Ozonolysis of ortho-alkenylanilines

Article abstract of DOI:10.1023/A:1024477115507

Ozonolysis of N-acyl-2-(1-methylbut-2-enyl)- and N-acyl-2-(cyclopent-2- enyl)anilines followed by treatment with NaBH₄ afforded the corresponding 2-(2-hydroxyethyl-1-methyl) and 2-(1,5-dihydroxypent-2-yl) derivatives. The reaction can be direct

Full text of DOI:10.1023/A:1024477115507

Russian Chemical Bulletin, International Edition, Vol. 52, No. 4, pp. 989—992, April, 2003
989
Ozonolysis of orthoꢀalkenylanilines
A. G. Mustafin, D. I. Dyachenko,ꢀ R. R. Gataullin, G. Yu. Ishmuratov,
R. Ya. Kharisov, I. B. Abdrakhmanov, and G. A. Tolstikov
Institute of Organic Chemistry, Ufa Research Center of the Russian Academy of Sciences,
71 prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347 2) 35 6066. Eꢀmail: chemorg@anrb.ru
Ozonolysis of Nꢀacylꢀ2ꢀ(1ꢀmethylbutꢀ2ꢀenyl)ꢀ and Nꢀacylꢀ2ꢀ(cyclopentꢀ2ꢀenyl)anilines
followed by treatment with NaBH4 afforded the corresponding 2ꢀ(2ꢀhydroxyethylꢀ1ꢀmethyl)
and 2ꢀ(1,5ꢀdihydroxypentꢀ2ꢀyl) derivatives. The reaction can be directed to indole derivatives
by varying the nature of both the acyl group and reducing reagent.
Key words: orthoꢀalkenylanilines, ozone, indoles, Nꢀacetylꢀ2ꢀhydroxyꢀ3,4,4a,9aꢀtetrahydroꢀ
2Hꢀpyrano[2,3ꢀb]indole.
Scheme 1
Alkaloids bearing oxygenꢀcontaining cyclic fragments,
such as (+)ꢀcodaphniphylline,1 deacetylisoipecoside,2 and
strychnos indole alkaloids,3—5 have attracted considerꢀ
able recent attention of researchers. Earlier, indole deꢀ
rivatives and compounds containing the aldehyde group
have been prepared by ozonolysis of orthoꢀalkenylanilines
or their Nꢀtrifluoroacetyl derivatives followed by treatꢀ
ment with Me2S. The synthesis of indole derivatives by
oxidation of orthoꢀalkenylanilines proceeds through the
interaction of the newly formed carbonyl group with the
amino group,6 whereas heterocyclization in the synthesis
involving Nꢀtrifluoroacetyl derivatives is preceded by the
formation of aldehydeꢀcontaining compounds, which unꢀ
dergo cyclization upon the removal of the protective
trifluoroacetyl group.7 As part of our continuing studies
on the use of alkenylarylamines in the synthesis of natural
compounds and their analogs,8,9 we investigated the transꢀ
formations of Nꢀacylated orthoꢀalkenylanilines in the
course of ozonolysis.
NꢀBenzoylꢀ and Nꢀacetylꢀ2ꢀ(1ꢀmethylbutꢀ2ꢀenyl)aniꢀ
lines (1a and 1b, respectively) were oxidized by an equimoꢀ
lar amount of ozone in MeOH at 0 °C followed by treatꢀ
ment with NaBH4, Me2S, or NH2OH•HCl at room
temperature. Ozonization of compounds 1a,b in MeOH
followed by reduction with NaBH4 afforded alcohols
2a,b. Treatment of a reaction mixture with Me2S or
NH2OH•HCl gave rise to aldehydes 3a,b. Compound 3a
underwent cyclization to form 2ꢀhydroxyꢀ3ꢀmethylꢀ
indoline (4a) in 81% yield upon storage for 2 days (20 °C,
MeOH). The addition of catalytic amounts of TFA to
compound 4a led to dehydration of the latter giving rise
to indole derivative 5a in 84% yield (Scheme 1).
