Lewis acid-controlled regioselectivity in reactions of styrenyl systems with benzoquinone monoimides: New regioselective syntheses of substituted 2-aryl-2,3-dihydrobenzofurans, 2-aryl-2,3-dihydroindoles, and 2-arylindoles

Article abstract of DOI:10.1021/jo9617068

Reactions of 4-(N-phenylsulfonyl)-2-alkoxy-1,4-benzoquinone monoimines 2-4 with electron-rich propenylbenzenes promoted by BF₃ yield 7-alkoxy-2-aryl-3-methyl-5-[(N-phenylsulfonyl)amino]-2,3-dihydrobenzofurans 5-7 nearly exclusively, whereas promotion of the reactions by Ti⁴⁺ gives mixtures of the dihydrobenzofurans and their N-(phenylsulfonyl)-6-alkoxy-2-aryl-5-hydroxy-3-methyl-2,3-dihydroindole isomers 8-10, depending upon substituents present on the propenylbenzene. However, reactions promoted with excess Ti⁴⁺, as mixtures of TiCl₄:Ti(OiPr)₄, give the dihydroindoles as nearly the exclusive products. Evidence for a mechanism involving initial 5 + 2 cycloaddition of the Lewis acid-bound quinone monoimide with the propenylbenzene is found in reactions of styrenes 1f/g with monoimide 3 in which 7-aryl-3-hydroxy-6-methylbicyclo[3.2.1]oct-3-ene-2,8-diones 33 (5 + 2 adducts) are isolated. These reactions have been applied to stereoselective syntheses of pterocarpans bearing N-phenylsulfonyl groups, azapterocarpans and diazapterocarpans. In addition, DDQ oxidation of derivatives of several of the 2-aryl-2,3-dihydroindoles afford the corresponding 2-arylindoles in good yield. Finally, the experimental details of a general synthetic approach to 7-alkoxy-benzofuranoid neolignans, including (±)-licarin B and eupomatenoids-1 and -12 are reported.

Full text of DOI:10.1021/jo9617068

J . Org. Chem. 1996, 61, 9297-9308
9297
Lew is Acid -Con tr olled Regioselectivity in Rea ction s of Styr en yl
System s w ith Ben zoqu in on e Mon oim id es: New Regioselective
Syn th eses of Su bstitu ted 2-Ar yl-2,3-d ih yd r oben zofu r a n s,
2-Ar yl-2,3-d ih yd r oin d oles, a n d 2-Ar ylin d oles
Thomas A. Engler,* Wenying Chai, and Kenneth O. LaTessa†
Department of Chemistry, University of Kansas, Lawrence, Kansas 66045
Received September 4, 1996X
Reactions of 4-(N-phenylsulfonyl)-2-alkoxy-1,4-benzoquinone monoimines 2-4 with electron-rich
propenylbenzenes promoted by BF3 yield 7-alkoxy-2-aryl-3-methyl-5-[(N-phenylsulfonyl)amino]-
2,3-dihydrobenzofurans 5-7 nearly exclusively, whereas promotion of the reactions by Ti4+ gives
mixtures of the dihydrobenzofurans and their N-(phenylsulfonyl)-6-alkoxy-2-aryl-5-hydroxy-3-
methyl-2,3-dihydroindole isomers 8-10, depending upon substituents present on the propenyl-
benzene. However, reactions promoted with excess Ti4+, as mixtures of TiCl4:Ti(OiPr)4, give the
dihydroindoles as nearly the exclusive products. Evidence for a mechanism involving initial 5 +
2 cycloaddition of the Lewis acid-bound quinone monoimide with the propenylbenzene is found in
reactions of styrenes 1f/g with monoimide 3 in which 7-aryl-3-hydroxy-6-methylbicyclo[3.2.1]oct-
3-ene-2,8-diones 33 (5 + 2 adducts) are isolated. These reactions have been applied to stereoselective
syntheses of pterocarpans bearing N-phenylsulfonyl groups, azapterocarpans and diazapterocarpans.
In addition, DDQ oxidation of derivatives of several of the 2-aryl-2,3-dihydroindoles afford the
corresponding 2-arylindoles in good yield. Finally, the experimental details of a general synthetic
approach to 7-alkoxy-benzofuranoid neolignans, including (()-licarin B and eupomatenoids-1 and
-12 are reported.
In tr od u ction
promoted reactions of styrenes with 2-alkoxy-4-(N-phen-
ylsulfonyl)benzoquinone monimines.4 Of particular note
is that the regioselectivity of these reactions is deter-
mined by the nature of the Lewis acid promoter providing
convenient access to either highly substituted 2-aryl-2,3-
dihydrobenzofurans or 2-aryl-2,3-dihydroindoles from the
same starting materials. Our interest in developing
these reactions stems from the presence of 2-aryl-2,3-
dihydrobenzofuran, -benzofuran, and 2-arylindole sub-
structures in a wide variety of biologically active mol-
ecules.
Substituted benzoquinones are remarkably versatile
starting materials and reagents for synthesis.1 Their
cycloaddition reactions, for example, have been used in
an impressive array of stereo- and regioselective synthe-
ses of complex natural and non-natural products. We
have recently developed Lewis acid-promoted cycloaddi-
tion reactions of quinones with styrenyl systems as
efficient routes to 2-aryl-2,3-dihydrobenzofuran and
bicyclo[3.2.1]octendione neolignans, and pterocarpan natu-
ral products and analogs.2
By comparison, reactions of quinone monoimides have
received relatively little attention,3 although their po-
tential in synthetic applications is arguably as high or
greater than that of the quinones. Herein, we report the
details of an initial study to explore the scope, limitations,
and potential for synthetic applications of Lewis acid-
Resu lts a n d Discu ssion
BF3-P r om oted Reaction s. Addition of styrenes 1a-c
bearing strong electron-donating substituents to solutions
of imides 2-4 and BF3‚OEt2 in CH2Cl2 at low tempera-
ture resulted in the formation of dihydrobenzofurans 5-7
as the major, if not exclusive, products (eq 1 and Table
1). Small amounts of dihydroindoles 8-10 were found
in some cases. Reactions of non-nucleophilic styrene 1d
required warming to room temperature, and even then
only a low yield of 5d was obtained. Attempted reactions
of styrenes 1f/g, without good electron-donating groups,
failed to provide a product; only starting materials were
evident by TLC. Reactions of acetoxystyrene 1e also
failed, perhaps due to competing complexation of the
ester moiety with the Lewis acid.
† Formerly Kenneth O. Lynch, J r.: current address; Stephens
College, Columbia, MO 65215.
X Abstract published in Advance ACS Abstracts, December 1, 1996.
(1) (a) The Chemistry of Quinonoid Compounds; Patai, S., Rap-
poport, Z., Eds.; J ohn Wiley and Sons: New York, 1988; Vol. II, Parts
1 and 2. (b) Bruce, J . M. In Rodd’s Chemistry of Carbon Compounds,
2nd ed.; Coffey, S., Ed.; Elsevier: Amsterdam, 1974; Vol. III (Aromatic
Compounds), Part B, Chapter 8. (c) See references cited in Engler, T.
A.; Letavic, M. A.; Lynch, K. O., J r.; Takusagawa, F. J . Org. Chem.
1994, 59, 1179-1183.
