Highly efficient one-pot, three-component Mannich reaction catalysed by boric acid and glycerol in water with major 'syn' diastereoselectivity

Article abstract of DOI:10.1016/j.tetlet.2009.04.135

Boric acid and glycerol efficiently catalysed the one-pot, three-component Mannich reaction of aldehydes, aromatic amines and cyclic ketones in water at ambient temperature to afford the corresponding β-amino carbonyl compounds in good yields. All but one

Full text of DOI:10.1016/j.tetlet.2009.04.135

Tetrahedron Letters 50 (2009) 4246–4250
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Tetrahedron Letters
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Highly efficient one-pot, three-component Mannich reaction catalysed
by boric acid and glycerol in water with major ‘syn’ diastereoselectivity
a
b
Chhanda Mukhopadhyay a, , Arup Datta , Ray J. Butcher
*
a Department of Chemistry, University of Calcutta, 92 APC Road, Kolkata 700 009, India
b Department of Chemistry, Howard University, Washington, DC 20059, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Boric acid and glycerol efficiently catalysed the one-pot, three-component Mannich reaction of alde-
hydes, aromatic amines and cyclic ketones in water at ambient temperature to afford the corresponding
b-amino carbonyl compounds in good yields. All but one reaction proceeded with moderate ‘syn’ diaste-
reoselectivity. This observation is just the reverse of the major anti diastereoselectivity obtained in most
of the earlier reported procedures. The methodology is mild and efficient using minute quantities of cat-
alyst with no side products and a very simple work-up procedure.
Received 18 March 2009
Revised 27 April 2009
Accepted 30 April 2009
Available online 5 May 2009
Keywords:
Ó 2009 Elsevier Ltd. All rights reserved.
Mannich reaction
Three-component reaction
syn Diastereoselectivity
Boric acid
Glycerol
Water
Green methodology
1. Introduction
phase separation was difficult. Very recently, use of heteropoly
acid as catalyst8 and a complex catalyst such as (sodium tetrakis
In recent years, water-mediated organic synthesis1 without
using organic solvents has become one of the most important as-
pects in Organic Chemistry in order to meet the environmental de-
mands.2 Carrying out organic synthesis in aqueous phase is highly
challenging both from the synthetic view point and also from the
impact of the environmental pollution. Apart from being environ-
mentally friendly, water possesses some unique properties (such
as being non-toxic, available in large quantities, cheap, non-flam-
mable and non-hazardous) that are different from other solvents
thus making it a very good reaction medium for organic synthesis.
It is very well known that the Mannich products, that is, b-ami-
no carbonyl compounds are extensively used for the synthesis of
the nitrogen-containing drugs and natural products.3,4 Classical
Mannich reactions have some disadvantages and limited applica-
tions.5 It was initially a two-component system using electrophiles
such as imines and nucleophiles like enolates, enol-ethers, enam-
ines and enol silyl ethers.6 However, there was a serious drawback
in that the nucleophiles had to be prepared from the corresponding
carbonyl compounds and in most cases, an organic solvent was
necessary. Use of surfactants such as SDS and DBSA produces col-
loidal dispersion by emulsion formation7 as a result of which,
3.5-trifluoro-methyl-phenyl) borate in water9 proved to be quite
efficient. Other three-component Mannich reactions particularly
of cyclohexanone are cited in Refs. 10–13. All these procedures
produced major anti diastereoisomers and also suffered from poor
diastereoselectivity. Therefore, modification of the existing proce-
dures by improved techniques is important to overcome the previ-
ous drawbacks and particularly to reverse the diastereoselectivity.
The development of new catalysts that increase the syn diastere-
oselectivity under mild reaction conditions would be highly useful.
2. Results and discussion
Herein we report an efficient method for the preparation of
Mannich products in water from aldehydes, aromatic amines and
cycloalkanones under very mild conditions by using boric acid
and glycerol (Scheme 1).
It is well known14 that boric acid and glycerol form a boron che-
late complex (BCC) in water (Scheme 2). Although boric acid is a
weak acid, its complex with polyhydroxy compounds such as glyc-
erol is stronger due to chelate formation and release of H+ ions in
the aqueous medium.
