Study of a 1,6-hydride shift in an open chain of hydroxylactam-triarylcarbinols

Article abstract of DOI:10.1016/S0040-4020(01)00437-9

Hydroxylactam-alcohols 5a,b,d (isoindole series), under acidic treatment gave phthalimides 7a,b,d via a hydride shift induced by an intramolecular π-stacking (benzene-benzene or benzene-thiophene interaction) which did not occur in 10a (succinimide series).

Full text of DOI:10.1016/S0040-4020(01)00437-9

TETRAHEDRON
Pergamon
Tetrahedron 57 ,2001) 4939±4943
Study of a 1,6-hydride shift in an open chain
of hydroxylactam-triarylcarbinols
a
Pascal Pigeon, Aõcha Mamouni, Jana Sikoraiova, Stefan Marchalin and Bernard Decroix
a
b
b
a,p
È
a
 Â
Laboratoire de Chimie, Faculte des Sciences et des Techniques de l'Universite du Havre, 25 rue Philippe Lebon, BP 540,
76058 Le Havre Cedex, France
Department of Organic Chemistry, Slovak University of Technology, Radlinskeho 9, 812 37 Bratislava, Slovak Republic
b
Â
Received 16 February 2001; revised 18 April 2001; accepted 20 April 2001
AbstractÐHydroxylactam-alcohols 5a,b,d ,isoindole series), under acidic treatment gave phthalimides 7a,b,d via a hydride shift induced
by an intramolecular p-stacking ,benzene±benzene or benzene±thiophene interaction) which did not occur in 10a ,succinimide series).
q 2001Elsevier Science Ltd. All rights reserved.
1. Introduction
with an alcohol or a thiol.5 Thus from compound 5a, we
expected either the formation of an ether or a nucleophilic
pinacol rearrangement if the geometry of the structure
permits the transfer of an atom similar to the one observed
in cyclodecanediol 1. The starting hydroxylactam-alcohols
5a±c were obtained in good yields by reducing the phthali-
mide-esters 3a±b6,7 with sodium borohydride and by subse-
quent addition of an excess of phenylmagnesium bromide
,Scheme 2). Thus, when 5a was subjected to a catalytic
amount of p-toluenesulfonic acid ,PTSA) in re¯uxing tolu-
ene for 2 h, a mixture of ether 6a ,80%) and imide 7a ,20%)
was formed. Compounds 5a, 6a and 7a were easily differen-
tiated by the analysis of their NMR ,1H and 13C) spectra.
Due to the presence of a stereogenic center, methylene
protons ,N±CH2) and carbon atoms of the two phenyl
groups are not equivalent for 5a and 6a in contrast to 7a.
When a catalytic amount of tri¯uoroacetic acid ,TFA) in
place of PTSA was used during 30 min, we observed the
ether 6a accompanied with traces of 7a. The imide 7a was
obtained from 5a or 6a as the sole product when the reaction
was carried out for 2 days with an excess of TFA. This
behavior was similar to a pinacol rearrangement. To prove
that the product 7a resulted of a hydrogen migration we
The pinacol rearrangement is a well-known reaction and it
has been demonstrated that the hydrogen has a greater
migratory aptitude than a phenyl group. Although direct
nucleophilic rearrangement over distances greater than 1,2
are rare, a shift across a ring of 8±11 members1,2 is still
possible as exempli®ed with cyclodecanediol 13 ,Scheme
1).
Based on these observations we intended to study structures
of type I, because during our investigations on the synthesis
of polyheterocycles containing an isoindole moiety, we
have prepared hydroxylactam-alcohols 5a±d. Actually, in
an acidic medium the hydroxylactam is a precursor of an
N-acyliminium ion,4 and the triarylcarbinol can also give a
carbocation. Consequently, it was reasonable to investigate
the possibilities of a hydrogen migration from the hydroxy-
lactam to the carbinol.
In a diol, as might be expected, the leaving hydroxy group is
the one which leads to the more stable carbocation. We have
recently described that an N-acyliminium ion reacts easily
Scheme 1.
Keywords: iminium salts; isoindole; oxazepines; polycyclic heterocyclic compounds.
Corresponding author. Tel.: 133-02-32-74-43-95; fax: 133-02-32-74-43-91; e-mail: bernard.decroix@univ-lehavre.fr
p
0040±4020/01/$ - see front matter q 2001Elsevier Science Ltd. All rights reserved.
