Efficient radical domino approach to β-aminoalcohols from arylamines and alcohols triggered by Ti(III)/t-BuOOH

Article abstract of DOI:10.1016/j.tet.2010.01.039

We report that an aqueous Ti(III)/t-BuOOH system promotes the efficient domino radical reaction of arylamines with alcohol cosolvents leading to β-aminoalcohols in good yields, in less than ten minutes at room temperature. The free-radical mechanism accor

Full text of DOI:10.1016/j.tet.2010.01.039

Tetrahedron 66 (2010) 2044–2052
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Efficient radical domino approach to
b-aminoalcohols from arylamines
and alcohols triggered by Ti(III)/t-BuOOH
,
*
y
*
Raffaele Spaccini, Alessandra Ghilardi, Nadia Pastori, Angelo Clerici, Carlo Punta , Ombretta Porta
Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘‘G. Natta’’, Politecnico di Milano, Sezione Chimica,Via Mancinelli 7, I-20131 Milano, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
We report that an aqueous Ti(III)/t-BuOOH system promotes the efficient domino radical reaction of
arylamines with alcohol cosolvents leading to -aminoalcohols in good yields, in less than ten minutes at
room temperature. The free-radical mechanism according to which the amine reacts with two molecules
of the alcohol is discussed.
Received 15 September 2009
Received in revised form
10 December 2009
Accepted 11 January 2010
Available online 18 January 2010
b
Ó 2010 Elsevier Ltd. All rights reserved.
keywords:
Aminoalcohols
Imine
Domino reaction
Free-radical addition
Titanium salts
R
1. Introduction
(a) ether
t-BuOOH
Ar
Ar
O
N
H
Ti(III), H+
H2O
The development of new processes involving one-pot more
bond-forming transformations (domino or cascade reactions)1 are
particularly fascinating towards the goal of decreasing waste and
minimizing handling, while increasing molecular complexity from
simple starting materials.
R
H
+
Ar NH2
R
O
(b) HCONH2
H2O2
NH2
N
H
O
This intriguing approach has been widely applied in the field
of nucleophilic free-radical addition to imines mediated by
transition metal derivatives, allowing the development of more
attractive synthetic routes2,3 as compared with the classical ionic
ones, which often require multidstep procedures, expensive
reagents, long reaction times and highly controlled operating
conditions.
Scheme 1. Radical versions of the Mannich reaction (a) and of the Strecker
synthesis (b).
More recently, we have found that an amine, an aldehyde and
methanol can be readily assembled in one-pot under very mild
conditions through a free radical multicomponent reaction, by us-
ing the same promoting system, to afford 1,2-aminoalcohols in fair
to excellent yields (Scheme 2).6
In this context, in the last years we have reported that the Ti(III)/
hydroperoxide [t-BuOOH or H2O2] system promotes both a radical
Mannich-type reaction leading to
b
-aminoethers (Scheme 1,
-aminoamides
path a)4 and a radical Strecker-type synthesis of
a
R
(Scheme 1, path b),5 starting from an aldehyde and an amine
in ether or formamide cosolvent, respectively.
R'
R
H
Ti(III)/t-BuOOH
R'
OH
CH3OH
+
+
N H
H+, H2O
N
R''
O
R''
R = Aryl, Alkyl, H
R' = Alkyl, H
R'' = Alkyl, Benzyl, Aryl
* Corresponding authors. Tel.: þ39 0223993026; fax: þ39 0223993180.
E-mail address: carlo.punta@polimi.it (C. Punta).
Deceased May 3, 2008.
Scheme 2. Hydroxymethylation of imines generated in situ mediated by TiCl3/t-
y
BuOOH system.
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.039

R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
2045
Table 1
As a part of our ongoing interest in exploiting the roles of tita-
nium salts in promoting one-pot multi-step transformations, we
now report that an aqueous-acidic Ti(III)/t-BuOOH system that
when used in combination with an alcoholic solvent different from
methanol, triggers cascade reactions with primary and secondary
Stoichiometry of the titration of t-BuOOH with an aqueous Ti(III) solution in dif-
ferent solvents
Entry
Solvent
Eꢀ
(V)a
Ti(III) (mmol)
Ratio Ti(III)/t-BuOOHb
red
1
2
3
4
MeOH
EtOH
i-PrOH
MeCOOH
ꢁ0.74
ꢁ0.94
ꢁ1.06
d
3.6
2.2
1.4
7.8
0.90
0.55
0.35
1.95
arylamines, leading to b-aminoalcohols in good yields, under very
simple experimental conditions (Scheme 3).
a
Taken from Ref. 11.
R'
Ar
b
4.0 mmol of t-BuOOH in 10 mL of solvent were titrated with an aqueous 15 %
TiCl3 solution.
Ti(III)/t-BuOOH
H+, H2O, R'CH2OH
Ar
OH
N H
N
R
R
R'
If the intervention of path iii were to occur and suitable con-
R = H, Me
R' = H, Me, Et, n-Pr
centrations of both the aldehyde and the ketyl could be settled,
then, on the basis of our previous findings,4,5 the addition of an
amine 1 in the Ti(III)/t-BuOOH/CH3CH2OH system would produce
a domino reaction leading to 1,2-aminoalcohols 2 in one-pot.
Initial experiments designed to confirm the intervention of path
iii are reported in Table 1. As can be seen from these data, there is an
obvious linear correlation (r2¼0.998) between the redox potentials
of the alcohol-derived radicals and the amount of Ti(III) ion re-
quired to titrate t-BuOOH in the absence of added amine (Fig. 1).
Scheme 3. Radical domino approach to
triggered by Ti(III)/t-BuOOH.
b-aminoalcohols from arylamines and alcohols
The chemical outcome of this process depends on the simulta-
neous roles played not only by the metal ions [Ti(III) and Ti(IV)], but
also by the alcoholic solvent and t-BuOOH in generating useful
concentrations of the reactive partners involved in subsequent C–N
and C–C bond-forming transformations, leading to
alcohols. These derivatives are suitable intermediates for the syn-
thesis of unnatural amino acids, -blockers, insecticidal agents,
b-amino-
b
-0,6
-0,65
-0,7
antibiotics and chiral auxiliaries or chiral catalysts for asymmetric
synthesis.7,8
2. Results and discussion
-0,75
-0,8
y = 0,1667x - 1,3101
a
-Hydroxyalkyl radicals (ketyls) are easily generated via a-H
r
2 = 0,9981
-0,85
-0,9
-0,95
-1
atom abstraction from the corresponding alcohols by either
hydroxyl9 or tert-butoxyl10 radicals, which in turn are formed by
reduction of the hydroperoxides with Ti(III) ion, according to paths
i-ii of Scheme 4 (shown for t-BuOOH and ethanol).
As shown by their redox potentials11 (Table 1, 3rd column), ketyls
have a strong nucleophilic character, which determines their fast
oxidation. In this contest, we have recently reported12 that, under
aqueous acidic conditions, they are stronger reducing agents than
Ti(III) ion itself towards aromatic aldehydes. Thus, it follows that
ketyls may well compete with the metal ion in reducing the
hydroperoxide (Scheme 4, path iii) leading to the oxidation product
of the alcohol and further tert-butoxyl radical in a chain reaction.
-1,05
-1,1
1
1,5
2
2,5
mmol Ti(III)
3
3,5
4
Figure 1. Stoichiometry of the titration of t-BuOOH with an aqueous Ti(III) solution in
different solvents.
Scheme 4. Proposed catalytic cycle of primary and secondary aromatic amines with ethanol triggered by t-BuOOH/Ti(III) system.

2046
R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
The stronger the reducing power of the ketyl, the more it
imine, and only one equivalent of hydroperoxide per equivalent of
product is required.
competes with the Ti(III) ion in reducing the hydroperoxide, as it
would be expected. The intervention of reaction iii is even more
clearly demonstrated by comparison of experiments in entries 1–3
with the one in entry 4. Acetic acid (entry 4) is considerably less
reactive than alcohols towards t-butoxyl radical H-atom abstrac-
tion13 and the resulting radical, having electrophilic character, does
not take part in a chain reaction with the peroxide. Thus, termi-
nation according to Eq. 1 is the preferred reaction and almost
2 equiv of Ti(III) are requested to titrate the peroxide. The overall
stoichiometry occurs according to the Eq. 2 in AcOH solution,
whereas in alcoholic solution the stoichiometry is mainly given by
Eq. 3, in which the reaction, initiated by the path i, is propagated by
the path iii of the Scheme 4.
Finally, by reversing the order of addition, 2a was obtained only
in 50% yield. In fact, in this case the reaction of Eq. 1 is favoured.
With the optimized conditions in hand, we sent out to ex-
amine the scope of the reaction. The results of Table 3 show that
the reactivity was general for a broad range of arylamines, in-
cluding both electron-donating and electron-withdrawing sub-
stituents on the aromatic ring. The reaction was very clean and
arylamines 1a–k afforded the corresponding 3-aminobutan-2-ols
2a–k as the only reaction products in a ca. 1:1 mixture of di-
astereoisomers, which in most cases were separated by silica gel
column chromatography.
Table 3
Hþ
t-BuOꢂ þ TiðIIIÞ / t-BuOH þ TiðIVÞ
(1)
Ti(III)/Peroxides mediated reaction of primary aromatic amines with ethanol
CH3
Ti(III), ROOH, EtOH
Ar
OH
CH3
2a-k
Ar NH2
t-BuOOHD2TiðIIIÞD2HD/t-BuOHD2TiðIVÞDH2O
(2)
(3)
H+, H2O, rt, 10 min.