R = Bz (a), Ac (b)
tions with the use of Me2S or NH2OH•HCl proceeded,
apparently, through dialdehydes A, which underwent cyꢀ
clization to indolines 8a,b. Interesting tandem cyclizaꢀ
tion was observed in the case of anilide 6b (R = Ac)
resulting in the further transformation of compound 8b
into hemiacetal 9b10 (Scheme 2).
The O3/NaBH4 synthetic algorithm applied to Nꢀbenꢀ
zoylꢀ and Nꢀacetylꢀ2ꢀ(cyclopentꢀ2ꢀenyl)anilines (6a
and 6b) afforded diols 7a and 7b, respectively. The reacꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 937—940, April, 2003.
1066ꢀ5285/03/5204ꢀ989 $25.00 © 2003 Plenum Publishing Corporation

990
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Mustafin et al.
Scheme 2
sponding signals of minor diastereomer 9b´ (δC 92.93
and 87.81). The signals of the C(2) and C(9a) atoms of
the major diastereomer are observed at high field due to
the 1,3ꢀsyn interaction between the hydroxy group and
the C(9a)—N bond.11 Consequently, the indole ring and
the hydroxy group are in the syn and anti orientations in
diastereomers 9b″ and diastereomer 9b´, respectively.
Hence, the diastereomers differ by the orientation of the
OH group at the C(2) atom.
Therefore, the results of our study led to the concluꢀ
sion that products, which hold considerable promise
as biologically active compounds, can be easily preꢀ
pared from readily accessible orthoꢀalkenylaniline deꢀ
rivatives.
Experimental
The IR spectra were measured on a URꢀ20 instrument (Nujol
mulls). The 1H and 13C NMR spectra were recorded on a Bruker
AMꢀ300 instrument (300.13 MHz) in CDCl3 and acetoneꢀd6
with Me4Si as the internal standard. The GLC analysis was
carried out on a Chromꢀ5 chromatograph (helium as the
carried gas, 1200×3ꢀmm column, 5% SEꢀ30 on Chromaton
NꢀAWꢀDMCS, thermal conductivity detector). Column chroꢀ
matography was performed on an L 40/100 µm silica gel
(Chemapol). The course of the reactions and purities of the
products were monitored by TLC on Silufol UV 254 plates
(Kavalier).
The solvents (benzene, hexane, MeOH, EtOH, AcOEt,
CHCl3, CH2Cl2, and Et2O) were treated according to standard
procedures.12
NꢀAcylation of orthoꢀalkenylanilines (general method). Aceꢀ
tic anhydride or BzCl (24 mmol) was added dropwise with stirꢀ
ring to a solution of 2ꢀ(1ꢀmethylbutꢀ2ꢀenyl)ꢀ or 2ꢀ(cyclopentꢀ2ꢀ
enyl)aniline13,14 (18 mmol), respectively, in anhydrous benzene
(15 mL) at 0 °C. The precipitate of compound 1a, 1b, 6a, or 6b
that formed was filtered off, washed with hexane (50 mL), and
dried in vacuo.
NꢀBenzoylꢀ2ꢀ(1ꢀmethylbutꢀ2ꢀenyl)aniline (1a). The yield was
93%, m.p. 106—107 °C (from EtOH). Found (%): C, 81.33;
H, 7.02; N, 5.17. C18H19NO. Calculated (%): C, 81.51; H, 7.17;
N, 5.28. IR, ν/cm–1: 3250 (N—H), 1620 (C=O). 1H NMR
(CDCl3), δ: 1.42 and 1.78 (both d, 3 H each, C(5´)H3, C(1´)H3,
J = 7.0 Hz); 3.59 (m, 1 H, C(4´)H); 3.88 (s, 1 H, NH); 5.59 (m,
1 H, C(3´)H); 5.68 (m, 1 H, C(2´)H); 7.18—7.59 (m, 4 H, Ar);
7.80—8.28 (m, 5 H, Ar´). 13C NMR, δ: 17.9 (C(1´)); 19.5
(C(5´)); 38.5 (C(4´)); 123.1 (C(6)); 125.3 (C(2´)); 125.5 (C(5));
125.8 (C(4″)); 126.1 (C(4)); 127.1 (C(3)); 127.1 (C(6″)); 128.7
(C(3″)); 128.8 (C(7″)); 131.8 (C(5″)); 134.9 (C(2)); 135.1
(C(3″)); 135.3 (C(2″)); 135.8 (C(1)); 165.4 (C(1″)).
