Synthesis of nonracemic 9-(1-methoxycarbonylethyl)-1,2,3,4-tetrahydrocarbazole

Article abstract of DOI:10.1023/B:COHC.0000014411.33252.d1

A new approach has been proposed to the synthesis of indole derivatives containing a chiral substituent at the nitrogen atom, comprizing Fischer indolization of phenylhydrazines with a chiral substituent at the α-nitrogen atom. The initial hydrazines were obtained by the alkylation (Mitsunobu reaction applying optically active esters of lactic acid) of anilines containing an electron-accepting substituent at the amino group. Subsequent removal of the activating acceptor grouping was realized by nitrosation of the chiral secondary aniline followed by reduction of the corresponding N-nitroso compound.

Full text of DOI:10.1023/B:COHC.0000014411.33252.d1

Chemistry of Heterocyclic Compounds, Vol. 39, No. 11, 2003
SYNTHESIS OF NONRACEMIC
9-(1-METHOXYCARBONYLETHYL)-
1,2,3,4-TETRAHYDROCARBAZOLE*
A. V. Kurkin, V. V. Nesterov, A. V. Karchava, and M. A. Yurovskaya
A new approach has been proposed to the synthesis of indole derivatives containing a chiral substituent
at the nitrogen atom, comprizing Fischer indolization of phenylhydrazines with a chiral substituent at
the α-nitrogen atom. The initial hydrazines were obtained by the alkylation (Mitsunobu reaction
applying optically active esters of lactic acid) of anilines containing an electron-accepting substituent
at the amino group. Subsequent removal of the activating acceptor grouping was realized by nitrosation
of the chiral secondary aniline followed by reduction of the corresponding N-nitroso compound.
Keywords: N-aryl-2,2,2-trichloroethylcarbamates, nonracemic 9-(1-methoxycarbonylethyl)-1,2,3,4-
tetrahydrocarbazole, N-trifluoroacetyl-, N-benzenesulfonyl, N-tosylanilines, chiral N-alkyl-N-phenyl-
hydrazine, (S)-lactic acid ethyl ester, Mitsunobu alkylation, desulfonylation, Fischer indolization,
removal of activating groups.
A whole series of indole derivatives, containing if only one asymmetric carbon atom, are of interest in
medicine and biochemistry. Most of the stereoselective methods of synthesizing chiral indole derivatives are
based on the use of natural tryptophan. A possible alternative approach to different chiral derivatives of indole
in our view might be based on the use of N-alkylanilines containing a chiral substituent at the nitrogen atom.
Examples of the synthesis of indole derivatives containing a chiral substituent at the nitrogen atom are
extremely rare. For example, such compounds of the indole series may be obtained by the transformation of
1-alkyl-3-nitropyridinium salts under the action of acetonimines of chiral primary amines [1], however this
reaction enables the preparation of indole derivatives containing alkyl (mostly methyl) groups in position 2 of
the indole ring. A second approach is based on the direct introduction of a chiral substituent at the indole
nitrogen atom by alkylation with optically active alcohols under the conditions of the Mitsunobu reaction [2,3],
but this is only possible in the presence of an acceptor group in positions 2 and 3 of the indole ring which
provides an increase in the NH acidity of such compounds compared with unsubstituted indole.
Our investigations in recent years have been linked to the search for a universal approach to the
synthesis of indole derivatives containing a chiral substituent at the nitrogen atom. N-Alkylanilines are widely
used as starting compounds for obtaining N-alkylindoles. The conversion of N-alkylanilines into the
corresponding indole derivatives may be effected by various methods [4,5]. Chiral N-alkylanilines may
therefore be used as universal synthetic precursors of indole derivatives containing a chiral substituent at the
nitrogen atom.
_______
* Dedicated to the remarkable heterocyclist A. F. Pozharskii on the occasion of his 65th birthday.
__________________________________________________________________________________________
Moscow M. V. Lomonosov State University, Moscow 119234, Russia; e-mail: indolecom@mtu-net.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1665-1677, November, 2003. Original
article submitted May 29, 2003.
1466
0009-3122/03/3911-1466$25.00©2003 Plenum Publishing Corporation

Recently we proposed a method of synthesis of racemic derivatives of 2-(1-indolyl)propionic acid
derivatives based on Fischer cyclization of the corresponding arylalkylhydrazones [6]. From these investigations
we have developed a modified variant of this method enabling nonracemic derivatives of indole to be obtained.
OH
O
Me
R
Me
R
R
O
Z
N
NH2
NHZ
O
Me
Me
2a-f
1a-c
O
3a-f
(99% ee)
R
R=R`=H
NH2
NO
N
N
NH
O
O
Me
Me
O
R`
Me
Me
Me
4a-d
O
6
O
O
O
5
(99-75% ee)
N
Amberlist-15
N
N
O
O
Me
Me
Me
O
Me
O
7
8
(75% ee)
1 a R = H, b R = NO2, c R = MeO; 2, 3 a-c R = H, d, e R = NO2, f R = OMe; a Z = COCF3;
b Z = SO2Ph; c Z = CO2CH2CCl3; d Z = COCF3; e, f Z = Ts; 4 a R = H, R' = Me; b R = R' = H;
c R = NO2, R' = Me; d R = OMe, R' = H
According to the above-mentioned scheme hydrazones of chiral N-alkyl-N-arylhydrazines may serve as
precursors of indole derivatives containing a chiral substituent at the nitrogen atom. The corresponding
hydrazines, in their turn, may be obtained from chiral N-alkylanilines by nitrosation and subsequent reduction.
Chiral N-alkylanilines therefore serve as starting materials in the synthesis of indoles with chiral substituents at
the nitrogen atom using the Fischer method.
Contemporary approaches to the synthesis of nonracemic N-alkylanilines with a chiral substituent at the
nitrogen atom are linked with the asymmetric hydrogenation of imines using chiral catalysts [7], or with the
asymmetric addition of organometallic reagents to imines catalyzed by chiral catalysts [8,9]. In spite of the
broad possibilities of these catalytic methods they are rarely able to give optically active compounds with high
enantiomeric purity.
