 5.87, N
3.22.
2-(Benzhydrylamino)-1-(3,4-dimethoxyphenyl)-2-phenylethanol (5c):
Preparation from amino nitrile 1a and aldehyde 3c according to
the general procedure furnished a slightly yellow oil (377.6 mg). A
portion (168.5 mg) of the crude product was purified by preparative
TLC (SiO2, cyclohexane/tert-butyl methyl ether, 1:1) to give amino
alcohol 5c (112.8 mg, 68%) as a colourless oil. Ratio of isomers:
anti/syn = 3.0:1. Rf (cyclohexane/tert-butyl methyl ether, 1:1) =
0.45. 1H NMR (300 MHz, CDCl3): δ = 7.34–7.13 (m, 26 H), 7.03–
6.98 (m, 2 H), 6.98–6.93 (m, 2 H), 6.77 (s, 2 H, 5Ј-H anti, 6Ј-H
anti), 6.61 (d, J = 8.1 Hz, 1 H, 5Ј-H syn), 6.56 (dd, J = 1.5, J =
8.1 Hz, 1 H, 6Ј-H syn), 6.48 (s, 1 H, 2Ј-H anti), 6.39 (d, J = 1.5 Hz,
1 H, 2Ј-H syn), 4.70 (d, J = 6.4 Hz, 1 H, 1-H anti), 4.64 (s, 1 H,
Ph2CH syn), 4.61–4.55 (m, 2 H, 1-H syn, Ph2CH anti), 3.86 (s, 3
H, OCH3 anti), 3.77 (s, 3 H, OCH3 syn), 3.73 (d, J = 6.4 Hz, 1 H,
2-H anti), 3.66 (s, 3 H, OCH3 anti), 3.60 (s, 3 H, OCH3 syn), 3.51
(d, J = 8.6 Hz, 1 H, 2-H syn) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 148.7, 148.6 (C-3Ј, C-4Ј anti), 148.2, 148.1 (C-3Ј, C-4Ј syn),
144.1, 142.7, 142.1, 139.7, 139.6, 133.4, 133.0, 128.6–126.9 (partly
overlapping signals), 119.5 (C-6Ј anti), 118.9 (C-6Ј syn), 110.4 (2
C), 109.9, 109.7 (C-2Ј, C-5Ј), 77.5 (C-1 syn), 77.3 (C-1 anti), 67.3
(C-2 syn), 65.8 (C-2 anti), 63.6 (Ph2CH syn), 63.0 (Ph2CH anti),
Materials: THF was distilled from potassium/benzophenone imme-
diately prior to use. Benzaldehyde (3a) was freshly distilled in
vacuo. All other solvents and reagents were purchased from com-
mercial suppliers and were used without further purification. TLC
was performed on aluminium sheets coated with silica gel (60 F254
,
E. Merck). Preparative TLC was performed on PSC glass plates
(silica gel 60 F254, 2 mm, 20ϫ20 cm, Macherey–Nagel). Flash col-
umn chromatography was carried out on silica gel (35–70 µm, 60 Å,
Acros).
General Procedure for the Synthesis of Amino Alcohols 5: A solution
of KHMDS (184.3 mg, 0.92 mmol) in dry THF (1 mL) was added
to a stirred solution of the amino nitrile 1 (0.84 mmol) in dry THF
(1.0 mL) at –50 °C under argon. After 3 min, a solution of the alde-
hyde 3 (0.84 mmol) in dry THF (1 mL) was added and the reaction
mixture was warmed to –20 °C within approx. 100 min. A solution
of BH3·THF (3.4 mL, 1  in THF) was added, the mixture was
warmed to room temperature and stirring was maintained for a
further 15 h. After addition of diethanolamine/water (1:1 v/v,
2 mL), the mixture was stirred for 4 d at room temperature[31] and
diluted with ethyl acetate. The organic layer was washed with HCl
(0.5 ), sat. NaHCO3 and brine, dried with Na2SO4 and the solvent
was removed in vacuo.
55.9–55.6 (4 C, OCH ) ppm. IR (NaCl, film): ν = 3506 (m), 3061
˜
3
(m), 3027 (m), 3003 (m), 2935 (m), 2835 (m), 1596 (m), 1516 (s),
1494 (s), 1454 (s), 1265 (vs), 1236 (s), 1154 (s), 1029 (s) cm–1. ESI-
MS: m/z (%) = 440.06 (100) [M + H]+. C29H29NO3 (439.55): calcd.
C 79.24, H 6.65, N 3.19; found C 79.30, H 6.54, N 3.12.