N
H
1a-k
t-BuOOHDRCH2OH/t-BuOHDRCHODH2O
2 (Yield %)a,b
The length of this chain process, as well as the more complex
chain process of Scheme 4, is relatively low, due to the fast reaction
of Eq. 1. Thus, the best results can be obtained by keeping low the
stationary concentration of the Ti(III) salt during the reaction.
On the basis of these results and with the aim of optimize the
reaction conditions, ethanol was firstly used as a model solvent and
p-methoxy aniline (PMPdNH2) 1a as a representative primary
arylamine, since the protective PMP group can be further removed
according to different methodologies.14
As shown in Table 2, the most satisfactory yield of 2a (80%) was
obtained by adding dropwise an aqueous acidic 15% TiCl3 solution
to a homogeneous mixture of 1a (2 mmol) and t-BuOOH (4 mmol of
a 80% aqueous solution) in 10 mL of ethanol under N2 at room
temperature.
Ar–NH2 (1)
Arꢁ
Method Ic (t-BuOOH) Method IId (H2O2)
80
75
60
1a
1b
1c
MeO
d
45
77
78
40
57
55
Table 2
OMe
Efficiency of t-BuOOH in the reaction of primary aromatic amine 1a with ethanol in
the presence of TiCl3
CH3O
CH3
Ti(III)/t-BuOOH
1d
Me
OH
CH3O
NH2
H+, H2O, CH3CH2OH
N
H
CH3
1a
2a
1e
Entry
t-BuOOH:1a
2a (yield %)a
Ratio t-BuOOH/2a
1
2
3
4
2.0
1.0
0.5
80 (50)b
44
27
38
w2:1
w2:1
w2:1
w1:1
Me
0.5þCH3CHOc
a
Yields, determined by 1H NMR of the crude reaction mixture with an internal
standard, refer to the starting amine; the syn : anti ratio is always 1:1.
1f
b
70
82
80
45
70
d
t-BuOOH is added dropwise to an aqueous solution of 1a and Ti(III).
c
1.0 equiv of acetaldehyde were added to the reaction mixture before Ti(III)
Me
addition.
The reaction proceeded like a titration and was complete within
ten minutes, e.g., by the time at which the last drop of the blue
Ti(III) reducing solution was not longer discharged, imparting a pale
violet colour to the reaction mixture.
The 2:1 ratio between the equivalents of t-BuOOH and of the
product 2a strongly supports the reaction mechanism suggested in
Scheme 2. Moreover, when acetaldehyde is directly added to the
reaction solution (Table 2, entry 4), t-BuOOH has the unique role of
generating the ketyl radical, which fast adds to the preformed
1g
Br
1h
NC

R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
2047
Table 3 (continued)
Table 4
Efficiency of t-BuOOH in the reaction of secondary aromatic amine 1l with ethanol
2 (Yield %)a,b
CH3
Method Ic (t-BuOOH) Method IId (H2O2)
CH3
NH
Ar–NH2 (1)
1i
Arꢁ
Ti(III)/t-BuOOH
H+, H2O, CH3CH2OH
OH
N
CH3 CH3
2l
47
d
1l
Entry
t-BuOOH:1l
2l a(Yield %)
Ratio t-BuOOH/2l
OH
1
2
3
4
5
2.0
1.0
0.5
82
74
50
92
50
w2:1
w1:1
w1:1
w1:2
w1:2
0.5þCH3CHOb
1j
0.25þCH3CHOb
52
48
d
d
a
See footnote a of Table 2.
1.0 equiv of acetaldehyde were added to the reaction mixture before Ti(III)
OH
b
addition.
1k
that, contrary to the observation in the presence of primary amines
(Table 2, entries 2 and 3), 1 equiv of t-BuOOH was sufficient to af-
ford 1 equiv of the desired product 2l (Table 4, entries 2 and 3).
The requirement for a lower amount of t-BuOOH can be
explained by considering the intervention of a competitive oxida-
tion step mediated by the aminium cation radical A chain carrier
(Scheme 5). It is well-known15 that aminium radicals, in the pres-
ence of a suitable substrate, may undergo intermolecular hydrogen
abstraction in highly acidic media.
According to this evidence, when RsH, radical A should be able
to abstract the hydrogen from the alcoholic solvent (Scheme 5, path
vi), affording the corresponding a-hydroxyalkyl radical. Thus, after
an initiation step, t-BuOOH seems to have the unique role of oxi-
dizing the ketyl radical to the corresponding aldehyde, while A is
responsible for the formation of new ketyl radicals.
a
See footnote a of Table 2.
Selectivity is in all cases>90%. The remaining material is mainly unreacted
imine.
b
c
Method I: the aqueous Ti(III) solution is added dropwise to the ethanol solution
of 1 and t-BuOOH.
d
Method II: the aqueous Ti(III) solution is added dropwise to the ethanol solution
of 1 and H2O2.
The independence of the reaction from the electronic nature of
the substituent (for example 2a and 2h were obtained in similar
yield) suggests that the polarization of the imine, induced by Ti(IV)
nitrogen complexation4,5 (Scheme 4, path iv), overcomes the
substituent effect.
On the contrary, steric effects seem to play a key role in these
kind of processes, as already observed for the direct hydroxy-
methylation of imines.6 In fact, in the case of ortho-substituted
anilines the chemical yields were lower.
We also checked the applicability of the method to aliphatic
amines, but any attempt was unsuccessful, while benzylamine was
rapidly oxidized to benzaldehyde before being able to form the
corresponding imine with the acetaldehyde generated in situ (the
Moreover, when 1 equiv of acetaldehyde was directly added to
the reaction mixture, the ratio t-BuOOH:2l became 1:2 (Table 4,
entries 4 and 5). Again, this result is in contrast with what observed
with primary amine 1a (Table 2, entry 4), and it confirms the su-
perimposition of a second competitive route leading to the for-
mation of the ketyl radical.
In order to extend the methodology to the synthesis of a wider
range of b-aminoalcohols, we also examined the reactivity of 1a
benzylic C–H bond is much more reactive than the
a
C–H bonds in
and 1l, chosen as representative primary and secondary aromatic
amines, respectively, in different alcoholic solvents (Table 5).
Methanol was, in both cases, the less reactive (Table 5, entries 1 and
6), due to the weaker reducing power of the corresponding ketyl
radical (Table 1, entry 1). A considerable increase in the yields was
hydrogen abstraction from alcohols by electrophilic radicals).
Next, the reactivity of N-methylaniline 1l, chosen as represen-
tative secondary amine, was tested in ethanol under the optimized
reaction conditions. The results, reported in Table 4, clearly show
Scheme 5. Proposed catalytic cycle of primary and secondary aromatic amines with ethanol triggered by t-BuOOH/Ti(III) system.

2048
R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
Table 6
observed in the presence of ethanol, while the moderate yields in
4a–4l and 5a–5l, obtained with n-propanol and n-butanol, re-
spectively (Table 5, entries 3, 4, 8 and 9) were probably due to an
enhanced steric hindrance around the carbon in a-position respect
to the nitrogen. No reaction was observed in iso-propanol.
Radical addition of alcohols to aldimines generated in situ
R"
Ti(III), t-BuOOH, RCH2OH
R'''
OH
R''' NHR' + R"CHO
H+, H2O, rt, 10 min.
N
R'
R
1
6-9
Table 5
Reaction of a primary (1a) and a secondary (1l) aromatic amine in different alcoholic
solvents
Entry Amine
R-CH2OH
R0CHO
Product yielda (%)
1
2
3
4
1a
1a
1a
1a
CH3–
CH3–
CH3CH2–
CH3CH2CH2– CH3–
CH3CH2–
CH3CH2–
CH3CH2CH2– 7a:44
6a:75
R
6a:41b
Ti(III), t-BuOOH, RCH2OH
Ar
OH
Ar NHR'
H+, H2O, rt, 10 min.
N
R'
8a:41
R
1a, 1l
2-5a, 2-5l
HN
NH
5
CH3–
H–
9m:54
Entry
Amine
R-CH2OH
Product
Product (yield %)a,b
1m
Method Ic
Method IId
(t-BuOOH)
(H2O2)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1l
1l
1l
1l
H–
CH3–
CH3CH2–
CH3CH2CH2–
(CH3)2CH–
H–
CH3–
CH3CH2–
CH3CH2CH2–
3a
2a
4a
5a
13
80e
59
37
d
d
46e
30
20
d
6
CH3–
H–
9n:32
1n
Yields, determined by 1H NMR of the crude reaction mixture with an internal
No reaction
a
3l
2l
4l
5l
31
82f
49
25
d
standard, are referred to the starting amine.
67
40
15
b
t-BuOOH is added dropwise to an aqueous solution of 1a, prionaldehyde and
Ti(III) in ethanol.
a
See footnote a of Table 2.
Selectivity is in all cases>90%. The remaining material is mainly unreacted
b
imine.
This amine/aldehyde ratio proved to be the best compromise to
obtain the highest selectivity in ‘multicomponent reaction’ product.
In fact, with a lower amount of aldehyde, the ‘domino reaction’ was
predominant while, with a higher excess, the aldol condensation
occurred, promoted by the strong acidic medium, leading to sec-
ondary transformations, among which the most significative was
the well-known Doebner–Miller reaction16 (Scheme 6).
