Regioselective reductive 2-oxoalkylation of N-methylquinolinium and -isoquinolinium iodides under sonochemical activation

Full text of DOI:10.1021/jo951766y

4830
J . Org. Chem. 1996, 61, 4830-4832
Sch em e 1
Regioselective Red u ctive 2-Oxoa lk yla tion
of N-m eth ylqu in olin iu m a n d
-isoqu in olin iu m Iod id es u n d er
Son och em ica l Activa tion
Fa¨ıza Diaba, Ifan Lewis,
Micheline Grignon-Dubois,* and Se´bastien Navarre
Laboratoire de Chimie Organique et Organome´tallique,
CNRS URA 35, Universite´ Bordeaux I, 351, Cours de la
Libe´ration, F-33405 Talence-Cedex, France
Received September 27, 1995
In tr od u ction
Nucleophilic addition to quinolinium salts is well
known for the functionalization of the quinoline ring.1
However, the regiochemistry of the addition is reported
to be dependent on substituent effects as well as on the
nature of the nucleophilic reagent, leading to a competi-
tion between C-2 and C-4 additions.1,2 We have recently
demonstrated that sonochemical activation allows re-
giospecific C-2 addition of trichloromethyl anion to quino-
linium iodides in good to quantitative yields.3 An ultra-
sound-promoted synthesis of 2-quinolones by reacting
quinolinium iodides with potassium tert-butylate has also
been proposed.4 As part of our continuing interest in the
development of new synthetic methods in heterocyclic
chemistry, we have investigated the oxoalkylation of a
series of quinoline and isoquinoline methiodides. Recent
attempts to synthesize acetonylquinolines and -isoquino-
lines have been reported to be difficult,5 and the products
were only observed by NMR. In contrast, berberine salts
have been known for a long time to react with acetone
in the presence of alkali to afford 8-acetonylberberine.6
Moreover, 6-acetonyl-5,6-dihydro-5-alkylphenanthridines
have been obtained from alkylphenanthridinium iodides
by Dostal et al.7 by reaction with K2CO3/acetone, and by
us,3 when using CCl3COONa/acetone. However, these
two reactions led to a mixture of products. We describe
here an efficient regioselective synthesis of 1-methyl-2-
(2-oxoalkyl)-1,2-dihydroquinolines and 2-methyl-1-(2-
oxoalkyl)-1,2-dihydroisoquinolines using NaOH/ketone
reagents under sonochemical activation.
yields (Scheme 1, Table 1). The reaction was regiospecific
with all quinolines, leading to the C-2 adducts 3a -d as
the only product. The 1-methyl-3-bromoquinolinium
iodide (1b) constituted the only exception and led, as
previously observed in the trichloromethylation reac-
tions,3 to a 83:17 mixture of the C-2 and C-4 adducts,
3b/4b. A simple steric effect cannot be invoked in this
case. Indeed, the nucleophilic addition was perfectly
regiospecific in the case of the 3-methyl derivative 1c,
despite the larger interference radius of the methyl group
compared to bromine (200 and 195 pm, respectively).8 The
efficiency of the procedure is well demonstrated by
obtaining 4e from the acridine methiodide, 1e. Indeed,
4e had been previously isolated as an oil by Bunting et
al.,5 but no yield was reported. Our process allowed us
to obtain 4e as an analytically pure solid in 81% yield.