NꢀAcetylꢀ2ꢀ(1ꢀmethylbutꢀ2ꢀenyl)aniline (1b). The yield was
95%, m.p. 95—98 °C (from EtOH). Found (%): C, 76.67;
H, 8.29; N, 6.67. C13H17NO. Calculated (%): C, 76.85; H, 8.37;
N, 6.79. IR, ν/cm–1: 3220 (N—H); 1650 (C=O). 1H NMR
(CDCl3), δ: 1.38 and 1.72 (both d, 3 H each, C(5´)H3, C(1´)H3,
J = 7.0 Hz); 2.15 (s, 3 H, C(2″)H3); 3.53 (m, 1 H, C(4´)H); 3.85
(s, 1 H, NH); 5.43 (m, 1 H, C(3´)H); 5.57 (m, 1 H, C(2´)H);
7.10—7.32 (m, 4 H, Ar). 13C NMR, δ: 17.9 (C(1´)); 19.7 (C(5´));
24.3 (C(2″)); 37.9 (C(4´)); 124.2 (C(6)); 124.9 (C(2´)); 125.4
R = Bz (a), Ac (b)
b´, syn; b″, anti
Compound 9b was produced as two diastereomers
(1 : 5), as evidenced by the fact that its 13C NMR specꢀ
trum has a double number of signals of virtually all C
atoms. In the 1H NMR spectrum of 9b, the signals of the
protons at the C(2), C(9a), and C(4a) atoms are also
doubled.
The spinꢀspin coupling constants of the protons at
C(9a) and C(4a) for both diastereomers (5.9 and 5.3 Hz,
respectively) are indicative of the cisꢀfusion of the rings at
the C(9a) and C(4a) bonds.
The major diastereomer (9b″) gives a pseudotriplet of
the acetal proton O—CH—OH (J = 4.9 and 4.8 Hz) in
the 1H NMR spectrum. In this diastereomer, the anomeric
effect takes place, i.e., the hydroxy group is in the axial
position and in the syn orientation with respect to the
C(9a)—N bond of the indole ring. For the minor diasteꢀ
reomer (9b´), the signal of the same proton is observed as
a doublet of doublets (J = 2.3 and 9.2 Hz). The large spinꢀ
spin coupling constant indicates that the interacting proꢀ
tons are in the transꢀdiaxial orientations and that this
minor diastereomer contains the equatorial hydroxy group.
In the 13C NMR spectrum, the signals of the C(2) and
C(9a) atoms of major diastereomer 9b″ are observed at
higher field (δC 91.02 and 83.13) compared to the correꢀ

Ozonolysis of orthoꢀalkenylanilines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
991
(C(5)); 126.9 (C(4)); 127.0 (C(3)); 135.0 (C(2)); 135.4 (C(3´));
135.8 (C(1)); 168.3 (C(1″)).
compound 1b (0.5 g, 2.5 mmol) in anhydrous MeOH (15 mL) at
0 °C until the starting compound was completely consumed
(TLC control). The reaction mixture was purged with argon,
Me2S (1.6 mL) was added, volatile components were removed
on a rotary evaporator, and the residue was washed with H2O
(3×10 mL). The crystals that formed were filtered off and dried
in vacuo. Compound 3b was obtained in a yield of 0.32 g (68%),
m.p. 128—130 °C (from EtOH), Rf 0.55 (95 : 5 CH2Cl2—MeOH
as the eluent). Found (%): C, 69.17; H, 6.89; N, 7.22.
NꢀBenzoylꢀ2ꢀ(cyclopentꢀ2ꢀenyl)aniline (6a). The yield was
91%, m.p. 113—115 °C (from EtOH). Found (%): C, 82.02;
H, 6.24; N, 5.14. C18H17NO. Calculated (%): C, 82.13; H, 6.46;
N, 5.32. IR, ν/cm–1: 3280 (NH); 1630 (C=O); 780 (Ar).
