Enantiopure 3-Amino-Substituted 1-Indanones, 1-Tetralones, and 1-Benzosuberones via Friedel-Crafts Cyclisation of ω-Aryl-β-benzamido Acids

Article abstract of DOI:10.1055/s-0034-1380675

Conjugate addition of enantiopure lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to a range of ω-aryl-α,β-unsaturated esters gives the corresponding ω-aryl-β-amino esters as single diastereoisomers in high yields. Friedel-Crafts cyclisation of the pendant c

Full text of DOI:10.1055/s-0034-1380675

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1541–1544
letter
1541
S. G. Davies et al.
Letter
Synlett
Enantiopure 3-Amino-Substituted 1-Indanones, 1-Tetralones, and
1-Benzosuberones via Friedel–Crafts Cyclisation of ω-Aryl-β-benz-
amido Acids
Stephen G. Davies*
Euan C. Goddard
Paul M. Roberts
Angela J. Russell
James E. Thomson
O
O
(i) TFA
(ii) (ClCO)2
(iii) AlCl3
Ph
NH
Ph
NH
CO2t-Bu
( )n
( )n
Friedel–Crafts
cyclisation
O
OMe
OMe
Department of Chemistry, University of Oxford, Chemistry Research
Laboratory, Mansfield Road, Oxford, OX1 3TA, UK
steve.davies@chem.ox.ac.uk
enantiopure w-aryl-
b-benzamido ester
(n = 0, 1, or 2)
3-amino-substituted
1-indanones, 1-tetralones,
and 1-benzosuberones
Dedicated to Peter Vollhardt on the occasion of his 69th birthday
Received: 06.03.2015
Accepted: 03.04.2015
Published online: 20.05.2015
DOI: 10.1055/s-0034-1380675; Art ID: st-2015-b0157-l
MeO
MeO
HO
O
NHAc
OMe
Abstract Conjugate addition of enantiopure lithium (R)-N-benzyl-N-
(α-methylbenzyl)amide to a range of ω-aryl-α,β-unsaturated esters
gives the corresponding ω-aryl-β-amino esters as single diastereoiso-
mers in high yields. Friedel–Crafts cyclisation of the pendant carbonyl
group onto the ω-aryl ring then gives a range of 3-amino-substituted 1-
indanones, 1-tetralones, and 1-benzosuberones, representing an effi-
cient and short protocol for the preparation of these benzo-fused car-
bocycles in enantiopure form.
NMe
O
H
HO
OMe
colchicine
morphine
HN
CO2H
N
H
Me
Key words 1-benzosuberone, conjugate addition, Friedel–Crafts, 1-
indanone, 1-tetralone
lysergic acid
Figure 1
Benzo-fused carbocycles bearing an exocyclic amino
functionality are substructural fragments within a range of
alkaloids, as illustrated by the structures of morphine, col-
chicine, and lysergic acid (Figure 1). Herein we describe the
development of a generally applicable, efficient, and short
protocol to facilitate the preparation of a range these scaf-
folds, viz. 3-amino-substituted 1-indanones, 1-tetralones,
and 1-benzosuberones, in enantiopure form. The synthetic
route employs the highly diastereoselective conjugate addi-
tion of an enantiopure lithium amide to an ω-aryl-α,β-un-
saturated ester as the key step to introduce the stereochem-
istry.1 This is followed by Friedel–Crafts cyclisation of the
corresponding β-amino acids to give the benzo-fused car-
bocyclic scaffolds.2
Conjugate addition of lithium (R)-N-benzyl-N-(α-meth-
ylbenzyl)amide to α,β-unsaturated esters 1–3 gave the cor-
responding β-amino esters 4–6 in ≥98% yield, and as a sin-
gle diastereoisomer in each case. The preparations of β-
amino esters 4 and 5 via this route have both been reported
previously,3,4 whilst the absolute (R,R)-configuration within
6 was confidently assigned by reference to our transition-
state mnemonic for this class of conjugate addition reac-
tion.5 Treatment of 4–6 with TFA gave the intermediate β-
amino acids (as the trifluoroacetate salts); treatment with
oxalyl chloride furnished the corresponding acid chlorides,
which were subjected to AlCl3 in the same reaction vessel to
give the corresponding benzo-fused carbocycles 7–9 as the
exclusive products in >90% mass return. It is interesting to
note that, in all these cases, cyclization onto the ω-phenyl
group is the exclusive reaction pathway, particularly in the
case of formation of 9: no traces of products arising from
cyclization on to either the N-benzyl or N-α-methylbenzyl
groups were formed in any case. A plausible rationale for
this observation is that cyclisation proceeding onto either
the N-benzyl or N-α-methylbenzyl groups results in the de-
velopment of 1,2-strain between the nonparticipating, exo-
cyclic N-substituent and the β-substituent, which may thus
retard this pathway. 1-Indanone 7 was isolated in 51% yield
as a single diastereoisomer after purification by column
chromatography on silica gel. The relative configuration
within 7 was confirmed by single-crystal X-ray diffraction
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1541–1544