2-(Benzhydrylamino)-1,2-diphenylethanol (5a): Preparation from
amino nitrile 1a and aldehyde 3a according to the general pro-
cedure furnished a colourless oil (346.3 mg). A portion (205.2 mg)
of the crude product was purified by flash column chromatography
(SiO2, cyclohexane/EtOAc, 10:1, + 1% EtNMe2) to give amino
alcohol 5a (139.2 mg, 74%) as a colourless solid. Ratio of isomers:
anti/syn = 3.2:1. Rf (cyclohexane/EtOAc 10:1 + 1% EtNMe2) =
2-(Benzhydrylamino)-2-phenyl-1-pyridin-4-ylethanol (5d): Prepara-
tion from amino nitrile 1a and aldehyde 3d according to the general
procedure furnished a yellow oil (334.8 mg). Purification by flash
column chromatography (SiO2, cyclohexane/EtOAc, 3:1) gave
amino alcohol 5d (180.0 mg, 56%) as a colourless solid. Ratio of
1
0.29. H NMR (400 MHz, CDCl3): δ = 7.32–6.93 (m, 40 H), 4.78
1
(d, J = 6.3 Hz, 1 H, 1-H anti), 4.65–4.63 (m, 2 H, 1-H syn, Ph2CH
syn), 4.58 (s, 1 H, Ph2CH anti), 3.78 (d, J = 6.3 Hz, 1 H, 2-H anti),
3.57 (d, J = 8.4 Hz, 1 H, 2-H syn) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 144.1 (2 C), 142.6, 142.1, 140.9, 140.6, 139.6, 139.3,
128.8–126.9 (partly overlapping signals), 77.9 (C-1 syn), 77.3 (C-1
anti), 67.2 (C-2 syn), 65.8 (C-2 anti), 63.6 (Ph2CH syn), 63.2
isomers: anti/syn = 2.5:1. Rf (cyclohexane/EtOAc, 2:1) = 0.24. H
NMR (300 MHz, CDCl3): δ = 8.34 (AAЈ part of AAЈXXЈ system,
2 H, 2Ј,6Ј-H anti), 8.27 (AAЈ part of AAЈXXЈ system, 2 H, 2Ј,6Ј-
H syn), 7.33–6.94 (m, 34 H), 4.93 (d, J = 5.3 Hz, 1 H, 1-H anti),
4.71–4.67 (m, 2 H, Ph2CH anti, 1-H syn), 4.62 (s, 1 H, Ph2CH syn),
3.82 (d, J = 5.3 Hz, 1 H, 2-H anti), 3.36 (d, J = 5.3 Hz, 1 H, 2-H
syn), 2.50 (br. s, 4 H, OH, NH) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 154.3 (C-4Ј syn), 154.1 (C-4Ј anti), 146.6 (2 C, C-2Ј,6Ј
syn), 146.5 (2 C, C-2Ј,6Ј anti), 143.4, 143.1, 142.0, 141.3, 137.9 (C-
1ЈЈ syn), 137.1 (C-1ЈЈ anti), 129.1–126.9 (partly overlapping signals),
123.3 (2 C, C-3Ј,5Ј anti), 123.2 (2 C, C-3Ј,5Ј syn), 75.9 (C-1 syn),
74.4 (C-1 anti), 66.7 (C-2 syn), 65.2 (C-2 anti), 63.8 (Ph2CH anti),
(Ph CH anti) ppm. IR (NaCl, film): ν = 3425 (m), 3061 (m), 3028
˜
2
(m), 2921 (w), 1699 (w), 1493 (s), 1454 (vs), 1266 (w), 1191 (w),
1028 (s) cm–1. ESI-MS: m/z (%) = 380.04 (100) [M + H]+.
C27H25NO (379.49): calcd. C 85.45, H 6.64, N 3.69; found C 85.40,
H 6.56, N 3.70.
2-(Benzhydrylamino)-1-(4-chlorophenyl)-2-phenylethanol (5b): Prep-
aration from amino nitrile 1a and aldehyde 3b according to the
general procedure furnished a colourless oil (417.7 mg). A portion
(162.2 mg) of the crude product was purified by preparative TLC
(SiO2, cyclohexane/tert-butyl methyl ether, 2:1) to give amino
alcohol 5b (82.2 mg, 61%) as a colourless solid. Ratio of isomers:
anti/syn = 4.0:1. Rf (cyclohexane/tert-butyl methyl ether, 2:1) =
0.52. 1H NMR (300 MHz, CDCl3): δ = 7.32–7.17 (m, 23 H), 7.10–
63.7 (Ph CH syn) ppm. IR (NaCl, film): ν = 3456 (m), 3027 (m),
˜
2
2364 (s), 1630 (s), 1494 (m), 1453 (s), 1436 (s), 1170 (m), 1072
(m) cm–1. ESI-MS: m/z (%) = 381.04 (100) [M + H]+. ESI-HRMS:
calcd. for [C26H24N2O + Na]+ 403.1787; found 403.1796.
2-(Methylamino)-2-(2-naphthyl)-1-phenylethanol (5e): Preparation
from amino nitrile 1b and aldehyde 3a according to the general
procedure furnished a yellow oil (266.3 mg). The crude product was
7.03 (m, 9 H), 7.01–6.87 (m, 6 H), 4.77 (d, J = 6.1 Hz, 1 H, 1-H crystallized from cyclohexane/EtOAc to yield exclusively the anti
anti), 4.63–4.58 (m, 3 H, 1-H syn, Ph2CH), 3.76 (d, J = 6.1 Hz, 1
isomer of amino alcohol 5e as colourless crystals (121.2 mg, 52%).
Ratio of isomers: anti/syn = 3.0:1. Rf (CH2Cl2/MeOH, 5:1) = 0.24.