1H NMR (CDCl3), δ: 1.82 and 2.41 (both m, 2 H each, C(5´)H2,
C(4´)H2); 3.72 (m, 1 H, C(1´)H); 4.10 (s, 1 H, NH); 5.90 (m,
1 H, C(2´)H); 6.08 (m, 1 H, C(3´)H); 7.12—7.49 (m, 4 H, Ar);
7.84—8.23 (m, 5 H, Ar´). 13C NMR, δ: 31.0 (C(5´)); 32.6
(C(4´)); 48.8 (C(1´)); 123.7 (C(6)); 125.1 (C(4)); 126.9 (C(5″));
127.2 (C(2)); 128.5 (C(2´)); 128.7 (C(5)); 128.8 (C(3″)); 131.8
(C(7″)); 133.3 (C(3´)); 133.8 (C(3)); 134.2 (C(2″)); 134.9
(C(6″)); 135.7 (C(4″)); 135.8 (C(1)); 165.5 (C(1″)).
NꢀAcetylꢀ2ꢀ(cyclopentꢀ2ꢀenyl)aniline (6b). The yield was
92%, m.p. 102—104 °C (from EtOH). Found (%): C, 77.40;
H, 7.22; N, 6.79. C13H15NO. Calculated (%): C, 77.61; H, 7.46;
N, 6.97. IR, ν/cm–1: 3220 (N—H); 1660 (C=O); 770 (Ar).
1H NMR (CDCl3), δ: 1.70 (m, 2 H, C(5´)H2); 2.12 (s, 3 H,
C(2″)H3); 2.45 (m, 2 H, C(4´)H2); 3.68 (m, 1 H, C(1´)H); 4.02
(s, 1 H, NH); 5.88 (m, 1 H, C(2´)H); 6.02 (m, 1 H, C(3´)H);
7.05—7.38 (m, 4 H, Ar). 13C NMR, δ: 24.1 (C(2″)); 31.5 (C(5´));
32.6 (C(4´)); 47.7 (C(1´)); 124.5 (C(6)); 125.5 (C(4)); 126.8
(C(2)); 128.3 (C(2´)); 133.0 (C(5)); 133.5 (C(3´)); 135.5 (C(3));
136.9 (C(1)); 168.7 (C(1″)).
C
11H13NO2. Calculated (%): C, 69.11; H, 6.81; N, 7.33. IR,
ν/cm–1: 3380 (OH); 1640 (C=O). 1H NMR (CDCl3), δ: 1.21
(d, 3 H, Me, J = 8.5 Hz); 2.38 (s, 3 H, Me); 3.13 (m, 1 H, CH);
5.23 (s, 1 H, NH); 6.98—7.27 (m, 4 H, Ar); 8.12 (s, 1 H, CH).
13C NMR, δ: 20.0 (C(3´)); 23.2 (C(1″)); 40.3 (C(2´)); 116.8
(C(4)); 124.0 (C(3)); 127.6 (C(5)); 127.7 (C(1)); 130.9 (C(6));
134.4 (C(2)); 170.5 (C(2″)); 180.1 (C(1´)).
B. An ozoneꢀoxygen mixture was passed with stirring through
a solution of compound 1b (0.5 g, 2.5 mmol) in anhydrous
MeOH (15 mL) at 0 °C until the starting compound was comꢀ
pletely consumed (TLC control). The reaction mixture was
purged with argon, NH2OH•HCl (0.55 g) was added, volatile
components were removed on a rotary evaporator, and the resiꢀ
due was washed with H2O (3×10 mL). The crystals that formed
were filtered off and dried in vacuo. Compound 3b was obtained
in a yield of 0.29 g (62%).
NꢀBenzoylꢀ2ꢀ(2ꢀhydroxyꢀ1ꢀmethylethyl)aniline (2a). An
ozoneꢀoxygen mixture was passed with stirring through a soluꢀ
tion of compound 1a (0.5 g, 1.9 mmol) in anhydrous MeOH
(15 mL) at 0 °C until the starting compound was consumed
(TLC control). The reaction mixture was purged with argon and
then NaBH4 (0.19 g, 5.0 mmol) was added. The mixture was
stirred for 1 h, a 1 : 10 AcOH—H2O mixture (2 mL) was added,
the resulting solution was stirred for 2 h, volatile components
were evaporated, and the residue was extracted with AcOEt
(3×10 mL). The extract was concentrated and dried in vacuo.