One of the most convenient methods of synthesizing optically active amines applicable to contemporary
synthetic practice is based on the alkylation of a substrate containing a labile hydrogen atom using the
stereospecific Mitsunobu reaction with alcohols with the participation of the oxidation–reduction system
triphenylphosphine–azodicarboxylic acid ester. The Mitsunobu reaction has one essential limitation, viz. the
substrate being used must possess enhanced acidity (pKa > 15). Certain modifications of the Mitsunobu reaction
have been developed recently enabling substrates with higher values of pKa to be introduced into the process of
alkylation with alcohols. The following systems have been proposed for use: azodicarboxylic acid dipiperidide–
tributylphosphine
[10],
cyanomethylenetributylphosphorane
[11],
and
azodicarboxylic
acid
N,N,N',N'-tetramethylamide [12].
1467

The NH-acidity of anilines is insufficient for their possible alkylation under the conditions of the
Mitsunobu reaction. We therefore used anilines containing trifluoroacetyl, 2,2,2-trichloroethoxycarbonyl,
benzenesulfonyl, and tosyl acceptor activating groups at the nitrogen atom. Cases are known of alkylation under
Mitsunobu conditions of sulfonamides, trifluoroacetylanilines [10], and 2,2,2-trichloroethoxycarbamates [13].
Trifluoroacetanilides 2a,d and 2,2,2-trichloroethyl N-phenylcarbamate 2c were obtained by the direct acylation
of the corresponding anilines in yields greater than 90%. N-Arylsulfonylanilides 2b,e,f were synthesized by the
interaction of the corresponding sulfonyl chlorides with the initial anilines. Tosylation was carried out by two
methods: 1) in THF using equimolar amount of triethylamine at room temperature, and 2) in pyridine in the
presence of 5% (molar) 4-(N,N-dimethylamino)pyridine with heating. On using the first method N-tosylanilines
2b,f were obtained, sulfonamide 2e was not detected under these conditions, only the disubstututed product,
N,N-bis(p-toluenesulfonyl)-4-nitroaniline was isolated. The use of the second method led to the preparation of
anilide 2e in 73% yield.
All the obtained anilides were used as substrates in the Mitsunobu reaction with commercially available
(S)-hydroxypropionic (lactic) acid ethyl ester. We investigated the use of various oxidation–reduction systems
for these substrates in the Mitsunobu reaction. These were diisopropyl ester of azodicarboxylic acid–
triphenylphosphine (A), dipiperidide of azodicarboxylic acid–tributylphosphine (B), and cyanomethylene-
tributylphosphorane (9) (C).
The conditions for alkylating different anilides 2a-f and the yields of the alkylation products are given
in Table 1. According to the data in the Table the yields of alkylation products 3a-e from substrates 2a-f using
system B exceeded the yields of alkylation products insignificantly than when using the oxidation–reduction
system A. In addition it may be concluded that activation of anilines by an arenesulfonyl group is more efficient
by virtue of the greater NH acidity of arenesulfonylanilides. On going from anilides with activating group
Z = CF3CO and Z = Cl3CCH2CO2 (compounds 3a,c) to benzenesulfonylanilide Z = PhSO2 (compound 3b) the
yields were increased from 30-60 to 68-80%. Evidence that the degree of NH acidity is the deciding factor
giving success in alkylation is provided by the fact that introduction of a nitro group into the aromatic ring
increases the yield of alkylation products significantly (to 87%, compound 3e), while the introduction of an
electron-donating methoxy group leads to its reduction (to 77%, compound 3f).
On using system C all the substrates participated in the Mitsunobu reaction in high yield, however the
difficult availability and instability of phosphorane 9 hindered its use to a significant extent. The maximum
yield of alkylation products was achieved using equimolar amounts of all reactants. Increase in the amount of
trifluoroacetanilide and oxidation–reduction system used to 1.2- and 1.5-fold in relation to the alcohol did not
lead to an increase in the yield of alkylation product 3a and only hindered its chromatographic isolation
extremely, due to the presence of the large quantity of unreacted reactants in the reaction mixture. A study of the
effect of the nature of the solvent (benzene, THF, and DMF) and the reaction time on the Mitsunobu alkylation
process showed (Table 1) that THF was the most effective solvent for system A keeping the reaction mixture at
TABLE 1. Yields of Alkylation Products with (S)-Lactic Acid Ethyl Ester 3
under Conditions of the Mitsunobu Reaction
Yield of reaction products, %
Reaction
Substrate
A
B
C
C6H6
product
THF
C6H6
DMF
THF C6H6
THF
47
51
11
68
77
65
31
37
—
54
58
59
—
—
—
12
18
6
38
32
27
60
74
60
52
57
42
78
81
69
—
—
—
—
—
—
34
31
56
54
75
64
61
70
83
80
87
77
—
—
—
—
—
—
3a
3d
3c
3b
3e
3f
2a
2d
2c
2b
2e
2f
1468

Fig. 1. Spatial model of the compound 3b molecule.
room temperature for 24 h (yield of compound 3d was 77%). Boiling for 24 h in benzene was optimal for
systems B and C (yields of compound 3d were 81 and 87% respectively). Considering all the factors mentioned
above a procedure is given in Experimental using the most convenient system A.
It is known that the Mitsunobu reaction is accompanied by complete inversion of the configuration of
the initial alcohol on forming the alkylation product [3]. Since we used an alcohol of the (S)-configuration as
alkylating agent the obtained derivatives of 2-aminopropionic acid must possess the (R)-configuration. To
confirm the (R)-configuration of the obtained alkylation products 3a-e X-ray structural investigation was carried
out on compound 3b, which completely confirmed the expected configuration. An overall view of the
compound 3b molecule is given in Fig. 1.
The following stage of our work was connected with a study of the possible removal of the activating
groups. Conversion of trifluoroacetanilides to the corresponding anilines is readily effected by various means
such as KOH/EtOH or K2CO3/MeOH–H2O, or NaBH4/EtOH [14,15]. Conversion of 2,2,2-trichloroethyl
arylcarbamates into N-alkylanilines also occurs under mild conditions, using the system Zn/NaH2PO4–THF
[13].
As is known benzene- and toluenesulfonyl groups are fairly difficult to remove from a nitrogen atom
and this usually requires extremely forcing conditions, such as the use of Na–liquid ammonia, Na–naphthalene
system, or concentrated H2SO4, and the yields do not usually exceed 60% [16]. The use of such conditions is
usually inappropriate for 2-aminopropionic acid derivatives due to the presence of groups capable of reduction.
