A BF3-mediated nitrogen-to-carbon rearrangement of N-protected 2,3-dihydro-3-hydroxy-1h-benzisoindol-1-ones, and its interception for a facile preparation of 3-substituted benzisoindolones

Article abstract of DOI:10.1055/s-2006-951495

A BF₃-mediated release of the hydroxy and the nitrogen-protecting group of N-(cumyl or 1,1-diphenylethyl)-2,3-dihydro-3- hydroxy-1H-benzisoindol-1-ones is accompanied by recombination of the nitrogen-protecting unit to the 3-position of the rin

Full text of DOI:10.1055/s-2006-951495

LETTER
3115
A BF3-Mediated Nitrogen-to-Carbon Rearrangement of N-Protected 2,3-Di-
hydro-3-hydroxy-1H-benzisoindol-1-ones, and Its Interception for a Facile
Preparation of 3-Substituted Benzisoindolones
Rearrangement of
d
N
-Protected
r
2,3-Dihy
i
dro-3-
a
H
n
-benzisoindol-1-
oL
a
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry, University of Guelph, Guelph,
ON, N1G 2W1, Canada
Fax +1(519)7661499; E-mail: schwan@uoguelph.ca
b
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, N1G 2W1, Canada
Received 25 May 2006
imidines (2,3-dihydro-3-hydroxy-1H-benz[e]isoindol-1-
ones, 3), which differ only by their protection on the nitro-
gen (Scheme 1). At this point, nitrogen deprotection was
Abstract: A BF3-mediated release of the hydroxy and the nitrogen-
protecting group of N-(cumyl or 1,1-diphenylethyl)-2,3-dihydro-3-
hydroxy-1H-benzisoindol-1-ones is accompanied by recombination
of the nitrogen-protecting unit to the 3-position of the ring system.
15
attempted with BF3·OEt2 and a surprising yet parallel
The addition of sulfur or carbon nucleophiles affords products of manifold of products was obtained for both compounds 3a
preferential capture of the rearrangement intermediate offering a
convenient and rapid synthetic route to N-unprotected 2,3-dihydro-
3-substituted-1H-benzisoindol-1-ones.
and 3b. Scheme 2 and the first two entries of Table 1 in-
dicate the assigned structures of the unexpected products.
In each product, the nitrogen-protecting group is appar-
ently lost and its carbon skeleton is reattached at the
Key words: rearrangements, iminium ions, nucleophile, aromatic
adjacent carbon atom.16
metalation, PARP inhibitors
HNR
O
NR
OLi
Li
The naphthyl amide organic fragment is prevalent in a
number of bioactive compounds1–6 including those target-
ing the NK1 receptor,1 the inhibition of aldosterone syn-
thase,3 the leukocyte proteases cathepsin G4 and
chymase,5 and a malarial receptor.2 Aromatic amides in-
cluding some naphthyl amides are also central to the inhi-
bition of a group of poly(ADP-ribose) polymerase
enzymes (PARPs)7–9 that bind NAD+ and have been im-
plicated in the cellular response to DNA injury.10 The cat-
alytic domain of the PARP enzymes has been shown to be
structurally similar to that of bacterial ribosyltransferases,
including Pseudomonas aeruginosa exotoxin A, which
we are currently studying. PARP inhibitors often contain
aromatic amide or lactam functionalities and operate by
preferentially binding to the nicotinamide portion of the
binding pocket normally occupied by NAD+.9,11,12 As
such, we have targeted novel amides and imides possess-
ing the naphthalene11 backbone as part of a study to find
inhibitors of exotoxin A.