As expected, the isoquinolinium iodides 2a ,b led to the
C-1 adducts in good yields (Table 1). However, in the
case of phenanthridine methiodide, the acetonyl deriva-
tive 5b (75% yield) was obtained in mixture with N-
methylphenanthridone (6; 24% yield). This side reaction
was probably due to the competition between the hy-
droxyl anion abstracting a proton from acetone and its
direct addition to the methiodide. We had previously
obtained 5b (45% yield) in mixture with the 5-trichlo-
romethyl derivative (9%) when reacting sodium trichlo-
roacetate and phenanthridine methiodide in acetone
medium.3 Under these conditions, no trace of phenan-
thridone was observed. We tried without success to
improve the yield of 5b by increasing the quantity of
acetone used (160 mL per mol instead of 80). This
procedure was also applied to 1,2-dimethylquinolinium
Resu lts a n d Discu ssion
Sonication of quinolinium and isoquinolinium methio-
dides 1 and 2 with sodium hydroxide in acetone solution
afforded the acetonyl products in good to quantitative
(1) For reviews, see: Sidgewick, N. Y.; Sidgewick, F. R. S. The
Organic Chemistry of Nitrogen; Clarendon: Oxford, 1966; p 718. Dyke,
S. F. Adv. Heterocycl. Chem. 1972, 14, 279. Gurnos, J . Quinolines;
Wiley: New York, 1982.
(2) See, for example: Leonard, N. J .; Foster, R. L. J . Am. Chem.
Soc. 1951, 73, 3325; ibid. 1952, 74, 2110. Metzgzer, J .; Larive´, H.;
Vincent, E.-J .; Dennilauler, R.; Baralle, R.; Gaurat, C. Bull. Soc. Chim.
Fr. 1967, 30. Metzgzer, J .; Larive´, H.; Vincent, E.-J .; Dennilauler, R.
Bull. Soc. Chim. Fr. 1967, 46. Pilygun, G. T.; Gutsulyak, B. M. Russ.
Chem. Rev. 1963, 32, 167. Bunting, J . W.; Meathrel, W. G. Tetrahedron
Lett. 1971, 133. Fukuzumi, S.; Noura, S. J . Chem. Soc., Chem.
Commun. 1994, 287. Maeda, M. Chem. Pharm. Bull. 1990, 38, 2577.
(3) Grignon-Dubois, M.; Diaba, F.; Grelier-Marly, M.-C. Synthesis
1994, 800.
(4) Grignon-Dubois, M.; Meola, A. Synth. Commun. 1995, 25, 2999.
(5) Chen, T.-K.; Bradsher, C. K. Tetrahedron 1973, 29, 2951.
Bunting, J . W.; Fu, C.; Tam, J . W. Can. J . Chem. 1990, 68, 1762.
(6) Schmidt, E.; Gaze, R. Arch. Pharm. 1890, 228, 604.
(7) Dostal, J .; Potacek, M.; Nechvatal, M. Collect. Chem. Commun.
1993, 58, 395.
(8) Pauling, L. In The Nature of Chemical Bond; Verlag Chemie:
Weinheim; 1962, p 242. Seebach, D. Angew. Chem., Int. Engl. 1990,
29, 1320.
S0022-3263(95)01766-X CCC: $12.00 © 1996 American Chemical Society

Notes
Ta ble 1. Oxoa lk yla tion of Com p ou n d s 1 a n d 2 u n d er
J . Org. Chem., Vol. 61, No. 14, 1996 4831
Sch em e 2
Son och em ica l Activa tion
product(s)
total
substrate
reagent
acetone
acetone
acetone
acetone
acetone
acetone
acetone
butanone
2-pentanone
butanone
2-pentanone
(ratio)
yield (%)
1a
1b
1c
1d
1e
2a
2b
1a
1a
1a
2a
3a /4a (100:0)
3b/4b (83:17)
3c/4c (100:0)
3d /4d (100:0)
97
98
98
91
81
95
75
4e
5a
5b
7
8
9
40,a 70b
72,a 82b
54,a 80b
67a 72b
10
a
b
Isolated yields using the typical procedure. isolated yields
when reactions are conducted in acetonitrile (see Experimental
Section for details).
1-methyl-2-(2-oxoalkyl)-1,2-dihydroquinolines and 2-meth-
yl-1-(2-oxoalkyl)-1,2-dihydroisoquinolines under very mild
and inexpensive conditions.
iodide, for which the acetonyl addition failed when using
the NaOH/acetone reagent. Indeed, in this case sonochem-
ical activation did not prevent the hydroxyl anion ab-
stracting a proton from the C-2 methyl group. These
attempts were unsuccessful and only led to the trichlo-
romethyl C-2 adduct (35% yield).