Compound 2a was obtained in a yield of 0.48 g (94%), Rf 0.40
(95 : 5 CH2Cl2—MeOH as the eluent). Found (%): C, 75.17;
H, 6.52; N, 5.34. C16H17NO2. Calculated (%): C, 75.29; H,
6.67; N, 5.49. IR, ν/cm–1: 3440 (OH); 3220 (NH); 1580 (C=O).
1H NMR (CDCl3), δ: 0.98 (d, 3 H, Me, J = 7.0 Hz); 2.88 (s,
1 H, CH); 3.30 (t, 1 H, OH, J = 9.7 Hz); 3.65 (dd, 2 H, CH2,
J = 3.4 Hz, J = 4.0 Hz); 4.85 (s, 1 H, NH); 6.91—7.43 (m, 4 H,
Ar); 7.44—7.70 (m, 5 H, Ar´). 13C NMR, δ: 16.3 (C(3´)); 34.7
(C(2´)); 68.7 (C(1´)); 123.1 (C(6)); 124.3 (C(4)); 124.8 (C(5));
125.3 (C(3)); 127.0 (C(3″)); 127.5 (C(5″)); 129.1 (C(2″)); 129.8
(C(6″)); 130.7 (C(4″)); 133.9 (C(1)); 135.2 (C(1″)); 135.7 (C(2));
163.4 (C(7″)).
NꢀAcetylꢀ2ꢀ(2ꢀhydroxyꢀ1ꢀmethylethyl)aniline (2b) was preꢀ
pared analogously from compound 1b in a yield of 0.46 g (97%),
Rf 0.35 (95 : 5 CH2Cl2—MeOH as the eluent). Found (%):
C, 68.43; H, 7.82; N, 7.34. C11H15NO2. Calculated (%):
C, 68.39; H, 7.77; N, 7.25. IR, ν/cm–1: 3480 (OH); 3260 (NH);
1560 (C=O). 1H NMR (CDCl3), δ: 1.13 (d, 3 H, Me, J =
7.0 Hz); 2.03 (s, 3 H, Me); 3.12 (s, 1 H, CH); 3.39 (t, 1 H, OH,
J = 9.5 Hz); 3.70 (dd, 2 H, CH2, J = 3.5 Hz, J = 4.0 Hz); 4.88 (s,
1 H, NH); 7.08—7.44 (m, 4 H, Ar). 13C NMR, δ: 16.7 (C(3´));
23.7 (C(1″)); 35.7 (C(2´)); 69.4 (C(1´)); 125.3 (C(6)); 126.2
(C(4)); 126.3 (C(5)); 126.6 (C(3)); 135.8 (C(1)); 138.0 (C(2));
170.0 (C(2″)).
NꢀBenzoylꢀ2ꢀhydroxyꢀ3ꢀmethylindoline (4a). Compound 4a
was prepared analogously to compound 3b (method A) from
compound 1a (0.5 g, 1.9 mmol) in a yield of 0.41 g (81%),
Rf 0.80 (95 : 5 CH2Cl2—MeOH as the eluent). Found (%):
C, 75.78; H, 5.81; N, 5.39. C16H15NO2. Calculated (%):
C, 75.89; H, 5.93; N, 5.53. 1H NMR (CDCl3), δ: 1.15 (m, 1 H,
CH); 1.23 (m, 1 H, CH); 3.18 (d, 3 H, Me, J = 7.0 Hz); 5.04 (s,
1 H, OH); 7.00—7.31 (m, 4 H, Ar); 7.36—7.68 (m, 5 H, Ar´).
13C NMR, δ: 19.5 (C(8)); 41.3 (C(7)); 97.3 (C(3)); 117.2 (C(6));
124.1 (C(4)); 124.4 (C(4´)); 127.4 (C(6´)); 127.4 (C(3a)); 127.5
(C(5)); 128.3 (C(3´)); 130.5 (C(7´)); 131.7 (C(5´)); 135.9
(C(2´)); 136.2 (C(2)); 140.8 (C(7a)); 170.3 (C(1´)).