H, 2-H anti), 3.48 (d, J = 8.6 Hz, 1 H, 2-H syn) ppm. 13C NMR
2742
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2740–2745

1,2-Amino Alcohols from α-Amino Nitriles
Data for the anti Isomer: M.p. 136 °C. 1H NMR (300 MHz,
55%) as a colourless solid. Ratio of isomers: anti/syn = 8.2:1. Rf
CDCl3): δ = 7.83–7.73 (m, 3 H), 7.64 (br. s, 1 H, 1Ј-H), 7.49–7.42 (CH2Cl2/MeOH, 20:1) = 0.44. 1H NMR (300 MHz, CDCl3): δ =
(m, 2 H), 7.32–7.16 (m, 6 H), 4.87 (d, J = 6.3 Hz, 1 H, 1-H), 3.91
(d, J = 6.3 Hz, 1 H, 2-H), 2.26 (s, 1 H, CH3) ppm. 13C NMR = 8.5 Hz, 1 H, 1-H syn), 3.88 (d, J = 5.7 Hz, 1 H, 2-H anti), 3.57
(75.5 MHz, CDCl3): δ = 140.6 (C6H5–C-1), 136.6 (C-2Ј), 133.1, (d, J = 8.5 Hz, 1 H, 2-H syn), 2.82–2.64 (m, 8 H, C2H4Ph), 2.21
133.1, 128.2–125.8 (partly overlapping signals), 76.7 (C-1), 71.2 (C- (br. s, 4 H, OH, NH) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
7.24–6.98 (m, 30 H), 4.77 (d, J = 5.7 Hz, 1 H, 1-H anti), 4.48 (d, J
2), 34.4 (CH ) ppm. IR (NaCl, film): ν = 3318 (m), 3058 (m), 2853
140.4, 139.7, 139.0, 128.7–126.7 (partly overlapping signals), 126.2,
126.1, 76.5 (C-1 anti), 70.5 (C-2 syn), 68.6 (C-2 anti), 48.5 (NH–
CH2 syn), 48.4 (NH–CH2 anti), 36.4 (PhCH2 syn), 36.2 (PhCH2
anti) ppm. The signal of C-1 syn is obscured by the solvent signal.
˜
3
(m), 2798 (m), 2364 (w), 1600 (m), 1452 (s), 1124 (m), 1079 (m),
1056 (s) cm–1. ESI-MS: m/z (%) = 277.96 (100) [M + H]+. ESI-
HRMS: calcd. for [C19H19NO + H]+ 278.1545; found 278.1551.
IR (NaCl, film): ν = 3355 (w), 3085 (m), 3061 (m), 3028 (s), 2861
˜
1-(4-Chlorophenyl)-2-(methylamino)-2-(2-naphthyl)ethanol
(5f):
(m), 2364 (w), 1491 (m), 1454 (s), 1428 (m), 1106 (m), 1087 (m),
1052 (s), 1029 (m) cm–1. ESI-MS: m/z (%) = 318.08 (100) [M +
H]+. ESI-HRMS: calcd. for [C22H23NO + H]+ 318.1858; found
318.1854.
Preparation from amino nitrile 1b and aldehyde 3b according to the
general procedure furnished a yellowish oil (248.9 mg). A portion
(187.9 mg) of the crude product was purified by preparative TLC
(SiO2, CH2Cl2/MeOH, 5:1) to give amino alcohol 5f (115.1 mg,
58%) as a colourless solid. Ratio of isomers: anti/syn = 2.4:1. Rf
(CH2Cl2/MeOH, 5:1) = 0.39. 1H NMR, HSQC (400 MHz, CDCl3):
δ = 7.82–7.69 (m, 6 H), 7.58 (br. s, 2 H, 1Ј-H), 7.48–7.42 (m, 4 H),
7.22 (dd, J = 8.4, 1.8 Hz, 2 H), 7.17 (AAЈ part of AAЈBBЈ system,
2 H, 3ЈЈ,5ЈЈ-H anti), 7.08–7.03 (m, 4 H, 3ЈЈ,5ЈЈ-H syn, 2ЈЈ,6ЈЈ-H
anti), 6.98 (BBЈ part of AAЈBBЈ system, 2 H, 2ЈЈ,6ЈЈ-H syn), 4.94
(d, J = 5.5 Hz, 1 H, 1-H anti), 4.70 (d, J = 8.8 Hz, 1 H, 1-H syn),
3.89 (d, J = 5.5 Hz, 1 H, 2-H anti), 3.60 (d, J = 8.8 Hz, 1 H, 2-H
syn), 3.23 (br. s, 4 H, OH, NH), 2.30 (s, 3 H, CH3 syn), 2.29 (s, 3
H, CH3 anti) ppm. 13C NMR, HSQC (100.6 MHz, CDCl3): δ =
139.8 (C-1ЈЈ syn), 139.2 (C-1ЈЈ anti), 136.1 (C-2Ј syn), 135.8 (C-
2Ј anti), 133.3, 133.1 (4 C), 133.0, 128.3–127.7 (partly overlapping
signals), 126.2, 126.1, 126.0, 125.9, 125.4, 76.6 (C-1 syn), 75.6 (C-