(2) (a) Engler, T. A.; Combrink, K. D.; Letavic, M. A.; Lynch, K. O.,
J r.; Ray, J . E. J . Org. Chem. 1994, 59, 6567-6587. (b) Engler, T. A.;
Wei, D.; Letavic, M. A.; Combrink, K. D.; Reddy, J . P. J . Org. Chem.
1994, 59, 6588-6599. (c) Engler, T. A.; Reddy, J . P.; Combrink, K. D.;
Vander Velde, D. J . Org. Chem. 1990, 55, 1248-1254. (d) Engler, T.
A.; Lynch, K. O., J r.; Reddy, J . P.; Gregory, G. S. Bioorg. Med. Chem.
Lett. 1993, 3, 1229-1232. (e) Engler, T. A.; LaTessa, K. O.; Iyengar,
R.; Chai, W.; Agrios, K. Bioorg. Med. Chem. 1996, 7, in press.
(3) (a) Brown, E. R. In The Chemistry of Quinonoid Compounds;
Patai, S.; Rappoport, Z., Eds.; J ohn Wiley and Sons: New York, 1988;
Vol. II, Part 2, Chapter 21. (b) Adams, R.; Reifschneider, W. Bull. Chim.
Soc. Fr. 1958, 23-65.
(4) For preliminary reports, see (a) Engler, T. A.; Lynch, K. O., J r.;
Chai, W.; Meduna, S. P. Tetrahedron Lett. 1995, 36, 2713-2716. (b)
Engler, T. A.; Chai, W.; Lynch, K. O., J r. Tetrahedron Lett. 1995, 36,
7003-7006.
(5) Dihydroquinoline 12 was actually prepared and used as a 2-3:1
mixture of 12 and its 5-methoxy isomer. The minor component did not
react in the Lewis acid-promoted reactions with the quinone monoim-
ides and could be recovered cleanly; see references 2e and 4a.
S0022-3263(96)01706-9 CCC: $12.00 © 1996 American Chemical Society

9298 J . Org. Chem., Vol. 61, No. 26, 1996
Engler et al.
activation7 of the quinone monoimides by coordination
of the BF3 to the basic sulfonyl nitrogen to afford complex
25 (Scheme 1). Cycloaddition2 with the styrenyl CdC
bond of 1 gives intermediate 26 which proceeds on to the
observed products by fragmentation to 27 followed by
C-O bond formation and loss of H+. Alternatively,
simple alkylation of 25 by the styrene may afford 27
directly which then proceeds on to 5-7.8 Formation of
13-18 likely occur in an analogous manner. The cy-
cloaddition route is suggested by similar processes pos-
tulated in Lewis acid-promoted reactions of 1,4-benzo-
quinones with styrenes.2
Ti(IV)/Sn (IV)-P r om oted Rea ction s. The results of
reactions of the styrenes with the quinone monoimides
promoted by Ti(IV) or Sn(IV) were influenced by the
substituents on the styrenes and, to a lesser extent, on
the monoimide (Table 2). More significantly, the number
of equiv of Lewis acid used had a dramatic impact. Initial
experiments focused on electron-rich styrenyl systems 1b/
c, 11, and 12. Reactions with 1 equiv of Lewis acid
produced either or both of the dihydrobenzofuran- or the
dihydroindole-type products as major products. Different
combinations of TiCl4 and Ti(OiPr)4 were surveyed
because of the varying sensitivity of the styrenes to
strongly acidic conditions.
In a similar manner, reactions of 2H-chromene 11 and
dihydroquinoline 125 were also examined (eq 2). These
electron-rich styrenyl systems also gave dihydrobenzo-
The different TiCl4:Ti(OiPr)4 mixtures vary signifi-
cantly in acidity, and this is but one of a number of issues
that confound a simple analysis of the data and prevent
a clear pattern from emerging. As a bidentate Lewis
acid, Ti4+ might be expected to complex with the C-1
carbonyl and C-alkoxy oxygens of the monoimide and
activate C-3 and C-5 to cycloaddition with, or alkylation
(6) The styrenes were purchased, or made,15 and used as is; 1a /f
were ∼100% (E), whereas the others were 3.5-15:1 mixtures of (E):
(Z)-isomers. The (Z)-isomer did not react competitively with the (E)-
isomer; see reference 2a for
a discussion of the relative rates of
reactions of (E) vs (Z) styrenes with quinones.
(7) Regioselective Lewis acid-activation of quinone bisimides has
been described in some detail by Boger and others. See reference 3
and (a) Boger, D. L.; Zarrinmayeh, H. J . Org. Chem. 1990, 55, 1379-
1390. (b) Boger, D. L.; Coleman, R. S. J . Am. Chem Soc. 1988, 110,
4796-4807. (c) Holmes, T. J ., J r.; Lawton, R. G. J . Org. Chem. 1983,
48, 3146-3150. Similarly, regioselective activation of substituted
quinones has been reported. (d) Tou, J . S.; Reusch, W. J . Org. Chem.
1980, 45, 5012-5014. (e) Dickinson, R. A.; Kubela, R.; MacAlpine, G.
A.; Stojanac, Z.; Valenta, Z. Can. J . Chem. 1972, 50, 2377-2380. (f)
Stojanac, Z.; Dickinson, R. A.; Stojanac, N.; Woznow, R. J .; Valenta,
Z. Can. J . Chem. 1975, 53, 616-618. (g) Das, J .; Kubela, R.; MacAlpine,
G. A.; Stojanac, Z.; Valenta, Z. Can J . Chem. 1979, 57, 3308-3319.
For reasons that are not clear, results of some Ti(IV)-promoted quinone
Diels-Alder reactions do not always fit this generalization; see, for
examples, (h) Hendrickson, J . B.; Singh, V. J . Chem. Soc., Chem.
Commum. 1983, 837-838. (i) Hendrickson, J . B.; Haestier, A. M.;
Stieglitz, S. G.; Foxman, B. M. New J . Chem. 1990, 14, 689-693. (j)
Engler, T. A.; Letavic, M. A.; Lynch, K. O., J r.; Takusagawa, F. J . Org.
Chem. 1994, 59, 1179-1183.
furan-type products nearly exclusively and in generally
good yield (Table 1).
The structures of dihydrobenzofurans 5-7 and 13-
18 are assigned by mass spectra, the presence of a
sulfonamide N-H stretch at ∼3360 cm-1 in their IR
spectra, and by NMR studies, including NOE and 2D
experiments. The signals for H-4 and H-6 in 5-7, and
H-7 and H-9 in 13-18, appear as doublets (J ) 1-2 Hz)
or broadened singlets at ∼6.38-6.52 and 6.48-6.54 ppm,
respectivley. 1H-1H Decoupling or COSY experiments
confirmed that these signals were coupled. The position
of the alkoxy group on the benzofuran ring was further
established by HETCOR and HMBC experiments on 5b
(Figure 1). In their 1H-NMR spectra, the H-2 and C-3
CH3 signals appear at 5.03-5.12 and 1.24-1.27 ppm,
respectively, with J H-2/H-3 ∼ 9 Hz. Similarly, signals for
H-11a in 13-15 are observed at ∼5.5 ppm, and those for
16-18 at ∼5.1 ppm; J H-11a/H-6a are ∼7-8 Hz. In 5b/6b,
strong 1H-1H NOE’s are observed between the C-3 methyl
and both H-2 and H-4 (Figure 2), and also between H-6a
and H-11a in 15 and 17, confirming the stereochemistry.