By reversing the order of addition of Ti(III) and t-BuOOH (Table
6, entry 2), the selectivity increased but yields in on the desired
products were poor. Moreover, also aliphatic amines 1m and 1n,
which resulted unreactive towards the ‘domino reaction’, afforded
the ‘multicomponent reaction’ products 9m and 9n in the presence
of formaldehyde in moderate yields. Also in these cases the re-
actions were sensitive to the steric hindrance.
c
Method I: the aqueous Ti(III) solution is added dropwise to the ethanol solution
of 1 and t-BuOOH.
d
Method II: the aqueous Ti(III) solution is added dropwise to the ethanol solution
of 1 and H2O2.
e
Data from Table 3 for comparison.
Data from Table 4 for comparison.
f
In all the examples, t-BuOOH proved to be more effective than
H2O2 in terms of recovery of the desired products. Two main factors
contribute to lower yields with H2O2; the ꢂOH radical is less selective
than t-BuOꢂ in the abstraction from alcohols and H2O2 is a stronger
oxidant than t-BuOOH, such that the oxidation of the ketyl radical is
favoured compared to its addition on the iminium bond.
Finally, with the aim of applying this procedure to the synthesis
of more complex b-aminoalcohols, we also investigated the possi-
bility of inhibiting the ‘domino reaction’ in favour of a one-pot
multicomponent process, carried out in the presence of an alde-
hyde different from that deriving by the direct oxidation of ketyl
radicals generated in situ (‘multicomponent reaction’). According to
this last procedure, we have already reported the good results
obtained with the selective hydroxymethylation of imines, gener-
ated in situ from a wide range of aldehydes, using methanol as
alcoholic solvent.6 In this case, the ‘domino reaction’ affords poor
conversions (Table 5, entries 1 and 6) and cannot be considered
competitive with the ‘multicomponent reaction’. On the contrary,
as we have already shown, primary alcohols with longer aliphatic
chains easily undergo the domino reaction, affecting the selectivity
in the desired products.
3. Conclusions
We have developed a new methodology for the synthesis of b-
aminoalcohols by a simple radical domino approach promoted by
titanium salts and t-BuOOH (Scheme 4). Titanium species play
a multiple key role. In the lower oxidation state, TI(III) ion acts as
a radical initiator inducing the decomposition of t-BuOOH to the
corresponding alkoxyl radical (path i), which is responsible for
the formation of the ketyl radical by hydrogen abstraction from the
alcohol (path ii); Ti(III) ion also acts as a radical terminator in
the reduction of the final aminium radical intermediate (path vi).
In the higher oxidation state, Ti(IV) ion behaves as a strong
Lewis acid promoting the formation of the imine in aqueous me-
dium (path iv) and its activation towards the ketyl radical addition,
The best results, reported in Table 6, were obtained by operating
with a fixed excess of aldehyde (2.5 equiv with respect to the
amine), favouring the formation of the desired imines in solution.
O
R
NH2
N
O
R
H
+
R
H
CH3O
CH3O
R
R
Scheme 6. Doebner–Miller reaction.

R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
2049
by increasing the electrophilicity of the carbon atom of the C]N
bond (path v).
In this cascade reaction t-BuOOH not only participates to the
formation of the a-hydroxyalkyl radicals (path ii), but it also con-
verts in part ketyls to the corresponding aldehydes (path iii), which
are involved in the formation of the imines (path v).
procedure and work up were analogous as for primary aromatic
amines. The resulting crude material was purified by flash chro-
matography (Hexane/EtOAc, 6/4) and 286 mg (1.6 mmol) of 2l were
recovered; total yield 82% (Method I) based on the starting N-
methylaniline (214 mg, 2 mmol) [67%, 1.3 mmol: Method II].
This methodology was extended to a wide range of aromatic
amines in the presence of different alcoholic solvents. Moreover, it
was possible to find the ideal conditions for the synthesis of
4.4. Procedure for the one-pot multicomponent synthesis of
b-aminoalcohol 6a starting from amine 1a, acetaldehyde and
ethanol
b
-aminoalcohols in the presence of aldehydes different from those
directly deriving by oxidation of the ketyls generated in situ, pro-
moting a one-pot multicomponent reaction.
To a well stirred homogeneous solution of ethanol (10 mL)
containing 4-methoxyaniline (246 mg, 2 mmol), acetaldehyde
(220 mg, 282 L, 5 mmol) and t-BuOOH (5 mmol) a 15 wt % TiCl3
solution was added dropwise such that a pale blue colour was just
maintained to ensure the complete decomposition of the peroxide.
Work up was as previously described. The resulting crude material
was purified by flash chromatography (Hexane/EtOAc, 7/3) and
315 mg (1.5 mmol) of 6a were recovered; total yield 75% based on
the starting amine.
The reaction does not require either preformation of the imine
or protection of the amino group and may be easily conducted
under aqueous conditions. The mild operating conditions (room
temperature under atmospheric pressure), the cheap and com-
mercially available starting materials and the very short reaction
times (w20 min) make this procedure competitive with the classic
m
ionic ones for the synthesis of
b-aminoalcohols.
4. Experimental
4.5. Spectroscopic data
4.1. General
4.5.1. 3-(4-Methoxy-phenylamino)-butan-2-ol (2a). Diasteroisomers
A and B were isolated by FCC (Hexane/EtOAc,7/3); total yield 80%.
Diast A (Rf major: 0.37); appearance pale yellow liquid; FTIR (liquid
All materials were purchased from commercial suppliers without
further purification. All reactions were performed at room temper-
ature (20 ꢀC) under atmosphere of nitrogen. Formaldehyde was
36%(T) in water solution. The following aqueous solutions were
used: acidic 15 wt % of TiCl3, 80 wt % of t-BuOOH and 35 wt % of H2O2.
NMR spectra were recorded at 400 MHz for 1H and 100 MHz for
13C, in CDCl3 or DMSO and chemical shifts were presented in parts
film) vmax 3415, 2972, 1736, 1601, 1513, 1222, 737 cmꢁ1 1H NMR
;
(CDCl3)
d
(ppm) 1.11 (3H, CH3, d, J¼6.6 Hz), 1.25 (3H, CH3, d,
J¼6.1 Hz), 3.16 (1H, CH, m), 3.56 (1H, CH, m), 3.75 (3H, OCH3, s),
6.65–6.67 (2H, CH Ar, d, J¼8.9 Hz), 6.77–6.79 (2H, CH Ar, d,
J¼8.9 Hz); 13C NMR (CDCl3)
d (ppm): 17.0, 19.3, 55.7, 57.9, 71.2, 114.9,
116.3, 141.6, 152.9; MS (m/z): 195 (12), 177 (3), 150 (100), 135 (15),
108 (9), 92 (6); HRMS calcd for C11H17NO2: 195.1259; found
195.1265; diast B (Rf minor: 0.33); FTIR (liquid film) vmax 3415, 2972,
per million (d) using TMS as reference. ESI-MS were performed
with an Esquire 3000 plus ion-trap mass spectrometer equipped
with an ESI source. Tandem mass spectra were obtained by
CID with helium collision gas after isolation of the precursor ion.
Flash column chromatography was performed by using 40–63 mm
silica gel packing; the eluent was chosen in order to move the de-
1736, 1601, 1513, 1222, 737 cmꢁ1 1H NMR (CDCl3) 1.11 (3H, CH3, d,
;
J¼6.6 Hz), 1.18 (3H, CH3, d, J¼6.6 Hz), 3.37 (1H, CH, m), 3.74 (3H,
OCH3, s); 3.97 (1H, CH, m), 6.66–6.67 (2H, CH Ar, d, J¼8.9 Hz), 6.76–
6.78 (2H, CH Ar, d, J¼8.9 Hz); 13C NMR (CDCl3)
d (ppm) 14.0, 18.9,
sired components to Rf¼0.35 on analytical TLC Here we report the
55.73, 55.67, 68.5, 114.9, 116.2, 140.4, 153.0; MS (m/z): 195 (12), 177
(3), 150 (100), 135 (15), 108 (9), 92 (6); HRMS calcd for C11H17NO2:
195.1259; found 195.1252.
procedures for the synthesis of 2a and 2l as representative b-ami-
noalcohols starting from primary and secondary aromatic amines
respectively, and of 6a as representative -aminoalcohol deriving
b
from the one-pot multicomponent approach.
4.5.2. 3-(Phenylamino)butan-2-ol (2b). Crude product, purity
ꢄ95%: no purification necessary to obtain a mix of the two dia-
steroisomers A and B in a ratio 1/1; total yield 75%; appearance
yellow liquid; FTIR (liquid film) vmax 3394, 2972, 1620, 1522, 1280,
4.2. Procedure for the domino synthesis of b-aminoalcohol
2a starting from primary aromatic amine 1a and ethanol
785.cmꢁ1; 1H NMR (CDCl3)
d
(ppm), 1.09 (3H, CH3, d, J¼6.4 Hz), 1.10
To a well stirred homogeneous solution of ethanol (10 mL) con-
taining 4-methoxyaniline 1a (246 mg, 2 mmol) and the hydroper-
oxide [Method I: 5 mmol of t-BuOOH; Method II: 5 mmol of H2O2],
a 15 wt % TiCl3 solution was added dropwise such that a pale blue
colour was just maintained to ensure the complete decomposition of
the peroxide. The alcoholic cosolvent was removed in vacuum and
a 30% aqueous NH3 solution was added to the leftover solution until
basic pH was achieved (a white precipitate of Ti(IV) hydroxide was
observed) and extracted with ethyl acetate (3ꢃ10 mL). The com-
bined organic layers were washed with water (2ꢃ5 mL), dried over
Na2SO4 and then concentrated. The resulting crude material was
purified by flash chromatography (Hexane/EtOAc,7/3) and 310 mg
(1.6 mmol) of 2a were recovered; total yield 80% (Method I) based on
the starting amine [60%, 1.2 mmol: Method II].