1 anti), 72.4 (C-2 syn), 70.9 (C-2 anti), 34.3 (CH3 anti), 34.1 (CH3
1-(4-Chlorophenyl)-2-phenethylamino-2-phenylethanol (5i): Prepara-
tion from amino nitrile 1c and aldehyde 3b according to the general
procedure furnished a colourless solid (323.1 mg). A portion
(168.2 mg) of the crude product was purified by preparative TLC
(SiO2, CH2Cl2/MeOH, 20:1) to give amino alcohol 5i (120.5 mg,
78%) as a colourless solid. Ratio of isomers: anti/syn = 5.3:1. Rf
(CH2Cl2/MeOH, 20:1) = 0.38. 1H NMR (300 MHz, CDCl3): δ =
7.32–6.85 (m, 28 H), 4.75 (d, J = 5.4 Hz, 1 H, 1-H anti), 4.44 (d, J
= 8.8 Hz, 1 H, 1-H syn), 3.83 (d, J = 5.4 Hz, 1 H, 2-H anti), 3.47
(d, J = 8.8 Hz, 1 H, 2-H syn), 2.84–2.67 (m, 8 H, C2H4Ph), 2.41
(br. s, 4 H, OH, NH) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
139.6, 139.5, 139.3, 138.9, 138.6, 133.2 (C-4Ј anti), 128.6–127.6
(partly overlapping signals), 126.2, 76.8 (C-1 syn), 75.6 (C-1 anti),
70.6 (C-2 syn), 68.5 (C-2 anti), 48.4 (NH–CH2 syn), 48.3 (NH–CH2
anti), 36.3 (PhCH2 syn), 36.2 (PhCH2 anti) ppm. IR (NaCl, film):
syn) ppm. IR (NaCl, film): ν = 3408 (s), 3055 (m), 2953 (m), 2853
˜
(m), 1600 (s), 1490 (vs), 1407 (s), 1090 (vs), 1015 (s) cm–1. ESI-MS:
m/z (%) = 312.15 (100) [M + H]+. ESI-HRMS: calcd. for
[C19H18ClNO + H]+ 312.1155; found 312.1165.
ν = 3379 (m), 3062 (m), 3029 (m), 2928 (w), 2864 (m), 1600 (m),
˜
1493 (vs), 1455 (vs), 1428 (s), 1113 (s), 1090 (s), 1058 (s), 1016
(s) cm–1. ESI-MS: m/z (%) = 352.02 (100) [M + H]+. ESI-HRMS:
calcd. for [C22H22ClNO + H]+ 352.1468; found 352.1472.
1-(3,4-Dimethoxyphenyl)-2-(methylamino)-2-(2-naphthyl)ethanol
(5g): Preparation from amino nitrile 1b and aldehyde 3c according
to the general procedure furnished a yellow oil (311.7 mg). A por-
tion (145.0 mg) of the crude product was purified by flash column
chromatography (SiO2, EtOAc/2-propanol, 4:1 + 1% EtNMe2) to
give amino alcohol 5g (63.2 mg, 48%) as a colourless solid. Ratio
of isomers: anti/syn = 3.1:1. Rf (EtOAc/2-propanol, 3:1 + 1%
EtNMe2) = 0.32, 0.23. 1H NMR (300 MHz, CDCl3): δ = 7.96–7.14
(m, 14 H), 6.84–6.74 (m, 2 H), 6.60–6.55 (m, 4 H), 4.81 (d, J =
6.3 Hz, 1 H, 1-H anti), 4.63 (d, J = 8.6 Hz, 1 H, 1-H syn), 3.88–
3.81 (m, 4 H, 2-H anti, OCH3 anti), 3.75 (s, 3 H, OCH3 syn), 3.62–
3.59 (m, 7 H, 2-H syn, 2ϫOCH3), 2.32 (s, 3 H, NCH3 syn), 2.27
(s, 3 H, NCH3 anti) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 148.7,
148.6 (C-3Ј, C-4Ј anti), 148.4, 148.2 (C-3Ј, C-4Ј syn), 137.1 (C-2ЈЈ
syn), 136.9 (C-2ЈЈ anti), 133.7, 133.2, 133.1, 132.9, 128.0–125.5
(partly overlapping signals), 125.4, 125.1, 119.2 (C-6Ј anti), 119.1
(C-6Ј syn), 110.6 (C-2Ј anti), 110.5 (C-2Ј syn), 109.9 (C-5Ј anti),
109.7 (C-5Ј syn), 77.2 (C-1 syn), 76.6 (C-1 anti), 72.5 (C-2 syn), 71.3
(C-2 anti), 55.8 (2 C, OCH3), 55.7 (OCH3 syn), 55.6 (OCH3 anti),
1-(3,4-Dimethoxyphenyl)-2-(phenethylamino)-2-phenylethanol (5j):
Preparation from amino nitrile 1c and aldehyde 3c according to