The spectra of the other dihydrobenzofurans are very
similar to those of 5b/6b and 15/17, and their structures
are assigned by analogy.
(8) Gates, B. D.; Dalidowicz, P.; Tebben, A.; Wang, S.; Swenton, J .
S. J . Org. Chem. 1992, 57, 2135-2143.
(9) Several studies indicate that with some carbonyl compounds
TiCl4 forms either 2:1 or 1:1 CdO:TiCl4 complexes depending upon
stoichiometry. In addition, the stereochemistry of Lewis acid-promoted
allylmetal-aldehyde reactions is dependent upon stoichiometry. Thus,
the complexes formed from the quinone monoimides with 1 equiv of
Ti4+ may not be 1:1 complexes as represented herein; i.e. with 1 equiv
of Ti(IV), 2:1 monoimide:Ti(IV) complexes may be present, whereas
excess Ti(IV) may shift an equilibrium to 1:1, and therefore bidentate,
complexes. Furthermore, concerns regarding the Curtin-Hammett
principle may be relevant to the results presently described. For
leading references and pertinent discussions, see, (a) Turin, E.; Nielson,
R.M.; Merbach, A. E. Inorg. Chim. Acta 1987, 134, 79-85, 67-78. (b)
Bachand, B.; Wuest, J . D.; Organometallics 1991, 10, 2015-2025. (c)
Denmark, S. E.; Almstead, N. G. Tetrahedron 1992, 48, 5565-5578.
(d) Denmark, S. E.; Almstead, N. G. J . Am. Chem. Soc. 1993, 115,
3133-3139. (e) Springer, J . B.; DeBoard, J .; Corcoran, R. C. Tetrahe-
dron Lett. 1995, 36, 8733-8736. For other discussions of carbonyl-
(Lewis acid)2 complexes as potential intermediates, see reference 2b
and references cited therein.
The formation of the major products in the BF3-
promoted reactions can be explained by regioselective

Reactions of Styrenyl Systems with Benzoquinone Monoimides
J . Org. Chem., Vol. 61, No. 26, 1996 9299
Ta ble 1. BF 3‚OEt2-P r om oted Rea ction s of Styr en yl System s 1 a n d 11/12 w ith Qu in on e Mon oim id es 2-4a
entry
styrene: Xb
monoimide: R
temp (°C)
time (h)
product(s)c
(% yields)d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a : 4-OCH3
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1d : 4-CH3
1e: 4-OAc
1f: H
1g: 3-OCH3
11: O
11: O
11: O
12: NTs
2: CH3
2: CH3
-78
<1
<1
<1
<1
<1
<1
<1
16
5a (91)
5b (81)
6b (86)
7b (89)
5c (82)
6c (73)
7c (48)
5d (14)
-
8a (8)
8b (1)
e
10b (10)
8c (13)
-78
3: CH2Ph
4: CH2CH(CH3)2
2: CH3
3: CH2Ph
4: CH2CH(CH3)2
2: CH3
-78
-78
-78
-78
9c (8)
-
-78
-78 to rt
-78 to rt
-78 to rt
-78
-
2: CH3
2: CH3
16
16
-
-
-
3: CH2Ph
2: CH3
3: CH2Ph
4: CH2CH(CH3)2
2: CH3
<1
<1
<1
<1
<1
<1
<1
-
-
-78
13 (87)
14 (91)
15 (81)
16 (70)
17 (53)
18 (29)
-
-78
-
-78
21 (2)
-
-78
12: NTs
12: NTs
3: CH2Ph
4: CH2CH(CH3)2
-78
-
-
-78
a
b
All reactions were done in CH2Cl2 with 1-1.3 equiv of BF3‚OEt2 (with respect to the monoimide) as promoter. Used as (E):(Z)
mixtures as purchased or prepared (see reference 6). c Substituents X and R same as starting 1/2-4. Isolated yields. e Indicates that
this product was not isolated.
d
Sch em e 2
F igu r e 1. Selected data from HETCOR and HMBC experi-
ments on 5b.
Sch em e 3
F igu r e 2. Summary of selected NOE data on 5b /6b and
15/17.
Sch em e 1
compete with the monoimides for complexation with the
Lewis acid and alter the electronics of the styrene CdC,
or act as ligands in addition to the monoimide. This is
perhaps particularly important in reactions of styrenes
1b and 11 and quinoline 12. Finally, different styrenes
may react via different mechanisms, i.e. nucleophilic
styrenes via an alkylation process directly accessing the
benzylic carbocations 27 or 29, and non-nucleophilic
styrenes via cycloaddition processes in which intermedi-
ate bicyclo[3.2.1] adducts are formed. In the latter
process, bicyclic-cationic intermediate 28 should be pre-
ferred over 26 due to stabilization of the positive charge
by oxygen.
by, the styrene ultimately resulting in dihydroindole
products 8-10/19-24 (Scheme 2). On the other hand,
monodentate binding to the sulfonyl nitrogen moiety
would lead to the dihydobenzofuran products 5-7/13-
18 (vide supra). It is not clear which mode of complex-
ation should prevail.9 Indeed, an equilibrium between
the two is possible, and the different steric bulk and
electronics of the alkoxy R groups may influence the
complexation and/or the cycloaddition step. In addition,
most of the styrenes also possess basic groups which may
To avoid the complications due to these mechanistic
issues, and others,9 reactions with greater than 2-3
equiv of the Lewis acid were studied anticipating that
monoimide-[Ti4+
] complexes 30 might be formed as
2
reactive species (Scheme 3). In such complexes, it is not
unreasonable to suspect that C-5 or C-3/C-5 would be the
more reactive site(s) if, as suggested by the reactions
promoted by 1 equiv of BF3, the C-4 imide nitrogen is
the most basic site; i.e. attachment of a second equivalent
of the Lewis acid to the C-1 carbonyl and C-2 alkoxy

9300 J . Org. Chem., Vol. 61, No. 26, 1996
Engler et al.
