Double functionalization of N-Boc-3-(tosylmethyr)indole exploiting the activating properties of the tosyl group

Article abstract of DOI:10.1055/s-2008-1078510

The anion prepared from N-Boc-3-(tosylmethyl)indole using NaH in DMF can be readily functionalized by reaction with various electrophiles. The obtained sulfonyl indoles, upon removal of the N-protecting group, undergo nucleophilic attack via a vinylogous imino derivative, leading to branched 3-substituted indoles. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1078510

LETTER
A
Double Functionalization of N-Boc-3-(Tosylmethyl)indole Exploiting the
Activating Properties of the Tosyl Group
D
ouble Functiona
l
l
ization
e
of
N
-
Boc-3
s
-
(Tosylm
s
ale ndro Palmieri, Marino Petrini,* Rafik R. Shaikh
Dipartimento di Scienze Chimiche, Università di Camerino, via S. Agostino 1, 62032 Camerino, Italy
Fax +39(0737)402297; E-mail: marino.petrini@unicam.it
Received 28 March 2008
SO2Ar
SO2Ar
SO2Ar
Abstract: The anion prepared from N-Boc-3-(tosylmethyl)indole
1. base
– P
R
R
R
using NaH in DMF can be readily functionalized by reaction with
various electrophiles. The obtained sulfonyl indoles, upon removal
of the N-protecting group, undergo nucleophilic attack via a vinyl-
ogous imino derivative, leading to branched 3-substituted indoles.
N
H
E
N
P
E
N
P
2. E-X
2
3
1
R = R1CO, Ts, Ar
Key words: carbanions, eliminations, indoles, nucleophilic addi-
P = protecting group
tions, sulfones
Nu
base
R
Nu
R
N
H
E
N
E
The sulfonyl group is widely recognized as an important
activating moiety for the assembly of various structural
entities through carbon–carbon bond formation.1 Stabili-
zation of carbanionic species at a-position of sulfonyl de-
rivatives provides an enolate-like reagent that is able to
react with various electrophilic systems.2 After this syn-
thetic operation, the sulfonyl group is usually removed
since it is hardly found in targets of practical interest.3 The
latter operation is often carried out by a reductive process
that entails substitution of the sulfonyl group with a
hydrogen atom.4 Alternatively, as in the Julia reaction, the
b-acyloxysulfone produced by condensation of sulfonyl
carbanions with aldehydes and subsequent acylation is re-
ductively converted into an olefin.5 The above cited pro-
cedures aimed to the removal of the sulfonyl group do not
introduce any significant structural modification into the
resulting molecule. From a synthetic standpoint reductive
alkylations and nucleophilic displacement of the sulfonyl
group represent a more appealing process that involves
implementation of the molecular carbon backbone. Re-
ductive alkylations are rather limited in scope while nu-
cleophilic displacement of the sulfonyl group is
particularly effective on allyl and vinylsulfonyl deriva-
tives by means of an addition–elimination process.6 An
opposite pattern is usually observed when a-alkoxy or
a-amido sulfones are involved in such reactions since in
this instance, elimination of the sulfonyl group must pre-
cede the nucleophilic addition.7 The nature of the interme-
diate observed after the elimination step is very likely an
oxonium or an iminium ion working under acidic (mostly
Lewis) conditions but N-acylimines8 are certainly in-
volved operating under basic conditions with a-amido
sulfones. Coupling the anionic stabilization properties of
the sulfonyl group with its ability to act as good leaving
group in elimination reactions it is possible to devise an
5
4
Scheme 1
R1
R1
SO2Ar
R1
Nu
Nu
base
R
R
N
R
N
N
H
H
6
7
8
Scheme 2
overall synthetic strategy as depicted in Scheme 1.9 Sul-
fone 1 can be alkylated leading to compound 2 via the cor-
responding stabilized carbanion and after removal of the
N-protecting group and transformation into the amino de-
rivative 3. Base-induced elimination of arenesulfinic acid
from 3 produces the intermediate imino derivative 4
which upon nucleophilic addition affords difunctionalized
amino compound 5. This synthetic strategy can be also ap-
plied to vinylogous imino derivatives provided that an ef-
ficient entry to their precursors is achievable.