the general procedure furnished a slightly yellow oil (344.3 mg). A
portion (144.6 mg) of the crude product was purified by flash col-
umn chromatography (SiO2, cyclohexane/EtOAc, 1:1
+ 1%
EtNMe2) to give amino alcohol 5j (83.1 mg, 63%) as a colourless
solid. Ratio of isomers: anti/syn = 2.9:1. Rf (cyclohexane/EtOAc,
1:1 + 1% EtNMe2) = 0.15. 1H NMR (400 MHz, CDCl3): δ = 7.25–
7.03 (m, 19 H), 6.91–6.87 (m, 2 H), 6.71 (d, J = 8.2 Hz, 1 H, 5Ј-H
anti), 6.67 (dd, J = 8.2, 1.8 Hz, 6Ј-H anti), 6.62 (d, J = 8.2 Hz, 1
H, 5Ј-H syn), 6.56 (dd, J = 8.2, 1.8 Hz, 1 H, 6Ј-H syn), 6.49 (d, J
= 1.8 Hz, 1 H, 2Ј-H syn), 6.39 (d, J = 1.8 Hz, 1 H, 2Ј-H anti), 4.17
(d, J = 5.7 Hz, 1 H, 1-H anti), 4.44 (d, J = 8.7 Hz, 1 H, 1-H syn),
3.83 (s, 3 H, OCH3 anti), 3.82 (d, J = 5.7 Hz, 1 H, 2-H anti), 3.78
(s, 3 H, OCH3 syn), 3.66 (s, 3 H, OCH3 syn), 3.62 (s, 3 H, OCH3
anti), 3.52 (d, J = 8.7 Hz, 1 H, 2-H syn), 2.86–2.64 (m, 8 H,
C2H4Ph), 2.44 (br. s, 4 H, OH, NH) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 148.4, 148.3 (C-3Ј, C-4Ј anti), 148.3, 148.1 (C-3Ј, C-4Ј
syn), 139.6, 139.5, 139.2, 133.5 (C-1Ј syn), 132.9 (C-1Ј anti), 128.7–
127.4 (partly overlapping signals), 126.2, 126.4, 118.9 (2 C, C-6Ј),
110.4 (2 C, C-5Ј), 109.8 (C-2Ј syn), 109.7 (C-2Ј anti), 77.2 (C-1 syn),
76.3 (C-1 anti), 70.7 (C-2 syn), 68.8 (C-2 anti), 55.8 (OCH3 anti),
55.7 (OCH3 syn), 55.6 (OCH3 syn), 55.6 (OCH3 anti), 48.4 (NH–
CH2 syn), 48.3 (NH–CH2 anti), 36.3 (PhCH2 syn), 36.1 (PhCH2
34.4 (NCH anti), 34.3 (NCH syn) ppm. IR (NaCl, film): ν = 3112
˜
3
3
(m), 3054 (m), 2936 (m), 2836 (m), 2796 (m), 1646 (m), 1601 (m),
1515 (s), 1464 (s), 1418 (m), 1263 (s), 1235 (s), 1139 (s), 1064 (m),
1028 (s) cm–1. ESI-MS: m/z (%) = 338.02 (100) [M + H]+. ESI-
HRMS: calcd. for [C21H23NO3 + H]+ 338.1756; found 338.1762.
2-(Phenethylamino)-1,2-diphenylethanol (5h): Preparation from
amino nitrile 1c and aldehyde 3a according to the general pro-
anti) ppm. IR (NaCl, film): ν = 3318 (m), 3061 (m), 3027 (m), 2935
˜
(s), 2835 (m), 1594 (m), 1516 (vs), 1454 (s), 1420 (m), 1264 (vs),
1236 (s), 1155 (s), 1139 (s), 1029 (vs) cm–1. ESI-MS: m/z (%) =
378.05 (100) [M + H]+. C24H27NO3 (377.48): calcd. C 76.36, H
cedure furnished
a colourless solid (292.4 mg). A portion
(176.8 mg) of the crude product was purified by preparative TLC
(SiO2, CH2Cl2/MeOH, 20:1) to give amino alcohol 5h (89.4 mg, 7.21, N 3.71; found C 76.35, H 7.16, N 3.65.
Eur. J. Org. Chem. 2008, 2740–2745
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2743

C. Kison, T. Opatz
FULL PAPER
1-(3-Furyl)-2-(phenethylamino)-2-phenylethanol (5k): Preparation
from amino nitrile 1c and aldehyde 3e according to the general
procedure furnished a yellowish oil (276.3 mg). Purification by
flash column chromatography (SiO2, cyclohexane/EtOAc, 2.5:1)
gave amino alcohol 5k (195.9 mg, 76%) as a colourless wax. Ratio
of isomers: anti/syn = 2.1:1. Rf (cyclohexane/EtOAc, 2:1) = 0.21.