1542
S. G. Davies et al.
Letter
Synlett
analysis (Figure 2),6 and the absolute (3S,αR)-configuration
could be assigned from the known configuration of the α-
methylbenzyl stereocenter. Unfortunately, all attempts to
purify 1-tetralone 8 and 1-benzosuberone 9 led to decom-
position: 1-naphthol (10) was produced from 8 and α,β-un-
saturated ketone 11 was produced from 9, along with (R)-
N-benzyl-N-(α-methylbenzyl)amine in both cases. These
observations are consistent with a retroconjugate addition
pathway being promoted by the chromatography medium;
in the case of 1-tetralone 8, the initially formed α,β-unsatu-
rated ketone undergoes tautomerisation to the correspond-
ing aromatic compound 10 (Scheme 1).
94%) over the two steps. Subsequent treatment with TFA,
conversion into the corresponding acid chlorides, and then
treatment with AlCl3 led to complete consumption of start-
ing material and the exclusive (>95%) formation of 1-inda-
none 15, 1-tetralone 16, and 1-benzosuberone 17, respec-
tively. All of these carbocycles were found to be stable to-
wards chromatography on silica gel, affording 15, 16, and
17 in 71%, 87%, and 71% isolated yields, respectively
(Scheme 2).
Ph
O
O
Ph
N
Ph
(i), (ii)
NH
Ph
(iii)–(v)
NH
CO2t-Bu
CO2t-Bu
Ph
Ph
( )n
( )n
( )n
Ph
N
Ph
N
O
(ii)–(iv)
(i)
CO2t-Bu
CO2t-Bu
( )n
( )n
( )n
n = 0, 4
n = 1, 5
n = 2, 6
n = 0, 12, 93%
n = 1, 13, 90%
n = 2, 14, 94%
n = 0, 15, 71%
n = 1, 16, 87%
n = 2, 17, 71%
O
Scheme 2 Reagents and conditions: (i) H2, Pd(OH)2/C, MeOH, H2O,
n = 0, 7, 51%a
n = 1, 8, 93%b
n = 2, 9, 91%b
n = 0, 1
n = 1, 2
n = 2, 3
n = 0, 4, quant.
n = 1, 5, 98%
n = 2, 6, quant.
AcOH, r.t., 72 h, then NaHCO3; (ii) PhCOCl, Et3N, CH2Cl2, 0 °C to r.t., 16
h; (iii) TFA, r.t., 30 min; (iv) (COCl)2, DMF, CH2Cl2, 30 min; (v) AlCl3,
CH2Cl2, 0 °C, 16 h. Compounds 4–6 are single diastereoisomers.
The effect of introduction of either a para- or meta-
methoxy group into the ω-aromatic ring upon the course of
the cyclization reaction for the 1-indanone and 1-tetralone
precursors was next investigated. The N-benzoyl-protected
cyclization precursors 26–29 were prepared in a similar
fashion to 15–17. Conjugate addition of lithium (R)-N-ben-
zyl-N-(α-methylbenzyl)amide to α,β-unsaturated esters
18–21 gave the corresponding β-amino esters 22–25 in
very high yield as single diastereoisomers. The preparations
of β-amino esters 223,7 and 247 via this route have both
been reported previously, whilst the absolute (R,R)-configu-
rations within 23 and 25 were confidently assigned by ref-
erence to our transition-state mnemonic for this class of
conjugate addition reaction.5 N-Protecting-group manipu-
lation then gave β-amido esters 26–29 (Scheme 3).
OH
O
10
11
Scheme 1 Reagents and conditions: (i) Lithium (R)-N-benzyl-N-(α-
methylbenzyl)amide, THF, –78 °C, 2 h; (ii) TFA, r.t., 30 min; (iii) (COCl)2,
DMF, CH2Cl2, 30 min; (iv) AlCl3, CH2Cl2, 0 °C, 16 h. Compounds 1–9 are
single diastereoisomers. a Isolated yield after chromatography on silica
gel. b Crude mass return.