NꢀBenzoylꢀ3ꢀmethylindole (5a). Trifluoroacetic acid
(0.5 mL) was added to a solution of compound 4a (0.41 g,
1.3 mmol) in CHCl3 (15 mL). After 15 min, the reaction mixꢀ
ture was successively washed with H2O (3×10 mL), 5% NaHCO3
(3×10 mL), and again with H2O. The solvent was removed on a
rotary evaporator. The residue was recrystallized from EtOH
and dried in vacuo. Compound 5a was prepared in a yield of
0.37 g (84%), m.p. 83—85 °C (from EtOH), Rf 0.85 (9 : 1
CH2Cl2—MeOH as the eluent). Found (%): C, 81.86; H, 5.68;
N, 6.12. C16H13NO. Calculated (%): C, 81.70; H, 5.53; N, 5.96.
1
IR, ν/cm–1: 1680 (C=O); 780 (Ar). H NMR (CDCl3), δ: 2.22
(s, 3 H, Me); 7.27—7.58 (m, 4 H, Ar); 7.52—7.75 (m, 5 H, Ar´);
8.33 (s, 1 H, CH). 13C NMR, δ: 10.6 (C(8)); 116.5 (C(7)); 117.9
(C(3)); 118.9 (C(6)); 124.4 (C(4)); 127.1 (C(4´)); 127.5 (C(6´));
128.4 (C(3a)); 128.7 (C(5)); 129.0 (C(3´)); 130.5 (C(7´));
131.6 (C(5´)); 131.8 (C(2´)); 135.0 (C(2)); 136.3 (C(7a));
168.4 (C(1´)).
NꢀBenzoylꢀ2ꢀ(1,5ꢀdihydroxypentꢀ2ꢀyl)aniline (7a). Comꢀ
pound 7a was prepared analogously to compound 2a from anilꢀ
ide 6a (0.5 g, 1.9 mmol) in a yield of 0.39 g (70%), Rf 0.30 (9 : 1
CH2Cl2—MeOH as the eluent). Found (%): C, 72.43; H, 9.93;
N, 4.81. C18H21NO3. Calculated (%): C, 72.24; H, 9.72; N, 4.68.
IR, ν/cm–1: 3340 (OH); 3240 (NH); 1600 (C=O). 1H NMR
(CDCl3), δ: 1.22 and 1.52 (both m, 2 H each, 2 CH2); 2.20 (m,
NꢀAcetylꢀ2ꢀ(1ꢀmethylꢀ2ꢀoxoethyl)aniline (3b). A. An ozoneꢀ
oxygen mixture was passed with stirring through a solution of

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Mustafin et al.
1 H, CH); 2.87 (dd, 2 H, CH2, J = 4.2 Hz, J = 5.0 Hz); 3.41 (m,
2 H, CH2); 3.97 (dd, 2 H, 2(OH), J = 8.0 Hz, J = 8.7 Hz); 4.63
(s, 1 H, NH); 7.86—7.10 (m, 4 H, Ar); 7.02—7.21 (m, 5 H, Ar´).
NꢀAcetylꢀ2ꢀ(1,5ꢀdihydroxypentꢀ2ꢀyl)aniline (7b). Compound
7b was prepared analogously to compound 7a from anilide 6b
(0.5 g, 2.5 mmol) in a yield of 0.50 g (85%), m.p. 54—56 °C,
Rf 0.30 (9 : 1 CH2Cl2—MeOH as eluent). Found (%): C, 66.04;
H, 8.24; N, 6.12. C13H19NO3. Calculated (%): C, 65.82; H, 8.02;
N, 5.91. IR, ν/cm–1: 3320 (OH); 3240 (NH); 1660 (C=O).