In the case of 1a , the reaction has also been conducted
under mechanical stirring. We obtained a 3a /4a mixture
(56:44; 95% yield) after 5 h at reflux instead of 1.5 h at
0 °C under ultrasound, and a 75:25 mixture of 3a /4a in
only 14% yield after 17 h at rt. These results demon-
strate the efficiency of ultrasonic waves upon the regi-
oselectivity and the reaction rate.
It is worth noting that the reaction outcome is more
sensitive to temperature with acridine and phenanthri-
dine methiodides than with the other substrates. In
these two cases, it is necessary to carefully maintain the
bath temperature between 0-5 °C during the sonication.
An increase of temperature resulted in the formation of
the corresponding quinolones along with the acetonyl
derivatives.
From a mechanistic point of view, these results are
consistent with the addition of the enolate ion of acetone
to the ortho position versus nitrogen. As previously
observed for trichloromethylation,3 sonochemical activa-
tion allowed kinetic control of the nucleophilic addition,
and the mild experimental conditions prevented the
isomerization of the C-2 adduct to its C-4 regioisomer.
In the case of dissymmetric ketones, the question arises
regarding the regiochemistry of the enolate formation
under sonochemical activation. For this purpose, we also
studied the reaction of 1a and 2a with butanone and
2-pentanone. In the conditions used for acetone, the C-2
or C-1 (2-oxoalkyl) adducts 7-10 were, respectively,
obtained as the only product, but in lower yields than
with acetone (Scheme 2, Table 1). Improvements in the
yields were achieved when the reaction was carried out
in acetonitrile solution (Table 1, see Experimental Section
for details). These results show that sonochemical
activation allows both the enolate formation and its
addition to the methiodide to be regiospecific. The
systematic formation of the less-subtituted enolate is in
good agreement with a kinetically controlled deprotona-
tion process.9
Exp er im en ta l Section
Melting points were uncorrected. 1H and 13C NMR spectra
were recorded at 250 and 63 MHz, respectively, with TMS as
internal standard. Elemental analyses were performed by
Service Central D’analyses du CNRS (F-69390 Vernaison).
Flash column chromatography techniques (30 cm × 2 cm
column) were employed to purify crude product using 70-230
mesh alumina (activity II-III, CH2Cl2) under positive air
pressure. Ultrasound-promoted reactions were carried out in a
common ultrasonic laboratory cleaner filled with thermostated
water at 0-5 °C. The reaction flask was partially submerged
in the sonicator water bath in a place that produced maximum
agitation.
Ma ter ia ls. Synthesis grade acetone (Aldrich) was used as
received. Commercial sodium hydroxide pellets (Aldrich, re-
agent ACS) were pulverized prior to use. Methiodides were
prepared according to literature procedures10 by alkylation of
the appropriate quinoline with methyl iodide in acetone (1a -d ,
2a ) or methylene chloride solution (1e, 2b). The mixture was
maintained at rt until the substrate had completely reacted, as
monitored by TLC (SiO2; Et2O/CH2Cl2, 30:70 v/v). The precipi-
tated salts were filtered and recrystallized. All data for these
compounds are identical to literature data.10
Typ ica l P r oced u r e for Aceton yla tion . To a sonicated
suspension of methiodide (22 mmol) in acetone (20 mL), 1.0 g of
pulverized sodium hydroxide (27 mmol) was added over 5 min.
The reaction was complete within 90 min, as monitored by TLC
(Al2O3; CH2Cl2). The reaction mixture was filtered through
Celite, and the filtrate was evaporated to dryness. The residue
was taken up with cyclohexane (40 mL), and insoluble materials,
if present, were removed by filtration and analyzed separately.