PII: S0040-4020,01)00437-9

4940
P. Pigeon et al. / Tetrahedron 57 62001) 4939±4943
Scheme 2.
prepared the deuterated hydroxylactam 5a. The latter
resulted of the reduction of 4a in the presence of deuterated
sodium borohydride. The deuterated compound 5a gave the
deuterated phthalimide 7a. A NMR analysis revealed the
absence of hydrogen in the a-position to the two phenyl
groups compared to that observed in the non-deuterated
product 7a ,dˆ6.22 ppm). The hydrogen migration can be
rationalized as depicted in Scheme 3. The more stable
carbocation A was ®rst formed, followed by a transfer of
deuterium which led to a new carbocation B stabilized by
both a nitrogen and an oxygen atom. Finally, loss of a proton
provided phthalimide 7a. This hydride transfer was
supposed to be due to the geometry of the carbocation A.
molecule did not permit either a cyclodehydration or a
hydrogen migration leading to 7c.
Another argument in favor of a p-stacking was obtained
during the investigation of diol 10a ,Scheme 4). We tested
the tetramethylsuccinimide in place of the isoindole moiety
,the methyl groups in 10 prevented loss of a proton in the a
position of the hydroxy group leading to an enamide). The
imide 8 was prepared via the alkylation of the tetramethyl-
succinimide with the methyl 3-bromomethylthiophene-2-
carboxylate in toluene using potassium carbonate as the
base. In contrast to the phthalimide series6 phenylmag-
nesium bromide in dichloromethane selectively reacted
with the ester function to give the alcohol-imide 9. Reduc-
tion of 9 with sodium borohydride at 08C in methanol as for
4a±d gave the diol 10a ,85%) accompanied with the ether
10b ,15%) in a 95% yield. The mixture 10a/10b was not
separated and was used in the next step without further
puri®cation. In a similar manner as above under acidic treat-
ment 10a ,and 10b) gave the ether 11 ,PTSA, dichloro-
methane) as the single product because the imide 12
,TFA, dichloromethane) was not observed. In the latter
case there is no p±p interaction and furthermore the
imide is shielded by the four methyl groups.
Actually, analysis of molecular models showed a proximity
between the hydrogen ,or deuterium) atom and the positive
carbon of carbocation A when one of the two phenyl groups
was parallel to the benzene ring of the isoindole moiety. To
con®rm this result, we tested the diol 5b ,the thiophene ring
of 5a has been replaced by a benzene ring). Under the same
acidic conditions ,TFA, dichloromethane) 5b gave the
cyclic ether 6b and the imide 7b. To show that the p-stack-
ing8±10 seems to be necessary we prepared the alcohol 5c.
Treated in the same manner as above ,TFA, CH2Cl2 or
PTSA, toluene, re¯ux) 5c gave no reaction, the starting
alcohol being recovered. In that case the geometry of the
As another example we prepared the oxazepine 6d and the
Scheme 3.

P. Pigeon et al. / Tetrahedron 57 62001) 4939±4943
4941
Scheme 4.
imide 7d from diol 5d. This diol resulted from the action of
6 equiv. of thien-2-ylmagnesium bromide onto the ester 4a.
The replacement of the two benzene rings ,5a,b) by two
thiophene rings ,5d) has modi®ed the p±p interaction.
Actually the hydride transfer was carried out in two days
for 5a,b while after seven days only 35% of 5d had reacted
with the formation of 13% of 7d accompanied with degra-
dation products. Furthermore, as in benzene series we did
not observe a reaction between the N-acyliminium ion and
one of the two thiophene rings whatever the conditions of
the reaction ,temperature, time).
,3.03 g, 10 mmol) at room temperature with stirring.
Stirring was continued for 3 h. The solution was then care-
fully poured into a 10% solution of ammonium chloride.