The in situ-generated chelate complex of boron in the reaction
mixture with corresponding increased acidity of the solvent in-
creases both the yield and diastereoselectivity of the Mannich
* Corresponding author. Tel.: +91 33 23371104; fax: +91 33 23519755.
E-mail addresses: csm@vsnl.net, cmukhop@yahoo.co.in (C. Mukhopadhyay).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.135

C. Mukhopadhyay et al. / Tetrahedron Letters 50 (2009) 4246–4250
4247
R2
R1
O
3'
HN
R2
2
O
3'
HN
1'
O
NH2
CHO
+
2
boric acid (10 mol%)
(CH )
R2
+
1'
R1
R1
+
(CH
)
glycerol (1-2 drops)
water (2 mL), 45 ºC
(CH )
3a: n=1
3b: n=2
2
1
A (2S, 1' R-syn)
B (2S, 1' S-anti)
(major)
(minor)
4a: n=1
4b: n=2
Scheme 1. Mannich reaction of aromatic aldehydes, aromatic amines and cycloalkanones catalysed by boric acid and glycerol in water.
CH2OH
OH
O
O
HO
B
B
+
2
CHOH
O
O
3H2O
H
OH
+
CH2OH
HOH2C
CH2OH
boron chelate complex (BCC)
in water
Scheme 2. Formation of boron chelate complex (BCC) in water.
products in water when carried out following the present method-
ology. Rather, the formation of this boron chelate reverses the dia-
stereoselectivity of the Mannich products: the syn diastereoisomer
being obtained in major amount.
Different polar and non-polar solvents have been used for opti-
misation of the solvent, though water is the only solvent where the
yield is maximum (Table 1). Use of either boric acid or glycerol in
water could not increase the yield much but on simultaneous use
of boric acid and glycerol, the product yield became exceedingly
high (Table 1, entry 10).
syn:anti ratio remains almost the same) rather than when carried
out in water. This indicates that the syn:anti ratio corresponds to
the thermodynamic mixture rather than to the kinetic distribution
of products. Therefore, use of a chiral catalyst for implementation
of enantioselectivity in the product would seem rather unlikely un-
der these reaction conditions as kinetic control of the reaction is
mandatory for enantioselectivity. Use of surfactants such as SDS
or CTAB did not improve the yield. It is therefore obvious from
Table 1, that boric acid and glycerol work best in aqueous medium
rather than in organic solvents.
Various organic solvents such as THF, CH2Cl2 and MeCN when
used, suppress the yield of the Mannich products (although the
Thus, the three-component Mannich reactions of various
aromatic amines (with both electron-withdrawing and
Table 1
Optimisation of solvent for the Mannich reaction catalysed by boric acid and glycerol
Cl
Cl
O
3'
HN
OMe
OMe
2
O
NH2
3'
OMe
HN
1'
O
OMe
OMe
CHO
+
+
2
_
boric acid (10 mol%)
1'
+
_
glycerol (1-2 drops)
water (2 mL), 45ºC
Cl
2
OMe
1
3a
A (2S, 1' R-syn)
B (2S, 1' S-anti)
(major)
(minor)
Entry
Solvent
Boric acid (isolated) (+) (present) (ꢀ) (absent)
Yield % (syn:anti)
1
2
3
4
5
6
7
8
9
10
CH2Cl2
CH2Cl2
THF
MeCN
MeOH
MeOH
H2O
H2O
H2O + glycerol
H2O + glycerol
(ꢀ)
(+)
(+)
(+)
(ꢀ)
(+)
(ꢀ)
(+)
(ꢀ)
(+)
—
—
—
15 (54:46)
10 (55:45)
20 (54:46)
20 (55:45)
45 (57:43)
35 (55:45)
85 (57:43)
Reagents: 2,5-dimethoxybenzaldehyde (1 mmol), 4-chloroaniline (1 mmol) and cyclohexanone (2 mmol).

4248
C. Mukhopadhyay et al. / Tetrahedron Letters 50 (2009) 4246–4250
Table 2
aldehydes, but also heteroaromatic aldehydes such as furfural
and thiophene-2-aldehyde worked well.