The cyclohexane solution was evaporated to dryness leading to
the analytically pure acetonyl derivatives as the only product,
except in the case of phenanthridine, for which it was obtained
in mixture with N-methylphenanthridone and chromatographed
on alumina (CH2Cl2). 5b was eluted first and then 6. The same
procedure was applied to purify the 3b/4b mixture of isomers
leading first to 3b then 4b.
1-Meth yl-2-a ceton yl-1,2-d ih yd r oqu in olin e (3a ): 4.29 g
isolated as a pale yellow liquid (97%); 1H NMR (CDCl3) δ 2.1
(3H, s), 2.8 (3H, s), 2.6 (1H, dd, J ) 15.8, 7.6 Hz), 2.7 (1H, dd, J
) 15.8, 5.5 Hz), 4.4 (1H, ddd, J ) 7.6, 5.5 Hz), 5.8 (1H, dd, J )
9.7, 5.5 Hz), 6.4 (1H, d, J ) 9.7 Hz), 6.5 (1H, d, J ) 8.1 Hz), 6.6
(1H, dd, J ) 7.3 Hz), 6.9 (1H, dd, J ) 7.3, 1.3 Hz), 7.1 (1H, ddd,
J ) 8.1, 7.3, 1.3 Hz); 13C NMR (CDCl3) δ 31.1, 36.5, 46.2, 56.5,
111.1, 117.2, 122.2, 124.8, 125.9, 126.9, 129.2, 144.3, 207.3; MS,
m/z (%) 201 (M+, 3.7), 144 (100); IR (NaCl) 1710 cm-1
. Anal.
In conclusion, this new procedure provides a facile and
very clean method for the regioselective synthesis of
(10) Doebner, O.; Miller, W. Ber, 1883, 16, 2464. Duffin, C. F. Adv.
Heterocycl. Chem. 1964, 3, 1. Marchwald, W.; Meijer, E. Ber. 1884,
33, 1990. Gurevitch, A. I.; Sheinker, Yu. N. Zhur. Fiz. Chim. 1959,
33, 883; Chem. Abstr. 1960, 4, 8285b. Zanker, V.; Cnobloch, H. Z.
Naturforsch. B Chem. Sci. 1962, 17, 819.
(9) Evans, D. A. In Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: New York, 1984; Vol. 3, p 1 and ref therein. D’Angelo,
J . Tetrahedron 1976, 32, 2979 and ref therein.

4832 J . Org. Chem., Vol. 61, No. 14, 1996
Notes
Calcd for C13H15NO: C, 77.58; H, 7.51; N, 6.96; O, 7.95.
Found: C, 77.22; H, 7.41; N, 7.01; O, 8.25.
ddd, J ) 7.3, 1.5 Hz), 7.1 (1H, ddd, J ) 7.3, 1.8 Hz); 13C NMR
(CDCl3) δ 31.7, 40.5, 44.7, 58.2, 97.5, 122.7, 124.8, 125.7, 127.5,
128.5, 132.5, 136.5, 208.0; MS, m/z (%) 201 (M+, 7.9), 144 (100);
IR (NaCl) 1707 cm-1. Anal. Calcd for C13H15NO: C, 77.58; H,
7.51; N, 6.96; O, 7.95. Found: C, 77.65; H, 7.43; N, 7.12; O,
7.68.