3.2 equiv s-BuLi
–78 °C, 3 h
2
1a R = CMePh2
1b R = CMe2Ph
R
O
N
DMF
OH
H
–78 °C to 0 °C
1 h
3a 27%
3b 84%
Scheme 1
Three more substrates were prepared in order to establish
the generality of the rearrangement. Application of the
Dai metalation conditions to the appropriate N-1,1-di-
phenylethyl and N-cumyl amides gave phthalimidines
(2,3-dihydro-3-hydroxy-1H-isoindol-1-ones) 4a (79%)
Specifically, we have been probing the functionalization and 4b15 (67%), respectively, and 3-hydroxy-2,3-dihydro-
of the 2-position of N-protected 1-naphthamides. We ap- 1H-benz[f]isoindol-1-one (5b, 50%, Table 1). As an
plied the Dai protocol for the ortho-metalation of N,N- aside, we are aware of only three reports of metalation of
disubstituted amides (3.2 equiv s-BuLi, THF, –78 °C, 3 1,3-unsubstituted-2-naphthylamides. Using only N,N-di-
h)13 to monosubstituted amides 1 (a: R = 1,1-diphenyleth- alkylated amides, yields are low and unselective17,18 or the
yl, b: R = cumyl) as a means to introduce additional func- reaction favors lithiation at the 1-position possibly due to
tionality. Consistent with the literature,14 the metalation 6-methoxy substitution.19 In our lithiation using an N-
proceeds at the 2-position rather than the 8-position giving monosubstituted amide, the 1-substituted product is iso-
dianions 2. Quenching with DMF affords two naphthal- lated in 22% yield. Even though this chemistry has not
been optimized, a 50% yield of 3-substituted product is
noteworthy20 and furthermore, the total yield of products
is quite high compared to the other examples in this
relatively unexplored series of substrates.
SYNLETT 2006, No. 18, pp 3115–3119
Advanced online publication: 25.10.2006
DOI: 10.1055/s-2006-951495; Art ID: S11606ST
© Georg Thieme Verlag Stuttgart · New York
0
3
.1
1
.2
0
0
6

3116
A. L. Schwan et al.
LETTER
O
R
Ph
O
+
N
NH
BF3·OEt2
R
BF3·OEt2
3, 4 or 5
Ph
3, 4 or 5
+
r.t.
r.t.
R = Me, Ph
H
OH
6
9
O
O
O
NH
R
Ph
R
NH
NH
+
H
or
Ph
OH
H
H
R
+ H2O
– H+
6
Ph
Ph
Ph
Ph
+
7
8
O
Ph
BF3·OEt2
– H2O
N
–
c, 2,3-benzo ([e]) fusion; d, no benzo fusion;
e, 3,4-benzo ([f]) fusion
R
Ph
O
R
Scheme 2
NH
10
– H+
Treatment of phthalimidines 4 and 5b with BF3·OEt2 pro-
vided the same rearrangement products demonstrating
that the benzo fusion on the aromatic is not a requirement
and that the placement of the benzo group has minimal ef-
fect (Scheme 2, Table 1).
Ph
R
7/8
Scheme 3
sequence of events distinguishes this rearrangement from
related N-to-C transformations entailing pericyclic azo-
nia-22 or aza-Cope23 rearrangements of N-acyliminium
ions.
A mechanism for the rearrangement is suggested in
Scheme 3. The products are consistent with Lewis acid
mediated iminium ion (9) formation, which can bring
about the loss of the nitrogen-protecting group from some
of the substrates, with the lost residue taking the form of
alkene (a-methylstyrene or 1,1-diphenylethene). This ma-
terial then recombines to the proximal carbon of another
iminium ion 9 offering carbocation 10. Loss of proton and
BF3-induced loss of the nitrogen-protecting group via
complexation with the carbonyl can explain products 7
and 8. Alcohols 6 form by reintroduction of nucleophilic
oxygen to cation 10 either before or after loss of the nitro-
gen substituent. A control experiment confirmed that alk-
enes 7 and 8 may also arise from the action of BF3 on
alcohols 6.21 Accordingly, longer reaction times give
more of the dehydrated products 7 and 8. A crossover ex-
periment was supportive of the intermolecularity of the re-
arrangement. The clean release and reattachment
The above mechanism featuring common N-acyliminium
ion chemistry24,25 can fully and adequately account for the
rearrangement products. However, as a means of continu-
ing the pursuit of aromatic amides, it was felt that this re-
action could be readily adapted to introduce alternative
groups at the 3-position and achieve loss of the nitrogen-
protecting unit in a single reaction mixture.26 Hence inter-
ception of the electrophilic intermediate 9 by an added nu-
cleophile should permit the introduction of diverse groups
at the 3-position while precluding re-attack of a-methyl-
styrene or 1,1-diphenylethylene. Given the large number
of known 3-substituted isoindolones27 and our interest in
naphthyl-derived targets, we focused primarily on substi-
tution of compounds 3b and 5b.