Mannich reaction of various aldehydes, aromatic amines and cycloalkanones
catalysed by boric acid and glycerol in water
The results proved to be very exciting with vanillin as the aro-
matic aldehyde. Use of vanillin resulted in a single diastereoisomer
in 95% isolated yield with cyclohexanone (3a, n = 1) and
4-chloroaniline (Table 2, entry 16). Thus the reaction was highly
diastereoselective in this case. With cycloheptanone (3b, n = 2)
and 4-chloroaniline, vanillin resulted in 80% yield with 61:39 dia-
stereoisomeric ratio (Table 2, entry 27). With regard to the cyclic
ketones, the reactivity order with respect to both yield and diaste-
reoselectivity was: cyclohexanone > cycloheptanone. b-Amino
carbonyl compounds were not obtained with cyclopentanone and
acetophenone. Cyclopentanone being most reactive, produced the
aldol product in major amount rather than the desired Mannich
product. Acetophenone having very low reactivity being conju-
gated, produced the Mannich product in only 10–15% yield (by
TLC) and hence could not be isolated from the reaction mixture
in pure form.
The high chemoselectivity of cyclohexanone towards aldimines
(generated by the reaction of aldehydes and amines) in preference
to aldehydes is shown in Scheme 3, using 4-bromobenzaldehyde
and 4-chloroaniline. Strong evidence for the above-mentioned che-
moselectivity was that the aldimine obtained from 4-bromobenz-
aldehyde and 4-chloroaniline was isolated (d 8.36 for the
imine proton in 1H NMR) from the reaction mixture of reaction 1
(Scheme 3).
Entry
R1
R2
3
Time
(h)
Yielda
(%)
(syn:anti
ratiob)references
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
H
H
H
H
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
b
b
b
44
36
35
32
36
37
32
36
38
35
42
35
37
40
33
30
36
44
42
40
43
45
35
40
32
38
36
80
84
76
73
78
82
62
85
80
85
75
85
80
75
83
95
81
73
78
80
74
76
80
77
75
79
80
(64:36)8
(61:39)8
(62:38)7
(64:36)7
(60:40)8
(50:50)8
(62:38)8
(56:44)8
(56:44)8
(61:39)8
(56:44)
(57:43)
(73:27)
(86:14)
(63:37)
(100:0)
(61:39)
(54:46)
(60:40)
(65:35)
(50:50)
(58:42)
(65:35)8
(60:40)8
(62:38)7
(65:35)
(61:39)
60-Cl
60-OMe
H
R1-C6H4 = 2-furyl
4-Cl
60-Cl
60-Cl
H
60-Cl
H
4-OMe
2-OMe
4-NO2
3-NO2
R1-C6H4 = 2-thienyl
H
60-Cl
50-NO2
60-Cl
60-Cl
60-Cl
60-Cl
60-Cl
60-Cl
50-NO2
50-NO2
50-NO2
50-NO2
50-NO2
H
2,5-(OMe)2
4-Br
2-NO2
2-Cl
4-OH-3-OMe
3,4-(OMe)2
3,4-(OMe)2
4-OH-3-OMe
4-OMe
2,5-(OMe)2
2-Cl
4-Cl
3-NO2
H
2-Cl
4-OH-3-OMe
4-Cl
60-OMe
60-Cl
60-Cl
The separation of the diastereoisomers were performed in two
cases as shown in Table 3 by means of a long column (20 in. in
height and 0.5 in. in diameter) with 100–200 mesh silica gel and
7-8% EtOAc/petroleum ether as eluant. From Table 3, entry 1, it
can be noticed that both the major and the minor isomers could
be separated and characterised (though being liquids). For entry
2, it was possible to isolate only the minor isomer because of its
lower solubility. In almost all the previous reports, it has been men-
tioned that the anti isomer is the major one with a comparatively
low d value and a high J value compared to the syn isomer with a
high d value and a low J value. From the rigorous analysis of the
1H NMR data of the crude Mannich reaction products, we find that
in all our major isomers, the d value is high and the J value is low.
Thus, by analogy, all our major diastereoisomers have been as-
signed as ‘syn’ in contrast to anti as reported earlier. When the reac-
tion was carried out with an aliphatic aldehyde (n-butanal), 4-
chloroaniline and cyclohexanone, the ‘syn’ diastereoisomer was
a
Isolated yields.
b
The syn:anti ratios were determined by the 1H NMR integration ratios of the
0
adjacent (C2–C1 ) hydrogens of the crude reaction products.
electron-donating substituents), aldehydes (heterocyclic, aromatic
with various substituents), cyclohexanone and cycloheptanone
were examined and the results are depicted in Table 2.