general procedure furnished a yellowish oil (269.4 mg). A portion
(148.1 mg) of the crude product was purified by flash column
chromatography (SiO2, cyclohexane/EtOAc, 1:1 + 1% EtNMe2) to
give amino alcohol 5n (84.4 mg, 32%) as a colourless solid. Ratio
of isomers: anti/syn = 7.3:1. Rf (cyclohexane/EtOAc, 1:1 + 1%
1
EtNMe2) = 0.10. H NMR (400 MHz, CDCl3): δ = 7.25–7.16 (m,
1H NMR (300 MHz, CDCl3): δ = 7.30–7.02 (m, 24 H), 6.01 (mc, 1 6 H), 7.05–7.01 (m, 2 H), 7.00–6.94 (m, 2 H), 6.72 (d, J = 8.2 Hz,
H, 4Ј-H syn), 6.00 (mc, 1 H, 4Ј-H anti), 4.74 (d, J = 5.5 Hz, 1 H,
1-H anti), 4.52 (d, J = 8.9 Hz, 1 H, 1-H syn) 3.86 (d, J = 5.5 Hz,
1 H, 2-H anti), 3.54 (d, J = 8.9 Hz, 1 H, 2-H syn), 2.84–2.69 (m, 8
1 H, 5Ј-H anti), 6.66 (dd, J = 8.2, 1.8 Hz, 1 H, 6Ј-H anti), 6.63 (d,
J = 8.2 Hz, 1 H, 5Ј-H syn), 6.58 (dd, J = 8.2, 1.8 Hz, 1 H, 6Ј-H
syn), 6.47 (d, J = 1.8 Hz, 1 H, 2Ј-H syn), 6.30 (d, J = 1.8 Hz, 1 H,
H, C2H4Ph), 2.34 (br. s, 4 H, OH, NH) ppm. 13C NMR (75.5 MHz, 2Ј-H anti), 4.75 (d, J = 5.1 Hz, 1 H, 1-H anti), 4.40 (d, J = 8.9 Hz,
CDCl3): δ = 142.8 (C-5Ј anti), 142.7 (C-5Ј syn), 140.1 (C-2Ј anti), 1 H, 1-H syn), 4.00 (d, J = 5.1 Hz, 1 H, 2-H anti), 3.82 (s, 3 H,
139.9 (2 C, C-2Ј syn), 139.7, 139.3, 128.6–127.6 (partly overlapping OCH3 anti), 3.77 (s, 3 H, OCH3 syn), 3.64 (s, 3 H, OCH3 syn), 3.58
signals), 126.2 (2 C), 125.7 (C-3Ј syn), 125.1 (C-3Ј anti), 108.9 (C-
4Ј anti), 108.8 (C-4Ј syn), 70.2 (C-1 syn), 69.9 (C-1 anti), 69.4 (C-2 2.61 [m, 2 H, CH(CH3)2], 0.10–0.95 [m, 12 H, CH(CH3)2] ppm. 13
syn), 67.7 (C-2 anti), 48.5 (NHCH2 syn), 48.4 (NHCH2 anti), 36.4 NMR (75.5 MHz, CDCl3): δ = 148.2 (4 C, C-3Ј, C-4Ј), 139.5, 132.9,
(s, 3 H, OCH3 anti), 3.53 (d, J = 8.9 Hz, 1 H, 2-H syn), 2.72–
C
(PhCH2 syn), 36.3 (PhCH2 anti) ppm. IR (NaCl, film): ν = 3296
128.3–127.3 (partly overlapping signals), 118.9 (C-6Ј syn), 118.8 (C-
6Ј anti), 110.4 (C-5Ј syn), 110.3 (C-5Ј anti), 110.0 (C-2Ј anti), 109.9
(C-2Ј syn), 77.1 (C-1 syn), 76.0 (C-1 anti), 68.1 (C-2 syn), 65.8 (C-
2 anti), 55.8 (2 C, OCH3), 55.6 (OCH3 syn), 55.5 (OCH3 anti), 46.0
[CH(CH3)2 syn], 45.4 [CH(CH3)2 anti], 24.3 [CH(CH3)2 syn], 24.0
[CH(CH3)2 anti], 22.2 [CH(CH3)2 anti], 22.1 [CH(CH3)2 syn] ppm.
˜
(m), 3027 (s), 2922 (m), 1602 (m), 1497 (s), 1454 (s), 1158, 1022
(s) cm–1. ESI-MS: m/z (%) = 308.15 (100) [M + H]+. ESI-HRMS:
calcd. for [C20H21NO2 + H]+ 308.1650; found 308.1646.
2-(Isopropylamino)-1,2-diphenylethanol (5l): Preparation from
amino nitrile 1d and aldehyde 3a according to the general pro-
IR (NaCl, film): ν = 3365 (m), 2962 (s), 2835 (m), 1594 (w), 1516
˜
cedure furnished
a colourless solid (244.4 mg). A portion
(vs), 1466 (s), 1264 (vs), 1235 (s), 1138 (s), 1028 (s) cm–1. ESI-MS:
m/z (%) = 316.09 (100) [M + H]+. ESI-HRMS: calcd. for
[C19H25NO3 + H]+ 316.1912; found 316.1916.
(144.2 mg) of the crude product was crystallized from cyclohexane/
EtOAc to yield exclusively the anti isomer of amino alcohol 5l as
colourless crystals (68.6 mg, 54%). Ratio of isomers: anti/syn =
6.2:1. Rf (CH2Cl2/MeOH, 10:1) = 0.44.
2-(Benzylamino)-1-(3-furyl)-2-(2-thienyl)ethanol (5o): Preparation
from amino nitrile 1e and aldehyde 3e according to the general
Data for the anti Isomer: M.p. 139 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.23–7.16 (m, 6 H), 7.03–6.96 (m, 4 H), 4.82 (d, J =
5.2 Hz, 1 H, 1-H), 4.06 (d, J = 5.2 Hz, 1 H, 2-H), 2.68 [sept, J =
6.3 Hz, 1 H, CH(CH3)2], 2.55 (br. s, 2 H, OH, NH), 1.02–0.96 [m,
6 H, CH(CH3)2] ppm. 13C NMR (75.5 MHz, CDCl3): δ = 140.4,
139.0 (C-1Ј, C-1ЈЈ), 128.1–126.7 (partly overlapping signals), 76.1
(C-1), 65.5 (C-2), 45.6 [CH(CH3)2], 23.9 [CH(CH3)2], 22.1
procedure furnished
a yellowish oil (246.3 mg). A portion
(188.7 mg) of the crude product was purified by flash column
chromatography (SiO2, cyclohexane/EtOAc, 4:1) to give amino
alcohol 5o (66.3 mg, 34%) as a colourless amorphous solid. Ratio
of isomers: anti/syn = 2.3:1. Rf (cyclohexane/EtOAc, 2:1) = 0.23.