Most of all, such conditions may lead to racemization of the products of alkylation with chiral alcohols. The
removal of sulfonyl groups by the action of magnesium in methanol under ultrasonic irradiation is also known
[17]. This method enabled us to obtain methyl esters of (R)-2-(N-phenyl)aminopropionic acid 4 from the
corresponding N-arylsulfonamides 3 in high yield.
Mg/MeOH
3b,d,e
4b,d
Removal of the sulfonyl group by the action of magnesium in methanol under ultrasonic irradiation
proved to be unsuitable for substrate 3e containing a nitro group. The reaction led to the formation of mixture of
unidentified compounds. Attempts were undertaken to remove the tosyl group using trimethyliodosilane [18],
however initial sulfonylaniline was isolated exclusively from the reaction mixture. Consequently the sole means
of obtaining compound 4c was mild hydrolysis of substrate 3d in the system K2CO3/MeOH–H2O.
1469

The formation of methyl esters under desulfonation conditions is in agreement with the report on
accompanying transesterification under the action of magnesium and ultrasonic irradiation [17].
When analyzing aniline 4b obtained in this way by HPLC on a chiral support it was discovered that it
contained admixture of the (S)-isomer (25%), which indicates partial racemization of the Mitsunobu reaction
1
product during removal of the activating group. In turn, a special H NMR spectroscopic investigation of the
diastereomers of N-phenylalanine methyl ester 4b with (S)-1,1-binaphthol (ratio 1:1) clearly indicates the
presence of two singlets for the signals for the (R)- and (S)-isomer OCH3 group protons at 3.14 ppm in a ratio of
4:1.
All the esters of 2-(N-aryl)aminopropionic acid obtained by us revealed optical activity.
The further sequence of conversions from the optically active alkylanilines 4 to indoles containing a
chiral substituent at the nitrogen atom was worked out using methyl ester of (R)-2-(N-phenyl)aminopropionic
acid (4b) as example, and comprised synthesis of (R)-2-(N-nitroso-N-phenyl)aminopropionic acid methyl ester
(5), its subsequent reduction to the corresponding hydrazine 6, the preparation of its hydrazone 7 with
cyclohexanone, and cyclization to the desired 9-(1-methoxycarbonylethyl)-1,2,3,4-tetrahydrocarbazole (8). The
nitrosation of aniline 4b with ethyl nitrite led to nitrosoamine 5 in quantitative yield. According to the data of
1H NMR spectra compound 5 exists as mixture of geometric isomers. For the reduction of nitrosoamine 5 to the
corresponding hydrazine 6 we used the zinc–hydrochloric acid–methanol system at -78°C [6], the application of
which led to practically no side reaction of N–N bond fission. Due to instability hydrazine 6 obtained by the
reduction was converted without further purification into hydrazone 7, which also without isolation and
purification was cyclized into tetrahydrocarbazole 8. Indolization of cyclohexanone hydrazone 7 proceeds
extremely readily and the formation of significant quantities of the indole derivative 8 is observed even on
stirring hydrazine 6 with cyclohexanone in the presence of catalytic amounts of p-toluenesulfonic acid.
TABLE 2. Bond Angles (ω) in Structure 3b
Angle
ω, deg.
Angle
ω, deg.
Angle
ω, deg.
О(2)–S(1)–O(1)
O(2)–S(1)–N(1)
O(1)–S(1)–N(1)
O(2)–S(1)–C(1)
O(1)–S(1)–C(1)
N(1)–S(1)–C(1)
120.8(1)
106.8(1)
106.5(1)
107.7(1)
107.3(1)
107.1(1)
C(2)–C(1)–S(1)
C(6)–C(1)–S(1)
C(3)–C(2)–C(1)
C(2)–C(3)–C(4)
C(5)–C(4)–C(3)
C(4)–C(5)–C(6)
C(5)–C(6)–C(1)
119.9(2)
119.0(2)
119.3(2)
120.3(2)
120.2(2)
120.3(2)
118.9(2)
C(10)–C(9)–C(8)
C(11)–C(10)–C(9)
C(10)–C(11)–C(12) 120.6(2)
C(7)–C(12)–C(11) 119.5(2)
N(1)–C(13)–C(14) 114.7(2)
N(1)–C(13)–C(15) 111.4(2)
C(14)–C(13)–C(15) 110.2(2)
120.0(2)
119.9(2)
C(15)–O(4)–C(16) 116.5(2)
C(7)–N(1)–C(13)
C(7)–N(1)–S(1)
C(13)–N(1)–S(1)
C(2)–C(1)–C(6)
120.0(2)
118.0(1)
120.6(2)
121.1(2)
C(12)–C(7)–C(8) 120.4(2)
C(12)–C(7)–N(1) 118.3(2)
O(3)–C(15)–O(4)
124.1(2)
O(3)–C(15)–C(13) 123.1(2)
O(4)–C(15)–C(13) 112.7(2)
O(4)–C(16)–C(17) 111.8(2)
C(8)–C(7)–N(1)
C(7)–C(8)–C(9)
121.3(2)
119.5(2)
TABLE 3. Bond Lengths (d) in Structure 3b
Bond
d, Å
Bond
d, Å
Bond
d, Å
S(1)–O(2)
S(1)–O(1)
S(1)–N(1)
S(1)–C(1)
O(3)–C(15)
O(4)–C(15)
O(4)–C(16)
N(1)–C(7)
1.437(2)
1.437(2)
1.638(2)
1.765(2)
1.205(3)
1.331(3)
1.464(3)
1.447(3)
N(1)–C(13)
C(1)–C(2)
C(1)–C(6)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
C(7)–C(12)
1.473(3)
1.397(3)
1.398(3)
1.384(4)
1.400(3)
1.389(4)
1.396(3)
1.388(3)
C(7)–C(8)
1.394(3)
1.400(3)
1.394(3)
1.379(4)
1.396(3)
1.515(4)
1.533(3)
1.506(4)
C(8)–C(9)
C(9)–C(10)
C(10)–C(11)
C(11)–C(12)
C(13)–C(14)
C(13)–C(15)
C(16)–C(17)
1470