The mixture was decanted and the aqueous layer was
extracted with dichloromethane. The combined organic
layers were dried on magnesium sulfate and ®ltered. The
solution was concentrated under reduced pressure. The
residue was chromatographed on silica gel ,dichloro-
methane until the biphenyl was removed, then dichloro-
methane/acetone 90/10). The diol was recrystallized from
ethanol to furnish pure product 5a. Yield 56%; mp 1628C;
IR: 3368 ,OH), 3330 ,OH), 1660 ,CvO) cm21; 1H NMR: d
4.14 ,d, Jˆ15 Hz, 1H, CH2), 4.22 ,s, 1H, OH), 4.49 ,d,
Jˆ15 Hz, 1H, CH2), 5.59 ,s, 1H, OH), 5.67 ,s, 1H, CH),
6.98 ,d, Jˆ5 Hz, 1H, Hthiophene), 7.03 ,d, Jˆ5 Hz, 1H,
Hthiophene), 7.06±7.63 ,m, 14H, Harom); 13C NMR: d 37.2
,CH2), 79.0 ,C), 81.5 ,CH), 123.2 ,CH), 123.3 ,CH),
124.5 ,CH), 127.2 ,2 CH), 127.5 ,2 CH), 127.6 ,CH),
127.7 ,CH), 127.9 ,4 CH), 129.7 ,CH), 130.5 ,CH), 131.2
,C), 132.3 ,CH), 134.3 ,C), 143.1 ,C), 146.7 ,C), 147.0 ,C),
148.5 ,C), 167.3 ,CO). Anal. Calcd for C26H21NO3S: C,
73.05; H, 4.95; N, 3.28. Found: C, 72.78; H, 4.89; N, 3.34.
In conclusion we have described an interesting hydride
transfer between a hydroxylactam and an alcohol in a
non-cyclic product. A p-stacking in the intermediate carbo-
cation seems to be necessary for this transfer. Further
studies are in progress to investigate scope and limitations
of this new type of hydrogen migration.
2. Experimental
2.1. General
2.1.2.
2,3-Dihydro-3-hydroxy-2-[2-)diphenylhydroxy-
methyl)phenylmethyl]-1H-isoindol-1-one )5b). This com-
pound was prepared from 4b using the same procedure as
for 5a. Yield 59%; mp 1188C; IR: 3306 ,OH), 1680
Melting points are uncorrected. The infrared spectra of
solids ,potassium bromide) were recorded on a Perkin±
1
Elmer FTIR paragon 1000 spectrometer. The H and 13C
1
,CvO) cm21; H NMR: d 4.40 ,d, Jˆ15 Hz, 1H, CH2),
NMR spectra were recorded on a Bruker AC-200
,200 MHz) instrument in deuterochloroform solution and
chemical shifts ,d) are expressed in ppm relative to internal
TMS. Thin layer chromatography was performed on
precoated plates of silica gel 60 F254 ,Merck) and the
spots visualized using an ultraviolet lamp or iodine vapor.
E. Merck silica gel 60 F ,70±300 mesh) was used for
column chromatography. The elemental analyses were
carried out by the microanalysis laboratory of INSA at
Rouen, F 76130 Mt. St. Aignan, France. Compounds 4a,b
were prepared as indicated in Refs. 6 and 7.
4.63 ,d, Jˆ15 Hz, 1H, CH2), 4.73 ,d, Jˆ7 Hz, 1H, OH),
5.59 ,d, Jˆ7 Hz, 1H, CH), 6.56 ,d, Jˆ8 Hz, 1H, Harom),
6.92±7.52 ,m, 16H, Harom), 7.61,d, Jˆ7 Hz, 1H, Harom);
13C NMR: d 41.2 ,CH2), 81.2 ,CH), 82.9 ,C), 123.0 ,2
CH), 126.3 ,CH), 127.0 ,CH), 127.1 ,CH), 127.3 ,2 CH),
127.7 ,2 CH), 127.8 ,2 CH), 127.9 ,2 CH), 128.2 ,CH),
129.3 ,CH), 129.8 ,CH), 131.3 ,CH), 131.4 ,C), 131.9
,CH), 137.1 ,C), 143.0 ,C), 144.2 ,C), 146.9 ,C), 147.0
,C), 167.5 ,CO). Anal. Calcd for C28H23NO3: C, 79.79; H,
5.50; N, 3.32. Found: C, 79.34; H, 5.62; N, 3.15.
2.1.3. 2,3-Dihydro-3-hydroxy-2-[2-)di)thien-2-yl)hydroxy-
methyl)thien-3-ylmethyl]-1H-isoindol-1-one )5d). This
compound was prepared from 4a using the same procedure
as for 5a,b but with 2-thienylmagnesium bromide. Yield
2.1.1.