Ta ble 2. Ti(IV)/Sn (IV)-P r om oted Rea ction s of Styr en yl System s 1 a n d 11/12 w ith Qu in on e Mon oim id es 2-4a
entry
styrene: Xb
monoimide: R
Lewis acid
temp (°C)
time (h)
product(s)c
(% yields)d
1
2
3
4
5
6
7
8
9
1a : OCH3
1a : OCH3
1a : OCH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
3: CH2Ph
3: CH2Ph
3: CH2Ph
3: CH2Ph
3: CH2Ph
3: CH2Ph
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
2: CH3
1:1 TiCl4:Ti(OiPr)4 (1)c
1:2 TiCl4:Ti(OiPr)4 (3)
1:2 TiCl4:Ti(OiPr)4 (6)
TiCl4 (1)
1:1 TiCl4:Ti(OiPr)4 (2)
1:2 TiCl4:Ti(OiPr)4 (6)
1:1 TiCl4:Ti(OiPr)4 (10)
1:1 TiCl4:Ti(OiPr)4 (2)
1:1 TiCl4:Ti(OiPr)4 (3)
2:1 TiCl4:Ti(OiPr)4 (3)
1:1 TiCl4:Ti(OiPr)4 (5)
1:2 TiCl4:Ti(OiPr)4 (7.5)
1:1 TiCl4:Ti(OiPr)4 (10)
TiCl4 (1)
1:1 TiCl4:Ti(OiPr)4 (1)
1:1 TiCl4:Ti(OiPr)4 (1)
1:1 TiCl4:Ti(OiPr)4 (10)
TiCl4 (1)
1:1 TiCl4:Ti(OiPr)4 (1)
1:1 TiCl4:Ti(OiPr)4 (2)
1:2 TiCl4:Ti(OiPr)4 (7.5)
1:1 TiCl4:Ti(OiPr)4 (2)
1:2 TiCl4:Ti(OiPr)4 (7.5)
1:1 TiCl4:Ti(OiPr)4 (10)
TiCl4 (1)
-78
<1
16
5a (8)
5a (13)
5a (3)
5b (80)
5b (23)
5b (11)
-
6b (76)
6b (63)
6b (65)
6b (31)
-
8a (82)
8a (76)
8a (81)
f
8b (57)
8b (60)
8b (89)
9b (21)
9b (9)
-
9b (40)
9b (100)
9b (79)
10b (19)
10b (7)
10b (64)
10b (64)
8c (25)
8c (52)
8c (67)
8c (73)
9c (59)
9c (59)
9c (67)
10c (13)
10c (60)
10c (87)
10c (93)
8d (61)
NR
8d (45)
8d (74)
8e (18)
8f (75)
8f (6)
-
-
19 (34)
19 (48)
20 (38)
20 (41)
20 (51)
21 (15)
21 (55)
21 (57)
-
-78 to rt
-78
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
16
<1
<1
<1
<1
16
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
16
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1b: 3,4-(OCH3)2
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1c: 3,4-OCH2O
1d : 4-CH3
1d : 4-CH3
1d : 4-CH3
1d : 4-CH3
1e: 4-OAc
1f: H
1f: H
11: O
11: O
11: O
11: O
11: O
11: O
11: O
11: O
11: O
11: O
12: NTs
12: NTs
12: NTs
12: NTs
12: NTs
-78
-78
-78
-78
-78
-78
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
-78
-78
-78
-78
6b (4)
7b (44)
7b (77)
7b (35)
7b (3)
-
-78
-78
-78
-78
-78
2: CH3
2: CH3
2: CH3
-78
-
-78
-
-78
-
3: CH2Ph
3: CH2Ph
3: CH2Ph
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
2: CH3
3: CH2Ph
3: CH2Ph
3: CH2Ph
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
2: CH3
2: CH3
2: CH3
2: CH3
3: CH2Ph
3: CH2Ph
3: CH2Ph
3: CH2Ph
3: CH2Ph
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
4: CH2CH(CH3)2
-78
6c (29)
-
-78
-78
-
-
-78
1:1 TiCl4:Ti(OiPr)4 (1)
1:1 TiCl4:Ti(OiPr)4 (2)
1:1 TiCl4:Ti(OiPr)4 (10)
TiCl4 (2)
1:2 TiCl4:Ti(OiPr)4 (3)
TiCl4 (4)
2:1 TiCl4:Ti(OiPr)4 (14)
TiCl4 (4)
TiCl4 (1)
-78
7c (9)
-
-78
-78
-
-78
-
-78 to rt
-78
NR
-
-78
-
-78
-
-78
-
1:1 TiCl4:Ti(OiPr)4 (2)
SnCl4 (1)
TiCl4 (1)
-78
-
-78
13 (85)
13 (90)
13 (15)
-
-78
1:2 TiCl4:Ti(OiPr)4 (2)
1:2 TiCl4:Ti(OiPr)4 (3)
1:1 TiCl4:Ti(OiPr)4 (1.3)
1:1 TiCl4:Ti(OiPr)4 (2)
1:1 TiCl4:Ti(OiPr)4 (4)
TiCl4 (1)
1:1 TiCl4:Ti(OiPr)4 (2)
1:1 TiCl4:Ti(OiPr)4 (3)
TiCl4 (1)
1:1 TiCl4:Ti(OiPr)4 (1)
1:1 TiCl4:Ti(OiPr)4 (2)
1:1 TiCl4:Ti(OiPr)4 (4)g
1:1 TiCl4:Ti(OiPr)4 (2)
1:1 TiCl4:Ti(OiPr)4 (2)
2:1 TiCl4:Ti(OiPr)4 (3)
1:1 TiCl4:Ti(OiPr)4 (3.4)
1:1 TiCl4:Ti(OiPr)4 (4)g
1:1 TiCl4:Ti(OiPr)4 (1)
1:1 TiCl4:Ti(OiPr)4 (2)
1:1 TiCl4:Ti(OiPr)4 (2)
2:1 TiCl4:Ti(OiPr)4 (3)
1:1 TiCl4:Ti(OiPr)4 (3.4)
1:1 TiCl4:Ti(OiPr)4 (4)g
-78
-78
-78
14 (9)
-
-
15 (15)
15 (2)
-
16 (10)
NR
-78
-78
-78
-78
-78
-78
-78 to rt
-78 to rt
-78 to rt
-78
NR
NR
NR
16
16
NR
NR
<1
<1
<1
<2
<1
<1
<1
<1
<1
<1
<1
17 (60)
17 (41)
17 (51)
17 (26)
17 (32)
18 (12)
18 (46)
18 (41)
18 (47)
18 (37)
18 (10)
23 (24)
23 (27)
23 (19)
23 (48)
23 (44)
-
24 (31)
24 (28)
24 (15)
24 (55)
24 (50)
12: NTs
12: NTs
12: NTs
12: NTs
12: NTs
12: NTs
12: NTs
12: NTs
-78
-78
-78
-78
-78
-78
-78
-78
12: NTs
12: NTs
-78
-78
a
b
All reactions were done in CH2Cl2. Used as (E):(Z) mixtures as purchased or prepared (see reference 6). c Substituents X and R
same as starting 1 and 2-4. Isolated yields. Total equivalents of Ti(IV)/Sn(IV) with respect to the monoimide. f Indicates that this
product was not isolated. Larger amounts of Ti(IV) led to much decomposition.
d
e
g
oxygens would perhaps be more activating than com-
plexation of the first Ti4+
In these reactions, the
up to large amounts of Ti(IV), particularly 11 and 12,
preventing high yields or optimization of the dihydroin-
dole:dihydrobenzofuran product ratio in these cases.
Although the intermediacy of monoimide-[Ti4+]2 com-
plexes is not unequivocally established, the data convinc-
ingly demonstrate that reversal of regioselectivity can be
achieved by use of large amounts of Ti(IV) Lewis acids
as promoters. We are continuing to examine these
phenomena.