5-Meth yl-6-aceton yl-5,6-dih ydr oph en an th r idin e (5b). The
typical procedure led to 5.30 g of a crude mixture. It produced
after flash chromatography (alumina, CH2Cl2), in order of
elution, 4.14 g of 5b as a pale yellow liquid (75%) and 1.10 g of
6 (24%), which was identical to literature data.3,4
1-Meth yl-2-a ceton yl-3-br om o-1,2-d ih yd r oqu in olin e (3b):
1
4.99 g isolated as a pale yellow liquid (81%); H NMR (CDCl3 )
δ 2.1 (3H, s), 2.8 (3H, s), 2.6 (1H, dd, J ) 16.2, 4.0 Hz), 2.8 (1H,
dd, J ) 16.2, 7.0 Hz), 4.7 (1H, dd, J ) 7.0, 4.0 Hz), 6.7 (1H, s),
6.5 (1H, d, J ) 8.2 Hz), 6.7 (1H, dd, J ) 7.4, 7.3 Hz), 6.9 (1H,
dd, J ) 7.4, 1.5 Hz), 7.1(1H, ddd, J ) 8.2, 7.3, 1.5 Hz); 13C NMR
(CDCl3) δ 31.0, 37.6, 44.9, 63.2, 112.1, 116.7, 117.9, 122.0, 126.5,
128.2, 129.6, 142.0, 206.3; MS, m/z (%) 279 (M+, 2.2), 224 (100);
IR (NaCl) 1720 cm-1. Anal. Calcd for C13H14BrNO: C, 55.73;
H, 5.04; N, 5.0; O, 5.71. Found: C, 55.76; H, 4.99; N, 4.87; O,
5.86.
5b: 1H NMR (CDCl3) δ 1.9 (3H, s), 3.0 (3H, s), 2.6 (1H, dd, J
) 15.6, 7.7 Hz), 2.7 (1H, dd, J ) 15.6, 5.4 Hz), 4.9 (1H, dd, J )
7.7, 5.4 Hz), 6.7-7.8 (8H, m); 13C NMR (CDCl3) δ 31.6, 37.4,
44.5, 59.8, 113.4, 118.4, 122.7, 123.0, 123.4, 126.1, 127.3, 127.9,
1,3-Dim eth yl-2-a ceton yl-1,2-d ih yd r oqu in olin e (3c): 4.64
1
g isolated as a pale yellow liquid (98%); H NMR (CDCl3) δ 1.8
(3H, d, J ) 1.3 Hz), 2.1 (3H, s), 2.8 (3H, s), 2.4 (1H, dd, J )
15.9, 4.9 Hz), 2.7 (1H, dd, J ) 15.9, 6.4 Hz), 4.3 (1H, dd, J )
6.4, 4.9 Hz), 6.2 (1H, d, J ) 1.3 Hz), 6.5 (1H, dd, J ) 8.1, 0.9
Hz), 6.7 (1H, ddd, J ) 7.3, 0.9 Hz), 6.9 (1H, dd, J ) 7.3, 1.5 Hz),
7.1 (1H, ddd, J ) 8.1, 7.3, 1.5 Hz); 13C NMR (CDCl3) δ 20.8,
31.0, 37.0, 44.7, 60.6, 111.2, 117.5, 121.8, 123.2, 126.0, 128.2,
133.6, 142.6, 207.5; MS, m/z (%) 215 (M+, 3.1), 158 (100); IR
(NaCl) 1711 cm-1. Anal. Calcd for C14H17NO: C, 78.10; H, 7.96;
N, 6.51; O, 7.43. Found: C, 77.81; H, 8.08; N, 6.40; O, 7.52.
1,4-Dim eth yl-2-a ceton yl-1,2-d ih yd r oqu in olin e (3d ): 4.30
129.4 130.6, 135.6, 144.4, 207.7; IR (NaCl) 1710 cm-1
.
Rea ction s w ith bu ta n on e a n d 2-p en ta n on e were per-
formed according to the typical procedure using 22 mmol of
methiodide and 0.6 mol of ketone (procedure a), and also in
acetonitrile solution (10 mL), using the same conditions (proce-
dure b).