Recently, we have demonstrated that 3-(1-arylsulfonyl-
alkyl)indoles 6 are able to eliminate arenesulfinic acid un-
der basic condition leading to reactive intermediates 7 that
closely resemble vinylogous imino derivatives which
upon nucleophilic addition afford the corresponding 1¢-
substituted indoles 8 (Scheme 2).10
In this context sulfonyl indoles 6 represent a valid alterna-
tive to the utilization of gramines (N,N-dialkyl-3-indolyl-
methanamines) that, in order to generate the intermediate
vinylogous imine 7, require harsh reaction conditions.11
The overall process allows a functional group implemen-
tation on 3-substituted indoles and complements direct
functionalization of indoles using strong electrophilic re-
agents, a process widely known as the Friedel–Crafts re-
action.12 Introduction of suitable frameworks in the indole
nucleus constitutes a gateway for the preparation of in-
dole-based biologically active compounds.13 The effec-
SYNLETT 2008, No. x, pp 000A–000G
x
x
.xx.
2
0
0
8
Advanced online publication: xx.xx.2008
DOI: 10.1055/s-2008-1078510; Art ID: D10108ST
© Georg Thieme Verlag Stuttgart · New York

B
A. Palmieri et al.
LETTER
1. NBS, AIBN
c-C6H12, ∆
tion of sulfonyl indole 11 is possible using allyl bromide
which is more effective than the corresponding sulfonate
in producing compound 12a (Table 1, entries 1 and 2).
Other functionalized allyl halides tested for this process
also provide satisfactory yields in this reaction. Particular-
ly, a considerable a-regioselectivity is observed in the re-
action of indole 11 with some substituted allyl chlorides
(Table 1, entries 3–5). The introduction of an alkynyl
group is efficiently achieved by reaction of 11 with prop-
argyl chloride leading to indole 12f (Table 1, entry 7).
Benzyl bromides are the most effective electrophiles in
the reaction with the sulfonyl anion generated from com-
pound 11, although simple alkyl iodides such as butyl
iodide and 1-chloro-4-iodobutane give satisfactory results
in the same process (Table 1, entries 10 and 11). The uti-
lization of reactive halides is instrumental for an efficient
reaction as demonstrated for the chemoselective nucleo-
philic substitution of 1-chloro-4-iodobutane and the mod-
est results obtained with 5-bromopent-1-ene (Table 1,
entry 12). Interestingly, 3-bromopropanenitrile gives bet-
ter results compared to 5-bromopent-1-ene (Table 1, entry
13). This outcome can be probably ascribed to a prelimi-
nary base-assisted elimination of HBr from 3-bromopro-
panenitrile generating acrylonitrile which undergoes
conjugate addition with the anion of compound 11. As a
matter of fact, acrylonitrile itself is able to provide the
same result when directly employed in this reaction
(Table 1, entry 14). Finally, conjugate addition to methyl
acrylate and phenylvinyl sulfone demonstrates that com-
pound 11 can be efficiently employed in Michael addi-
tions with electron-poor olefins as well (Table 1, entries
15 and 16).
Boc2O
DMAP, MeCN, r.t.
90%
2. TolSO2Na
DMF, r.t.