1H NMR (300 MHz, CDCl3): δ = 7.35–7.23 (m, 8 H), 6.99–6.93
(m, 3 H, 3Ј-H anti, 4Ј-H), 6.80 (br. d, J = 3.3 Hz, 1 H, 3Ј-H syn),
6.14 (mc, 1 H, 4ЈЈ-H anti), 6.12 (s, 1 H, 4ЈЈ-H syn), 4.77 (d, J =
5.8 Hz, 1 H, 1-H anti), 4.65 (d, J = 8.4 Hz, 1 H, 1-H syn), 4.12 (d,
J = 5.8 Hz, 1 H, 2-H anti), 3.93 (d, J = 8.4 Hz, 1 H, 2-H syn), 3.84
(d, J = 13.0 Hz, 1 H, CH2Ph syn), 3.82 (d, J = 13.2 Hz, 1 H, CH2Ph
anti), 3.63 (d, J = 13.0 Hz, 1 H, CH2Ph syn), 3.62 (d, J = 13.2 Hz,
1 H, CH2Ph anti), 2.53 (br. s, 4 H, OH, NH) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 143.8 (C-2Ј syn), 143.5 (C-2Ј anti), 143.2
(C-5ЈЈ anti), 142.8 (C-5ЈЈ syn), 140.6 (C-2ЈЈ anti), 140.2 (C-2ЈЈ syn),
139.6 (C-1ЈЈЈ anti), 139.4 (C-1ЈЈЈ syn), 128.5–124.8 (partly overlap-
ping signals), 108.8 (C-4ЈЈ anti), 108.7 (C-4ЈЈ syn), 70.9 (C-1 syn),
70.0 (C-1 anti), 63.7 (C-2 syn), 62.9 (C-2 anti), 51.2 (2 C,
CH2Ph) ppm. ESI-MS: m/z (%) = 300.96 (100) [M + H]+. ESI-
HRMS: calcd. for [C17H17NO2S + H]+ 300.1058; found 300.1066.
C17H17NO2S (299.39): calcd. C 68.20, H 5.72, N 4.68; found C
68.20, H 5.75, N 4.85.
[CH(CH ) ] ppm. IR (NaCl, film): ν = 3388 (m), 3296 (m), 3024
˜
3 2
(m), 2960 (m), 2869 (m), 1601 (m), 1452 (m), 1088 (m), 1056 (s),
1029 (m) cm–1. ESI-MS: m/z (%) = 256.00 (100) [M + H]+. ESI-
HRMS: calcd. for [C17H21NO + H]+ 256.1701; found 256.1698.
1-(4-Chlorophenyl)-2-(isopropylamino)-2-phenylethanol (5m): Prepa-
ration from amino nitrile 1d and aldehyde 3b according to the gene-
ral procedure furnished a slightly yellow solid (269.4 mg). A por-
tion (152.7 mg) of the crude product was purified by flash column
chromatography (SiO2, CH2Cl2/MeOH, 20:1) to give amino
alcohol 5m (64.9 mg, 47%) as a colourless solid. Ratio of isomers:
anti/syn = 4.7:1. Rf (CH2Cl2/MeOH, 20:1) = 0.25. 1H NMR
(300 MHz, CDCl3): δ = 7.23–7.08 (m, 10 H), 7.01–6.84 (m, 8 H),
4.83 (d, J = 4.9 Hz, 1 H, 1-H anti), 4.47 (d, J = 9.0 Hz, 1 H, 1-H
syn), 4.03 (d, J = 4.9 Hz, 1 H, 2-H anti), 3.53 (d, J = 9.0 Hz, 1 H,
2-H syn), 2.77–2.64 [m, 2 H, CH(CH3)2], 1.28–1.12 [m, 6 H,
CH(CH3)2 syn], 1.06–0.96 [m, 6 H, CH(CH3)2 anti] ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 138.9, 138.5, 133.0 (ClC6H4 C-4), 128.1–
127.6 (partly overlapping signals), 75.2 (C-1 anti), 67.9 (C-2 syn),
65.3 (C-2 anti), 46.2 [CH(CH3)2 syn], 45.6 [CH(CH3)2 anti], 24.1
[CH(CH3)2 syn], 23.8 [CH(CH3)2 anti], 22.2 [CH(CH3)2 anti], 21.8
[CH(CH3)2 syn] ppm. The signal of C-1 syn is obscured by the sol-
Crystal Data for anti-5h: Formula C22H23NO, monoclinic, space
group P21/n, a = 12.4405(5), b = 5.7873(1), c = 24.5948(5) Å, β =
92.697(2)°, V = 1768.80(6) Å3, Z = 4, D = 1.192 gcm–3, T = 193 K,
R = 0.042, Rw = 0.1113.
vent signal. IR (NaCl, film): ν = 3412 (s), 2965 (m), 2926 (w), 2871
˜
CCDC-670570 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
(w), 2360 (m), 1637 (m), 1492 (m), 1455 (m), 1174 (m), 1090 (s),
1074 (s), 1015 (m) cm–1. ESI-MS: m/z (%) = 289.95 (100) [M +
H]+. ESI-HRMS: calcd. for [C17H20ClNO + H]+ 290.1311; found
290.1315.