1H NMR (CDCl3), δ: 1.23 and 1.58 (both m, 2 H each, 2 CH2);
2.13 (s, 3 H, Me); 2.27 (m, 1 H, CH); 2.95 (dd, 2 H, CH2, J =
4.7 Hz, J = 5.7 Hz); 3.48 (m, 2H, CH2); 4.05 (dd, 2 H, 2(OH),
J = 8.0 Hz, J = 8.5 Hz); 4.72 (s, 1 H, NH); 7.05—7.33
(m, 4 H, Ar).
antiꢀDiastereomer (9b″). 1H NMR (CDCl3), δ: 1.6 (m, 1 H,
C(3)Ha); 1.83 (m, 1 H, C(3)Hb); 1.86 (m, 1 H, C(4)Ha); 2.31 (s,
3 H, C(2´)H3); 2.40 (m, 1 H, C(4)Hb); 3.41 (dd, 1 H, C(4a)H,
J = 7.05 Hz, J = 6.0 Hz); 4.99 (br.s, 1 H, OH); 5.20 (m, 1 H,
C(2)H, J = 4.8 Hz); 5.89 (d, 1 H, C(9a)H, J = 6.0 Hz); 7.05—7.24
(m, 3 H, Ar); 8.12 (d, 1 H, C(8)H, J = 7.95 Hz). 13C NMR, δ:
18.1 (C(4)); 22.8 (C(2´)); 26.7 (C(3)); 39.8 (C(4a)); 83.1
(C(9a)); 91.0 (C(2)); 116.6 (C(8)); 122.9 (C(5)); 123.9 (C(6));
127.5 (C(7)); 132.5 (C(4b)); 142.0 (C(8a)); 170.1 (C(1´)).
References
1. C. H. Heathcock, J. C. Kath, and R. B. Ruggeri, J. Org.
Chem., 1995, 60, 1120.
NꢀBenzoylꢀ2ꢀhydroxyꢀ3ꢀ(3ꢀoxopropyl)indoline (8a). A. Comꢀ
pound 8a was prepared analogously to compound 3b (method A)
from anilide 6a (0.5 g, 1.9 mmol) in a yield of 0.39 g (70%), m.p.
55—57 °C, Rf 0.45 (9 : 1 CH2Cl2—MeOH as the eluent).
Found (%): C, 73.41; H, 5.92; N, 4.69. C18H17NO3. Calcuꢀ
lated (%): C, 73.22; H, 5.76; N, 4.75. IR, ν/cm–1: 3350 (OH);
1660 (C=O); 780 (Ar). 1H NMR (CDCl3), δ: 1.72 and 1.98
(both m, 1 H each, C(3)H, C(4)H); 3.31 (m, 1 H, C(4a)H);
4.38 (dd, 1 H, C(2)H, J = 5.5 Hz, J = 6.7 Hz); 5.18 (d, 1 H,
C(9a)H, J = 7.7 Hz); 5.80 (br.s, 1 H, OH); 7.05—7.32 (m, 4 H,
Ar); 7.38—7.75 (m, 5 H, Ar). 13C NMR, δ: 16.8 (C(4)); 27.6
(C(3)); 40.0 (C(4a)); 89.7 (C(9a)); 91.6 (C(2)); 118.0 (C(8));
122.7 (C(5)); 123.9 (C(6)); 124.5 (C(3´)); 125.3 (C(7´)); 127.8
(C(7)); 128.5 (C(4´)); 128.7 (C(6´)); 130.7 (C(5´)); 133.2
(C(4b)); 135.8 (C(2´)); 142.2 (C(8a)); 169.4 (C(1´)).
B. Compound 8a was prepared analogously to compound 3b
(method B) from anilide 6a (0.5 g, 1.9 mmol) in a yield of
0.34 g (61%).
NꢀAcetylꢀ2ꢀhydroxyꢀ3,4,4a,9aꢀtetrahydroꢀ2Hꢀpyraꢀ
no[2,3ꢀb]indole (9b) (mixture of diastereomers). A. Compound 9b
was prepared analogously to compound 3b (method A) from
anilide 6b (0.5 g, 2.5 mmol) in a yield of 0.49 g (85%), m.p.