73%
N
N
Boc
H
10
9
SO2Tol
N
Boc
11
Scheme 3
tiveness of sulfonyl indoles 6 for this purpose have been
proved in the reaction with stabilized carbanions, Grig-
nard and Reformatsky reagents as well as in different re-
ductive removals of the arenesulfonyl group. In order to
evaluate the viability of the overall synthetic plan por-
trayed in Scheme 1 we decided to prepare N-Boc 3-(tosyl-
methyl)indole (11) starting from 3-methyl indole 9 that
upon protection gives the corresponding N-Boc derivative
10 (Scheme 3).14 Radical bromination of indole 10 fol-
lowed by nucleophilic displacement by sodium p-toluene-
sulfinate finally leads to compound 11 in satisfactory
overall yield.15
Generally, a-sulfonyl anions are generated by reaction of
the corresponding sulfones with n-BuLi or LDA in ethe-
real solvents. However, we observed that NaH in DMF at
0 °C is effective in converting sulfonyl indole 11 into the
corresponding anion which can be subsequently made to
react with a wide range of electrophilic reagents leading to
the corresponding adducts 12 (Table 1).16 Simple allyla-
Table 1 Reaction of Sulfonyl Indole 11 with Electrophiles in the Presence of NaH in DMF
SO2Tol
electrophile (E)
NaH, DMF, 0 °C
SO2Tol
E
N
N
Boc
Boc
11
12
Entry
Electrophile
Product
Time (h)
Yield (%)a
SO2Tol
Br
1
2
2
6
70
53
N
Boc
12a
12a
SO3Me
SO2Tol
Ph
3
1
74
Cl
N
Boc
Ph
12b
Synlett 2008, No. x, A–G © Thieme Stuttgart · New York

LETTER
Double Functionalization of N-Boc-3-(Tosylmethyl)indole
C
Table 1 Reaction of Sulfonyl Indole 11 with Electrophiles in the Presence of NaH in DMF (continued)
SO2Tol
electrophile (E)
NaH, DMF, 0 °C
SO2Tol
E
N
N
Boc
Boc
11
12
Entry
Electrophile
Product
Time (h)
Yield (%)a
SO2Tol
Cl
4
5
4
54
N
Boc
12c
SO2Tol
Cl
4
60
Cl
N
Boc
Cl
12d
12e
12f
12g
SO2Tol
SO2Tol
SO2Tol
6
7
8
4
4
2
61
72
84
Cl
N
Boc
Cl
N
Boc
Ph
Ph
Br
N
Boc
SO2Tol
Br
9
3
88
Br
Br
N
Boc
12h
12i
SO2Tol
10
11
2
2
80
65
I
N
Boc
SO2Tol
Cl
N
I
Boc
Cl
12j
Synlett 2008, No. x, A–G © Thieme Stuttgart · New York

D
A. Palmieri et al.
LETTER
Table 1 Reaction of Sulfonyl Indole 11 with Electrophiles in the Presence of NaH in DMF (continued)
SO2Tol
electrophile (E)
NaH, DMF, 0 °C
SO2Tol
E
N
N
Boc
Boc
11
12
Entry
Electrophile
Product
Time (h)
14
Yield (%)a
SO2Tol
12
52
N
Boc
Br
12k
SO2Tol
Br
13
3
70
N
N
Boc
N
12l
12l
14
15
3
1
63
77
CN
SO2Tol
CO2Me
N
CO2Me
Boc
12m
12n
SO2Tol
16
1
64
SO2Ph
N
SO2Ph
Boc
a Yields of pure, isolated products.