1-(3,4-Dimethoxyphenyl)-2-(isopropylamino)-2-phenylethanol (5n): Supporting Information (see also the footnote on the first page of
1
Preparation from amino nitrile 1d and aldehyde 3c according to the
this article): H and 13C NMR spectra of all amino alcohols.
2744
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2740–2745

1,2-Amino Alcohols from α-Amino Nitriles
[16]
[17]
[18]
[19]
S. P. McManus, C. A. Larson, R. A. Hearn, Synth. Commun.
1973, 3, 177–180.
L. E. Martínez, J. L. Leighton, D. H. Carsten, E. N. Jacobsen,
J. Am. Chem. Soc. 1995, 117, 5897–5898.
L. Henry, C. R. Hebd. Seances Acad. Sci. 1895, 120, 1265–
1268.
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
(DFG) and the University of Mainz. We thank H. Kolshorn (Uni-
versity of Mainz) for the NMR spectroscopical analyses and Dr. D.
Schollmeyer (University of Mainz) for the X-ray crystallographic
analysis of anti-5h.
E. W. Colvin, D. Seebach, J. Chem. Soc., Chem. Commun.
1978, 16, 689–691.
[20]
[21]
D. Seebach, D. Enders, Angew. Chem. 1975, 87, 1–18.
C. Palomo, M. Oiarbide, A. Laso, Eur. J. Org. Chem. 2007, 16,
2561–2574.
[1] J. Howarth, D. G. Lloyd, J. Antimicrob. Chemother. 2000, 46,
625–627.
[2] W. H. Hartung, Chem. Rev. 1932, 9, 389–465.
[3] E. J. Corey, R. K. Bakshi, S. Shibata, J. Am. Chem. Soc. 1987,
109, 5551–5553.
[22]
[23]
D. Enders, J. P. Shilvock, Chem. Soc. Rev. 2000, 29, 359–373.
G. Stork, R. M. Jacobson, R. Levitz, Tetrahedron Lett. 1979,
9, 771–774.
I. Bergner, T. Opatz, Synthesis 2007, 918–928.
C. Kison, N. Meyer, T. Opatz, Angew. Chem. 2005, 117, 5807–
5809.
N. Meyer, F. Werner, T. Opatz, Synthesis 2005, 945–956.
C. Kison, T. Opatz, Synthesis 2006, 3727–3738.
N. A. Hassan, E. Bayer, J. C. Jochims, J. Chem. Soc. Perkin
Trans. 1 1998, 3747–3757.
J.-P. Leblanc, H. W. Gibson, J. Org. Chem. 1994, 59, 1072–
1077.
B. C. Ranu, S. S. Dey, A. Hajra, Tetrahedron 2002, 58, 2529–
2532.
Several methods for the cleavage of the surprisingly stable bo-
rane–amino alcohol adducts were tested. Although the treat-
ment with iodine or hydrogen peroxide led to the decomposi-
tion of the sample, acidic work up by addition of aqueous citric
acid or HCl appeared to have no beneficial effect. The best
results were obtained by treatment of the borane complexes
with diethanolamine, see: H. C. Brown, J. Chandrasekharan,
P. V. Ramachandran, J. Am. Chem. Soc. 1988, 110, 1539–1546.
Received: December 19, 2007
[4] D. J. Ager, I. Prakash, D. R. Schaad, Chem. Rev. 1996, 96, 835–
[24]
[25]
875.
[5] M. R. Paleo, I. Cabeza, F. J. Sardina, J. Org. Chem. 2000, 65,
2108–2113.
[6] J. Mulzer in Stereoselective Synthesis (Ed.: B.-G. Schultz),
Springer, Berlin, 1993, pp. 37–61.
[7] A. Abiko, S. Masamune, Tetrahedron Lett. 1992, 33, 5517–
5518.
[26]
[27]
[28]
[29]
[30]
[31]
[8] M. J. McKennon, A. I. Meyers, J. Org. Chem. 1993, 58, 3568–
3571.
[9] M. Tramontini, Synthesis 1982, 605–644.
[10] R. V. Hoffman, N. Maslouh, F. Cervantes-Lee, J. Org. Chem.
2002, 67, 1045–1056.
[11] D. S. Fraser, S. B. Park, J. M. Chong, Can. J. Chem. 2004, 82,
87–101.
[12] E. W. Colvin, A. K. Beck, D. Seebach, Helv. Chim. Acta 1981,
64, 2264–2271.
[13] M. T. Reetz, Angew. Chem. Int. Ed. Engl. 1991, 30, 1531–1546.
[14] L. R. Krepski, K. M. Jensen, S. M. Heilmann, J. K. Ras-
mussen, Synthesis 1986, 301–303.
[15] G. Cainelli, E. Mezzina, M. Panunzio, Tetrahedron Lett. 1990,
31, 3481–3484.
Published Online: April 17, 2008
Eur. J. Org. Chem. 2008, 2740–2745
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2745