2,3-Dihydro-3-hydroxy-2-[2-)diphenylhydroxy-
methyl)thien-3-ylmethyl]-1H-isoindol-1-one )5a). To a
freshly prepared solution of phenylmagnesium bromide
,60 mL of 1M solution in ether) in dry dichloromethane
,60 mL) was added portionwise solid hydroxylactam 4a
1
64%; mp 2028C; IR: 3422 ,OH), 1656 ,CvO) cm21; H

4942
P. Pigeon et al. / Tetrahedron 57 62001) 4939±4943
NMR: d 3.50 ,s broad, 1H, N±C±OH), 4.37 ,d, Jˆ15 Hz,
1H, CH2), 4.64 ,d, Jˆ15 Hz, 1H, CH2), 5.70 ,s broad, 1H,
N±CH), 6.46 ,s broad, 1H, OH), 6.80±6.98 ,m, 4H,
Hthiophene), 7.01,d, Jˆ5 Hz, 1H, H3), 7.08 ,d, Jˆ5 Hz, 1H,
H2), 7.18±7.58 ,m, 5H, 3Harom12Hthiophene), 7.64 ,d, Jˆ
7 Hz, 1H, Harom); 13C NMR: d 37.5 ,CH2), 74.4 ,C), 81.2
,CH), 122.4 ,CH), 123.6 ,CH), 124.0 ,CH), 125.6 ,CH),
125.7 ,2 CH), 125.8 ,CH), 126.5 ,2 CH), 129.1 ,CH),
129.4 ,CH), 131.1 ,C), 132.1 ,CH), 135.4 ,C), 145.0 ,C),
145.8 ,C), 152.1 ,C), 152.2 ,C), 166.6 ,CO). Anal. Calcd for
C22H17NO3S3: C, 60.11; H, 3.90; N, 3.19. Found: C, 60.02;
H, 3.85; N, 3.24.
,CH), 134.5 ,C), 142.2 ,C), 144.4 ,C), 146.0 ,C), 150.2
,C), 166.7 ,CO). Anal. Calcd for C22H15NO2S3: C, 62.68;
H, 3.59; N, 3.32. Found: C, 62.88; H, 3.68; N, 3.46.
2.1.7. 2,3-Dihydro-2-[2-)hydroxy-diphenylmethyl)thien-
3-ylmethyl]-1H-isoindole-1,3-dione )7a). Compound 7a
was synthesized using the same procedure as for the syn-
thesis of 6a ,starting from 5a or 6a) but with 1mL of TFA in
place of PTSA and with a reaction time of 2 days: Yield
1
90%; mp 1508C; IR: 1718 ,CvO) cm21; H NMR: d 4.62
,s, 2H, CH2), 6.22 ,s, 1H, CH), 7.02±7.26 ,m, 12H, Harom),
7.57±7.67 ,m, 2H, Hphthalimide), 7.67±7.78 ,m, 2H,
Hphthalimide); 13C NMR: d 34.5 ,CH2), 49.2 ,CH), 123.0 ,2
CH), 123.8 ,CH), 126.5 ,2 CH), 128.2 ,4 CH), 128.7 ,4 CH),
129.5 ,CH), 131.8 ,2 C), 132.1 ,C), 133.7 ,2 CH), 143.7 ,2
C), 145.8 ,C), 167.8 ,2 CO). Anal. Calcd for C26H19NO2S:
C, 76.26; H, 4.68; N, 3.42. Found: C, 75.82; H, 4.61; N,
3.25.