Sulfonyl indoles 12 prepared by this alkylative process from compounds 1217 affords the corresponding sulfonyl
can be fruitfully used in a subsequent process involving a indoles 13 that, following our synthetic protocol, react
base-promoted elimination of arenesulfinic acid followed with various methylene active compounds in the presence
by nucleophilic addition to the resulting vinylogous imino of KF and basic alumina leading to 3-substituted indoles
derivative.10c Thus removal of the N-Boc protecting group 14 in satisfactory yields (Table 2).18
Table 2 Deprotection of Sulfonyl Indoles 12 and Reaction with Methylene Active Compounds in the Presence of KF and Basic
Alumina
Nu
SO2Tol
E
NuH
TFA
E
12
CH2Cl2
r.t., 3 h
KF, Al2O3
CH2Cl2, r.t., 4 h
N
N
H
H
13
14
Entry
1
Indole
Yield of 13 (%)a
Nucleophile
Product
Yield of 14 (%)a
EtO2C
CO2Et
CO2Et
CO2Et
12a
89
75
N
H
14a
Synlett 2008, No. x, A–G © Thieme Stuttgart · New York

LETTER
Double Functionalization of N-Boc-3-(Tosylmethyl)indole
E
Table 2 Deprotection of Sulfonyl Indoles 12 and Reaction with Methylene Active Compounds in the Presence of KF and Basic
Alumina (continued)
Nu
SO2Tol
E
NuH
TFA
E
12
CH2Cl2
r.t., 3 h
KF, Al2O3
CH2Cl2, r.t., 4 h
N
N
H
H
13
14
Entry
2
Indole
Yield of 13 (%)a
Nucleophile
Product
Yield of 14 (%)a
NO2
NO2
12a
12g
12g
90
76
83
64
N
H
14b
CO2Et
NHAc
EtO2C
CO2Et
CO2Et
Ph
3
4
86
87
AcHN
N
H
14c
14g
MeOC
COMe
Ph
COMe
COMe
N
H
EtO2C
CO2Et
CO2Et
CO2Et
5
6
7
12h
12h
12j
86
85
81
74
66
77
Br
N
H
14e
NO2
MeNO2
Br
N
H
14f
NO2
EtNO2
N
H
Cl
14g
a Yields of pure, isolated products.
The mild basic conditions required for the elimination– with diethyl 2-(acetylamino) malonate, is particularly in-
addition process on sulfonyl indoles 13 do not promote teresting since its hydrolysis and decarboxylation pro-
any double-bond isomerization of compounds 14a,b vides a straightforward entry to tryptophan analogues.19
(Table 2, entries 1 and 2). Furthermore, the poor reactivity
shown by nitroalkanes toward C-alkylation allows a
chemoselective addition of nitroethane on sulfonyl indole
obtained by deprotection of 12j leading to compound 14g
In conclusion, the tosyl group in N-Boc-3-(tosylmeth-
yl)indole (11) assists deprotonation at a-position allowing
an easy reaction of the corresponding carbanion with dif-
ferent electrophilic reagents. Subsequently, the aptitude
of the tosyl group in acting as a good leaving group in
(Table 2, entry 7). Compound 14c, obtained by reaction
Synlett 2008, No. x, A–G © Thieme Stuttgart · New York

F
A. Palmieri et al.
LETTER
solid; mp 124–126 °C. IR (Nujol): 1374, 1151 cm–1.
elimination processes can be utilized to generate a vinyl-
ogous imino derivative, which can be made to react with
stabilized carbanions. The overall strategy represents a
new example of umpoled synthon, which can be profit-
ably used to prepare branched 3-substituted indoles bear-
ing different functional groups.
1H NMR (400 MHz, CDCl3): d = 1.63 (s, 9 H), 2.37 (s, 3 H),
4.42 (s, 2 H), 7.08–7.12 (m, 1 H), 7.19 (d, 2 H, J = 10.7 Hz),
7.21–7.28 (m, 2 H), 7.45 (s, 1 H), 7.59 (d, 2 H, J = 8.5 Hz),
8.09 (d, 1 H, J = 8.1). 13C NMR (75 MHz, CDCl3): d = 21.7,
28.2, 54.0, 84.3, 107.9, 115.2, 119.0, 122.9, 124.8, 126.2,
127.4, 128.7, 129.7,135.2, 136.7, 144.9, 149.8.
(16) Reaction of N-Boc-3-(Tosylmethyl) indole (11) with
Electrophiles
Acknowledgment
To a mixture of NaH (2 mmol) in anhyd DMF (5 mL),
sulfonyl indole 11 (1 mmol) was added at 0 °C. After 20 min
stirring at this temperature, the electrophile (1.1 mmol) was
added and stirring was continued for the appropriate time at
0 °C (see Table 1). The mixture was then cautiously
quenched by addition of cold H2O and then acidified with
AcOH. After extraction with Et2O (3 × 15 mL) the organic
phase was dried over MgSO4 and after removal of the
solvent the residue was purified by column chromatography
(hexanes–EtOAc, 8:2).