(3H, CH3, d, J¼6.2 Hz), 1.14 (3H, CH3, d, J¼6.4 Hz), 1.19 (3H, CH3, d,
J¼6.2 Hz), 3.07 (1H, br sign with D2O ex), 3.28 (1H, CH, dq, J¼12.6,
6.2 Hz), 3.40 (1H, CH, m), 3.58 (1H, CH, dq, J¼12.4, 6.2 Hz), 3.89 (1H,
CH, m), 6.58 (2H, 2Ar0H, d, J¼8.1 Hz), 6.62 (2H, 2Ar0H, d, J¼8.1 Hz),
6.68 (2H, 2ꢃAr0H, m), 7.11 (4H, 2ꢃ2Ar0H, m); 13C NMR (CDCl3)
d
(ppm) 13.6, 16.6, 18.5, 18.9, 53.1, 55.2, 68.2, 70.58, 113.7, 113.6,
117.0, 117.5, 128.8 (2C, AþB), 146.8, 147.2; MS (m/z): 165 (8), 147 (3),
120 (100), 92 (5); HRMS calcd for C10H15NO: 165.1154; found
165.1147 (mix AþB).
4.5.3. 3-(2-Methoxy-phenylamino)-butan-2-ol (2c). The mix of the
diasteroisomers A and B (Rf¼0.35) was isolated by FCC (Hexane/
EtOAc, 65/35) in a ratio 77/23; total yield 45%; appearance pale
yellow liquid; FTIR (liquid film) vmax 3415, 2972, 1736, 1601, 1513,
1222, 737 cmꢁ1 1H NMR (CDCl3)
; d (ppm) 1.15 (3H, CH3 A, d,
4.3. Procedure for the domino synthesis of
starting from secondary aromatic amine 1l and ethanol
b
-aminoalcohol 2l
J¼6.4 Hz), 1.16 (3H, CH3 B, d, J¼6.7 Hz), 1.21 (3H, CH3 B, d, J¼6.7 Hz),
1.26 (3H, CH3 A, d, J¼6.4 Hz), 3.32 (1H, CH A, m), 3.46–3.52 (1H, CH
B, m), 3.69 (1H, CH A, m), 3.84 (3H, OCH3 BþA, s), 3.98–4.03 (1H, CH
B, m), 6.67–6.71 (2H, 2CH Ar B, m), 6.72–6.76 (2H, CH Ar A, m), 6.80
(1H, CH Ar BþA, m), 6.83–6.88 (1H, CH Ar BþA, m); 13C NMR
With the exception of the amount of hydroperoxide required
[Method I: t-BuOOH (2.5 mmol); Method II: H2O2 (2.5 mmol), both

2050
R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
(CDCl3)
d
(ppm) 14.4, 17.1, 18.8, 19.3, 53.8, 55.4 (2C, AþB), 55.9, 68.8,
119 (42), 118 (50), 91 (14); HRMS calcd for C10H14BrNO: 243.0259;
found 243.0266 (mix AþB).
71.3, 109.8 (2C, AþB), 111.1, 111.7, 117.0, 117.4, 121.2 (2C, AþB), 137.0,
137.3, 147.2, 147.6; MS (m/z): 195 (12), 180 (3), 151(10), 150 (100),
120 (45); HRMS calcd for C11H17NO2: 195.1259; found 195.1253
(mix AþB).
4.5.8. 4-(2-Hydroxy-1-methyl-propylamino)-benzonitrile (2h). The
mix of the diasteroisomers A and B (Rf¼0.35) was isolated by FCC
(Hexane/EtOAc, 45/55) in a ratio 1/1; total yield 80%; appearance
pale yellow liquid; FTIR (liquid film) nmax 3373, 2975, 2931, 2212,
4.5.4. 3-p-Tolylamino-butan-2-ol (2d). Diasteroisomers A and B
have been isolated by FCC (Hexane/EtOAc, 8/2); total yield 77%.
Diast A (Rf major: 0.37); appearance pale yellow liquid; FTIR
1607, 1525, 1342, 1173 cmꢁ1 1H NMR (CDCl3)
; d (ppm) 1.16–1.25
(12H, 4CH3, m), 1.82 (1H, br sign., D2O ex), 2.09 (1H, br sign., D2O
ex), 3.42 (1H, CH, m), 3.51 (1H, CH, m), 3.80 (1H, CH, m), 3.97 (1H,
1CH, m), 4.37 (1H, br sign., D2O ex), 4.46 (1H br sign., D2O ex) 6.57
(liquid film) vmax 3396, 2973, 1617, 1520, 1300, 809 cmꢁ1 1H NMR
;
(CDCl3)
d
(ppm) 1.12 (3H, CH3, d, J¼6.4 Hz), 1.24 (3H, CH3, d,
J¼6.4 Hz), 2.23 (3H, CH3, s), 3.25 (1H, CH, m), 3.60 (1H, CH, m),
(4H, 4Ar0H, m) 7.38 (4H, 4Ar0H, m); 13C NMR (CDCl3)
d (ppm) 13.9,
6.60–6.62 (2H, CH Ar, d, J¼8.7 Hz), 6.97–6.99 (2H, CH Ar, d,
17.7, 20.0, 20.5, 53.2, 54.2, 71.7, 69.5, 98.9 (2C, AþB), 113.1, 113.2,
120.8 (2C, AþB), 134.1 (2C, AþB), 151.0, 151.6; MS (m/z): 190 (7), 145
(100), 102 (10); HRMS calcd for C11H14N2O: 190.1106; found
190.1115 (mix AþB).
J¼8.7 Hz); 13C NMR (CDCl3)
d (ppm) 17.1, 19.4, 20.3, 56.8, 71.2,
114.8, 127.7, 129.8, 145.2; MS (m/z): 179 (10), 164 (2), 146 (1), 118
(9), 91 (15); HRMS calcd for C11H17NO: 179.1310; found 179.1314;
diast. B (Rf minor: 0.33); FTIR (liquid film) vmax 3396, 2973, 1617,
1520, 1300, 809 cmꢁ1
;
1H NMR (CDCl3)
d
(ppm) 1.11 (3H, CH3, d,
4.5.9. 3-(3-Hydroxymethyl-phenylamino)-butane-2-ol
(2i). Diasteroisomers A and B were isolated by FCC (CHCl3/MeOH:
1/9); total yield 47%. Diast A (Rf major¼0.36); FTIR (liquid film) vmax
J¼6.7 Hz), 1.18 (3H, CH3, d, J¼6.7 Hz), 2.23 (3H, CH3, s), 3.39–3.45
(1H, CH, m), 3.91–3.97 (1H, CH, m), 6.55–6.57 (2H, CH Ar, d,
J¼8.4 Hz), 6.96–6.98 (2H, CH Ar, d, J¼8.4 Hz); 13C NMR (CDCl3)
3355, 2973, 1607, 1489 cmꢁ1 1H NMR (CDCl3)
; d (ppm) 1.10 (3H,
d
(ppm)14.2, 18.9, 20.3, 54.3, 68.7,. 114.2, 127.8, 129.8, 144.8; MS
CH3, d, J¼6.4 Hz), 1.19 (3H, CH3, d, J¼6.4 Hz), 3.31 (1H, CH, m), 3.66
(1H, CH, m), 3.50–3.70 (2H, br sign., D2O ex), 4.53 (2H, CH2, s), 6.59
(1H, Ar0H d, J¼7.9 Hz), 6.6–6.72 (2H, 2Ar0H, m), 7.11 (1H, Ar0H, dd,
(m/z): 179 (10), 164 (2), 146 (1), 118 (9), 91 (15); HRMS calcd for
C11H17NO: 179.1310; found 179.1301.
J1¼J2¼7.9 Hz); 13C NMR (CDCl3)
d (ppm) 16.7, 19.4, 56.2, 64.9, 70.7,
4.5.5. 3-m-Tolylamino-butan-2-ol (2e). The mix of the diaster-
oisomers A and B (Rf¼0.35) was isolated by FCC (Hexane/EtOAc, 8/2)
in a ratio 7/3; total yield 78%; appearance pale yellow liquid; FTIR
113.3, 113.7, 117.2, 129.3, 142.4, 147.0; MS (m/z) (m/z): 195(8) 150
(26), 132 (100), 117 (21), 91 (47); HRMS calcd for C11H17NO2:
195.1259; found 195.1251; diast B (Rf minor¼0.33); FTIR (liquid
(liquid film) vmax 3396, 2973, 1617, 1520, 1300, 809 cmꢁ1
;
1H NMR
film) nmax 3355, 2973, 1607, 1489 cmꢁ1 1H NMR (CDCl3)
; d (ppm)
(CDCl3)
d
(ppm) 1.12 (3H, CH3 B, d, J¼6.7 Hz), 1.14 (3H, CH3 A, d,
1.12 (3H, CH3, d, J¼6.6 Hz),1.20 (3H, CH3, d, J¼6.6 Hz),1.70–2.15 (2H,
br sign., D2O ex), 3.49 (1H, CH, qd, J¼3.9, 6.6 Hz), 3.96 (1H, CH, qd,
J¼3.9, 6.6 Hz), 4.58 (2H, CH2, s), 6.55 (1H, Ar0H, d, J¼8.0 Hz), 6.64–
6.68 (2H, 2Ar0H, m), 7.14 (1H, ArH, dd, J¼8.0 Hz); 13C NMR (CDCl3)
J¼6.2 Hz), 1.19 (3H, CH3 B, d, J¼6.7 Hz), 1.24 (3H, CH3 A, d, J¼6.2 Hz),
2.26 (3H, CH3 B, s), 2.27 (3H, CH3 A, s), 3.30 (1H, CH A, m), 3.43–3.49
(1H, CH B, m), 3.61 (1H, CH A, m), 3.92–3.98 (1H, CH B, m), 6.43–6.59
(3H, 3CH Ar AþB, m), 7.03–7.08 (1H, CH Ar AþB, m); 13C NMR
d
(ppm) 14.5, 19.4, 54.0, 65.8, 69.2, 112.5, 113.3, 116.5, 129.9, 142.6,
(CDCl3)
d
(ppm) 14.2, 17.2, 19.0, 19.5 (2C, AþB), 21.5 , 53.9 , 56.2 , 68.8
148.0; MS (m/z): 195 (8) 150 (26), 132 (100), 117 (21), 91 (47); HRMS
calcd for C11H17NO2: 195.1259; found 195.1253.