.
dihydroindoles were uniformly formed as the major
products in good yield, accompanied by lesser amounts
of the dihydrobenzofurans. Reactions promoted by large
amounts of Ti(IV) were best conducted with mixtures of
TiCl4:Ti(OiPr)4 to minimize degradation of the styrene
or monoimide. In general, for any one styrene-monoim-
ide combination, the more Ti(IV) used as promoter, the
higher the dihydroindole:dihydrobenzofuran product ra-
tio. Unfortunately, some of the styrenes did not stand
Finally, Ti(IV)-promoted reactions of styrenes 1f/g (X
) H/3-OCH3) with quinone monoimide 3 gave bicyclo-

Reactions of Styrenyl Systems with Benzoquinone Monoimides
J . Org. Chem., Vol. 61, No. 26, 1996 9301
[3.2.1] adducts 33 (eq 3). Large amounts of Ti(IV)-
F igu r e 3. Summary of selected NOE data on 8b /9c and
21/24.
promoter were required to sufficiently activate the mon-
imides to reaction, presumably because of the lower
nucleophilicity of these styrenes. These products, which
were also obtained in reactions of quinones with styrenes,
support a cycloaddition mechanism (Scheme 3).2 We
reason that cycloaddition of 30 with the styrene gives
intermediate 31 which proceeds on to the observed
products by fragmentation to 32 followed by C-N bond
formation and loss of H+ (path a) or by dealkylation and
hydrolysis of the bridging sulfonylimine (path b).10 With
electron-rich styrenes 1a -c, the dihydroindoles 8-10 are
formed because the fragmentation is faster than dealky-
lation due to stabilization of the benzylic carbocation in
32 by the aryl ring. With more neutral styrenyl systems
1f/g, and with an R group that is easily displaced (e.g.
CH2Ph) presumably by Cl- in either an SN1 or SN2
fashion, dealkylation competes.2a,b Nevertheless, the
data do not exclude the alkylation/cyclization alternative
since 32 may also cyclize to 31 and then undergo
dealkylation/hydrolysis to 33.
F igu r e 4. Summary of selected NOE data on 36a .
Sch em e 4
the indole nucleus and the C-2 aryl group display
significant antiestrogenic activity.12 Since Ti(IV)-pro-
moted reactions of styrenes 1a -c with the monoimides
provide dihydroindoles 8-10 in good yield, their direct
oxidation to the corresponding indoles were examined.
Attempted reactions of the free phenols with DDQ
produced extensive decomposition, perhaps due to oxida-
tion of the phenolic moiety. However, conversion of the
phenol moiety in 8a and 8b to methyl ether 34 and
triflate 35, respectively, followed by DDQ oxidation
afforded indoles 36a /b in good yields (Scheme 4). To
further demonstrate the potential of this approach for
synthesis of other indoles, a Pd(0)-catalyzed reduction of
triflate 36b was carried out producing 36c in good yield.
The latter reaction suggests that similar Pd(0)-promoted
alkenyl-/alkynyl-/arylations or carbonylations could be
used to access a wide variety of 2-arylindoles for SAR
studies. In addition to the NMR/NOE studies carried out
on dihydroindoles 8-10, similar experiments on indole
36a further confirm the position of the C-6 alkoxy group
(Figure 4).
Structural assignments for dihydroindoles 8-10 and
19-24 are supported by the observance of molecular ions
in their mass spectra and an O-H stretch at 3540 cm-1
in the their IR spectra. Signals for H-4 in 8-10 appear
1
as singlets at ∼6.56-6.58 ppm in their H NMR spectra
(signals for H-7 are buried at ∼7.4 ppm). The H-2 and
C-3 CH3 resonances are found at 4.48-4.60 and 0.63-
0.68 ppm, respectively. Again, strong 1H-1H NOE’s are
observed between the C-3 methyl and both H-2 and H-4
in 8b/9c (Figure 3), supporting a cis stereochemistry
between the CH3 and H-2. Although the C-3 CH3
chemical shifts are upfield, H-2/H-3 coupling constants
of ∼3 Hz are also considerably different than those found
in the dihydrobenzofurans 5-7 (vide supra). A possible
explanation is some type of π-π interaction between the
N-phenylsulfonyl moiety and the C-2 aryl groups signifi-
cantly altering the H-2/H-3 dihedral angle.11 The spectra
of the other dihydroindoles are very similar to those of
8b/9c, and the structures are assigned by analogy.
For azapterocarpans 19-21, signals for H-11a appear
at 5.35-5.53 ppm and J H-11a/H-6a are ∼8 Hz; in diaz-
apterocarpans 22-24, the H-11a signals are found at
∼4.4 ppm with J H-11a/H-6a ∼9.5 Hz. In the former series,
H-7 are observed as singlets at ∼6.7 ppm and in the latter
series, these signals are found at ∼6.5 ppm. Finally, 1H-
1H NOE experiments on 21/24 confirm the ring fusion
stereochemistry.
Pterocarpans are naturally occurring plant products
possessing the fused benzofuranyl-benzopyran ring sys-
tem. Many are phytoalexins displaying potent antifungal
and antibacterial activity.2c In addition, several ptero-
carpans have been reported to inhibit HIV-1 reverse
transcriptase and the cytopathic effect of HIV-1 in cell
culture.2 These novel anti-HIV agents represent new
lead structures for potential drug development. The SAR
Syn th etic Ap p lica tion s. 2-Arylindoles possessing
C-1/3 alkyl substituents and oxygen substitution on both
(10) The hydrolysis of the bridging N-(phenylsulfonyl)imine, either
on workup or silica gel chromatography, is remarkably facile. Even
though a basic workup was used, we were unable to find, or detect, a
product with this group intact.
(11) Eto, M.; Ito, F.; Kitamura, T.; Harano, K. Heterocycles 1996
43, 1159-1163.
(12) (a) von Angerer, E.; Knebel, N.; Kager, M.; Ganss, B. J . Med.
Chem. 1990, 33, 2635-2640. (b) von Angerer, E.; Prekajac, J .; Berger,
M. Eur. J . Cancer Clin. Oncol. 1985, 21, 531-537. (c) von Angerer,
E.; Strohmeier, J . J . Med. Chem. 1987, 30, 131-136. (d) von Angerer,
E.; Prekajac, J .; Strohmeier, J . J . Med. Chem. 1984, 27, 1439-1447.
(e) von Angerer, E.; Prekajac, J . J . Med. Chem. 1983, 26, 113-116.

9302 J . Org. Chem., Vol. 61, No. 26, 1996
Engler et al.
EtOH:EtOAc (32 mL). The solution was heated to 70 °C, and
SnCl2‚2H2O (6.16 g, 27.3 mmol) was added. The reaction
mixture was stirred for 7 h, cooled to rt, diluted with water
(50 mL), and neutralized by the careful addition of solid
NaHCO3. The aqueous layer was separated and extracted
with EtOAc (3 × 20 mL). The combined extracts were washed
with H2O (50 mL) and brine (65 mL), dried (Na2SO4), filtered,
and concentrated to give the corresponding amine as a red
solid (1.21 g, 86%). The amine was used routinely without
further purification.
profiles of the pterocarpans have not been comprehen-
sively examined, particularly regarding potential nitro-
gen bioisosteres, and there has been recent interest in
synthesis of azapterocarpans.4,13 The development of the
reactions employing 2H-chromene 11 and dihydroquino-
line 12 as the styrenyl components described above were
in fact explored with the intent of developing an efficient
route to amino-substituted pterocarpans, and aza- and
diazapterocarpan isosteres. As described, all of the
desired products can be obtained in reasonably good to
excellent yields.
Finally, we have recently reported a route to 7-alkoxy-
2-arylbenzofuranoid neolignans licarin B and eupo-
matenoids-1 and -12 starting from 5b/c.14 Full experi-
mental details for these syntheses are presented in the
supporting information. We are presently exploring
further applications of this new methodology.