Spectroscopic Data for Representative Compounds
Compound 12a: mp 58–60 °C. IR (Nujol): 1598, 1370, 1155
cm–1. 1H NMR (400 MHz, CDCl3): d = 1.67 (s, 9 H), 2.35 (s,
3 H), 2.83–3.06 (m, 1 H), 3.10–3.28 (m, 1 H), 4.39 (dd, 1 H,
J = 4.0, 11.4 Hz), 4.92–5.12 (m, 2 H), 5.52–5.75 (m, 1 H),
7.05–7.21 (m, 3 H), 7.23–7.37 (m, 2 H), 7.44–7.60 (m, 3 H),
8.09 (d, 1 H, J = 8.4 Hz). 13C NMR (75 MHz, CDCl3): d =
21.8, 28.4, 32.6. 63.4, 84.5, 112.2, 115.3, 118.6, 119.4,
122.9, 124.8, 126.7, 129.4, 129.6, 133.3, 134.4, 135.3,
144.9, 149.5.
Compound 12f: mp 55–57 °C. IR (Nujol): 3310, 2133, 1368,
1151 cm–1. 1H NMR (400 MHz, CDCl3): d = 1.67 (s, 9 H),
1.85 (s, 1 H), 2.36 (s, 3 H), 3.04–3.11 (m, 1 H), 3.27–3.32
(m, 1 H), 4.56 (dd, 1 H, J = 4.1, 10.7 Hz), 7.10–7.17 (m, 3
H), 7.20–7.27 (m, 2 H), 7.52–7.62 (m, 3 H), 8.10 (d, 1 H,
J = 8.1 Hz). 13C NMR (75 MHz, CDCl3): d = 19.5, 21.8,
28.4, 62.2, 71.3, 79.3, 84.6, 115.4, 119.3, 123.0, 124.9,
126.7, 129.4, 129.5, 129.6, 129.8, 133.9, 135.2, 145.3,
149.5.
Financial support from University of Camerino and MIUR (Natio-
nal Project ‘Sintesi organiche ecosostenibili mediate da nuovi
sistemi catalitici’) is gratefully acknowledged.
References and Notes
(1) Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon
Press: Oxford, 1993.
(2) Nájera, C.; Sansano, J. M. Recent Res. Dev. Org. Chem.
1998, 2, 637.
(3) Nájera, C.; Yus, M. Tetrahedron 1999, 55, 10547.
(4) (a) Das, I.; Pathak, T. Org. Lett. 2006, 8, 1303.
(b) Berkowitz, D. B.; Bose, M.; Asher, N. Org. Lett. 2001, 3,
2009. (c) For a classical procedure, see: Corey, E. J.;
Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1345.
(5) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563.
(6) (a) Nenajdenko, V. G.; Krasovskiy, A. L.; Balenkova, E. S.
Tetrahedron 2007, 63, 12481. (b) Meadows, D. C.; Gervay-
Hague, J. Med. Chem. Rev. 2006, 26, 793. (c) Back, T. G.
Tetrahedron 2001, 57, 5263.
(7) Petrini, M. Chem. Rev. 2005, 105, 3949.
(8) Petrini, M.; Torregiani, E. Synthesis 2007, 159.
(9) For some papers dealing with alkylation of a-amido sulfones
and elimination to the corresponding enecarbamates, see:
(a) Alonso, D. A.; Alonso, E.; Nájera, C.; Ramón, D. J.; Yus,
M. Tetrahedron 1997, 53, 4835. (b) Berthon, L.; Uguen, D.
Tetrahedron Lett. 1985, 26, 3975.