1-Meth yl-2-(2-oxobu tyl)-1,2-d ih yd r oqu in olin e (7). Iso-
lated as a pale yellow liquid: 1.89 g (40%) using procedure a;
3.30 g (70%) using procedure b; 1H NMR (CDCl3) δ 1.0 (3H, t, J
) 7.3 Hz), 2.4 (2H, dq, J ) 7.3, 2.8 Hz), 2.5 (1H, dd, J ) 15.6,
7.5 Hz), 2.7 (1H, dd, J ) 15.6, 5.3 Hz), 2.8 (3H, s), 4.5 (1H, ddd,
J ) 7.5, 5.7, 5.3 Hz), 5.8 (1H, dd, J ) 9.7, 5.7 Hz), 6.4 (1H, d, J
) 9.7 Hz), 6.6 (1H, dd, J ) 8.3, 1.0 Hz), 6.7 (1H, ddd, J ) 7.6,
7.3, 1.0 Hz), 6.9 (1H, dd, J ) 7.3, 1.5 Hz), 7.1 (1H, ddd, J ) 8.3,
7.6, 1.5 Hz); 13C NMR (CDCl3) δ 7.7, 36.5, 37.4, 44.9, 56.7, 111.0,
117.1, 122.0, 124.9, 125.9, 126.9, 129.2, 144.3, 210.0; MS, m/z
(%) 215 (M+, 3), 144 (100); IR (NaCl) 1702 cm-1. Anal. Calcd
for C14H17NO: C, 78.10; H, 7.96; N, 6.51; O, 7.43. Found: C,
78.28; H, 7.82; N, 6.49; O, 7.29.
1-Meth yl-2-(2-oxop en tyl)-1,2-d ih yd r oqu in olin e (8). Iso-
lated as a pale yellow liquid: 3.63 g (72%) using procedure a;
4.13 g (82%) using procedure b; 1H NMR (CDCl3) δ 0.9 (3H, t, J
) 7.4 Hz), 1.5(2H, sextet, J ) 7.4 Hz), 2.3 (2H, t, J ) 7.4 Hz),
2.6 (1H, dd, J ) 15.6, 7.5 Hz), 2.7 (H, dd, J ) 15.6, 5.5 Hz), 2.9
(3H, s), 4.5 (1H, ddd, J ) 7.5, 5.7, 5.5 Hz), 5.8 (1H, dd, J ) 9.7,
5.7 Hz), 6.4 (1H, d, J ) 9.7 Hz), 6.5 (1H, dd, J ) 8.1, 0.9 Hz), 6.7
(1H, ddd, J ) 7.4, 7.7, 0.9 Hz), 6.9 (1H, dd, J ) 7.4, 1.5 Hz), 7.1
(1H, ddd, J ) 8.1, 7.7, 1.5 Hz); 13C NMR (CDCl3) δ 11.0, 13.7,
17.1, 36.5, 45.2, 46.2, 56.6, 117.1, 122.0, 124.9, 125.8, 126.9,
129.1, 144.3, 210.0; MS, m/z (%) 229 (M+, 4.9), 144 (100); IR
(NaCl) 1705 cm-1. Anal. Calcd for C15H19NO: C, 78.56; H, 8.35;
N, 6.11; O, 6.98. Found: C, 78.70; H, 8.26; N, 6.30; O, 6.65.
1
g isolated as a pale yellow liquid (91%); H NMR (CDCl3) δ 2.0
(3H, d, J ) 1.3 Hz), 2.1 (3H, s), 2.9 (3H, s), 2.6 (1H, dd, J )
15.9, 7.9 Hz), 2.7 (1H, dd, J ) 15.9, 5.2 Hz), 4.4 (1H, ddd, J )
7.9, 5.8, 5.2 Hz), 5.7 (1H, dd, J ) 5.8, 1.3 Hz), 6.5 (1H, dd, J )
8.2, 1.2 Hz), 6.7 (1H, ddd, J ) 7.6, 1.2 Hz), 7.1 (1H, dd, J ) 7.6,
1.5 Hz), 7.1 (1H, ddd, J ) 8.2, 7.6, 1.5 Hz); 13C NMR (CDCl3) δ
18.8, 27.0, 36.8, 45.9, 56.4, 111.2, 117.0, 122.3, 123.5, 123.8,
129.0, 130.7, 144.3, 207.6; MS, m/z (%) 215 (M+ , 2.7), 158 (100);
IR (NaCl) 1709 cm-1. Anal. Calcd for C14H17NO: C, 78.10; H,
7.96; N, 6.51; O, 7.43. Found: C, 78.0; H, 8.14; N, 6.72; O, 7.08.