, 71.2 , 111.0 , 111.6 , 114.7, 115.2, 118.8, 119.3, 129.2 (2C, AþB), 139.1
(2C, AþB), 147.2, 147.5; MS (m/z): 179 (9), 134 (100), 118 (9), 91 (16),
65 (10), 45 (4); HRMS calcd for C11H17NO: 179.1310; found 179.1307
(mix AþB).
4.5.10. 3-(2-Hydroxymethyl-phenylamino)-butan-2-ol (2j). The mix
of the diasteroisomers A and B (Rf¼0.35) was isolated by FCC
(CHCl3/Hexane/MeOH, 6/3/1) in a ratio 1/1; total yield 52%; ap-
pearance pale yellow liquid; FTIR (liquid film) nmax 3395, 3019,
4.5.6. 3-o-Tolylamino-butan-2-ol (2f). The mix of the diaster-
oisomers A and B (Rf¼0.35) was isolated by FCC (Hexane/EtOAc, 85/
15) in a ratio 1/1; total yield 70%; appearance pale yellow liquid;
2977, 1607, 1515, 1215 cmꢁ1 1H NMR (CDCl3)
; d (ppm) d 1.15 (9H,
3CH3, m),1.24 (3H, CH3, d, J¼6.6 Hz), 2.59 (1H, br sign., D2O ex), 2.85
(1H, br sign., D2O ex), 3.38 (1H, CH, qd, J¼3.1, 6.3 Hz), 3.51 (1H, CH,
qd, J¼3.1, 6.6 Hz), 3.67 (1H, CH, qd, J¼3.1, 6.6 Hz) 3.96 (1H, CH, qd,
J¼3.1, 6.3 Hz), 4.55–4.63 (4H, 2ꢃCH2, m) 6.64–6.69 (3H, 3Ar0H, m),
6.75 (1H, ArH, d, J¼8.3 Hz), 7.03 (2H, 2Ar0H, m), 7.16–7.20 (2H,
FTIR (liquid film) vmax 3396, 2973, 1617, 1520, 1300, 809 cmꢁ1 1H
;
NMR (CDCl3)
d
(ppm) 1.16 (3H, CH3, d, J¼6.4 Hz), 1.17 (3H, CH3, d,
J¼6.4 Hz), 1.21 (3H, CH3, d, J¼6.4 Hz), 1.26 (3H, CH3, d, J¼6.4 Hz),
2.14 (6H, 2 CH3, s), 3.38 (1H, CH, m), 3.49–3.55 (1H, CH, m); 3.69
(1H, CH, m); 3.95–4.01 (1H, CH, m); 6.62–6.71 (4H, CH Ar, m); 7.02–
2Ar0H, m); 13C NMR (CDCl3)
d (ppm) 14.4, 17.5, 19.1, 19.9, 53.6, 55.4,
7.12 (4H, CH Ar, m); 13C NMR (CDCl3)
d
(ppm) 14.3, 17.4, 17.5, 17.6,
64.8, 64.9, 68.7, 71.7, 112.3, 112.4, 117.2, 117.3, 125.3, 125.5, 129.7 (2C,
AþB), 129.9 (2C, AþB), 146.9, 147.5; MS (m/z): 195 (8), 150 (26), 132
(100), 117 (21), 91 (47); HRMS calcd for C11H17NO2: 195.1259; found
195.1250 (mix AþB).
19.1, 19.5, 53.5, 55.6, 68.8, 71.2, 110.9, 111.5, 117.3, 117.7, 122.5, 123.0,
127.1 (2C, AþB), 130.4 (2C, AþB), 145.1, 145.5; MS (m/z): 179 (9), 134
(100), 118 (13), 91 (15); HRMS calcd for C11H17NO: 179.1310; found
179.1303 (mix AþB).
4.5.11. 3-(Naphthalen-1-ylamino)-butan-2-ol (2k). The mix of the
diasteroisomers A and B (Rf¼0.35) was isolated by FCC (Hexane/
EtOAc, 3/7) in a ratio 44/66; total yield 48%; appearance pale yellow
liquid; FTIR (liquid film) vmax 3425, 2974, 1726, 1580, 769 cmꢁ1; 1H
4.5.7. 3-(4-Bromo-phenylamino)-butan-2-ol (2g). The mix of the
diasteroisomers A and B (Rf¼0.35) was isolated by FCC (Hexane/
EtOAc, 65/35) in a ratio 77/23; total yield 82%; appearance pale
yellow liquid; FTIR (liquid film) nmax 3405, 2975, 1736, 1594, 1496,
NMR (CDCl3)
d
(ppm) 1.26 (6H, CH3 AþB , m), 1.28 (3H, CH3 A, d,
757 cmꢁ1; 1H NMR (CDCl3)
d
(ppm) 1.12 (3H CH3 B, d, J¼6.7 Hz), 1.14
J¼6.4 Hz), 1,32 (3H, CH3 B, d, J¼6.2 Hz), 3.56 (1H, CH B, qd, J¼12.5,
6.4 Hz), 3.66 (1H, CH A, m), 3.83 (1H, CH B, qd, J¼12.3, 6.1 Hz), 4.09
(1H, CH A, m), 6.64 (1H, Ar0H A, d, J¼7.56 Hz), 6.71 (1H, Ar0H B, d,
J¼7.28 Hz), 7.24 (2H, 2Ar0H, m), 7.29–7.35 (2H, 2Ar0H, m), 7.41–7.45
(3H CH3 A, d, J¼6.4 Hz), 1.20 (3H CH3 B, d, J¼6.7 Hz), 1.24 (3H CH3 A,
d, J¼6.4 Hz), 3.27 (1H, CH A, m), 3.38–3.44 (1H, CH B, m), 3.65 (1H,
CH A, m), 3.90–3.96 (1H, CH B, m), 6.48–6.51 (2H, 2CH Ar B, d,
J¼9.0 Hz), 6.52–6.55 (2H, 2CH Ar A, d, J¼9.0 Hz), 7.21–7.26 (4H, 2CH
(4H, 4Ar0H, m), 7.76–7.84 (4H, 4Ar0H, m); 13C NMR (CDCl3)
d (ppm)
Ar Bþ2CH Ar A, m); 13C NMR (CDCl3)
d
(ppm) 13.9, 17.1, 19.2, 19.7,
13.9, 17.1, 19.2, 19.8, 53.6, 55.5, 68.7, 71.4, 105.5, 106.1, 117.7, 118.0,
119.9, 123.9 (2C, AþB), 124.2, 124.7, 124.8, 125.7 (2C, AþB), 126.5
(2C, AþB), 128.7,128.8, 134.5, 134.6, 142.3, 142.7; MS (m/z): 215 (16),
54.0, 56.1, 68.9, 71.1, 109.5 (2C, AþB), 115.5, 115.9, 132.0 (2C, AþB),
146.1,146.4; MS (m/z): 245 (6), 243 (6), 201 (13), 200 (95),198 (100),

R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
2051
170 (100), 154 (16), 127 (17), 115 (13); HRMS calcd for C14H17NO:
4CH2, m), 3.11–3.15 (1H, CH, m), 3.50–3.54 (1H, CH, m), 3.74 (3H,
215.1310; found 215.1317 (mix AþB).
OCH3, s), 6.61 (2H, 2ArH, d, J¼9.0 Hz), 6.75 (2H, 2ArH, d, J¼9.0 Hz);
13C NMR (CDCl3)
d (ppm) 14.4, 14.5, 19.4, 19.7, 35.2, 36.6, 56.1, 60.1,
4.5.12. 3-(Methyl-phenyl-amino)-butan-2-ol (2l). Diasteroisomers A
and B were isolated by FCC (Hexane/EtOAc ,6/4); total yield 82%.