Pyridine (0.67 mL, 8.3 mmol) and benzenesulfonyl chloride
(1.0 mL, 7.84 mmol) were added to a solution of the amine
prepared above (1.72 g, 7.5 mmol) in THF (250 mL). The
reaction mixture was stirred for 22 h at rt, diluted with H2O
(100 mL), and acidified with concentrated aqueous HCl (100
mL, pH ∼ 1-2). The aqueous layer was separated and
extracted with CH2Cl2 (3 × 75 mL). The combined extracts
were washed with 10% aqueous HCl (150 mL), H2O (2 × 150
mL), and brine (200 mL) and dried (MgSO4). The solution was
treated with charcoal, filtered through Celite, and concentrated
to a purple oil. Addition of hexanes gave a light purple solid.
Recrystallization from EtOH gave the title compound (2.45 g,
88%) as a light tan solid, mp 144-145 °C; Rf 0.20 (2:5 EtOAc:
hexanes); 1H NMR (300 MHz) 7.61 (d, J ) 8.5, 2H), 7.54-
7.30 (m, 8H), 6.76 (d, J ) 2.4, 1H), 6.69 (d, J ) 8.6, 1H), 6.56
(bs, 1H), 6.49 (dd, J ) 2.4, 8.6, 1H), 5.05 (s, 2H), 3.81 (s, 3H);
13C NMR (75 MHz) 148.2, 148.1, 138.7, 136.6, 132.8, 129.0,
128.9, 128.6, 128.0, 127.4, 127.3, 116.1, 111.8, 110.1, 70.9, 56.1;
HRMS m/ z 369.1045 (M+) (calcd for C20H19NO4S 369.1035).
(B) Mon oim id e 3. A solution of ceric ammonium nitrate
(8.90 g, 16.2 mmol) in H2O (15 mL) was added quickly dropwise
to a solution of N-[3-(benzyloxy)-4-methoxyphenyl]benzene-
sulfonamide (2.00 g, 5.41 mmol) in CH3CN (8 mL) at 0 °C.
The ice bath was removed, and the reaction mixture was
stirred at rt for 15 min and then diluted with CH2Cl2 (50 mL).
The aqueous layer was separated and extracted with CH2Cl2
(2 × 30 mL). The combined organic extracts were washed with
H2O (2 × 50 mL) and brine (60 mL), dried (Na2SO4), decanted,
and concentrated to an orange oil. Chromatography (2:2:6
CH2Cl2:Et2O:hexanes) afforded monoimide 3 (1.24 g, 65%) as
a bright yellow solid, mp 162-163 °C; Rf 0.45 (2:2:6 CH2Cl2:
Et2O:hexanes); 1H NMR (500 MHz) 7.99 (d, J ) 8.5, 2H), 7.65
(apparent t, J ) 7.4, 1H), 7.56 (apparent t, J ) 8.0, 7.4, 2H),
7.48-7.35 [H-2 and benzyl-ring protons, m], 6.89 (dd, J ) 2.4,
10, 1H), 6.65 (d, J ) 10, 1H), 5.19 (s, 2H); 13C NMR (75 MHz)
180.0, 165.3, 156.2, 141.1, 134.1, 133.6, 133.5, 129.1, 129.0,
Exp er im en ta l Section 15
N-(3-Meth oxy-4-oxo-2,5-cycloh exa d ien -1-ylid en e)ben -
zen esu lfon a m id e (2). A solution of ceric ammonium nitrate
(14.67 g, 26.76 mmol) in H2O (40 mL) was added dropwise
rapidly to a solution of N-(3,4-dimethoxyphenyl)benzene-
sulfonamide16 (2.63 g, 8.96 mmol) in acetonitrile (35 mL). The
reaction mixture was stirred for 10 min and then diluted with
CH2Cl2 (100 mL). The aqueous layer was separated and
extracted with CH2Cl2 (3 × 40 mL). The combined extracts
were washed with water (2 × 100 mL) and brine (150 mL),
dried (Na2SO4), decanted, and concentrated to a dark orange
oil. Chromatography (2:2:6 CH2Cl2:Et2O:hexanes) afforded
monoimide 2 (1.60 g, 64%) as a bright yellow powder, mp 135-
136 °C (EtOAc/hexanes); Rf 0.32 (2:2:6 CH2Cl2:Et2O:hexanes);
1H NMR (300 MHz) 8.03 (d, J ) 7.4, 2H), 7.71-7.50 (m, 3H),
7.27 (d, J ) 2.4, 1H), 6.92 (dd, J ) 2.4, 10, 1H), 6.67 (d, J )
10, 1H), 3.97 (s, 3H); 13C NMR (75 MHz) 180.1, 165.2, 157.3,
141.4, 133.9, 133.5, 130.5, 129.1, 127.4, 102.0, 56.8. Anal.
Calcd for C13H11NO4S: C, 56.30; H, 4.01; N, 5.05. Found: C,
56.60; H, 3.76; N, 4.80.
128.9, 128.3, 127.6, 127.4, 103.1, 71.6. Anal. Calcd for C19H15
-
NO4S: C, 64.57; H, 4.29; N, 3.96. Found: C, 64.39; H, 3.89;
N, 3.78.
N-(3-Isobu toxy-4-oxo-2,5-cycloh exa d ien -1-ylid en e)ben -
zen esu lfon a m id e (4). (A) 2-Isobu toxy-4-n itr oa n isole. A
slurry of 2-methoxy-5-nitrophenol (3.00 g, 17.7 mmol) and K2-
CO3 (2.94 g, 21.3 mmol) in acetone (60 mL) at rt was treated
with isobutyl bromide (6.08 mL, 55.9 mmol) and (nBu)4N+ I-
(328 mg, 0.887 mmol). The reaction mixture was refluxed
under nitrogen for 48 h, cooled to rt, and then poured into
water (150 mL). CH2Cl2 (100 mL) was added, and the aqueous
layer was separated and extracted with CH2Cl2 (3 × 50 mL).
The combined extracts were washed with H2O (150 mL), brine
(150 mL), dried (Na2SO4), and concentrated to afford the title
compound (3.97 g, 99.5%) as a dark yellow solid, mp 74-75
°C (EtOAc/hexanes); Rf 0.15 (1:5 EtOAc:hexanes); 1H NMR
(300 MHz) 7.81 (dd, 1H, J ) 2.0, 9.0), 7.64 (d, 1H, J ) 2.0),
6.83 (d, 1H, J ) 9.0), 3.89 (s, 3H), 3.76 (d, 2H, J ) 7.0), 2.12
(m, 1H), 0.99 (d, 6H, J ) 7.0); 13C NMR (75 MHz) 155.3, 148.9,
141.7, 117.9, 110.4, 108.0, 76.0, 56.8, 28.5, 19.6. Anal. Calcd
for C11H15NO4: C, 58.65; H, 6.77; N, 6.22. Found: C, 59.00;
H, 6.90; N, 6.18.
(B) N-(3-Isobu toxy-4-m eth oxyp h en yl)ben zen esu lfon a -
m id e. 2-Isobutoxy-4-nitroanisole (3.97 g, 17.6 mmol) was
dissolved in 1:1 EtOH/EtOAc (80 mL). The solution was
heated to 70 °C and SnCl2‚2H2O (19.9 g, 88.2 mmol) added.