1-Meth yl-4-a ceton yl-1,4-d ih yd r oqu in olin e (4a ). The reac-
tion was conducted under mechanical stirring at reflux for 5 h
leading to 4.32 g of a crude mixture. It produced after flash
chromatography (alumina, CH2Cl2), in order of elution, 2.35 g
of 3a (53%) and 1.85 g of 4a (42%) both as slightly-colored liquid.
4a : 1H NMR (CDCl3) δ 2.0 (3H, s), 3.0 (3H, s), 2.5 (1H, dd, J
) 16.2, 5.1 Hz), 2.7 (1H, dd, J ) 16.2, 8.4 Hz), 6.0 (1H, d, J )
7.8 Hz), 4.6 (1H, dd, J ) 7.8, 5.0 Hz), 4.0 (1H, ddd, J ) 8.4, 5.1,
5.0 Hz), 6.6 (1H, dd, J ) 7.6, 1.1 Hz), 6.8 (1H, ddd, J ) 7.5, 1.1
Hz), 7.0 (1H, d, J ) 7.5 Hz), 7.1 (1H, dd, J ) 7.6, 7.5 Hz); 13C
NMR (CDCl3) δ 31.0, 35.5, 37.9, 54.8, 99.3, 111.2, 121.0, 124.1,
127.2, 128.7, 133.0, 141.3, 207.7; MS, m/z (%) 201 (M+ , 3.7),
144 (100); IR (NaCl) 1705 cm-1. Anal. Calcd for C13H15NO: C,
77.58; H, 7.51; N, 6.96; O, 7.95. Found: C, 77.62; H, 7.53; N,
7.16; O, 7.60.
2-Meth yl-1-(2-oxobu tyl)-1,2-d ih yd r oisoqu in olin e (9). Iso-
lated as a pale yellow liquid: 2.55 g (54%) using procedure a;
1
1-Meth yl-3-br om o-4-a ceton yl-1,4-d ih yd r oqu in olin e (4b):
3.78 g (80 %) using procedure b; H NMR (CDCl3) δ 0.9 (3H, t,
1
1.02 g isolated as a pale yellow liquid (17%); H NMR (C6D6) δ
J ) 7.2 Hz), 2.0 (1H, dq, J ) 18.0, 7.2 Hz), 2.2 (1H, dq, J ) 18.0,
7.2 Hz), 2.7 (2H, d, J ) 6.4 Hz), 2.9 (3H, s), 4.8 (1H, t, J ) 6.4
Hz), 5.3 (1H, d, J ) 7.2 Hz), 6.0 (1H, dd, J ) 7.2, 1.0 Hz), 6.7-
7.4 (4H, m); 13C NMR (CDCl3) δ 7.6, 37.9, 40.5, 43.3, 58.6, 97.5,
122.7, 124.7, 125.6, 127.5, 128.5, 132.5, 136.5, 210.5; MS, m/z
(%) 215 (M+, 4.1), 144 (100); IR (NaCl) 1706 cm-1. Anal. Calcd
for C14H17NO: C, 78.10; H, 7.96; N, 6.51; O, 7.43. Found: C,
78.16; H, 8.02; N, 6.48; O, 7.10.