Table 1 Products from the BF3-Induced Rearrangement of N-Substituted Phthalimidines (Scheme 2)
Starting material
R
Products (%)
6
7
8
O
Ph
3a
3b
Ph
Me
ac, 26
bc, 50
c, 47
–
–
c, 38
N
R
OH
H
O
4a
4b
Ph
Me
ad, 8
bd, 42
d, 75
–
–
N
Ph
d, 28
R
OH
H
O
5b
Me
e, 52
–
e, 38
N
Ph
R
OH
H
Synlett 2006, No. 18, 3115–3119 © Thieme Stuttgart · New York

LETTER
Rearrangement of N-Protected 2,3-Dihydro-3-hydroxy-1H-benzisoindol-1-ones
3117
Ontario Government for graduate scholarships. M.M.P. thanks
NSERC for a USRA scholarship.
A wide variety of common neutral carbon nucleophiles
proved amenable for this chemistry. Thiols are also via-
ble, whether bearing hydrophobic or hydrophilic substitu-
ents. The products namely 2,3-dihydro-3-substituted 1H-
benzisoindol-1-ones,28 could be obtained in 58–80%
yields after chromatographic purification (Table 2).29
References and Notes
(1) Albert, J. S.; Ohnmacht, C.; Bernstein, P. R.; Rumsey, W. L.;
Aharony, D.; Alelyunas, Y.; Russell, D. J.; Potts, W.;
Sherwood, S. A.; Shen, L.; Dedinas, R. F.; Palmer, W. E.;
Russell, K. J. Med. Chem. 2004, 47, 519.
(2) Baldwin, J.; Michnoff, C. H.; Malmquist, N. A.; White, J.;
Roth, M. G.; Rathod, P. K.; Phillips, M. A. J. Biol. Chem.
2005, 280, 21847.
(3) Voets, M.; Antes, I.; Scherer, C.; Mueller-Vieira, U.;
Biemel, K.; Barassin, C.; Marchais-Oberwinkler, S.;
Hartmann, R. W. J. Med. Chem. 2005, 48, 6632.
(4) Greco, M. N.; Hawkins, M. J.; Powell, E. T.; Almond, H. R.
Jr.; Corcoran, T. W.; de Garavilla, L.; Kauffman, J. A.;
Recacha, R.; Chattopadhyay, D.; Andrade-Gordon, P.;
Maryanoff, B. E. J. Am. Chem. Soc. 2002, 124, 3810.
(5) de Garavilla, L.; Greco, M. N.; Sukumar, N.; Chen, Z.-W.;
Pineda, A. O.; Mathews, F. S.; Di Cera, E.; Giardino, E. C.;
Wells, G. I.; Haertlein, B. J.; Kauffman, J. A.; Corcoran, T.
W.; Derian, C. K.; Eckardt, A. J.; Damiano, B. P.; Andrade-
Gordon, P.; Maryanoff, B. E. J. Biol. Chem. 2005, 280,
18001.
(6) (a) Kohrt, J. T.; Filipski, K. J.; Rapundalo, S. T.; Cody, W.
L.; Edmunds, J. J. Tetrahedron Lett. 2000, 41, 6041. (b)
Jia, Z. J.; Wu, Y.; Huang, W.; Goldman, E.; Zhang, P.;
Woolfrey, J.; Wong, P.; Huang, B.; Sinha, U.; Park, G.;
Reed, A.; Scarborough, R. M.; Zhu, B.-Y. Bioorg. Med.