The reaction mixture was stirred for 12 h, cooled to rt, diluted
with ice-water (80 mL), and neutralized by the careful
addition of solid NaHCO3. The resulting mixture was filtered
through Celite, the Celite was rinsed with CH2Cl2, and the
N-[3-(Ben zyloxy)-4-oxo-2,5-cycloh exa d ien -1-ylid en e]-
ben zen esu lfon a m id e (3). A) N-[3-(Ben zyloxy)-4-m eth -
oxyph en yl]ben zen esu lfon am ide. 2-(Benzyloxy)-1-methoxy-
4-nitrobenzene17 (1.60 g, 6.17 mmol) was dissolved in 1:1
(13) To¨ke´s, A. L.; Antus, S. Liebigs Ann. Chem. 1994, 911-915.
(14) Engler, T. A.; Chai, W. Tetrahedron Lett. 1996, 37, 6969-6970.
(15) All compounds were prepared as racemic mixtures. All reactions
were done in oven- or flame-dried glassware under
a nitrogen
atmosphere with magnetic stirring. CH2Cl2, BF3‚OEt2, and TiCl4 were
distilled under nitrogen from CaH2 immediately before use. Brine
refers to saturated aqueous sodium chloride. NMR spectra were
recorded on samples dissolved in CDCl3, unless otherwise noted, and
chemical shifts are reported in δ (ppm) relative to internal Me4Si or
residual CHCl3. Coupling constants (J ) are reported in Hz. Reactions
were monitored by thin-layer chromatography (TLC) on precoated 0.25
mm silica gel plates with a fluorescent indicator (Merck Kieselgel
60F254); visualization was effected with a UV lamp or by staining with
solutions of p-anisaldehyde/H2SO4 or phosphomolybdic acid. Rf’s
reported are from TLC. Chromatography refers to flash chromatog-
raphy on silica gel [EM-Kieselgel 60 (0.04-0.063 mm mesh) or Selectro
Scientific (0.032-0.063 mm mesh)] with the eluent indicated. Melting
points are uncorrected. Styrenes 1a -c,f were commercially available;
1d and chromene 11 and quinoline 12 were prepared as described
previously; and the preparations of 1e and 1g are described in the
supporting information.2
(16) Adachi, T.; Otsuki, K. Chem. Pharm. Bull. 1976, 24, 2803-
2809.
(17) White, R. L., J r.; Schwan, T. J .; Alaino, R. J . J . Heterocycl.
Chem. 1980, 17, 817-18.

Reactions of Styrenyl Systems with Benzoquinone Monoimides
J . Org. Chem., Vol. 61, No. 26, 1996 9303
filtrate was extracted with CH2Cl2 (3 × 80 mL). The extracts
were washed with brine (100 mL), dried (Na2SO4), and
concentrated to give 3-isobutoxy-4-methoxyaniline as a red
solid (2.77 g, 81%) which was used without futher purification.
Pyridine (2.85 mL, 35.3 mmol) and benzenesulfonyl chloride
(2.70 mL, 21.2 mmol) were added to a solution of the aniline
prepared as described above (2.77 g, 14.2 mmol) in THF (200
mL). The reaction mixture was stirred for 24 h at rt, diluted
with water (150 mL), and acidified with concentrated aqueous
HCl (pH ) 1-2). The aqueous layer was separated and
extracted with CH2Cl2 (3 × 70 mL). The combined organic
extracts were washed with brine (150 mL), dried (Na2SO4),
and concentrated. The residue was passed through neutral
alumina with 1:5 EtOAc:hexanes as eluent. Concentration
gave the title benzenesulfonamide (3.94 g, 83%) as a white
solid, mp 103-104 °C (EtOAc/hexanes); Rf 0.10 (2:2:6 CH2Cl2:
0.20 (3:3:4 Et2O:CH2Cl2:hexanes); 1H NMR (500 MHz) 7.73 (d,
2H, J ) 6.5), 7.56 (t, 1H, J ) 7.4), 7.47 (apparent t, 2H), 7.31
(d, 2H, J ) 8.5), 6.68 (d, 2H, J ) 8.5), 6.49 (s, 1H), 6.40 (s,
1H), 5.10 (d, 1H, J ) 9.2), 3.80 (s, 3H), 3.74 (s, 3H), 3.37
(apparent quintet, 1H), 1.26 (d, 3H, J ) 6.8); 13C NMR (125
MHz) 159.7, 146.1, 144.1, 138.8, 133.4, 132.9,131.8, 129.2,
128.9, 127.9, 127.4, 113.9, 112.6, 108.8, 93.5, 56.0, 55.3, 45.4,
17.6. Anal. Calcd for C23H23NO5S: C, 64.92; H, 5.45; N, 3.29.
Found: C, 64.60; H, 5.18; N, 3.00.
Compound 8a was identified by spectral comparison to the
product isolated from the Ti(IV)-promoted reaction, see below.
N -[(2R *,3R *)-2,3-Dih yd r o-7-m e t h oxy-2-(3,4-d im e t h -
oxyp h en yl)-3-m et h ylb en zofu r a n -5-yl]b en zen esu lfon a -
m id e (5b). According to general method A, (E)-1,2-dimethoxy-
4-propenylbenzene (50 µL, 0.30 mmol) was added to a solution
of BF3‚OEt2 (40 µL, 0.32 mmol) and monoimide 2 (72 mg, 0.26
mmol) in CH2Cl2 (2 mL). Workup and chromatography (2:5
EtOAc:hexanes) afforded 5b (97 mg, 82%) as a white solid,
mp 179-180 °C (CH2Cl2/Et2O/hexanes); Rf 0.18 (2:4:4 CH2Cl2:
Et2O:hexanes); 1H NMR (500 MHz) 7.75 (d, J ) 7.5, 2H), 7.57
(apparent t, J ) 7.4, 1H), 7.46 (apparent t, J ) 7.5, 2H), 6.93
(s, 1H), 6.92 (d, J ) 8.0, 1H), 6.84 (d, J ) 8.0, 1H), 6.50 [H-6
(s)], 6.48 [N-H (s)], 6.42 [H-4 (s)], 5.09 (d, J ) 9.5, 1H), 3.88 (s,
3H), 3.87 (s, 3H), 3.75 (s, 3H), 3.39 (dq, J ) 6.7, 9.5, 1H), 1.27
(d, J ) 6.8, 3H); 13C NMR (75 MHz) 149.2, 149.1, 146.0, 144.1,
138.9, 133.4, 132.9, 132.1, 129.4, 128.9, 127.5, 119.2, 112.4,
110.8, 109.5, 108.7, 93.8, 56.0, 55.9 (2C), 45.4, 17.5; HRMS
m/ z 456.1487 (M+ + 1) (calcd for C24H25NO6S 456.1481).