TABLE 4. Coordinates of Atoms (×104) and Their Isotropic Equivalent (for
H isotropic) Thermal Parameters (U) in Structure 3b
Atom
x
y
z
U
S(1)
O(1)
O(2)
O(3)
O(4)
N(1)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
2202(1)
3086(2)
1093(2)
-1403(2)
-550(1)
5042(1)
6696(3)
5570(3)
2152(3)
5460(3)
3856(3)
3107(4)
1567(5)
8(5)
1581(1)
2233(1)
565(1)
2634(2)
2689(1)
2443(2)
1216(2)
379(2)
19(1)
24(1)
25(1)
31(1)
25(1)
19(1)
19(1)
25(1)
28(1)
26(1)
24(1)
23(1)
19(1)
21(1)
24(1)
23(1)
23(1)
24(1)
23(1)
25(1)
20(1)
30(1)
33(1)
28(7)
29(8)
26(7)
22(6)
11(6)
18(6)
23(7)
22(7)
24(7)
17(5)
10(4)
28(7)
68(12)
18(7)
33(8)
38(9)
44(9)
43(9)
32(8)
1615(2)
3159(2)
2542(2)
3299(2)
4669(2)
5278(2)
4526(2)
2464(2)
3300(2)
4102(2)
4057(2)
3242(2)
2437(2)
388(2)
134(2)
710(2)
-11(5)
1545(4)
3117(4)
3682(4)
1917(4)
1804(4)
3446(4)
5201(5)
5333(4)
2589(4)
167(5)
3344(4)
6313(5)
5655(5)
1580(50)
-1000(60)
-1110(50)
1620(50)
4240(40)
860(50)
560(50)
3260(50)
6520(50)
6560(40)
3010(40)
-130(60)
-170(90)
-590(50)
5570(60)
7690(70)
6090(60)
6700(70)
4070(60)
1530(2)
1795(2)
3631(2)
4039(2)
5196(2)
5932(2)
5514(2)
4361(2)
1989(2)
2120(2)
2489(2)
3202(2)
4430(2)
-10(20)
-420(30)
540(30)
1880(20)
2400(20)
3600(20)
5470(20)
6710(20)
6010(20)
4046(19)
1210(18)
2940(20)
1730(30)
1690(20)
2780(30)
3010(30)
4820(30)
4750(30)
4550(30)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
H(2)
H(3)
H(4)
H(5)
H(6)
H(8)
H(9)
H(10)
H(11)
H(12)
H(13)
H(141)
H(142)
H(143)
H(161)
H(162)
H(171)
H(172)
H(173)
576(2)
-611(2)
-1442(2)
-1025(3)
1590(30)
2870(30)
5110(30)
6220(30)
4960(20)
3420(30)
4600(30)
4530(30)
3250(30)
1950(20)
-21(19)
980(30)
1220(40)
-200(30)
-2360(30)
-1410(30)
-50(40)
-1560(30)
-1220(30)
Determination of the enantiomeric composition of indole 8 by HPLC using a chiral mobile phase
showed the presence of both (S)- and (R)-enantiomers in the ratio 1:3.97 (~75% ee).
The results obtained by us therefore permit the suggestion that partial racemization occurs only at the
desulfonation step. The ratio of enantiomers remains the same in all the remaining steps of the conversion of
hydrazine to indole.
1471

EXPERIMENTAL
The IR spectra were obtained on a UR 20 instrument for nujol suspensions or pure compounds.
Chromato-mass spectral investigations of reaction mixtures and isolated compounds was carried out using a
Carlo Erba/Kratos Fractovap Series 4200 gas-liquid chromatograph, Hewlett Packard Ultra 1 column
(25 m × 0.2 mm, thickness of stationary phase 0.33 µm), carrier gas was helium (1 ml/min), stream divider 1:10,
evaporator temperature 280°C, temperature gradient from 150 to 280°C (5°C/min), ITD 700 (Finnigan MAT)
1
mass spectral detector, ionization by electron impact, 70 eV, mass range m/z 45-400. The H and 13C NMR
spectra were obtained on a Bruker AMX 400 (400 and 100 MHz respectively) spectrometer in DMSO-d6, if no
other solvent is indicated, internal standard was TMS. Specific rotation was measured on a Jasco DIP 360
polarimeter (589 nm). Melting points were measured in open capillaries, values given are not corrected. A check
on the course of reactions and the purity of isolated compounds was effected by TLC on Silufol UV 254 plates
and by gas chromatography with the mass spectral detector.
X-Ray Structural Investigations. In molecule 3b the dihedral angle between the planes of the benzene
rings C(1)–C(2)–C(3)–C(4)–C(5)–C(6) and C(7)–C(8)–C(9)–C(10)–C(11)–C(12) was 138.3°. The remaining
geometric parameters in the investigated molecule have the usual values [19]. The colorless crystals of
compound 3b were monoclinic, at -163°C: a = 10.962(4), b = 6.191(2), c = 12.699(5) Å; β = 112.23(1)°;
V = 798(1) Å3; dcalc = 1.388 g/cm3; Z = 2; space group P2(1). Unit cell parameters and intensities of
4308 independent reflections were measured on a SMART 1000 CCD diffractometer (λMoKα = 0.71073 Å,
graphite monochromator, ω-scanning with 0.3° step, exposure time 10 sec. The structure was solved by the
direct method, revealing all the non-hydrogen atoms, and refined by a full-matrix least-squares method in
anisotropic approach for the non-hydrogen atoms. Hydrogen atoms were revealed objectively with Fourier
difference syntheses and refined isotropically. The final values of the divergence factors were R1 = 0.05 for
3910 reflections with I > 2σ and Rw = 0.131 for 4308 reflections. All calculations were carried out with the
programs SAINT [20] and SHELXTL-97 [21] (PC version). Bond angles and bond lengths for compound 3b are
given in Tables 2 and 3.
Trifluoroacetanilide (2a) [22], 4-Nitrotrifluoroacetanilide (2d) were obtained by the methods
described [23]. Melting points and spectral characteristics agreed with literature data.