Substituted aldehydes with electron-donating groups, 4-chloro-
aniline and cyclohexanone gave excellent yields. Thus, 2,5-DMB, 4-
chloroaniline and cyclohexanone (Table 2, entry 12) produced the
product in 85% yield with syn:anti ratio 57:43. On the other hand,
3-nitroaniline, under the same reaction conditions, did not yield to
that extent (Table 2, entry 21) due to deactivation by the nitro
group. All the reactions were completed within 30–45 h which is
either less or comparable to previously reported procedures. The
reactivity of the aromatic amines follows the order: 4-chloroani-
line > aniline > 4-anisidine > 3-nitroaniline. Not only aromatic
major.15 mmax (liquid film: 2943, 1685, 1607, 1496, 1313 cmꢀ1
[ ;
1H NMR (300 MHz, CDCl3, major:minor = 71:29) d: 0.85–1.10 (m,
Cl
O
HN
H
NH2
Cl
CHO
Br
O
boric acid (10 mol%)
+
+
glycerol (1-2 drops)
water (2 mL), 45 oC, 35 h
Br
reaction 1
syn : anti =73: 27 (yield 80 %)
O
CHO
same reaction conditions
reaction 2
no reaction
+
Br
Scheme 3. Chemoselectivity of cyclohexanone towards aldimine.

C. Mukhopadhyay et al. / Tetrahedron Letters 50 (2009) 4246–4250
4249
Table 3
Separation of diastereoisomers resulting in diastereopure forms
Entry
R1
R2
Reactant 3
syn:anti ratio
syn (yield) (isolated)
anti (yield) (isolated)
NMR (pure syn) 1H, 13C d
NMR (pure anti) 1H, 13C d
1
2
2-Cl
2,5-(OMe)2
60-Cl
60-Cl
n = 1
n = 1
63:37
57:43
40
—
25
35
5.28 (J = 3.6 Hz) 53.90
—
4.83 (J = 4.5 Hz) 55.68
4.89 (J = 7.2 Hz) 55.56
8H), 1.12–1.86 (m, 7H), 3.24–3.37 (m, 1H, COCH), 3.88 (br s, 1H,
NH), 4.30 (major d, J = 2.4 Hz, 0.71H, CHNH), 4.66–4.67 (minor d,
J = 4.6 Hz, 0.29H, CHNH), 6.57 (major td, J = 8.7 Hz and 1.8 Hz,
0
0
1.42 H, C4 -H and C8 -H), 6.63 (minor td, J = 7.5 Hz and 2.4 Hz, 0.58
H, C4 -H and C8 -H), 7.11-7.17 (m, 2H, C5 -H and C7 -H); 13C NMR
(75 MHz, CDCl3, major:minor = 71:29) d: 14.1 (CH3), 21.7 (CH2),
23.3 (CH2), 23.6 (CH2), 26.6 (CH2), 29.8 (CH2), 40.1 (COCH2), (49.6,
0
0
0
0
0
0
49.7) (COCH), 53.0 (CHNH), (114.4, 114.6) (C4 and C8 ), (129.2,
7
0
0
0
0
0
0
129.32) (C5 and C7 ), 143.0 (C3 /C6 ), 144.9 (C6 /C3 ), 201.2(C@O)].
Further and final confirmation comes from X-ray crystallo-
graphic data. Using vanillin, 4-chloroaniline and cyclohexanone
(Table 2, entry 16) with our present methodology, only one diaste-
reoisomer (crude 1H NMR) was isolated (4aA). The coupling con-
stant value (J = 4.5 Hz) indicates the diastereopure isomer to be
syn (2S,10R). Finally, the single crystal analysis of 4aA obtained
from Table 2, entry 16 was done and is shown (CCDC 709686) in
Figure 1. The reaction was therefore 100% stereoselective in this
case.
From the ortep plot, we clearly see that the adjacent C1- and C-
(ortep numbering) hydrogens have the ‘syn’ configuration (2S,10R)
which is in total agreement with our previously assigned stereo-
chemistry. With 2,5-dimethoxybenzaldehyde, 4-chloroaniline and
cyclohexanone, two diastereoisomers were obtained in 57:43 ratio.