Ph
O
Ph
N
Ph
NH
CO2t-Bu
CO2t-Bu
CO2t-Bu
(i)
(ii), (iii)
( )n
( )n
( )n
OMe
OMe
OMe
Figure 2 Single crystal X-ray structure of 7. Some H atoms have been
n = 0, 3-MeO, 26, 96%
n = 1, 3-MeO, 27, 80%
n = 0, 4-MeO, 28, 95%
n = 1, 4-MeO, 29, 79%
omitted for clarity.
n = 0, 3-MeO, 18
n = 1, 3-MeO, 19
n = 0, 4-MeO, 20
n = 1, 4-MeO, 21
n = 0, 3-MeO, 22, 93%
n = 1, 3-MeO, 23, 97%
n = 0, 4-MeO, 24, 95%
n = 1, 4-MeO, 25, 96%
An alternative N-protecting-group strategy was next in-
vestigated. β-Amino esters 4–6 were subjected to hydroge-
nolysis followed by treatment with PhCOCl to furnish N-
benzoyl-protected β-amido esters 12–14 in high yield (90–
Scheme 3 Reagents and conditions: (i) Lithium (R)-N-benzyl-N-(α-
methylbenzyl)amide, THF, –78 °C, 2 h; (ii) H2, Pd(OH)2/C, MeOH, H2O,
AcOH, r.t., 72 h, then NaHCO3; (iii) PhCOCl, Et3N, CH2Cl2, 0 °C to r.t., 16
h. Compounds 18–25 are single diastereoisomers.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1541–1544

1543
S. G. Davies et al.
Letter
Synlett
Sequential treatment of 3-methoxy-substituted 26 with
TFA, oxalyl chloride, and then AlCl3 gave a mixture of prod-
ucts, containing 1-indanones 30 and 31 in a 53:47 ratio.
Column chromatography furnished 30 and 31 in 32% and
28% isolated yields, respectively. Cyclisation of the homolo-
gous substrate 27, meanwhile, gave 1-tetralones 32 and 33
in a 60:40 ratio, contaminated with small amounts of un-
identifiable byproducts. 1-Tetralones 32 and 33 were isolat-
ed in 58% and 34% yields, respectively, after column chro-
matography. These product distributions are consistent ei-
ther with the directing effect of the methoxy group
promoting the attack para and ortho to itself, and so form-
ing a mixture of 30/31 or 32/33 directly, or a mechanism in-
volving the initial formation of a spirocyclic intermediate
being followed by acyl migration and re-aromatization8
(Scheme 4).
In conclusion, it has been demonstrated that Friedel–
Crafts cyclisation of a range of ω-aryl-β-amino acids gives
the corresponding 3-amino-substituted 1-indanone, 1-te-
tralone, and 1-benzosuberone motifs in good yield. The
synthetic route reported herein represents an efficient and
short protocol for the preparation of these carbocycles in
enantiopure form.9
References and Notes
(1) (a) Davies, S. G.; Price, P. D.; Smith, A. D. Tetrahedron: Asymme-
try 2005, 16, 2833. (b) Davies, S. G.; Fletcher, A. M.; Roberts, P.
M.; Thomson, J. E. Tetrahedron: Asymmetry 2012, 23, 1111.
(2) For related examples, see: (a) Horton, W. J.; Thompson, G. J Am.
Chem. Soc. 1954, 76, 1909. (b) Zymalkowski, P.; Dornhege, E.
Tetrahedron Lett. 1968, 55, 5743. (c) Rault, S.; Dallemange, P.;
Robba, M. Bull. Soc. Chim. Fr. 1987, 6, 1079. (d) Kimbara, K.;
Katsumata, Y.; Saigo, K. Chem. Lett. 2002, 266.
(3) For the preparation of 4 and 22, see: Davies, S. G.; Garrido, N.
M.; Kruchinin, D.; Ichihara, O.; Kotchie, L. J.; Price, P. D.; Price
Mortimer, A. J.; Russell, A. J.; Smith, A. D. Tetrahedron: Asymme-
try 2006, 17, 1793.
(4) For the preparation of 5, see: (a) Bunnage, M. E.; Davies, S. G.;
Goodwin, C. J. Synlett 1993, 731. (b) Bunnage, M. E.; Davies, S.