N-Benzenesulfonylaniline (2b). Triethylamine (11.11 g, 110 mmol) was added dropwise to solution of
aniline (10.22 g, 110 mmol) in THF (150 ml). The mixture was stirred for 15 min in an ice bath, then
benzenesulfonyl chloride (19.38 g, 110 mmol) was added dropwise, and the mixture stirred for 6 h at room
temperature. The reaction mixture was poured into ice–water (120 ml), the resulting oil was extracted with
chloroform (3 × 100 ml), the organic layer was washed with 5% hydrochloric acid solution (200 ml), with water
(3 × 100 ml), and dried with anhydrous sodium sulfate. After removing volatile components in vacuum and
storing in a desiccator over P2O5, the residue was recrystallized from benzene–hexane. White crystals (22.1 g,
1
86%) were obtained; mp 105°C (benzene). According to [24] mp 103°C. H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 7.19 (2H, dt, J = 7.0, J = 2.0, Ar); 7.25-7.35 (3H, m); 7.42 (2H, tt, J = 7.0, J = 2.0, Ar); 7.53 (1H, tt,
J = 7.0, J = 2.0, Ar); 7.70 (2H, dt, J = 7.0, J = 2.0, Ar); 11.10 (1H, br s, NH).
N-(4-Toluenesulfonyl)-4-methoxyaniline (2f) was obtained analogously. Yield 96%; mp 110-112°C
(benzene–hexane). According to [25] mp 110-112°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.32 (3H, s, CH3); 3.31
(3H, s, CH3O); 7.09 (2H, d, J = 8.7, Ar); 7.39 (2H, d, J = 8.1, Ar); 7.76 (2H, d, J = 8.1, Ar); 8.13, 7.09 (2H, d,
J = 8.7, Ar); 9.40 (1H, br. s, NH).
1
N,N-Bis(4-toluenesulfonyl)-4-nitroaniline. Yield 80%; mp 224-226°C (ethanol). H NMR spectrum,
δ, ppm (J, Hz): 2.46 (6H, s, CH3); 7.32 (2H, d, J = 8.8); 7.51 (4H, d, J = 8.1); 7.71 (4H, d, J = 8.1); 8.30 (2H, d,
J = 8.8).
N-(4-Toluenesulfonyl)-4-nitroaniline (2e). p-Nitroaniline (6.9 g, 50 mmol) was dissolved in pyridine
(30 ml), then 4-(N,N-dimethylamino)pyridine (0.3 g, 2.5 mmol) and p-toluenesulfonyl chloride (9.53 g,
50 mmol) were added. The mixture was stirred at room temperature for 15 min, then 5 h at 90-100°C. The
1472

reaction mixture was poured into mixture of concentrated HCl (40 ml) with ice, the precipitated solid was
filtered off, washed on the filter with ice-water, air-dried, and recrystallized from ethanol. A bright yellow
crystalline substance (10.5 g, 73%) was obtained; mp 189-190°C (ethanol). According to [26], mp 189-190°C.
IR spectrum, ν, cm-1: 3340 (NH), 1170, 1350 (SO2), 1320, 1520 (NO2). 1H NMR spectrum, δ, ppm (J, Hz): 2.33
(3H, s, CH3); 7.30 (2H, d, J = 9.0); 7.39 (2H, d, J = 8.1); 7.76 (2H, d, J = 8.1); 8.13 (2H, d, J = 9.0); 11.24 (1H,
s, NH).
2,2,2-Trichloroethyl N-Phenylcarbamate (2c) was obtained according to the method of [27]. The
melting point and spectral characteristics agreed with the literature data.
Cyanomethyltributylphosphonium Chloride [11], Cyanomethylenetributylphosphorane [11], and
Azodicarboxylic Acid Dipiperidinediamide were obtained according to the methods described [28]. The
melting points and spectral characteristics agreed with the literature data.
N-Acyl-N-arylalanine Ethyl Esters (General Procedure). A. Solution of diisopropyl ester of
azodicarboxylic acid (2.61 g, 13 mmol) in freshly distilled THF (5 ml) was added dropwise to mixture of
triphenylphosphine (3.36 g, 13 mmol), substrate (13 mmol) and (S)-lactic acid ethyl ester (13 mmol) in THF
(50 ml) with ice and water cooling and stirring. The reaction mixture was left at room temperature for 24 h, after
which the solvent was removed under reduced pressure. The residue was chromatographed on a column of silica
gel in the solvent system ethyl acetate–petroleum ether, 1:5.
B. Mixture of tributylphosphine (1.5 mmol) and azodicarboxylic acid dipiperidide (1.5 mmol) was
added with stirring in an atmosphere of argon to solution of (S)-lactic acid ethyl ester (1 mmol) and substrate
(1.5 mmol) in dry benzene (3 ml). The reaction mixture was maintained at 100°C for 24 h, the solvent was
removed under reduced pressure, and the residue chromatographed on a column of silica gel in the solvent
system ethyl acetate–petroleum ether, 1:5.
C. Cyanomethylenetributylphosphorane (0.36 g, 1.5 mmol) was added with stirring in an atmosphere of
argon to solution of (S)-lactic acid ethyl ester (1 mmol) and substrate (1.5 mmol) in dry benzene (10 ml). The
reaction mixture was maintained at 100°C for 24 h, the solvent was removed under reduced pressure, and the
residue chromatographed on a column of silica gel in the solvent system ethyl acetate–petroleum ether, 1:5.
R
Yield 61% (C) of a
( )-2-(N-Phenyl-N-trifluoroacetyl)aminopropionic Acid Ethyl Ester (3a).
viscous oil. IR spectrum, ν, cm-1: 1730 (C=O). Mass spectrum, m/z (I, %): 193 (13) [M-COCF3]+, 120 (100), 77
(10). 1H NMR spectrum, δ, ppm (J, Hz): 1.16 (3H, t, J = 7.1, CH2CH3); 1.37 (3H, d, J = 7.1, CHCH3); 4.03 (1H,
q, J = 7.1, CHCH3); 4.09 (2H, q, J = 7.1, CH3CH2); 6.52-6.60 (3H, m, Ar); 7.08 (2H, t, J = 7.8, Ar). 13C NMR
spectrum, δ, ppm: 15.01 (CH3CH2); 18.88 (CH3CH); 52.25 (CH); 61.21 (CH2CH3); 113.7 (2C, CH); 116.07
(CF3, q, J = 289); 117.81 (C, CH); 129.85 (2C, CH); 148.06 (C); 159.30 (COCF3, q, J = 38); 175.15 (C=O).
23
Found, %: C 53.41; H 5.18; N 4.46. C13H14F3NO3. Calculated, %: C 53.98; H 4.88; N 4.84. [α]D 2.5 (CHCl3,
c 0.03).