Chem. Lett. 2002, 12, 1651. (c) Parmee, E. R.; He, J.;
Mastracchio, A.; Edmondson, S. D.; Colwell, L.; Eiermann,
G.; Feeney, W. P.; Habulihaz, B.; He, H.; Kilburn, R.;
Leiting, B.; Lyons, K.; Marsilio, F.; Patel, R. A.; Petrov, A.;
Di Salvo, J.; Wu, J. K.; Thornberry, N. A.; Weber, A. E.
Bioorg. Med. Chem. Lett. 2004, 14, 43. (d) Gyoergydeak,
Z.; Hadady, Z.; Felfoeldi, N.; Krakomperger, A.; Nagy, V.;
Toth, M.; Brunyanszki, A.; Docsa, T.; Gergely, P.; Somsak,
L. Bioorg. Med. Chem. 2004, 12, 4861.
In this transformation, the already-incorporated formyl
unit, originally from DMF, and the nucleophile combine
to represent the doubly electrophilic synthetic equivalents
HC+2SR or HC+2CR3. Moreover, the method is superior to
other iminium substitutions in that the hydroxyl group
does not require conversion to a methoxy group prior to its
displacement.30 Also, the substitution at the 3-position
and the deprotection conveniently occur as a one-pot pro-
tocol.
In summary, we report what is believed to be a new rear-
rangement of N-cumyl (and N-diphenylethyl)-3-hydroxy-
isoindolones to 3-substituted isoindolones by way of
Lewis acid mediated release and recombination of the N-
protecting group. The addition of carbon- or sulfur-based
nucleophiles permits capture of the transient iminium and
formation of a series of N-unprotected-2,3-dihydro-3-
substituted 1H-benzisoindol-1-ones. The preparation of
these potential PARP inhibitors is a facile and appealing
2-step procedure from simple N-protected aromatic
amides. We also suggest the results of past ortholithiation/
quenching chemistry of N,N-dialkyl-2-naphthyl amides
may not be fully indicative of the synthetic potential avail-
able and such a reaction with N-monosubstituted ana-
logues may prove more useful.
Acknowledgment
The authors thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) and the Canadian Cystic Fibrosis
Foundation for funding this research. P.A.D. thanks NSERC and the
(7) Zhang, J.; Li, J.-H. Drugs Fut. 2002, 27, 371.
(8) Southan, G. J.; Szabo, C. Curr. Med. Chem. 2003, 10, 321.
(9) Jagtap, P.; Szabo, C. Nat. Rev. Drug Discovery 2005, 4, 421.
Table 2 The Formation of 2,3-Dihydro-3-substituted 1H-(Benz)isoindol-1-ones by Capture of Transient Iminium Ions
Starting material
Added nucleophile
Product
Product R¢ group
Yield (%)
3b
C16H33SH
HO(CH2)2SH
CH2=CHCH2TMS
1-(TMSO)cyclopentene
11
12
13
14
-SC16H33
-S(CH2)2OH
-CH2CH=CH2
2-Cyclopentan-1-onyl
78
70
80
58
O
NH
R'
H
4a
5b
C16H33SH
15
-SC16H33
84
O
NH
R'
H
HOC(O)CH2SH
Furan
HC≡CCH2TMS
16
17
18
-SCH2CO2H
2-Furyl
Allenyl
67
64
80
O
NH
R'
H
Synlett 2006, No. 18, 3115–3119 © Thieme Stuttgart · New York

3118
A. L. Schwan et al.
LETTER
(20) Compound 5 and its isomer were not amenable to flash
(10) Lautier, D.; Lagueux, J.; Thibodeau, J.; Menard, L.; Poirier,
G. G. Mol. Cell. Biochem. 1993, 122, 171.
(11) Armstrong, S.; Li, J.-H.; Zhang, J.; Merrill, A. R. J. Enzyme
Inhib. Med. Chem. 2002, 17, 235.
chromatography, but fortunately 5 could be cleanly
separated from the more soluble isomer by toluene
recrystallization.