G.; Goodwin, C. J.; Ichihara, O. Tetrahedron 1994, 50, 3975.
(5) Costello, J. F.; Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry
1994, 5, 1999.
O
O
O
Ph
NH
Ph
NH
Ph
NH
(i)–(iii)
CO2t-Bu
( )n
( )n
( )n
+
30/31 = 53:47
32/33 = 60:40
O
O
OMe
MeO
OMe
n = 0, 26
n = 1, 27
n = 0, 30, 32%
n = 1, 32, 58%
n = 0, 31, 28%
n = 1, 33, 34%
(6) Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 1044396.
Scheme 4 Reagents and conditions: (i) TFA, r.t., 30 min; (ii) (COCl)2,
DMF, CH2Cl2, 30 min; (iii) AlCl3, CH2Cl2, 0 °C, 16 h.
(7) For the preparation of 22 and 24, see: Davies, S. G.; Mulvaney, A.
W.; Russell, A. J.; Smith, A. D. Tetrahedron: Asymmetry 2007, 18,
1554.
(8) (a) Coote, S. J.; Davies, S. G.; Middlemiss, D.; Naylor, A. J. Chem.
Soc., Perkin Trans. 1 1989, 2223. (b) Coote, S. J.; Davies, S. G.;
Fletcher, A. M.; Roberts, P. M.; Thomson, J. E. Chem. Asian J.
2010, 5, 589.
(9) General experimental procedure (ester hydrolysis/acid chloride
formation/Friedel–Crafts cyclisation sequence). The requisite β-
benzamido tert-butyl ester (1 mmol) was dissolved in TFA (2
mL) and the solution was stirred at r.t. for 30 min. After this
time the TFA was removed in vacuo. The residue was co-evapo-
rated with PhMe (3 × 4 mL), then dried under high vacuum. The
residue was then dissolved in CH2Cl2 (2 mL) and one drop of
DMF, then (COCl)2 (1.1 mmol) was added drop-wise. The resul-
tant solution was stirred until cessation of effervescence, then
cooled to 0 °C. AlCl3 (2.0 mmol) was added portion-wise, and
the resultant solution was stirred for 16 h. The reaction was
quenched with H2O (0.5 mL) and the resultant mixture was
stirred for 10 min. The layers were separated and the aqueous
layer was extracted with CH2Cl2 (3 × 5 mL). The combined
organic layers were washed sequentially with 10% aq HCl (20
mL), sat. aq NaHCO3 (20 mL) and brine (20 mL), then dried
(MgSO4), filtered and concentrated in vacuo.
Following an analogous sequence of transformations,
cyclization of 4-methoxy-substituted 28 resulted in com-
plete consumption of the starting material to give a mixture
of products containing 1-indanone 36. Chromatography al-
lowed the isolation of 36 in 41% yield. In contrast, reaction
of the homologous compound 29 resulted in the exclusive
formation of a single product 37, which was isolated in 73%
yield. Again considering the strong directing effect of the
methoxy group, which in both of these cases would direct
attack exclusively para to itself (attack ortho being geomet-
rically impossible), these cyclisation reactions presumably
proceed via a spirocyclic, cationic intermediate8 (Scheme
5).
O
O
O
Ph
NH
Ph
NH
NH
CO2t-Bu
Ph
( )n
( )n
( )n
(i)–(iii)
O
O
Data for 16: solid; mp 168–169 °C; [α]21D +23.1 (c 1.1, CHCl3);
IR: νmax 1679, 1642; 1H NMR (400 MHz, CDCl3): δ = 2.83 (1 H,
dd, J = 16.9, 8.8 Hz), 3.05 (1 H, ddd, J = 16.9, 4.2, 0.9 Hz), 3.12 (1
H, dd, J = 16.1, 8.0 Hz), 3.43 (1 H, dd, J = 16.1, 4.5 Hz), 4.80–4.88
(1 H, m), 6.33 (1 H, d, J = 7.0 Hz), 7.27–7.72 (8 H, m), 8.05–8.08
(1 H, m); 13C NMR (100 MHz, CDCl3): δ = 35.7, 44.6, 46.0, 126.9,
127.2, 128.6, 129.6, 131.7, 132.1, 134.3, 140.6, 167.2, 195.7;
OMe
n = 0, 28
n = 1, 29
OMe
n = 0, 34
n = 1, 35
OMe
n = 0, 36, 41%
n = 1, 37, 73%
Scheme 5 Reagents and conditions: (i) TFA, r.t., 30 min; (ii) (COCl)2,
DMF, CH2Cl2, 30 min; (iii) AlCl3, CH2Cl2, 0 °C, 16 h.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1541–1544

1544
S. G. Davies et al.
Letter
Synlett
+
HRMS (ESI+): m/z calcd for C17H16NO2 ([M+H]+): 266.1181;
found: 266.1185.