R
Yield 80% (C),
( )-2-(N-Benzenesulfonyl-N-phenyl)aminopropionic Acid Ethyl Ester (3b).
mp 55°C (ethanol). IR spectrum, ν, cm-1: 1140, 1340 (SO2), 1730 (C=O). Mass spectrum, m/z (I, %): 333 (5)
[M]+, 260 (70) [M-PhSO2]+, 119 (100). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.20 (3H, t, J = 7.0,
1
CH3CH2); 1.28 (3H, d, J = 7.0, CH3); 4.10 (2H, q, J = 7.0, CH3CH2); 5.09 (1H, q, J = 7.0, CH); 7.19 (2H, dt,
J = 7.0, J = 2.0); 7.25-7.35 (3H, m); 7.42 (2H, tt, J = 7.0, J = 2.0); 7.53 (1H, tt, J = 7.0, J = 2.0); 7.70 (2H, dt,
J = 7.0, J = 2.0). 13C NMR spectrum (CDCl3), δ, ppm: 16.03 (CH3CH2); 19.27 (CH3); 59.34 (CH); 63.68 (CH2);
130.13 (2C, CH); 130.81 (2C, CH); 131.21 (2C, CH); 134.24 (2C, CH); 134.80 (CH); 134.90 (CH); 138.07 (C);
142.45 (C); 173.68 (C=O). Found, %: C 61.31; H 6.00; N 4.08. C17H19NO4S. Calculated, %: C 61.23; H 5.76;
N 4.20. [α]21D –15.2 (CH3OH, c 1.2).
R
( )-2-(N-Phenyl-N-2,2,2-trichloroethoxycarbonyl)aminopropionic Acid Ethyl Ester (3c).
Yield 83% (C), viscous liquid. Mass spectrum, m/z (I, %): 298 (16), 296 (43), 294 (44) [M-CO2Et]+, 192 (7),
133 (33), 131 (35), 120 (95), 119 (99), 104 (81), 95 (35), 77 (100), 61 (24), 51 (45), 44 (26). 1H NMR spectrum,
δ, ppm (J, Hz): 1.21 (3H, J = 7.0, CH3CH2); 1.33 (3H, m); 4.15 (2H, q, J = 7.0, CH3CH2); 4.69 (1H, q, J = 7.0,
1473

13
CH); 4.77-4.89 (2H, m, CH2CCl3); 7.31-7.37 (3H, m, Ar); 7.39-7.46 (2H, m, Ar). C NMR spectrum, δ, ppm:
14.51 (CH3CH2) 16.06 (CH3); 58.12 (CH2); 61.43 (CHN); 75.12 (CH2CCl3); 96.23 (CCl3); 128.16 (CH); 128.88
(2C, CH); 129.39 (2C, CH); 140.09 (C); 153.48 (CO2CH2CCl3); 171.45 (C=O). Found, %: C 45.82; H 4.43;
N 3.86. C14H16Cl3NO4. Calculated, %: C 45.61; H 4.37; N 3.80. [α]D22 2.1 (CHCl3, c 0.09).
R
Yield 70% (C),
( )-2-(N-4-Nitrophenyl-N-trifluoroacetyl)aminopropionic Acid Ethyl Ester (3d).
viscous liquid. Mass spectrum, m/z (I, %): 334 (17) [M]+, 289 (13), 260 (43) [M-CO2Et]+, 234 (43), 217 (59),
1
204 (11), 171 (14), 165 (28), 122 (27), 101 (53), 73 (100). H NMR spectrum, δ, ppm (J, Hz): 1.88 (3H, t,
J = 7.0, CH3CH2); 2.25 (3H, d, J = 7.0, CH3); 4.85 (2H, q, J = 7.0, CH3CH2); 5.80 (1H, q, J = 7.0, CH); 7.47
(2H, d, J = 9.0); 8.77 (2H, d, J = 9.0). 13C NMR spectrum, δ, ppm: 14.90 (CH3CH2); 17.53 (CH3CH); 62.24
(CH); 73.56 (CH2CH3); 116.51 (CF3, q, J = 287); 121.05 (2C, CH); 125.87 (2C, CH); 144.69 (COCF3, q,
J = 36); 144.83 (C); 150.39 (C); 170.16 (C=O). Found, %: C 46.81; H 3.94; N 8.40. C13H13F3N2O5.
Calculated, %: C 46.71; H 3.92; N 8.38. [α]D22 1.7 (CHCl3, c 0.5).
R
Yield 77%
( )-2-(N-4-Methoxyphenyl-N-4-toluenesulfonyl)aminopropionic Acid Ethyl Ester (3f).
(C); mp 69°C (ethanol–hexane). IR spectrum, ν, cm-1: 1160, 1340 (SO2), 1605 (Ar), 1750 (C=O). Mass
spectrum, m/z (I, %): 377 (2) [M-H]+, 304 (10), 187 (45), 174 (42), 149 (65), 128 (85), 105 (95), 101 (100),
1
91 (100). H NMR spectrum, δ, ppm (J, Hz): 1.10-1.20 (6H, m); 2.09 (3H, s, CH3); 3.74 (3H, s, OCH3); 4.03
(2H, q, J = 7.0, CH3CH2); 4.99 (1H, q, J = 7.0, CH); 6.88 (2H, d, J = 7.0); 6.99 (2H, d, J = 7.0); 7.37 (2H, d,
J = 7.0); 7.55 (2H, d, J = 7.0). 13C NMR spectrum, δ, ppm: 13.83 (CH3CH2); 16.72 (CH3); 20.99 (CH3Tos);
55.26 (CH3O); 56.78 (CH); 60.88 (CH3CH2); 114.08 (2C); 127.33 (2C); 127.79, 129.45 (2C); 132.80 (2C);
137.20, 143.23, 159.25, 170.97 (C=O). Found, %: C 60.39; H 6.26. C19H23NO5S. Calculated, %: C 60.46;
H 6.14. [α]D21 13.0 (CHCl3, c 4.6).
R
Yield 87% (C);
( )-2-(N-4-Nitrophenyl-N-4-toluenesulfonyl)aminopropionic Acid Ethyl Ester (3e).