2.1.4. 4,12-Dihydro-12,12-diphenylthieno[30,20:5,6][1,3]-
oxazepino[2,3-a]isoindol-6)10bH)-one )6a). A solution of
compound 5a ,10 mmol), a catalytic amount of PTSA in
dichloromethane ,20 mL) was stirred for 30 min ,reaction
was monitored by TLC). The solution was washed succes-
sively with a saturated sodium hydrogen carbonate solution,
then with water and was dried ,magnesium sulfate) and
®ltered. The solution was concentrated under reduced pres-
sure and the residue was recrystallized from ethanol to
furnish pure 6a: Yield 88%; mp 1788C; IR: 1707
2.1.8. 2,3-Dihydro-2-[2-)hydroxy-diphenylmethyl)phenyl-
methyl]-1H-isoindole-1,3-dione )7b). Compound 7b was
synthesized using the same procedure as for the synthesis
of 7a ,starting from 5b or 6b). Yield 96%; mp 1768C; IR:
1710 ,CvO) cm21; 1H NMR: d 4.77 ,s, 2H, CH2), 6.21,s,
1H, CH), 6.76±6.90 ,m, 1H, Harom), 6.97±7.46 ,m, 13H,
Harom), 7.56±7.69 ,m, 2H, Hphthalimide), 7.69±7.81,m, 2H,
Hphthalimide); 13C NMR: d 39.2 ,CH2), 52.3 ,CH), 123.2 ,2
CH), 126.2 ,2 CH), 126.7 ,CH), 127.8 ,CH), 128.3 ,4 CH),
129.6 ,4 CH), 130.0 ,CH), 130.2 ,CH), 131.9 ,2 C), 133.8 ,2
CH), 134.4 ,C), 141.9 ,C), 143.6 ,2 C), 168.1 ,2 CO). Anal.
Calcd for C28H21NO2: C, 83.35; H, 5.25; N, 3.47. Found: C,
82.99; H, 5.05; N, 3.39.
1
,CvO) cm21; H NMR: d 4.19 ,d, Jˆ16 Hz, 1H, H4),
5.36 ,d, Jˆ16 Hz, 1H, H4), 6.01,s, 1H, H 10b), 7.05 ,d,
Jˆ5 Hz, 1H, H3), 7.11 ,d, Jˆ5 Hz, 1H, H2), 7.20±7.57
,m, 13H, Harom), 7.78 ,d, Jˆ7 Hz, 1H, H7); 13C NMR: d
40.8 ,CH2), 84.7 ,CH), 86.3 ,C), 123.2 ,CH), 123.5 ,CH),
124.7 ,CH), 127.5 ,2 CH), 127.8 ,2 CH), 128.0 ,CH), 128.7
,CH), 128.8 ,2 CH), 129.1 ,CH), 129.4 ,2 CH), 129.6 ,CH),
131.7 ,C), 132.0 ,CH), 135.3 ,C), 141.4 ,C), 142.6 ,C),
144.7 ,C), 146.6 ,C), 166.5 ,CO). Anal. Calcd for
C26H19NO2S: C, 76.26; H, 4.68; N, 3.42. Found: C, 75.89;
H, 4.81; N, 3.28.
2.1.9. 2,3-Dihydro-2-[2-)hydroxy-di)thien-2-yl)methyl)-
thien-3-ylmethyl]-1H-isoindole-1,3-dione )7d). Com-
pound 7d was synthesized using the same procedure as for
the synthesis of 7a ,starting from 5d or 6d) but the reaction
time was 6 days: Yield 28%; mp 1598C; IR: 1713
2.1.5. 5,13-Dihydro-5,5-diphenylisoindolo[1,2-c][2,4]benz-
oxazepin-11)6aH)-one )6b). This compound was prepared
from 5b using the same procedure as for 5a. Yield 93%; mp
1
1
1758C; IR: 1677 ,CvO) cm21; H NMR: d 4.48 ,d, Jˆ
,CvO) cm21; H NMR: d 4.76 ,s, 2H, CH2), 6.72 ,s, 1H,
15 Hz, 1H, H5), 4.65 ,d, Jˆ15 Hz, 1H, H5), 6.21,s, 1H,
H11b), 6.61,d, Jˆ8 Hz, 1H, Harom), 7.05±7.61,m, 16H,
Harom), 7.78 ,d, Jˆ6 Hz, 1H, H8); 13C NMR: d 45.8 ,CH2),
83.3 ,CH), 89.1 ,C), 123.0 ,CH), 123.0 ,CH), 127.2 ,CH),
127.4 ,3 CH), 127.7 ,2 CH), 127.9 ,CH), 128.2 ,2 CH),
128.5 ,CH), 129.1 ,2 CH), 129.3 ,CH), 130.2 ,CH), 131.4
,CH), 131.6 ,CH), 132.2 ,C), 135.3 ,C), 142.1 ,C), 142.2
,C), 142.4 ,C), 145.7 ,C), 165.8 ,CO). Anal. Calcd for
C28H21NO2: C, 83.35; H, 5.25; N, 3.47. Found: C, 82.93;
H, 5.40; N, 3.32.