The major diastereoisomer has been again assigned as ‘syn’ in anal-
ogy with previous reports as it reveals a higher d value and a low J
value [d 5.13 (major d, J = 4.8 Hz, 0.57H)] compared to the minor
‘anti’ isomer (2S,10S) possessing a lower d value and high J value.
[4.88 (minor d, J = 7.2 Hz, 0.43H)]. The ‘minor’ isomer in this case
with a lower solubility could be separated and isolated in pure
form (4aB, Table 2, entry 12). Finally, X-ray crystal of its single
crystal was done (CCDC 709650) and is shown in Figure 2.
From the ortep plot, we clearly see that the adjacent C1–C (ortep
numbering) hydrogens have the ‘anti’ configuration (2S,10S)
Figure 2. Ortep diagram of single crystal of 4aB (minor isomer) obtained from
Table 2, entry 12 showing the crystallographic numbering.
which is in complete agreement with our earlier assigned
stereochemistry.
3. Conclusion
We have developed a rather novel protocol for the three-com-
ponent Mannich reaction for aldehydes, aromatic amines and
cycloalkanones catalysed by boric acid and glycerol in water with
major ‘syn’ diastereoselectivity in contrast to major ‘anti’ diastere-
oselectivity in all the earlier reported methods. These reactions,
which proceed very slowly in organic solvents, take place quite fast
in water that is attributed to its unique property as a reaction med-
ium. The formation of the boron chelate complex in water in-
creases its acidity, thus accelerating the reaction. This catalyst
system probably increases and at the same time reverses the dia-
stereoselectivity compared to earlier reported procedures. This
procedure offers several advantages such as high diastereoselectiv-
ity, high yields, mild reaction conditions and very simple work-up
procedures. The separation of the diastereoisomers could be effi-
ciently achieved in two cases. These b-amino carbonyl compounds
are important synthetic intermediates for various pharmaceuticals
and natural products.
4. Experimental
4.1. General procedure for the Mannich reaction catalysed by
boric acid and glycerol in water
Aromatic aldehyde (1 mmol), aromatic amine (1 mmol) and
[cyclohexanone or cycloheptanone (2 mmol)] were successively
added to a solution of boric acid (10 mol %) and glycerol (1–2
drops) in water (2 mL) placed in a 25 mL round-bottomed flask.
The reaction mixture was vigorously stirred at 45 °C on a water
bath for 35–50 h. It was then diluted with ethyl acetate (10 mL),
extracted further from the aqueous layer with ethyl acetate
Figure 1. Ortep diagram of single crystal of 4aA (single isomer) obtained from
Table 2, entry 16 showing the crystallographic numbering.

4250
C. Mukhopadhyay et al. / Tetrahedron Letters 50 (2009) 4246–4250
(5 mL) and the combined organic layers were washed with water
(2 ꢁ 5 mL) to remove glycerol and boric acid. The organic layer
was dried with anhydrous Na2SO4. The solvent was distilled out
on a hot water bath to give desired products. The crude products
were purified either by crystallisation from ethanol or by column
chromatography (10% ethyl acetate/90% petroleum ether). The first
aqueous extract could be utilised for further Mannich reaction at
least twice. The syn:anti ratio of the diastereoisomeric mixture
was determined by 1H NMR of the crude reaction mixture. The
physical and spectral data of one unknown compound are given
below. The data for all the other unknown compounds are given
in Supplementary data.
(153.6, 153.7) (C–OMe), (211.4, 213.5) (C@O); MS (EI) m/z: 373
(M+,100), 375 (32), 374 (23).
Acknowledgement
We thank the CAS Instrumentation Facility, University of
Calcutta for spectral data.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.04.135.
4.2. 2-[10–(N-p-chlorophenylamino)-10-2,5-
dimethoxyphenyl]methylcyclohexanone (Table 2, entry 12)
References and notes
1. (a) Varma, R. S. Org. Chem. Highlights, (2007), Clean Chemical Synthesis in Water,
http://www.organic-chemistry.org/Highlights/2007/01February,shtm.;
Hayashi, Y. Angew. Chem., Int. Ed. 2006, 45, 8103.