Diast A (Rf major¼0.37); appearance pale yellow liquid; FTIR (liquid
73.5, 115.3, 115.4, 143.1, 152.6; MS (m/z) 251(3), 178 (100); HRMS
calcd for C15H25NO2: 251.1885; found 251.1889; mix A and B; ap-
pearance pale orange liquid; FTIR (liquid film) nmax 3418, 3018, 2960,
1512, 1216 cmꢁ1; 1H NMR CDCl3 d (ppm) 0.87 (3H, CH3 A, t, J¼7.1 Hz),
0.90 (3H, CH3 B, t, J¼7.1 Hz), 0.93 (3H, CH3 A, t, J¼7.1 Hz), 0.95 (3H,
CH3 B, t, J¼7.1 Hz), 1.25–1.60 (16H, 4CH2 Aþ4CH2 B, m), 3.11–3.15
(1H, CH A, m), 3.27–3.31 (1H, CH B, m), 3.50–3.54 (1H, CH A, m),
3.69–3.73 (1H, CH B, m), 3.73 (3H, OCH3 AþOCH3 B, s), 6.59 (2H,
2ArH Aþ2ArH B, d, J¼8.8 Hz), 6.76 (2H, 2ArH Aþ2ArH B, d,
film) vmax 3355, 3019, 1583, 1216, 758 cmꢁ1 1H NMR (CDCl3)
;
d
(ppm) 1.01 (3H, CH3, d, J¼6.7 Hz), 1.25 (3H, CH3, d, J¼5.9 Hz), 2.70
(3H, CH3, s), 3.16 (1H, br sign., D2O ex), 3.51 (1H, CH, dq, J¼9.3,
6.7 Hz), 3.76 (1H, CH, dq, J¼9.3, 5.9 Hz), 6.83 (1H, CH Ar, t, J¼7.5 Hz),
6.95 (2H, CH Ar, d, J¼8.5 Hz), 7.23 (2H, CH Ar, dd, J¼7.5, 8.5 Hz);13C
NMR (CDCl3)
d (ppm) 11.5, 19.3, 30.8, 64.0, 67.8, 116.2, 119.1, 129.0,
151.2; MS (m/z): 179 (5), 164 (1), 134 (100), 104 (14), 77 (21); HRMS
calcd for C11H17NO: 179.1310; found 179.1306; diast (Rf
minor¼0.33); appearance pale yellow liquid; FTIR (liquid film) vmax
3355, 3019, 1583, 1216, 758 cmꢁ1; 1H NMR (CDCl3)
(ppm) 1.19 (3H,
J¼8.8 Hz); 13C NMR (CDCl3)
d
(ppm) 14.4 (2C, AþB), 14.5 (2C, AþB),
B
19.4, 19.7, 19.8, 20.0, 32.6, 35.2 (2C, AþB), 36.6, 56.1 (2C, AþB), 59.4,
60.1, 72.6, 73.5, 115.3 (2C, AþB), 115.4 (2C, AþB), 142.8, 143.2, 152.6
(2C, AþB); MS (m/z) 251(3), 178 (100); HRMS calcd for C15H25NO2:
251.1885; found 251.1877.
d
CH3, d, J¼6.7 Hz), 1.22 (3H, CH3, d, J¼6.7 Hz), 1.87 (1H, br sign., D2O
ex), 2.75 (3H, CH3, s), 3.69 (1H, CH, dq, J¼6.7 Hz), 3.89 (1H, CH, dq,
J¼6.7 Hz), 6.71 (1H, CH Ar, t, J¼7.2 Hz), 6.79 (2H, CH Ar, d, J¼8.02 Hz),
4.5.16. 2-(N-methyl-N-phenyl)ethanol (3l). Ref. 6. Purified by FCC
(Hexane/EtOAc, 6/4) (Rf¼0.35); pale yellow liquid; total yield31%. FTIR
7.22 (2H, CH Ar, dd, J¼7.2, 8.0 Hz);13C NMR (CDCl3)
d (ppm) 12.8, 21.1,
31.9, 59.5, 70.4, 113.2, 116.8, 129.1, 150.2; MS (m/z): 179 (5), 164 (1),
134 (100), 104 (14), 77 (21); HRMS calcd for C11H17NO: 179.1310;
found 179.1303.
(liquid film) vmax 3374,1595,1500, 1042 cmꢁ1 1H NMR (400 MHz,
;
CDCl3) d (ppm) 2.17 (1H, OH br.s, ex D2O); 2.93 (3H, CH3, s); 3.43 (2H,
CH2, t, J¼5.70 Hz); 3.76 (2H, CH2, t, J¼5.70 Hz); 6.69–6.83 (3H, 3CH Ar,
m), 7.19–7.26 (2H, 2CH Ar, m); 13C CDCl3 d (ppm): 38.8, 55.4, 60.0,113.1,
117.3,129.2,150.0. EIMS m/z 151 (Mþ16), 132 (1), 120 (100), 104 (18), 77
(25). HMRS calcd for C9H13NO: 151.0997; found 151.0995.
4.5.13. 2-(4-Methoxyphenylamino)ethanol (3a). Ref. 6. Purified by
FCC (Hexane/EtOAc, 3/7)(Rf¼0.35); totalyield13%; paleyellowliquid;
FTIR (liquid film) vmax 3352, 2925, 1602, 1238, 1060 cmꢁ1 1H NMR
;
(400 MHz, CDCl3)
d
(ppm) 3.01 (2H,NHand OH, br.s, ex D2O), 3.24 (2H,
4.5.17. 4-(Methyl-phenyl-amino)-hexan-3-ol (4l). Diasteroisomers A
and B were isolated by FCC (Hexane/EtOAc, 8/2); total yield 49%.
Diast A (Rf major¼0.37); appearance pale yellow liquid; FTIR (liquid
film) vmax 3627, 3425, 2969, 1598, 1505, 1216, 755; 1H NMR CDCl3
CH2, t, J¼5.2 Hz); 3.74 (3H, OCH3, s); 3.80 (2H, CH2, t, J¼5.2 Hz); 6.65
(2H, CH Ar, d, J¼8.8 Hz); 6.78 (2H, CH Ar, d, J¼8.8 Hz). 13C CDCl3
d
(ppm): 47.6, 55.7, 61.0, 114.9, 115.2, 141.5, 152.9. EIMS m/z (added
HCOOH 0.1%) 169(Mþþ1, 88),168 (100),151 (16),150(56),136(7),123
d
(ppm) 0.75 (3H, CH3, t, J¼7.6 Hz), 1.07 (3H, CH3, t, J¼7.6 Hz), 1.42–
(32), 119 (12); HMRS calcd for C9H13NO2: 167.0946; found 167.0949.
1.49 (1H, CH, m), 1.52–1.59 (2H, CH2, m), 1.66–1.75 (1H, CH, m), 2.78
(3H, CH3, s); 3.51–3.58 (2H, CH2, m), 6.75 (1H, CH Ar, t, J¼7.3 Hz),
6.89–6.91 (2H, CH Ar, m, J¼8.9 Hz), 7.20–7.24 (2H, CH Ar, m, J¼7.3,
4.5.14. 4-(4-Methoxy-phenylamino)-hexan-3-ol (4a). Diasteroisomer
A
(Rf major¼0.36) and
a
mix of diastereoisomers
A
and
B
8.9 Hz); 13C NMR (CDCl3)
d (ppm) 9.8,11.5, 21.9, 26.7, 30.6, 66.9, 72.4,
(Rf minor¼0.34) in a ratio 25/75 were isolated by FCC (Hexane/
114.2, 117.8, 129.1, 152.3; MS (m/z) 207 (3), 190 (2), 178 (3), 148 (100),
132 (13), 77 (13); HRMS calcd for C13H21NO: 207.1623; found
207.1630; diast B (Rf minor¼0.34); appearance pale yellow liquid;
FTIR (liquid film) nmax 3627, 3425, 2969, 1598, 1505, 1216, 755; 1H
EtOAc, 6/4); total yield 59%. Diast. A; appearance pale yellow liquid;
FTIR (liquid film) nmax 3413, 2968, 1730, 1600, 1513, 1228, 732 cmꢁ1
;
1H NMR CDCl3
d
(ppm) 0.92 (3H, CH3, t, J¼7.3 Hz), 1.00 (3H, CH3, t,
J¼7.28 Hz), 1.43–1.56 (2H, CH2, m), 1.59–1.71 (2H, CH2, m), 3.06–3.11
(1H, CH, dt, J¼5.3, 7.3 Hz), 3.45–3.49 (1H, CH, dq, J¼3.9, 5.3 Hz), 3.74
(3H, OCH3, s), 6.61–6.64 (2H, CH Ar, m, J¼8.9 Hz), 6.75–6.77 (2H, CH
NMR CDCl3
d
(ppm) 0.84 (3H, CH3, t, J¼7.3 Hz), 0.94 (3H, CH3, t,
J¼7.3 Hz),1.28–1.37 (1H, CH, m),1.54–1.72 (3H, CH2þOH, m, D2O ex),
1.83–1.93 (1H, CH, m), 2.76 (3H, CH3, s), 3.56–3.64 (1H, CH2, m), 6.66
(1H, CH Ar, t, J¼7.3 Hz), 6.77–6.79 (2H, CH Ar, m, J¼8.9 Hz), 7.18–7.23
Ar, m, J¼8.9 Hz); 13C NMR (CDCl3)
d (ppm) 10.1, 10.4, 24.8, 26.9, 55.8,
61.2, 74.3,115.0,115.7,142.1,152.6; MS (m/z) 223 (6), 206 (12),194 (2),
176 (6), 164 (100), 134 (15); HRMS calcd for C13H21NO2: 223.1572;
found 223.1581; mix A and B (ratio 25/75); appearance pale yellow
liquid; FTIR (liquid film) nmax 3413, 2968, 1730, 1600, 1513, 1228,
732 cmꢁ1; 1H NMR CDCl3 d (ppm) 0.92 (3H, CH3 A, t, J¼7.3 Hz), 0.96
(3H, CH3 B, t, J¼7.3 Hz),1.00 (3H, CH3 A, t, J¼7.3 Hz),1.01 (3H, CH3 B, t,
J¼7.3 Hz), 1.42–1.68 (8H, 2CH2 Aþ2CH2 B, m), 3.08–3.12 (1H, CH A,
dt, J¼5.3, 7.3 Hz), 3.22 (1H, CH B, dt, J¼4.5, 8.4 Hz), 3.47–3.52 (1H, CH
A, dt, J¼3.9, 5.3 Hz), 3.63–3.67 (1H, CH B, dt, J¼3.6, 7.8 Hz), 3.74 (3H,
OCH3 B, s), 3.76 (3H, OCH3 A, s), 6.66–6.69 (4H, CH Ar AþB, m), 6.76–
(2H, CH Ar, m, J¼7.3, 8.9 Hz); 13C NMR (CDCl3)
d (ppm) 10.3, 11.3,
21.5, 27.7, 31.3, 64.0, 75.7, 112.4, 116.1, 129.1, 151.1; MS (m/z) 207 (3),
190 (2), 178 (3), 148 (100), 132 (13), 77 (13); HRMS calcd for
C13H21NO: 207.1623; found 207.1620.