8.8, 1.9 Hz), 7.23–7.52 (4 H, m), 7.70 (2 H, d, J = 8.1 Hz); 13C NMR
(100 MHz, CDCl3): δ = 31.9, 44.9, 46.2, 55.6, 112.6, 126.8, 128.3,
130.4, 131.6, 131.7, 132.8, 141.4, 142.7, 164.3, 166.4, 195.1;
Data for 17: oil; [α]22D +19.8 (c 1.4, CHCl3); IR: νmax 1674, 1627;
1H NMR (400 MHz, CDCl3): δ = 1.74–1.82 (1 H, m), 2.46–2.55 (1
H, m), 2.83 (1 H, dd, J = 17.0, 1.6 Hz), 2.94 (1 H, dd, J = 14.0, 6.3
Hz), 3.18 (1 H, dt, J = 14.0, 4.2 Hz), 3.82 (1 H, ddd, J = 17.0, 11.9,
1.8 Hz), 4.57–4.66 (1 H, m), 6.80 (1 H, br s), 7.21–7.48 (5 H, m),
7.66–7.81 (3 H, m), 8.04 (1 H, d, J = 8.0 Hz); 13C NMR (100 MHz,
CDCl3): δ = 31.1, 32.9, 45.7, 47.0, 123.3, 126.8, 127.1, 127.3,
129.1, 130.2, 131.6, 133.1, 134.2, 137.5, 138.5, 142.2, 167.9,
HRMS (ESI+): m/z calcd for C18H17NNaO3 ([M+Na]+): 318.1101;
+
found: 318.1092.
Data for 33: solid; mp 84–85 °C; [α]22D +2.4 (c 1.2, CHCl3); IR:
ν
max 1682; 1H NMR (400 MHz, CDCl3): δ = 2.77 (1 H, dd, J = 16.8,
8.1 Hz), 2.96 (1 H, dd, J = 16.8, 4.6 Hz), 3.07 (1 H, dd, J = 15.4, 6.5
Hz), 3.25 (1 H, dd, J = 15.4, 3.1 Hz), 3.86 (3 H, s), 4.78–4.85 (1 H,
m), 6.40 (1 H, d, J = 7.5 Hz), 7.41–7.57 (5 H, m), 7.82 (2 H, d, J =
7.2 Hz); 13C NMR (100 MHz, CDCl3): δ = 31.3, 42.4, 46.7, 55.9,
109.9, 122.6, 124.0, 126.8, 128.4, 131.6, 133.8, 134.9, 146.2,
+
201.6; HRMS (ESI+): m/z calcd for C18H17NNaO2 ([M+Na]+):
302.1156; found: 302.1151.
+
Data for 30: solid; mp 80–81 °C; [α]23D +4.6 (c 0.7, CHCl3); IR:
161.2, 166.7, 195.0; HRMS (ESI+): m/z calcd for C18H17NNaO3
ν
max 1682; 1H NMR (400 MHz, CDCl3): δ = 2.58 (1 H, dd, J = 19.0,
([M+Na]+): 318.1106; found: 318.1105.
3.3 Hz), 2.96 (1 H, dd, J = 19.0, 7.7 Hz), 3.88 (3 H, s), 5.86–5.90 (1
H, m), 6.78 (1 H, d, J = 8.3 Hz), 6.95 (1 H, dd, J = 8.6, 2.1 Hz), 7.08
(1 H, d, J = 2.1 Hz), 7.44–7.48 (2 H, m), 7.52–7.54 (1 H, m), 7.61
(1 H, d, J = 8.6 Hz), 7.84–7.86 (2 H, m); 13C NMR (100 MHz,
CDCl3): δ = 45.1, 47.7, 55.9, 109.0, 117.4, 125.1, 127.1, 128.7,
131.9, 133.5, 137.4, 157.1, 166.0, 167.4, 201.7; HRMS (ESI+): m/z
calcd for C17H16NO3+ ([M+H]+): 282.1130; found: 282.1130.