(b)
The title compound was obtained as yellowish brown oil
(317.8 mg, 85%) in 57:43 (syn:anti) ratio of the diastereoisomers;
[Calcd for C21H24NO3Cl: C, 67.46; H, 6.47; N, 3.75%. Found: C,
67.68; H, 6.64; N, 3.97%.]; Rf (25% EtOAc/petroleum ether) [0.48
(syn) and 0.38 (anti)]; mmax (neat): 3336, 2932, 1704, 1601.
2. (a)Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie A & P: London, 1998;
(b)Organic Reactions in Water; Lindstrom, U. M., Ed.; Blackwell Publishing:
Oxford, 2007.
3. Ting, A.; Schaus, S. E. Eur. J. Org. Chem. 2007, 5797.
4. Marques, M. M. B. Angew. Chem., Int. Ed. 2006, 45, 348.
5. (a) Blatt, A. H.; Gross, N. J. Org. Chem. 1964, 29, 3306; (b) Kobayashi, S.; Ishitani,
H. Chem. Rev. 1999, 99, 1069; (c) Mannich, C.; Krosche, W. Arch. Pharm. 1912,
250, 674.
6. Trost, B. M.; Terrell, L. R. J. Am. Chem. Soc. 2003, 125, 338.
7. Manabe, K.; Kobayashi, S. Org. Lett. 1999, 1, 1965. and the references cited
therein.
8. Azizi, N.; Torkiyan, L.; Saidi, M. R. Org. Lett. 2006, 8, 2079.
9. Chang, C.-T.; Liao, B.-S.; Liu, S.-T. Tetrahedron Lett. 2006, 47, 9257.
10. Yi, L.; Zou, J.; Lei, H.; Lin, X.; Zhang, M. Org. Prep. Proced. Int. 1991, 23, 673.
11. Wu, Y.-S.; Cai, J.; Hu, Z.-Y.; Lin, G.-X. Tetrahedron Lett. 2004, 45, 8949.
12. Akiyama, T.; Matsuda, K.; Fuchibe, K. Synlett 2005, 322.
13. Wei, H.-L.; Yan, Z.-Y.; Niu, Y.-N.; Li, G.-Q.; Liang, Y.-M. J. Org. Chem. 2007, 72,
8600.
1499 cmꢀ1 1H NMR (300 MHz, CDCl3, major:minor = 57:43) d:
;
1.53–1.68 (m, 4H, –CH2–CH2), 1.72–1.92 (m, 2H, –CH2), 2.28–
2.44 (m, 2H, COCH2), 2.84–2.88 (m, 1H, –COCH), 3.68 (s, 3H, –
OMe), [3.81 (major, s, 1.71H), 3.85 (minor, s, 1.29H)] (OMe), 4.49
(br s, 1H, NH), [4.89 (minor d, J = 7.2 Hz, 0.43H), 5.13 (major d,
0
0
J = 4.8 Hz, 0.57H)] (CH–NH), 6.43–6.47 (m, 2H, C4 –H and C8 –H),
6.66–6.70 (m, 1H, aromatic C4–H/C3–H), 6.76–6.79 (m, 1H, aro-
matic C3–H/C4–H), 6.87–6.92 (d, J = 3 Hz, 1H, C6–H), 6.95–6.99
(m, 2H, C5 –H and C7 –H); 13C NMR (75 MHz, CDCl3, major:mi-
nor = 57:43) d: (23.7, 24.7) (CH2), (27.2, 28.3) (CH2), 31.7 (CH2),
(41.9, 42.3) (COCH2), (51.4, 52.7) (COCH), (54.5, 55.5) (CH–NH),
(55.5, 55.8, 55.9) (2 ꢁ OMe), (111.0, 111.3) (aromatic C3/C6),
0
0
14. Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, 5th ed.; John Wiley
and Sons, 1988.
15. The assignment of the major diastereoisomer as ‘syn’ with n-butanal as the
aliphatic aldehyde was done by analogy with earlier reports (Ref. 7), where of
course, the major isomer obtained was ‘anti’ in contrast to our present
observation.
0
0
(111.9, 112.3) (aromatic C6/C3), (114.3, 114.6) (C4 + C8 ), (115.0,
115.2) (aromatic C4), (121.8, 122.0) (aromatic C1),(128.7, 128.8)
0
0
0
0
(C5 + C7 ), 130.2 (C6 ), (145.9, 146.3) (C3 ), (150.9, 151.4) (C–OMe),