136—137 °C (from EtOH), Rf 0.4 (9 : 1 CH2Cl2—MeOH as the
eluent). Found (%): C, 67.09; H, 6.25; N, 5.73. C13H15NO3.
Calculated (%): C, 66.95; H, 6.44; N, 6.01.
2. A. Itoh, T. Tanahashi, and N. Nagakura, Chem. Pharm.
Bull., 1994, 42, 2208.
3. M. E. Kuehne and F. Xu, J. Org. Chem., 1993, 58, 7490.
4. M. E. Kuehne, F. Xu, and C. S. Brook, J. Org. Chem., 1994,
59, 7803.
5. J. Bonjoch, D. Sole, and J. Bosch, J. Am. Chem. Soc., 1995,
117, 11017.
6. S. J. Danishefsky and G. B. Phillips, Tetrahedron Lett., 1984,
25, 3159.
7. W. B. Lutz, C. R. McNamara, M. R. Olinger, D. F. Schmidt,
D. E. Doster, and M. D. Fiedler, J. Heterocycl. Chem., 1984,
21, 1183.
8. A. G. Mustafin, I. N. Khalilov, V. M. Sharafutdinov, D. I.
D´yachenko, I. B. Abdrakhmanov, and G. A. Tolstikov, Izv.
Akad. Nauk, Ser. Khim., 1997, 630 [Russ. Chem. Bull., 1997,
46, 608 (Engl. Transl.)].
9. D. I. D´yachenko, A. G. Mustafin, V. V. Shereshovets, N. N.
Kabal´nova, V. P. Kazakov, I. B. Abdrakhmanov, and G. A.
Tolstikov, Izv. Akad. Nauk, Ser. Khim., 1998, 1654 [Russ.
Chem. Bull., 1998, 47, 1611 (Engl. Transl.)].
10. A. G. Mustafin, D. I. D´yachenko, T. V. Khakimova, L. V.
Spirikhin, G. Yu. Ishmuratov, I. B. Abdrakhmanov, and
G. A. Tolstikov, Mendeleev Commun., 2001, 146.
11. J. B. Stothers, Carbonꢀ13 NMR Spectroscopy, Academic
Press, New York, 1972, p. 56.
B. Compound 9b was prepared analogously to compound 3b
(method B) from anilide 6b (0.5 g 2.5 mmol) in a yield of
0.45 g (78%).
12. A. J. Gordon and R. A. Ford, The Chemist´s Companion,
Wiley, New York, 1972, 520 pp.
13. I. B. Abdrakhmanov, V. M. Sharafutdinov, and G. A.
Tolstikov, Izv. Akad. Nauk SSSR, Ser. Khim., 1982, 2160
[Bull. Acad. Sci. USSR, Div. Chem. Sci., 1982, 31, 1910 (Engl.
Transl.)].
1
synꢀDiastereomer (9b´). H NMR (CDCl3), δ: 1.6 (m, 1 H,
C(3)Ha); 1.83 (m, 1 H, C(3)Hb); 1.86 (m, 1 H, C(4)Ha); 2.39 (s,
3 H, C(2´)H3); 2.40 (m, 1 H, C(4)Hb); 3.28 (m, 1 H, C(4a)H);
4.88 (dd, 1 H, C(2)H, J = 5.3 Hz, J = 9.1 Hz); 5.00 (br.s, 1 H,
OH); 5.70 (d, 1 H, C(9a)H, J = 5.3 Hz); 7.05—7.24 (m, 3 H,
Ar); 8.09 (d, 1 H, C(8)H, J = 7.8 Hz). 13C NMR, δ: 20.6 (C(4));
22.9 (C(2´)); 27.6 (C(3)); 38.5 (C(4a)); 87.8 (C(9a)); 92.9
(C(2)); 116.6 (C(8)); 122.5 (C(5)); 123.8 (C(6)); 127.5 (C(7));
132.5 (C(4b)); 141.9 (C(8a)); 170.1 (C(1´)).
14. Ch. Duschek, W. Hobold, R. Naick, H. Schmidt, and N. T.
Yen, J. Prakt. Chem., 1975, 317, 491.
Received September 23, 2002;
in revised form December 15, 2002