CH), 6.84±6.95 ,m, 4H, Hthiophene), 7.05±7.15 ,m, 2H,
Hthiophene), 7.18 ,dd, Jˆ5 and 2 Hz, 2H, Hthiophene), 7.64±
7.75 ,m, 2H, Hphthalimide), 7.76±7.86 ,m, 2H, Hphthalimide);
13C NMR: d 34.3 ,CH2), 40.0 ,CH), 123.2 ,2 CH), 124.0
,CH), 124.7 ,2 CH), 126.0 ,2 CH), 126.4 ,2 CH), 129.4
,CH), 131.9 ,2 C), 132.1 ,C), 133.8 ,2 CH), 145.5 ,C),
147.1 ,2 C), 167.8 ,2 CO). Anal. Calcd for C22H15NO2S3:
C, 62.68; H, 3.59; N, 3.32. Found: C, 62.78; H, 3.59; N,
3.24.
2.1.10. 3,3,4,4-Tetramethyl-1-[2-carbomethoxythien-3-yl-
methyl]succinimide )8). A mixture of tetramethylsuccini-
mide ,1.55 g, 10 mmol), crown ether 18-C-6 ,0.01 g),
potassium carbonate ,1.52 g, 11 mmol), potassium iodide
,0.166 g, 1 mmol), and dry toluene was stirred for 10 min.
A solution of methyl 3-bromomethylthiophene-2-carboxyl-
ate ,2.82 g, 12 mmol) in toluene ,10 mL) was added drop-
wise. The mixture was re¯uxed for 24 h. After cooling, the
mixture was ®ltrated on celite and was then concentrated
under reduced pressure. The residue was recrystallized from
ethanol to furnish pure 8 with a yield of 79%, mp 1548C; IR:
2.1.6. 4,12-Dihydro-12,12-di)thien-2-yl)thieno[30,20:5,6]-
[1,3]oxazepino[2,3-a]isoindol-6)10bH)-one )6d). This
compound was prepared from 5d using the same procedure
as for 6a. Yield 100%; mp 2178C; IR: 1703 ,CvO) cm21
;
1H NMR: d 4.34 ,d, Jˆ16 Hz, 1H, H4), 5.34 ,d, Jˆ16 Hz,
1H, H4), 6.14 ,s, 1H, H10b), 6.80 ,dd, Jˆ4 and 2 Hz, 1H,
Hthiophene), 6.87±6.94 ,m, 2H, H31Hthiophene), 6.95±7.07 ,m,
2H, Hthiophene), 7.14 ,d, Jˆ5 Hz, 1H, H2), 7.27 ,dd, Jˆ5 and
1Hz, 1H, H thiophene), 7.40±7.59 ,m, 4H, 3Harom1Hthiophene),
7.78 ,d, Jˆ6 Hz, 1H, H7); 13C NMR: d 40.9 ,CH2), 82.1,C),
84.5 ,CH), 123.4 ,CH), 123.4 ,CH), 124.9 ,CH), 125.5
,CH), 126.2 ,CH), 126.7 ,CH), 126.9 ,CH), 128.6 ,CH),
129.0 ,CH), 129.7 ,CH), 130.0 ,CH), 131.6 ,C), 132.1
1
1696 ,CvO) cm21; H NMR: d 1.10 ,s, 12H, 4CH3), 3.83
,s, 3H, OCH3), 5.02 ,s, 2H, CH2), 6.77 ,d, Jˆ5 Hz, 1H,
Hthiophene), 7.36 ,d, Jˆ5 Hz, 1H, Hthiophene). Anal. Calcd for

P. Pigeon et al. / Tetrahedron 57 62001) 4939±4943
4943
C15H19NO4: C, 58.23; H, 6.19; N, 4.53. Found: C, 58.04; H,
6.15; N, 4.35.
3H, CH3), 1.01 ,s, 3H, CH3), 3.44 ,s, 3H, OCH3), 4.04 ,d,
Jˆ15 Hz, 1H, CH2), 4.14 ,d, Jˆ15 Hz, 1H, CH2), 4.20 ,s,
1H, OH), 6.98 ,d, Jˆ5 Hz, 1H, Hthiophene), 7.03 ,d, Jˆ5 Hz,
1H, Hthiophene), 7.16±7.52 ,m, 10H, Hphenyl).