1.6 (3H, s), 2.4 (3H, s), 2.5 (1H, dd, J ) 16.4, 7.6 Hz), 2.7 (1H,
dd, J ) 16.4, 4.0 Hz), 6.0 (1H, s), 4.6 (1H, dd, J ) 7.6, 4.0 Hz),
6.4 (1H, dd, J ) 8.2, 1.1 Hz), 6.8 (1H, ddd, J ) 7.5, 1.1 Hz), 7.2
(1H, dd, J ) 7.5, 1.6 Hz), 7.0 (1H, ddd, J ) 8.2, 7.5, 1.6 Hz); 13
C
NMR (C6D6) δ 30.5, 41.9, 51.3, 63.2, 94.9, 111.7, 121.9, 124.0,
128.4, 129.4, 133.8, 140.0, 207.0; MS, m/z (%): 279 (M+, 1.5),
222 (100); IR (NaCl) 1715 cm-1. Anal. Calcd for C13H14BrNO:
C, 55.73; H, 5.04; N, 5.0; O, 5.71. Found: C, 56.01; H, 5.20; N,
5.0; O, 5.68.
2-Met h yl-1-(2-oxop en t yl)-1,2-d ih yd r oisoq u in olin e (10).
Isolated as a pale yellow liquid: 3.37 g (67%) using procedure
a; 3.62 g (72%) using procedure b; 1H NMR (CDCl3) δ 0.9 (3H, t,
J ) 7.4 Hz), 1.5 (2H, sextet, J ) 7.4 Hz), 2.0 (1H, td, J ) 17.1,
7.4 Hz), 2.1 (1H, td, J ) 17.1, 7.4 Hz), 2.7 (2H, d, J ) 6.4 Hz),
2.9 (s, 3H), 4.8 (1H, t, J ) 6.5 Hz), 5.3 (1H, d, J ) 7.1 Hz), 6.0
(1H, d, J ) 7.1 Hz), 6.8 (1H, d, J ) 7.3 Hz), 6.8 (1H, d, J ) 7.3
Hz), 6.9 (1H, ddd, J ) 7.3, 1.2 Hz), 7.0 (1H, ddd, J ) 7.3, 1.5
Hz); 13C NMR (CDCl3) δ 11.0, 13.7, 17.1, 36.5, 45.2, 46.2, 56.6,
117.1, 122.0, 124.9, 125.8, 126.9, 129.1, 144.3, 210.0; MS, m/z
(%) 229 (M+ , 4.9), 144 (100); IR (NaCl) 1707 cm-1 . Anal. Calcd
for C15H19NO: C, 78.56; H, 8.35; N, 6.11; O, 6.98. Found: C,
78.22; H, 8.04; N, 6.39; O, 7.20.
9-Aceton yl-10-m eth yl-9,10-d ih yd r oa cr id in e (4e): 4.47 g
isolated as a solid (81%); mp 127 °C; 1H NMR (CDCl3 ) δ 1.9
(3H, s), 3.4 (3H, s), 2.7 (2H, d, J ) 7.0 Hz), 4.6 (1H, t, J ) 7.0
Hz), 7.0 (4H, m), 7.3 (4H, m); 13C NMR (CDCl3) δ 31.3, 33.1,
50.4, 39.6, 112.3, 121.0, 127.3, 128.2, 126.9, 142.7, 207.5; MS,
m/z (%) 251 (M+ , 6.9), 194 (100); IR (NaCl) 1712 cm-1. Anal.
Calcd for
C17H17NO: C, 81.24; H, 6.82; N, 5.57; O, 6.37.
Found: C, 81.08; H, 6.68; N, 5.78; O, 6.18.
1-Aceton yl-2-m eth yl-1,2-d ih yd r oisoqu in olin e (5a ): 4.20
1
g isolated as a pale yellow liquid (95%); H NMR (CDCl3) δ 1.9
(3H, s), 2.9 (3H, s), 2.8 (2H, m), 4.8 (1H, ddd, J ) 7.0, 6.7, 1.2
Hz), 5.3 (1H, d, J ) 7.3 Hz), 6.0 (1H, dd, J ) 7.3, 1.2 Hz), 6.9
(H, dd, J ) 7.3, 1.5 Hz), 6.9 (1H, dd, J ) 7.3, 1.8 Hz), 7.0 (1H,
J O951766Y