Data for 31: solid; mp 83–85 °C; [α]23D +6.9 (c 0.5, CHCl3); IR:
Data for 36: solid; mp 79–81 °C; [α]23D +5.7 (c 0.5, CHCl3); IR:
ν
max 1682; 1H NMR (400 MHz, CDCl3): δ = 2.63 (1 H, dd, J = 19.3,
3.1 Hz), 3.36 (1 H, dd, J = 19.3, 7.4 Hz), 3.86 (3 H, s), 5.86 (1 H, td,
J = 7.8, 3.0 Hz), 6.51 (1 H, d, J = 8.0 Hz), 7.20 (1 H, d, J = 2.5 Hz),
7.26 (1 H, dd, J = 8.5, 2.5 Hz), 7.45 (2 H, t, J = 7.7 Hz), 7.54 (1 H, t,
J = 7.3 Hz), 7.58 (1 H, d, J = 8.5 Hz), 7.80 (2 H, d, J = 7.5 Hz); 13
C
NMR (100 MHz, CDCl3): δ = 45.8, 47.5, 55.7, 104.8, 124.7, 126.9,
127.0, 128.7, 131.9, 133.7, 138.3, 146.4, 160.9, 166.8, 203.2;
+
ν
max 1682; 1H NMR (400 MHz, CDCl3): δ = 2.56 (1 H, dd, J = 19.0,
HRMS (ESI+): m/z calcd for C17H15NNaO3 ([M+Na]+): 304.0944;
3.3 Hz), 3.20 (1 H, dd, J = 19.0, 7.7 Hz), 3.84 (3 H, s), 5.82 (1 H, td,
J = 8.1, 3.3 Hz), 6.89 (1 H, dd, J = 8.5, 2.2 Hz), 7.04 (1 H, d, J = 2.2
Hz), 7.09 (1 H, d, J = 8.5 Hz), 7.41–7.44 (2 H, m), 7.56–7.58 (2 H,
m), 7.85 (2 H, d, J = 7.4 Hz); 13C NMR (100 MHz, CDCl3): δ = 44.9,
47.6, 55.9, 109.0, 117.4, 124.9, 127.1, 128.7, 129.8, 131.9, 133.7,
found: 304.0934.
Data for 37: solid; mp 86–87 °C; [α]22D +7.2 (c 0.3, CHCl3); IR:
ν
max 1682; 1H NMR (400 MHz, CDCl3): δ = 2.78 (1 H, dd, J = 16.8,
9.3 Hz), 2.97 (1 H, dd, J = 16.8, 3.7 Hz), 3.02 (1 H, dd, J = 15.9, 8.5
Hz), 3.29 (1 H, dd, J = 16.8, 4.1 Hz), 3.79 (3 H, s), 4.70–4.79 (1 H,
m), 6.78 (1 H, d, J = 7.6 Hz), 7.09 (1 H, dd, J = 8.4, 2.8 Hz), 7.17 (1
H, d, J = 8.4 Hz), 7.33–7.37 (2 H, m), 7.43–7.45 (1 H, m), 7.46 (1
H, d, J = 2.8 Hz), 7.71 (2 H, d, J = 7.3 Hz); 13C NMR (100 MHz,
CDCl3): δ = 34.9, 44.4, 46.2, 55.5, 109.2, 122.5, 127.1, 128.6,
130.7, 131.7, 132.8, 133.3, 134.1, 158.8, 167.4, 196.0; HRMS
157.1, 165.9, 167.5, 201.9; HRMS (ESI+): m/z calcd for C17H15NNaO3
+
([M+Na]+): 304.0944; found: 304.0937.
Data for 32: solid; mp 80–83 °C; [α]23D +10.6 (c 1.0, CHCl3); IR:
ν
max 1682; 1H NMR (400 MHz, CDCl3): δ = 2.79 (1 H, dd, J = 16.9,
8.3 Hz), 2.97 (1 H, dd, J = 16.9, 4.1 Hz), 3.09 (1 H, dd, J = 15.9, 7.5
Hz), 3.28 (1 H, dd, J = 15.9, 6.1 Hz), 3.88 (3 H, s), 4.80–4.88 (1 H,
m), 6.20 (1 H, d, J = 7.2 Hz), 6.76 (1 H, app s), 6.90 (1 H, dd, J =
(ESI+):m/z calcd for C18H18NO3 ([M+H]+): 296.1287; found:
296.1286.
+
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1541–1544