4.5.18. 5-(Methyl-phenyl-amino)-octan-4-ol (5l). Diasteroisomers
A and B were isolated by FCC (Hexane/CHCl3/Et2O, 6/3/1); total
yield 25%. Diast. A (Rf major¼0.37); appearance pale orange liquid;
FTIR (liquid film) vmax 3423, 3018, 2960, 1598, 1505, 1215 cmꢁ1; 1H
NMR (CDCl3)
d
(ppm) 0.79 (3H, CH3, t, J¼7.1 Hz), 0.97 (3H, CH3, t,
6.78 (4H, CH Ar AþB, m); 13C NMR (CDCl3)
d
(ppm) 10.1, 10.4, 10.7,
J¼7.1 Hz), 1.04–1.23 (2H, CH2, m), 1.40–1.64 (6H, 3CH2, m), 2.76 (3H,
OCH3, s), 3.59–3.61 (2H, 2CH, m), 6.75 (1H, ArH, t, J¼7.3 Hz), 6.88
(2H, 2ArH, d, J¼8.9 Hz), 7.22 (2H, 2 ArH, dd, J¼7.3, 8.9 Hz); 13C NMR
11.1, 22.7, 24.8, 26.9, 25.7, 55.8 (2C, AþB), 61.4, 61.6, 73.9, 74.3, 115.0
(2C, AþB), 115.8, 116.0, 141.4, 141.9, 152.8, 152.9; MS (m/z) 223 (6),
206 (12), 194 (2), 176 (6), 164 (100), 134 (15); HRMS calcd for
C13H21NO2: 223.1572; found 223.1569 (mix AþB).
(CDCl3)
d (ppm) 14.0, 14.2, 18.9, 20.0, 30.5, 31.1, 36.2, 65.6, 70.9,
114.2, 117.8, 129.1, 152.2; MS (m/z) 235 (2), 192 (3), 162 (100); HRMS
calcd for C15H25NO: 235.1936; found 235.1941; diast (Rf
minor¼0.35); appearance pale orange liquid; FTIR (liquid film) nmax
3423, 3018, 2960, 1598, 1505, 1215 cmꢁ1; 1H NMR (CDCl3)
(ppm)
B
4.5.15. 5-(4-Methoxy-phenylamino)-octan-4-ol (5a). Diasteroisomer
A (Rf major¼0.37) and a mix of diastereoisomers A and B (Rf
minor¼0.35) in a ratio 3/7 were isolated by FCC (Hexane/EtOAc, 7/3);
total yield 37%. Diast. A; appearance pale orange liquid; FTIR (liquid
film) nmax 3418, 3018, 2960, 1512, 1216 cmꢁ1; 1H NMR CDCl3 d (ppm)
0.88 (3H, CH3, t, J¼7.1 Hz), 0.94 (3H, CH3, t, J¼7.1 Hz), 1.25–1.63 (8H,
d
0.85–0.90 (6H, 2 CH3, m), 1.21–1.34 (4H, 2CH2, m), 1.49–1.53 (2H,
CH2, m), 1.66–1.75 (2H, CH2, m), 2.76 (3H, CH3, s), 3.68–3.73 (2H,
2CH, m) 6.66 (1H, ArH, t, J¼7.3 Hz), 6.76 (2H, 2 ArH, d, J¼8.9 Hz),
7.20 (2H, 2 ArH, dd, J¼7.3, 8.9 Hz); 13C NMR (CDCl3)
d (ppm) 13.9,

2052
R. Spaccini et al. / Tetrahedron 66 (2010) 2044–2052
14.1, 19.1, 19.9, 30.7, 31.5, 36.9, 62.3, 74.0, 112.3, 116.0, 129.1, 151.0;
MS (m/z) 235 (2), 192 (3), 162 (100); HRMS calcd for C15H25NO:
235.1936; found 235.1944.
1H NMR (CDCl3)
d
(ppm), 1.12 (3H, CH3, d, J¼6.1 Hz), 2.23 (3H, CH3,
s), 2.30 (1Ha, CHab, dd, J¼12.2, 3.3 Hz) 2.38 (1Hb, CHab, dd, J¼12.2,
10.0 Hz), 3.45 (1Ha, CHab, d, J¼12.2 Hz), 3.58 (1H, OH, brs), 3.66
(1Hb, CHab, d, J¼12.2 Hz), 3.87 (1H, CH, m), 7.23–7.34 (5H, 5Ar0H,
4.5.19. 3-(4-Methoxyphenylamino)pentan-2-ol(6a). Diasteroisomers
A and B were isolated by FCC (Hexane/EtOAc, 7/3); total yield 65%.
Diast A (Rf major¼0.37); appearance pale yellow liquid; FTIR (liquid
m); 13C CDCl3
d (ppm): 20.4, 42.3, 62.9, 63.4, 65.4, 127.6, 128.7,
129.4, 138.7; ESI-MS m/z 180[MþþH], 202 [MþþNa]; HRMS calcd
for C11H17NO: 179.1310; found 179.1307.
film) vmax 2967, 2933, 2976, 2833, 1511, 1464, 1230, 1037 mꢁ1 1H
;
NMR (CDCl3)
d
(ppm), 0.90 (3H, CH3, t, J¼7.5 Hz), 1.23 (3H, CH3, d,
4.5.23. 1-(piperidin-1-yl)propan-2-ol (9n). The product was isolated
J¼6.0 Hz), 1.43 (1H, CHab, m), 1.65 (1H, CHab, m), 3.01 (3H, CH, NH,
pure from the reaction; appearance yellow liquid; total yield 32%. FTIR
OH, br sign., D2O ex), 3.70 (1H, CH, m), 3.72 (3H, OH3, s) 6.61 (2H,
(liquid film) nmax 3375, 2933,1666,1093 cmꢁ1;1HNMR(CDCl3)
d(ppm),
2Ar0H, d, J¼8.9 Hz), 6.74 (2H, 2Ar0H, d, J¼8.9 Hz); 13C CDCl3
d
(ppm):
1.02 (3H, CH3, d, J¼6.7 Hz), 1.35 (2H, CH2, m),1.48 (4H, 2ꢃCH2, m), 2.07
(1Hb, CHab, t, J¼12.2 Hz), 2.16 (1Ha, CHab, m), 2.21 (2Ha, CHab, m), 2.50
(2Hb, CHab, m), 3.61 (1H, br sign. D2O ex), 73.7 (1H, CH, m); 13C CDCl3
10.5, 20.1, 24.9, 55.9, 63.0, 69.3, 115.1, 115.5, 142.9, 152.5; ESI-MS m/z
210 [MþþH], 232 [MþNa]; HRMS calcd for C12H19NO2: 209.1416;
found 209.1412; diast B (Rf minor¼0.34); appearance pale yellow
liquid; FTIR (liquid film) nmax 2965, 2933, 2976, 2833, 1511, 1464,
d
(ppm): 19.9, 24.1, 25.9, 54.5, 62.1, 66.3; ESI-MS m/z 144 [MþþH], 166
[MþþNa]; HRMS calcd for C8H17NO: 143.1310; found 143.1315.
1230, 1037 mꢁ1; 1H NMR (CDCl3)
d
(ppm), 0.95(3H, CH3, t, J¼7.5 Hz),
1.16 (3H, CH3, d, J¼6.7 Hz),1.43 (1H, CHab, m), 1.57 (1H, CHab, m), 2.87
(br sign., D2O ex), 3.20 (1H, CH, m), 3.72 (3H, OCH3, s) 3.91 (1H, CH,
m), 6.63 (2H, 2Ar0H, d, J¼8.9 Hz), 6.76 (2H, 2Ar0H, d, J¼8.9 Hz); 13C
Acknowledgements
Financial support from MURST (Prin 2006) and Politecnico di
Milano is gratefully acknowledged. We thank Prof. Francesco
Minisci for fruitful chemical discussions. The co-authors dedicate
this article to the memory of Prof. Ombretta Porta.
CDCl3
d (ppm): 11.2, 18.5, 23.7, 55.9, 61.9, 68.5, 115.1, 115.4, 142.8,
152.4; ESI-MS m/z 210 [MþþH], 232 [MþNa]; HRMS calcd for
C12H19NO2: 209.1416; found 209.1418.
4.5.20. 4-(4-Methoxyphenylamino)heptan-3-ol (7a). Diasteroisomers
A and B were isolated by FCC (Hexane/EtOAc, 8/2); total yield 44%.