1
mp 81°C (ethyl acetate–hexane). IR spectrum, ν, cm-1: 1320, 1520, 1168, 1350 (SO2), 1750 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.2, CH3CH2); 1.23 (3H, d, J = 7.2, CH3CH); 2.40 (3H, s, CH3Tos);
4.08 (2H, t, J = 7.2, CH3CH2); 5.07 (1H, q, J = 7.2, CH3CH); 7.40 (2H, d, J = 7.8); 7.44 (2H, d, J = 9.0); 7.61
(2H, d, J = 8.1); 8.24 (2H, d, J = 9.3). 13C NMR spectrum, δ, ppm: 13.82 (CH3CH2); 16.78 (CH3); 21.02
(CH3Tos); 57.36 (CH); 61.22 (CH3CH2); 124.31 (2C); 127.37 (2C); 129.77 (2C); 131.82 (2C); 136.44, 142.44,
143.94, 146.86, 170.79 (C=O). Found, %: C 55.05; H 5.06; N 6.99. C18H20N2O6S. Calculated, %: C 55.09; H
5.14; N 7.14. [α]D21 20.5 (CHCl3, c 4.6).
R
Zinc dust (4 g, 62 mmol) and then aqueous 1 M
( )-N-Phenylalanine Ethyl Ester Hydrochloride (4a).
NaH2PO4 solution (8 ml, dropwise) were added to solution of 2,2,2-trichloroethyl N-phenylcarbamate (3c)
(1.47 g, 4 mmol) in THF (40 ml) with cooling to -10°C and vigorous stirring in an atmosphere of argon. The
reaction mixture was stirred vigorously for 6-8 h at 15°C in an argon atmosphere. The completeness of the
reaction was checked by TLC (silica gel, ethyl acetate–petroleum ether, 1:3). The excess of zinc was filtered
off, the solid was washed with THF (20 ml), the filtrate evaporated in vacuum, and the residue dissolved in
diethyl ether (50 ml). The solution was washed with 0.2 M aqueous citric acid solution (50 ml), with 1 M
aqueous NaHCO3 solution (50 ml), and with saturated sodium chloride solution (30 ml), and dried over
anhydrous Na2SO4. After removing the solvent in vacuum a white crystalline powder (0.65 g, 84%) was
obtained having mp 175-176°C (ethanol). IR spectrum, ν, cm-1: 1730 (C=O). Mass spectrum, m/z, (I, %): 193
1
(15) [M]+, 120 (100) [M-CO2Et]+, 77 (12). H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.0, CH3CH2);
1.37 (3H, d, J = 7.2, CH3); 4.06 (2H, q, J = 7.0, CH3CH2); 4.17 (1H, q, J = 7.2, CH); 6.81 (3H, m, Ph); 7.19
+
(2H, t, J = 8.1, Ph); 8.09 (3H, br. s, NH3 ). 13C NMR spectrum, δ, ppm: 14.43 (CH3CH2); 18.22 (CH3CH); 52.58
(CH); 60.78 (CH2CH3); 114.33 (2C, CH); 118.28 (CH); 129.29 (2C, CH); 148.12 (C); 174.65 (C=O). Found, %:
C 57.61; H 7.18; N 6.36. C11H16ClNO2. Calculated, %: C 57.52; H 7.02; N 6.10. [α]D22 5.9 (CHCl3, c 0.09).
R
Sodium borohydride (0.3 g,
( )-2-(N-4-Nitrophenyl)aminopropionic Acid Ethyl Ester (4c).
7.2 mmol) was added with vigorous stirring in an atmosphere of argon with cooling to 5°C to solution of
compound 3d (0.3 g, 9 mmol) in absolute ethanol (10 ml). The reaction mixture was stirred vigorously for 4 h at
1474

room temperature in the argon atmosphere. The completeness of the reaction was checked by TLC (silica gel,
ethyl acetate–petroleum ether, 1:3). The reaction mixture was poured into water and ice, and 5 M HCl solution
was added dropwise to pH ~4. The mixture was extracted with methylene chloride (2 × 100 ml). The organic
extract was dried with anhydrous Na2SO4. After removing volatile components in vacuum and storing in a
desiccator over P2O5 the residue was recrystallized. Yield 85%, mp 147°C (ethanol). IR spectrum, ν, cm-1: 1605
(Ar), 1750 (C=O). Mass spectrum, m/z (I, %): 238 (9) [M]+, 165 (100) [M-CO2Et]+, 149 (5), 119 (38). 1H NMR
spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.0, CH3CH2); 1.23 (3H, d, J = 7.0, CH3); 4.07 (2H, q, J = 7.0,
CH3CH2); 5.06 (1H, q, J = 7.0, CH); 7.44 (2H, d, J = 9.0); 8.24 (2H, d, J = 9.0); 8.87 (NH). [α]D21 3.7 (CHCl3,
c 0.1).
Removal of N-(4-Toluenesulfonyl) Activating Group (General Procedure). Magnesium dust (4.80 g,
200 mmol) was added to solution of substrate (10 mmol) in absolute methanol (50 ml). The reaction mixture
was placed in an ultrasound bath and subjected to ultrasonic irradiation for 30 min. Magnesium residue was
filtered off, and magnesium washed with methanol (50 ml). The solution was concentrated in vacuum, poured
into saturated ammonium chloride solution, the mixture was extracted with ether, the extract was washed with
saturated ammonium carbonate solution (30 ml), and with saturated sodium chloride solution (50 ml), then dried
over anhydrous Na2SO4. The solvent was removed at reduced pressure, the residue was dissolved in a small
quantity of methanol, and an excess of a saturated solution of hydrogen chloride in ether was added. The solvent
was removed in vacuum, and the residue recrystallized from methanol–ether. The solid precipitated on cooling
was filtered off, and dried in vacuum over alkali and phosphorus pentoxide.
R
Yield 64.2%, mp 135-137°C. IR spectrum,
( )-N-Phenylalanine Methyl Ester Hydrochloride (4b).
+
ν, cm-1: 750 (Ph), 1740 (C=O), 2200-2600 (NH2 ). Mass spectrum, m/z (I, %): 179 (45) [M]+, 148 (46), 120
(100), 91 (40), 76 (45). 1H NMR spectrum, δ, ppm (J, Hz): 1.38 (3H, d, J = 7.0); 3.57 (3H, s, CH3O); 4.21 (1H,
q, J = 7.0, CH); 6.80 (2H, d, J = 7.0); 7.00 (NH); 7.10-7.25 (3H, m). [α]D21 -1.0 (CH3OH, c 0.48).