(10) (a) Ballini, R.; Palmieri, A.; Petrini, M.; Torregiani, E. Org.
Lett. 2006, 8, 4093. (b) Palmieri, A.; Petrini, M. J. Org.
Chem. 2007, 72, 1863. (c) Ballini, R.; Palmieri, A.; Petrini,
M.; Shaikh, R. R. Adv. Synth. Catal. 2008, 350, 129.
(11) (a) For some recent applications of gramines in synthesis,
see: Semenov, B. B.; Granik, V. G. Pharm. Chem. J. 2004,
38, 287. (b) de la Herrán, G.; Segura, A.; Csákÿ, A. G. Org.
Lett. 2007, 9, 961. (c) Semenov, B. B.; Novikov, K. A.;
Lysenko, K. A.; Kachala, V. V. Tetrahedron Lett. 2006, 47,
3479. (d) Low, K. H.; Magomedov, N. A. Org. Lett. 2005, 7,
2003.
(12) Bandini, M.; Melloni, A.; Tommasi, S.; Umani-Ronchi, A.
Synlett 2005, 1199.
(13) (a) Faulkner, D. J. Nat. Prod. Rep. 2002, 19, 1. (b) Saxton,
J. E. In The Alkaloids; Cordell, G. A., Ed.; Academic Press:
New York, 1998. (c) Sundberg, R. J. Indoles; Academic
Press: New York, 1997. (d) Saxton, J. E. Nat. Prod. Rep.
1997, 559.
Compound 12l: mp 56–58 °C. IR (Nujol): 2248, 1376, 1153
cm–1. 1H NMR (400 MHz, CDCl3): d = 1.67 (s, 9 H), 2.35 (s,
3 H), 2.46–2.62 (m, 2 H), 2.80–2.96 (m, 2 H), 4.46 (dd, 1 H,
J = 4.7, 10.7 Hz), 7.12–7.18 (m, 3 H), 7.26–7.38 (m, 2 H),
7.51–7.60 (m, 3 H), 8.10 (d, 1 H, J = 8.1 Hz). 13C NMR (75
MHz, CDCl3): d = 15.5, 21.7, 24.7, 28.3, 62.3, 84.9, 110.5,
115.5, 118.3, 119.3, 123.3, 125.2, 126.7, 129.3, 129.8,
134.1, 137.8, 145.3, 149.7.
Compound 12m: mp 52–54 °C. IR (Nujol): 1742, 1374,
1156 cm–1. 1H NMR (400 MHz, CDCl3): d = 1.66 (s, 9 H),
2.34 (s, 3 H), 2.36–2.49 (m, 2 H), 2.67–2.78 (m, 2 H), 3.58
(s, 3 H), 4.52 (dd, 1 H, J = 4.3, 10.7 Hz), 7.10–7.20 (m, 3 H),
7.22–7.34 (m, 2 H), 7.48 (s, 1 H), 7.55 (d, 2 H, J = 8.1 Hz),
8.09 (d, 1 H, J = 8.1 Hz). 13C NMR (75 MHz, CDCl3): d =
21.7, 24.1, 28.3, 31.1, 51.8, 62.5, 84.6, 111.9, 115.4, 119.4,
123.0, 125.0, 126.6, 129.3, 129.6, 134.5, 135.4, 144.9,
149.8, 172.8.
(17) The free NH on the indole ring is mandatory for a successful
process since none of the nucleophilic reagents tested in this
reaction gives any result with N-Boc indoles 12.
(14) Liu, R.; Zhang, P.; Gan, T.; Cook, J. M. J. Org. Chem. 1997,
62, 7447.