Diast A (Rf major¼0.36); appearance pale yellow liquid; FTIR (liquid
Supplementary data
Supplementary data (1H and 13C spectra of compounds 2a–l, 3a,
3l, 4a, 4l, 5a, 5l, 6a, 7a, 8a and 9m–n and general procedure) as-
sociated with this article can be found in the online version. Sup-
plementary data associated with this article can be found in the
online version doi:10.1016/j.tet.2010.01.039.
film) nmax 2967, 2933, 2974, 2828, 1511, 1460, 1232, 1037 cmꢁ1 1H
;
NMR (CDCl3)
d
(ppm) 0.89 (3H, CH3, t, J¼7.0 Hz), 1.01 (3H, CH3, t,
J¼7.3 Hz), 1.23–1.68 (6H, 3CH2, m), 3.16 (1H, CH, m), 3.45 (1H, CH, m),
3.74 (3H, OCH3, s) 6.63 (2H, 2Ar0H, d, J¼8.7 Hz), 6.77 (2H, 2Ar0H, d,
J¼8.7 Hz); 13C CDCl3
d (ppm) 10.2, 14.2, 19.3, 26.9, 34.9, 55.7, 59.2,
74.9, 114.9, 115.1, 142.8, 152.3; ESI-MS m/z 238 [MþþH], 260 [MþNa];
HRMS calcd for C14H23NO2: 237.1729; found 237.1736; diast B (Rf
minor¼0.33); appearance pale yellow liquid; FTIR (liquid film) vmax
2967, 2933, 2974, 2828, 1511, 1460, 1232, 1037 cmꢁ1; 1H NMR (CDCl3)
References and notes
1. For reviews see: (a) Tieze, L. F. Chem. Rev. 1996, 96, 115–136; (b) Wasilke, J. C.;
Obrey, S. J.; Baker, R. T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001–1020.
2. For background reviews in the field see: (a) Friestad, G. K. Tetrahedron 2001, 57,
5461–5496; (b) Miyabe, H.; Ueda, M.; Naito, T. Synlett 2004, 1140–1157; (c)
Friestad, G. K. Eur. J. Org. Chem. 2005, 3157–3172; (d) Yamada, K.; Tomioka, K.
Chem. Rev. 2008, 108, 2874–2886; (e) Akindele, T.; Yamada, K.; Tomioka, K. Acc.
Chem. Res. 2009, 42, 345–355.
3. Pastori, N.; Gambarotti, C.; Punta, C. Mini-Rev. Org. Chem. 2009, 6, 184–195.
4. Cannella, R.; Clerici, A.; Panzeri, W.; Pastori, N.; Porta, O. Tetrahedron 2006, 62,
5986–5994.
d
(ppm) 0.91 (3H, CH3, t, J¼7.0 Hz), 1.02 (3H, CH3, t, J¼7.3 Hz), 1.21–
1.59 (6H, 3CH2, m), 3.30(1H, CH, m), 3.62 (1H, CH, m), 3.74 (3H, OCH3,
s) 6.62 (2H, 2Ar0H, d, J¼8.6 Hz), 6.76 (2H, 2Ar0H, d, J¼8.6 Hz); 13C
CDCl3
d (ppm) 10.6, 14.1, 19.7, 25.6, 32.1, 55.7, 58.9, 74.1, 114.9, 115.2,
142.8, 152.3; ESI-MS m/z 238 [MþþH], 260 [MþNa]; HRMS calcd for
C14H23NO2: 237.1729; found 237.1725.
5. Cannella, R.; Clerici, A.; Panzeri, W.; Pastori, N.; Punta, C.; Porta, O. J. Am. Chem.
Soc. 2006, 128, 5358–5359.
4.5.21. 2-(4-Methoxyphenylamino)hexan-3-ol (8a). Diasteroisomers
A and B were isolated by FCC (Hexane/EtOAc, 7/3); total yield 41%.
Diast A (Rf major¼0.35); appearance pale yellow liquid; FTIR (liquid
6. Clerici, A.;Ghilardi, A.;Pastori, N.;Punta,C.;Porta,O. Org.Lett. 2008,10, 5063–5066.
7. (a) Yadav, J. S.; Reddy, A. R.; Narsaiah, A. V.; Reddy, B. V. S. J. Mol. Cat. A 2007, 261,
207–212; (b) Corey, E. J.; Zhang, F. Angew. Chem., Int. Ed. 1999, 38, 1931–1934; (c)
Bose, D. S.; Narsaiah, A. V. Bioorg. Med. Chem. 2005, 3, 627–630.
8. Ager, D. J.; Prakash, I.; Shaad, D. R. Chem. Rev. 1996, 96, 835–875.
9. (a) Norman, R. O. C.; West, P. R. J. Chem. Soc. B 1969, 389–399; (b) Dixon, W. T.;
Norman, R. O. C. J. Chem. Soc. B 1963, 3119–3124.
10. (a) Gilbert, B. C.; Marshall, P. D. R.; Norman, R. O. C.; Pineda, N.; Williams, P. S.
J. Chem. Soc., Perkin Trans. 2 1981, 1392–1400; (b) Paul, H.; Small, R. D.; Scaiano,
J. C. J. Am. Chem. Soc. 1978, 100, 4520–4524; (c) Wang, S. K. J. Am. Chem. Soc.
1979, 101, 1235–1239; (d) Finn, M.; Friedline, R.; Suleman, N. K.; Wohl, C. J.;
Tanko, J. M. J. Am. Chem. Soc. 2004, 126, 7578–7584.
11. (a) Lilie, J.; Beck, G.; Henglein, A. Ber. Bunsen-Ges. Phys. Chem. 1971, 75, 458–465;
(b) General Aspects of the Chemistry of Radicals; Alfassi, Z. B., Ed.; Wiley Inter-
science: Chichester, UK, 1999; p 420.
12. Clerici, A.; Greco, C.; Panzeri, W.; Pastori, N.; Punta, C.; Porta, O. Eur. J. Org.
Chem. 2007, 4050–4055.
13. Dixon, W. T.; Norman, R. O. C.; Buley, A. L. J. Chem. Soc. B 1964, 3625–3634.
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(b) Verkade, J. M. M.; van Hemert, L. J. C.; Quaedflieg, P. J. L. M.; Alsters, P. L.; van
Delft, F. L.; Rutjes, F. P. J. T. Tetrahedron Lett. 2006, 47, 8109–8113; (c) Verkade, J.
M. M.; van Hemert, L. J. C.; Quaedflieg, P. J. L. M.; Schoemaker, H. E.; Schu¨ rmann,
M.; van Delft, F. L.; Rutjes, F. P. J. T. Adv. Synth. Catal. 2007, 349, 1332–1336.
15. (a) Alder, W. R. J. Chem. Soc., Perkin Trans. 2 1986, 277–284; (b) Chow, Y. L.; Dane,
W. C.; Nelsen, S. F.; Rosenblatt, D. H. Chem. Rev. 1978, 78, 243–274; (c) Stella, L.
Angew. Chem., Int. Ed. Engl. 1983, 22, 337–350.
film) nmax 2959, 2930, 2872, 1512, 1464, 1233, 1037 cmꢁ1 1H NMR
;
(DMSO ex D2O)
d
(ppm), 0.82 (3H, CH3, t, J¼6.8 Hz), 1.00 (3H, CH3, d,
J¼6.8 Hz),1.12–1.41 (4H, 2CH2, m), 3.26 (1H, CH, m), 3.44 (1H, CH, m),
3.61 (3H, OCH3, s) 6.55 (2H, 2Ar0H, d, J¼8.9 Hz), 6.69 (2H, 2Ar0H, d,
J¼8.9 Hz); 13C CDCl3
d (ppm): 14.0, 17.1, 18.8, 35.7, 55.7, 56.2, 74.7,
114.9, 116.4, 141.2, 152.9; ESI-MS m/z 224 [MþþH], 246 [MþNa];
HRMS calcd for C13H21NO2: 223.1572; found 223.1574; diast B (Rf
minor¼0.32); appearance pale yellow liquid; FTIR (liquid film) nmax
2959, 2930, 2872, 1512, 1464, 1233, 1037 cmꢁ1; (DMSO ex D2O)
d
(ppm), 0.85 (3H, CH3, t, J¼6.7 Hz), 0.98 (3H, CH3, d, J¼6.7 Hz), 1.21–
1.45 (4H, 2CH2, m), 3.20 (1H, CH, m), 3.44 (1H, CH, m), 3.61 (3H,
OCH3, s) 6.51 (2H, 2Ar0H, d, J¼8.9 Hz), 6.68 (2H, 2Ar0H, d, J¼8.9 Hz);
13C CDCl3
d (ppm): 13.9 , 14.1, 29.6, 35.6, 53.9, 55.7, 72.4, 115.0, 115.5,
141.3, 152.5; ESI-MS m/z 224 [MþþH], 246 [MþNa]; HRMS calcd for
C13H21NO2: 223.1572; found 223.1577.
4.5.22. 1-(Benzyl(methyl)amino)propan-2-ol (9m). The product vas
isolated by FCC (Hexane/CH2Cl2/MeOH/NH3, 6/3,5/0,5/10ꢁ3) (Rf
minor¼0.35); appearance colourless oil; total yield 54%. FTIR (liq-
16. (a) Doebner, O.; Miller, W. Bericht 1883, 16, 2464–2472; (b) Forrest, T. P.;
Dauphinee, G. A.; Miles, W. F. Can. J. Chem. 1969, 47, 2121–2122; (c) Schindler,
O.; Michaelis, W. Helv. Chim. Acta 1970, 53, 776–779.
uid film) vmax 3439, 2974–2800, 1454, 1216, 1065, 1025, 756 cmꢁ1
;