2.1.11. 3,3,4,4-Tetramethyl-1-[2-)diphenylhydroxymethyl)-
thien-3-ylmethyl]succinimide )9). This compound was
obtained as an oil with a yield of 74%, H NMR: d 1.10
1
2.2.3. 4,7,8,10-tetrahydro-7,7,8,8-tetramethyl-10,10-di-
phenylpyrrolo[2,1-b]thieno[3,2-e][1,3] oxazepin-6)8aH)-
one )11). This compound was prepared from the mixture
of 10a and 10b using the same procedure as for the synthesis
of 6a,b. Yield 100%; mp 1578C; IR: 1665 ,CvO) cm21; 1H
NMR: d 0.80 ,s, 3H, CH3), 0.98 ,s, 3H, CH3), 1.09 ,s, 3H,
CH3), 1.31 ,s, 3H, CH3), 3.85 ,d, Jˆ15 Hz, 1H, CH2), 4.66
,s, 1H, CH), 5.14 ,d, Jˆ15 Hz, 1H, CH2), 6.88±7.10 ,m, 2H,
Hthiophene), 7.12±7.46 ,m, 10H, Hphenyl); 13C NMR: d 17.8
,CH3), 18.4 ,CH3), 24.4 ,CH3), 25.6 ,CH3), 41.0 ,CH2), 42.8
,C), 45.3 ,C), 86.6 ,C), 92.4 ,CH), 124.5 ,CH), 127.5 ,2
CH), 127.7 ,2 CH), 127.8 ,CH), 128.4 ,CH), 128.5 ,2
CH), 128.9 ,CH), 129.5 ,2 CH), 136.3 ,C), 141.9 ,C),
144.6 ,C), 147.2 ,C), 179.0 ,CO). Anal. Calcd for
C26H27NO2S: C, 74.79; H, 6.52; N, 3.35. Found: C, 74.35;
H, 6.64; N, 3.31.
,s, 12H, 4CH3), 4.30 ,s, 2H, CH2), 6.20 ,s, 1H, OH), 6.82 ,d,
Jˆ5 Hz, 1H, Hthiophene), 7.04 ,d, Jˆ5 Hz, 1H, Hthiophene),
7.19±7.57 ,m, 10H, Hphenyl); 13C NMR: d 21.2 ,4 CH3),
36.5 ,CH2), 46.9 ,2 C), 124.9 ,CH), 127.2 ,4 CH), 127.3
,2 CH), 127.7 ,4 CH), 128.6 ,CH), 132.5 ,C), 147.3 ,2 C),
149.5 ,C), 183.2 ,2 CO).
2.2. Reduction of imide 9, formation of 10a110b
To a mixture of imide 9 ,1.73 g, 4 mmol) in dry methanol
,40 mL) at 08C was added sodium borohydride ,0.9 g,
24 mmol) by portions. To this mixture were added ®ve
drops of ethanolic hydrochloric acid solution ,prepared
from nine drops of concentrated hydrochloric acid in etha-
nol ,15 mL) at regular intervals ,10 min). The reaction was
monitored by TLC. The excess of sodium borohydride was
decomposed by careful addition of cold water ,15 mL) and
diluted hydrochloric acid. Sodium hydrogen carbonate was
added and the solvent was evaporated. The residue was
dissolved in a mixture of dichloromethane/water. The
organic layer was dried on magnesium sulfate and was
then concentrated under reduced pressure giving a mixture
of 10a/10b ,85/15) in a 95% yield.
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thien-3-ylmethyl]succinamidal )10a). 1H NMR: d 0.84 ,s,
3H, CH3), 0.88 ,s, 3H, CH3), 0.89 ,s, 3H, CH3), 1.03 ,s, 3H,
CH3), 3.82 ,m, 1H, OH), 4.04 ,d, Jˆ15 Hz, 1H, CH2), 4.32
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OH), 6.97 ,d, Jˆ5 Hz, 1H, Hthiophene), 7.05 ,d, Jˆ5 Hz, 1H,
Hthiophene), 7.21±7.60 ,m, 10H, Hphenyl); 13C NMR: d 17.4
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1H NMR: d 0.85 ,s, 3H, CH3), 0.89 ,s, 3H, CH3), 0.94 ,s,