(12) Yates, S. P.; Taylor, P. L.; Jørgensen, R.; Ferraris, D.;
Zhang, J.; Andersen, G. R.; Merrill, A. R. Biochem. J. 2005,
385, 667.
(13) Dai, W.-M.; Zhang, Y.; Zhang, Y. Tetrahedron: Asymmetry
2004, 15, 525.
(21) The ketimine arising from loss of styryl or 1,1-diphenylethyl
cation from 9 may also be implicated in this mechanism.
However, efforts to detect or isolate the ketimine and a more
stabilized version of it proved fruitless. The analogous cyclic
sulfonimines(benzisothiazoles) exhibit more stability and
can be obtained by a related N-decumylation/dehydration
treatment. See: Metallinos, C. Synlett 2002, 1556.
(22) Ent, H.; De Koning, H.; Speckamp, W. N. J. Org.Chem.
1986, 51, 1687.
(23) Ent, H.; De Koning, H.; Speckamp, W. N. Tetrahedron Lett.
1985, 26, 5105.
(24) Maryanoff, B. E.; Zhang, H.-C.; Cohen, J. H.; Turchi, I. J.;
Maryanoff, C. A. Chem. Rev. 2004, 104, 1431.
(14) Clayden, J.; Frampton, C. S.; McCarthy, C.; Westlund, N.
Tetrahedron 1999, 55, 14161.
(15) Metallinos, C.; Nerdinger, S.; Snieckus, V. Org. Lett. 1999,
1, 1183; comparable results were found using TFA.
(16) Rearrangement products 7 and 8 could be identified through
spectral analysis including the observation of vinylic
resonances in the 1H NMR spectra. Tertiary alcohols 6,
obtained as mixtures of diastereomers, were identified with
the assistance of IR spectroscopy and mass spectrometry
where applicable. Strong M+ peaks were seen under CI
conditions. Full characterization data including elemental
analysis or HRMS was obtained for all new compounds.
Sample procedure for rearrangement: Isoindolone 3a (154
mg, 0.406 mmol, 1.0 equiv) was dissolved in 2.5 mL dry
CH2Cl2 in a flame-dried flask under argon and cooled to
0 °C. Then, BF3·OEt2 (0.06 mL, 0.570 mmol, 1.4 equiv) was
dissolved in 2.5 mL of dry CH2Cl2 in a flame-dried flask
under argon and transferred to the solution of 3a via cannula,
followed by a 2.5 mL CH2Cl2 rinse. The resulting dark
brown solution quickly became clear and colorless, and was
stirred overnight at r.t. The reaction was quenched with H2O,
extracted with CH2Cl2, dried with brine and MgSO4 and
concentrated. Flash chromatography with 15% EtOAc in
hexane gave 69.0 mg (47% yield) of 7c and 39.6 mg (26%
yield) of 6ac.
(25) Speckamp, W. N.; Moolenaar, M. J. Tetrahedron 2000, 56,
3817.
(26) Generally cyclic N-acyliminium ion chemistry involves
carbon substitution and then introduction of another reagent
for nitrogen deprotection, if desired. Some examples of the
one-pot realization of both reactions are known: (a) Pinder,
J. L.; Weinreb, S. M. Tetrahedron Lett. 2003, 44, 4141.
(b) Reichelt, A.; Bur, S. K.; Martin, S. F. Tetrahedron 2002,
58, 6323. (c) Lundkvist, J. R. M.; Wistrand, L. G.; Hacksell,
U. Tetrahedron Lett. 1990, 31, 719. (d) Botman, P. N. M.;
Dommerholt, F. J.; de Gelder, R.; Broxterman, Q. B.;
Schoemaker, H. E.; Rutjes, F. P. J. T.; Blaauw, R. H. Org.
Lett. 2004, 6, 4941. (e) Granier, T.; Vasella, A. Helv. Chim.