(15) Synthesis of N-Boc-3-(Tosylmethyl) indole (11)
To a solution of N-Boc-3-(bromomethyl) indole (5 mmol,
1.55 g) in DMF (10 mL), Bu4NI (0.5 mmol, 0.18 g) and
TolSO2Na were added at r.t. After stiring for 2 h at this
temperature, cold H2O (30 mL) was added and the mixture
was extracted with EtOAc (3 × 30 mL). The organic phase
was dried over MgSO4, and after removal of the solvent the
residue was purified by column chromatography (hexanes–
EtOAc, 8:2) giving 1.54 g (80% yield) of pure 11 as a white
(18) Deprotection of N-Boc Sulfonyl Indoles 12 and Their
Reaction with Nucleophiles
N-Boc indole 12 (1 mmol) was dissolved in a mixture of
TFA–CH2Cl2 (1:1, 10 mL) and stirring was continued for 3
h at r.t. After evaporation of the solvents at reduced pressure,
the crude sulfonyl indole was purified by column
chromatography (hexanes–EtOAc, 8:2). Reaction of
sulfonyl indoles 13 with nucleophiles was carried out
according to our previously published procedure (ref. 10c).
Synlett 2008, No. x, A–G © Thieme Stuttgart · New York

LETTER
Spectroscopic Data for Representative Compounds
Double Functionalization of N-Boc-3-(Tosylmethyl)indole
G
J = 3.4, 11.5 Hz), 4.80 (d, 1 H, J = 9.9 Hz), 4.95 (dd, 1 H,
Compound 14a: oil. IR (neat): 3393, 1739, 1603, 1463 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.86 (t, 2.3 H, J = 7.3 Hz),
1.27 (t, 2.5 H, J = 6.8 Hz), 1.28 (t, 1.2 H, J = 7.3 Hz), 2.55–
2.69 (m, 2 H), 3.84–3.92 (m, 3 H), 4.16–4.28 (m, 3 H), 4.87–
4.99 (m, 2 H), 5.61–5.68 (m, 1 H), 7.02 (d, 1 H, J = 2.1 Hz),
7.08–7.18 (m, 2 H), 7.31 (d, 1 H, J = 7.7 Hz), 7.66 (d, 1 H,
J = 7.7 Hz), 8.24 (br s, 1 H). 13C NMR (75 MHz, CDCl3): d
= 13.8, 14.3, 37.0, 38.0, 57.6, 57.6, 61.4, 61.7, 111.4, 115.2,
116.9, 119.5, 119.6, 122.1, 122.8, 127.0, 136.1, 136.4,
168.6, 168.9.
J = 1.3, 17.1 Hz), 5.48–5.55 (m, 1 H), 7.04 (d, 1 H, J = 2.6
Hz), 7.13–7.23 (m, 2 H), 7.37 (d, 1 H, J = 8.1 Hz), 7.68 (d, 1
H, J = 7.7 Hz), 8.19 (br s, 1 H). 13C NMR (75 MHz, CDCl3):
d = 21.8, 26.8, 34.9, 45.7, 93.0, 111.5, 113.3, 116.7, 119.7,
120.1, 122.4, 123.4, 128.3, 136.1, 136.2.
(19) (a) Jones, D. T.; Hartman, G. T. III; Williams, R. M.
Tetrahedron Lett. 2007, 48, 1291. (b) Teng, X.; Degterev,
A.; Jagtap, P.; Xing, X.; Choi, S.; Denu, R.; Yuan, J.; Cuny,
G. D. Bioorg. Med. Chem. Lett. 2005, 15, 503.
(c) Williams, R. M.; Cao, J.; Tsujishima, H.; Cox, R. J.
J. Am. Chem. Soc. 2003, 125, 12172. (d) Marcq, V.;
Mirand, C.; Decarme, M.; Emonard, H.; Hornebeck, W.
Bioorg. Med. Chem. Lett. 2003, 13, 2843.
Compound 14b: oil. IR (neat): 3389, 1622, 1583, 1458 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.51 (s, 3 H), 1.65 (s, 3 H),
2.33–2.39 (m, 1 H), 2.59–2.68 (m, 1 H), 3.82 (dd, 1 H,
Synlett 2008, No. x, A–G © Thieme Stuttgart · New York

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