R
Yield 86%, mp 129-130°C. IR
( )-N-(4-Methoxyphenyl)alanine Methyl Ester Hydrochloride (4d).
+
spectrum, ν, cm-1: 750 (Ph), 1740 (C=O), 2200-2600 (NH2 ). Mass spectrum, m/z (I, %): 209 (61) [M]+, 150
1
(100), 134 (63), 123 (11), 119 (34), 108 (43), 92 (31), 77 (34), 63 (19). H NMR spectrum (D2O), δ, ppm
(J, Hz): 1.24 (3H, d, J = 7.2, CH3CH); 3.54 (3H, s, CH3O); 3.56 (3H, s, CH3O2C); 4.21 (1H, q, J = 7.0,
CH3CH); 6.83 (2H, d, J = 8.7); 7.10 (2H, d, J = 8.7). 13C NMR spectrum, δ, ppm: 15.79 (CH3CH); 51.76 (CH);
54.99 (CH3O2C); 55.22 (CH3O); 114.47 (2C, CH); 119.64 (2C, CH); 140.14 (C); 155.43 (C); 171.42 (C=O).
Found, %: C 55.61; H 7.14; N 5.56. C12H18ClNO3. Calculated, %: C 55.49; H 6.99; N 5.39. [α]D21 -1.0 (CH3OH,
c 5.82).
R
Cold aqueous solution (50 ml) of potassium
( )-N-Nitroso-N-phenylalanine Methyl Ester (5).
hydroxide (0.29 g, 5.2 mmol) was added in one portion with cooling and vigorous stirring to solution of
compound 4b (1.12 g, 5.2 mmol) in water (20 ml). Amine was extracted with ether (3 × 50 ml), the extract
washed with water, with saturated sodium chloride solution, and dried with anhydrous Na2SO4. The solvent was
removed at reduced pressure, the residue (1 g) was dissolved in anhydrous THF (10 ml), and a 14% solution
(4.5 ml) of ethyl nitrite (~7.2 mmol) in alcohol was added in portions with stirring and cooling. The reaction
mixture was stored in the dark for 12 h at room temperature. Volatile components were removed in vacuum at a
bath temperature of 40°C, and a yellow oily liquid (1.08 g, 99%) was obtained. The compound was used in
1
further conversions without additional purification. IR spectrum, ν, cm-1: 1730 (C=O), 1430 (N=O). H NMR
spectrum, δ, ppm (J, Hz): 1.41 (3H, d, J = 7.1, CH3); 3.63 (3H, s, CH3O); 5.15 (1H, q, J = 7.1, CH); 7.31-7.60
(5H, m, Ph). Mass spectrum, m/z, (I, %): 208 (7) [M]+, 178 (23) [M-N=O]+, 120 (100), 104 (38), 91 (7), 77 (32).
R
Concentrated HCl (6 ml, 72 mmol) was
( )-2-(1-Phenylhydrazino)propionic Acid Methyl Ester (6).
added to solution of nitrosoamine 5 (9 mmol) in absolute methanol (100 ml) cooled to -80°C and in atmosphere
of argon. Zinc dust (4.68 g) was added in portions with vigorous stirring to the solution. The reaction mixture
was stirred vigorously for 6-8 h at -80 to -70°C in atmosphere of argon. The completeness of the reduction was
checked by TLC (silica gel, ethyl acetate–petroleum ether, 1:3, visualizing with an alcoholic solution of ferric
1475

chloride). The excess of zinc was filtered off, the solid was washed with methanol (20 ml), the filtrate
evaporated in vacuum at room temperature to a volume of ~20 ml, poured into water and ice (100 ml), and made
alkaline by adding of 24% aqueous ammonia solution (20 ml) (pH ~12). The mixture was extracted with
methylene chloride (4 × 50 ml), the extract washed with saturated sodium chloride solution (30 ml), and dried
over anhydrous Na2SO4. After removing the solvent in vacuum a yellowish brown oily substance (1.65 g, 95%)
was obtained, which was used to prepare hydrazones without further purification. Mass spectrum, m/z (I, %):
194 (25) [M]+, 135 (100) [M-CO2Me]+, 118 (26), 104 (20), 91 (18), 77 (45).
R
Cyclohexanone (0.39 g, 4 mmol)
( )-1-(1-Methoxycarbonylethyl)-2,3,4,5-tetrahydrocarbazole (8).
and a catalytic amount of p-toluenesulfonic acid were added to solution of compound 6 (0.78 g, 4 mmol) in
benzene (10 ml), and the mixture boiled for 8 h with a Dean and Stark stillhead. The formation of hydrazone 7
was confirmed by chromato-mass spectrometry {m/z (I, %): 274 (5) [M]+, 215 (100) [M-CO2Me]+, 118 (50),
104 (15), 96 (80), 77 (63), 69 (18), 55 (30)}. Benzene was removed under reduced pressure, the residue
dissolved in toluene (40 ml), Amberlist 15 (2 g) was added, and the mixture stirred vigorously for 3 h at
90-100°C. The resin was filtered off, washed with ethyl acetate (60 ml), the filtrate was evaporated in vacuum,
and the residue chromatographed on a column of silica gel, mobile phase hexane–ethyl acetate with
1
concentration gradient up to 5 vol. % of the latter. A viscous liquid (0.63 g, 61%) was obtained. H NMR
spectrum, δ, ppm (J, Hz): 1.59 (3H, d, J = 7.2, CH3CH); 1.73-1.92 (4H, m); 2.54-2.74 (4H, m); 3.64 (3H, s,
CH3O); 5.40 (1H, q, J = 7.2, CH3CH); 6.98 (1H, t, J = 7.4); 7.02 (1H, t, J = 7.1); 7.22 (1H, d, J = 8.1); 7.38
(1H, d, J = 7.1). Mass spectrum, m/z (I, %): 257 (35) [M]+, 198 (100) [M-CO2Me]+, 170 (30), 156 (5), 143 (3),
128 (4), 115 (4), 98 (3), 77 (3). Found, %: C 74.73; H 7.50; N 5.35. C16H19NO2. Calculated, %: C 74.68; H 7.44;
N 5.44. [α]D21 4.2 (CHCl3, c 0.04).
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