Acta 1998, 81, 865. (f) Lundkvist, J. R. M.; Vargas, H. M.;
Caldirola, P.; Ringdahl, B.; Hacksell, U. J. Med. Chem.
1990, 33, 3182.
(27) Stajer, G.; Csende, F. Curr. Org. Chem. 2005, 9, 1277.
(28) This general family of compounds has biological
significance in a variety of areas: (a) Wrobel, J.; Dietrich,
A.; Woolson, S. A.; Millen, J.; McCaleb, M.; Harrison, M.
C.; Hohman, T. C.; Sredy, J.; Sullivan, D. J. Med. Chem.
1992, 35, 4613. (b) Andrews, M. D.; Brewster, A. G.;
Chuhan, J.; Ibbett, A. J.; Moloney, M. G.; Prout, K.; Watkin,
D. Synthesis 1997, 305. (c) Toyooka, K.; Kanamitsu, N.;
Yoshimura, M.; Kuriyama, H.; Tamura, T. WO 048332,
2004; Chem. Abstr. 2004, 141, 38525. (d) Guillaumel, J.;
Leonce, S.; Pierre, A.; Renard, P.; Pfeiffer, B.; Peruchon, L.;
Arimondo, P. B.; Monneret, C. Oncol. Res. 2003, 13, 537.
(e) Mertens, A.; Zilch, H.; Koenig, B.; Schaefer, W.; Poll,
T.; Kampe, W.; Seidel, H.; Leser, U.; Leinert, H. J. Med.
Chem. 1993, 36, 2526.
3-(2,2-Diphenylethenyl)-2,3-dihydro-1H-benzo[e]isoindol-
1-one (7c): mp: 199-200 °C. 1H NMR (400 MHz, DMSO-
d6): d = 9.08 (d, J = 8.3 Hz, 1 H), 8.14 (d, J = 8.4 Hz, 1 H),
8.04 (d, J = 8.2 Hz, 1 H), 7.68–7.65 (m, 1 H), 7.61–7.41 (m,
9 H), 7.29–7.19 (m, 3 H), 5.81 (d, J = 9.9 Hz, 1 H), 5.04
(d, J = 9.9 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6): d =
170.6, 170.5, 147.1, 145.3, 140.6, 138.5, 132.9, 132.7,
129.7, 128.83, 128.77, 128.4, 127.9, 127.8, 127.0, 126.5,
125.5, 125.4, 122.9, 120.8, 55.4. IR (neat) 3447, 1690 cm–1.
MS (EI): m/z (%) = 362 (29), 361 (100) [M+], 284 (37). Anal.
Calcd (%): C, 86.40; H, 5.30; N, 3.88. Found: C, 86.20; H,
5.54; N, 3.95.
3-(2,2-Diphenyl-2-hydroxyethyl)-2,3-dihydro-1H-
benzo[e]isoindol-1-one (6ac): 1H NMR (400 MHz, CDCl3):
d = 8.88 (d, J = 8.3 Hz, 1 H), 7.84 (d, J = 8.3 Hz, 1 H), 7.74
(d, J = 8.1 Hz, 1 H), 7.47–7.36 (m, 4 H), 7.25–7.20 (m, 5 H),
7.15–7.03 (m, 4 H), 4.32 (d, J = 10.4 Hz, 1 H), 2.96 (d,
(29) Representative Procedure.
Isoindolone 3b (125 mg, 0.395 mmol, 1.0 equiv) and
allyltrimethylsilane (0.25 mL, 1.57 mmol, 4.0 equiv) were
slurried in 2.5 mL of dry CH2Cl2 in a flame-dried flask under
argon and cooled to 0 °C. Then, BF3·OEt2 was dissolved in
2.5 mL of dry CH2Cl2 in a flame-dried flask under argon and
transferred to the solution of 3b and thiol via cannula,
followed by a 2.5 mL CH2Cl2 rinse. The clear colorless
reaction mixture was stirred at r.t. overnight before
quenching with H2O, extracting with CH2Cl2, drying with
brine and MgSO4 and concentrating. Flash chromatography
with 20% EtOAc in hexane gave 71 mg (80% yield) of 13.
3-Allyl-2,3-dihydro-1H-benz[e]isoindol-1-one (13): 1H
NMR (400 MHz, CDCl3): d = 9.22 (d, J = 8.4 Hz, 1 H), 8.02
(d, J = 8.4 Hz, 1 H), 7.92 (d, J = 8.4 Hz, 1 H), 7.67 (t, J = 7.2
Hz, 1 H), 7.57 (t, J = 7.2 Hz, 1 H), 7.52 (d, J = 8.4 Hz, 1 H),
5.89–5.78 (m, 1 H), 5.19 (d, J = 16.4 Hz, 1 H), 5.16 (d,
J = 10.0 Hz, 1 H), 4.72 (dd, J = 8.0, 4.5 Hz, 1 H), 2.85–2.79
(m, 1 H), 2.42–2.35 (m, 1 H). 13C NMR (100.6 MHz,
J = 13.8 Hz, 1 H), 2.17 (dd, J = 13.8, 10.4 Hz, 1 H). 13
C
NMR (75.5 MHz, acetone-d6): d = 170.8, 151.8, 149.9,
148.9, 148.8, 147.3, 134.1, 133.2, 130.4, 129.1, 129.0,
128.4, 127.9, 127.6, 127.1, 127.0, 124.3, 121.2, 78.6, 54.2,
47.4. IR (nujol): 3426, 3353, 1668 cm–1. MS (EI): m/z (%) =
379 (8) [M+], 361 (32), 284 (16), 196 (42), 184 (27), 183
(32), 182 (59), 105 (27). MS (CI): m/z (%) = 380 (90) [M +
H]+, 362 (44), 213 (53), 200(100), 196 (55), 183 (39). HRMS
(EI): m/z calcd for C26H19NO [M – 18]+: 361.1468; found:
361.1470.
(17) Watanabe, M.; Snieckus, V. J. Am. Chem. Soc. 1980, 102,
1457.
(18) Chen, C. W.; Beak, P. J. Org. Chem. 1986, 51, 3325.
(19) Bindal, R. D.; Katzenellenbogen, J. A. J. Org. Chem. 1987,
52, 3181.
Synlett 2006, No. 18, 3115–3119 © Thieme Stuttgart · New York

LETTER
Rearrangement of N-Protected 2,3-Dihydro-3-hydroxy-1H-benzisoindol-1-ones
3119
CDCl3): d = 171.9, 147.5, 133.1, 133.0, 132.7, 129.5, 128.1,
Lovely, C. J. Tetrahedron Lett. 2005, 46, 1251.
(c) Aggarwal, V. K.; Astle, C. J.; Iding, H.; Wirz, B.;
Rogers-Evans, M. Tetrahedron Lett. 2005, 46, 945.
(d) Huang, P.-Q.; Wei, B.-G.; Ruan, Y.-P. Synlett 2003,
1663. (e) Gloanec, P.; Herve, Y.; Bremand, N.; Lecouve, J.-
P.; Breard, F.; De Nanteuil, G. Tetrahedron Lett. 2002, 43,
3499. (f) Okitsu, O.; Suzuki, R.; Kobayashi, S. J. Org.
Chem. 2001, 66, 809.
127.9, 126.5, 125.9, 123.9, 119.6, 119.1, 55.7, 38.7. IR:
3448, 3215, 1690 cm–1. MS (EI): m/z (%) = 223 (8) [M+],
183 (14), 182 (100), 127 (13). Anal. Calcd: C, 80.69; H,
5.87. Found: C, 80.90; H, 5.85.
(30) (a) Duggan, H. M. E.; Hitchcock, P. B.; Young, D. W. Org.
Biomol. Chem. 2005, 3, 2287. (b) He, Y.; Moningka, R.;
Synlett 2006, No. 18, 3115–3119 © Thieme Stuttgart · New York