N-[(2R*,3R*)-2,3-Dih yd r o-7-m eth oxy-3-m eth yl-2-[(3,4-
m eth ylen edioxy)ph en yl]ben zofu r an -5-yl]ben zen esu lfon a-
m id e (5c). According to general method A, (E)-1,2-(methyl-
enedioxy)-4-propenylbenzene (115 µL, 0.794 mmol), was added
to a solution of BF3‚Et2O (57 µL, 0.45 mmol) and monoimide
2 (100 mg, 0.361 mmol) in CH2Cl2 (10 mL). Workup and
chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the
crude yellow oil afforded 8c (20 mg, 13%) and 5c (130 mg,
82%). Physical and spectral properties of 5c, a white solid,
mp 145-146 °C (EtOAc/hexanes); Rf 0.22 (3:3:4 Et2O:CH2Cl2:
hexane); 1H NMR (500 MHz) 7.76 (d, 2H, J ) 7.0), 7.54
(apparent t, 1H, J ) 7.4), 7.43 (apparent t, 2H), 7.09 (s, 1H,
NH), 6.84 (d, 1H, J ) 1.5), 6.81 (dd, 1H, J ) 1.5, 8.0), 6.75 (d,
1H, J ) 8.0), 6.52 (d, 1H, J ) 1.0), 6.44 (d, 1H, J ) 1.0), 5.93
(s, 2H), 5.03 (d, 1H, J ) 9.0), 3.72 (s, 3H), 3.30 (apparent
quintet, 1H), 1.24 (d, 3H, J ) 6.9), 13C NMR (125 MHz) 147.9,
147.7, 145.7, 144.0, 138.7, 133.8, 133.2, 132.9, 129.6, 128.9,
127.4, 120.2, 112.1, 108.5, 108.0, 106.6, 101.1, 93.4, 56.0, 45.6,
17.7. Anal. Calcd for C23H21NO6S: C, 62.86; H, 4.82; N, 3.19.
Found: C, 63.12; H, 4.96; N, 3.18.
Compound 8c was identified by spectral comparison to the
product isolated from the Ti(IV)-promoted reaction, see below.
N -[(2R *,3R *)-2,3-Dih yd r o-7-m e t h oxy-3-m e t h yl-2-(4-
m eth ylph en yl)ben zofu r an -5-yl]ben zen esu lfon am ide (5d).
According to general method A, (E)-1-methyl-4-propenylben-
zene (79 mg, 0.60 mmol) in CH2Cl2 (2 mL) was added to a
solution of BF3‚Et2O (87 µL, 0.69 mmol) and monoimide 2 (150
mg, 0.542 mmol) in CH2Cl2 (10 mL). Workup and chroma-
tography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the crude
brown oil afforded 5d (30 mg, 14%) as a white solid, mp 132-
133 °C (Et2O/hexanes); Rf 0.13 (3:3:4 Et2O:CH2Cl2:hexanes);
1H NMR (500 MHz) 7.74 (d, 2H, J ) 8.1), 7.57 (t, 1H, J ) 7.4),
7.45 (apparent t, 2H), 7.27 (d, 2H, J ) 8.0), 7.16 (d, 2H, J )
8.0), 6.58 (s, 1H, NH), 6.51 (d, 1H, J ) 1.6), 6.40 (apparent s,
1H), 5.12 (d, 1H, J ) 9.0), 3.75 (s, 3H), 3.37 (apparent quintet,
1H), 2.34 (s, 3H), 1.27 (d, 1H, J ) 6.8); 13C NMR (125 MHz)
146.1, 144.1, 138.8, 138.1, 137.3, 133.4, 132.8, 129.3, 129.2,
128.9, 127.4, 126.2, 112.5, 108.8, 93.5, 56.0, 45.6, 21.2, 17.8;
HRMS m/ z 409.1332 (M+) (Calcd for C23H23NO4S 409.1348).
N -[(2R *,3R *)-7-(B e n zy lo x y )-2,3-d ih y d r o -2-(3,4-d i-
m e t h ox yp h e n yl)-3-m e t h ylb e n zo fu r a n -5-yl]b e n ze n e -
su lfon a m id e (6b). According to general method A, (E)-1,2-
dimethoxy-4-propenylbenzene (50 µL, 0.30 mmol) was added
to a solution of BF3‚OEt2 (40 µL, 0.32 mmol) and monoimide
3 (91 mg, 0.26 mmol) in CH2Cl2 (2 mL). Workup and
chromatography (2:5 EtOAc:hexanes) furnished 6b (118 mg,
86%) as a white solid, mp 136-137 °C (CH2Cl2/Et2O/hexanes);
Rf 0.25 (3:3:4 CH2Cl2/Et2O/hexanes); 1H NMR (500 MHz) 7.66
1
Et2O:hexanes); H NMR (300 MHz) 7.71 (m, 2H), 7.49 (t, 1H,
J ) 7.5), 7.40 (apparent t, 2H), 7.11 (s, 1H, NH), 6.65 (m, 2H),
6.52 (dd, 1H, J ) 2.4, 8.4), 3.75 (s, 3H), 3.59 (d, 2H, J ) 7.0),
2.02 (m, 1H), 0.94 (d, 6H, J ) 7.0); 13C NMR (75 MHz) 149.5,
148.4, 139.3, 139.2, 129.6, 129.3, 127.8, 116.2, 112.6, 110.1,
75.8, 56.7, 28.4, 19.6. Anal. Calcd for C17H21NO4S: C, 60.87;
H, 6.31; N, 4.18. Found: C, 60.60; H, 6.68; N, 4.10.
(C) Mon oim id e 4. A solution of ceric ammonium nitrate
(3.55 g, 6.45 mmol) in water (12 mL) was added dropwise to a
solution of N-(3-isobutoxy-4-methoxyphenyl)benzenesulfona-
mide (720 mg, 2.15 mmol) in CH3CN (12 mL) at 0 °C. The
mixture was stirred for 0.5 h and diluted with CH2Cl2 (50 mL).
The aqueous layer was separated and extracted with CH2Cl2
(2 × 30 mL). The extracts were dried (Na2SO4), decanted, and
concentrated. Chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:
hexanes) of the red residue afforded 4 as a 4:1 (E):(Z) mixture
of isomers (400 mg, 58.3%) as a yellow oil; Rf 0.28 (2:2:6 CH2-
Cl2:Et2O:hexanes); 1H NMR (500 MHz) (E)-isomer: 7.95 (d,
2H, J ) 7.5), 7.58 (t, 1H, J ) 7.5), 7.51 (apparent t, 2H, J )
7.5), 7.14 (d, 1H, J ) 2.4), 6.82 (dd, 1H, J ) 2.4, 10.0), 6.57 (d,
1H, J ) 10.0), 3.76 (d, 2H, J ) 6.6), 2.14 (m, 1H), 0.98 (d, 6H,
J ) 6.6); 13C NMR (125 MHz) (E)-isomer: 179.7, 165.3, 156.6,
140.8, 140.2, 133.7, 133.2, 128.9, 127.0, 101.9, 75.6, 27.4, 18.8;
HRMS m/ z 319.0856 (M+) (Calcd for C16H17NO4S 319.0878).
Gen er a l Met h od A: Gen er a l P r oced u r e for t h e
BF 3‚Et2O-P r om oted Rea ction s of Styr en es w ith 1,4-
Ben zoqu in on e Mon oim id es. BF3‚Et2O was added to a
solution of the imide in CH2Cl2 maintained at -78 °C followed,
after 5-15 min, by the styrene, either neat or as a solution in
CH2Cl2. The reaction mixture was stirred until no imide was
present by TLC, generally 15-60 min, and then quenched by
the addition of saturated aqueous sodium bicarbonate. The
resulting mixture was extracted with CH2Cl2, and the extracts
were washed with water and brine, dried (Na2SO4), and
concentrated. Purification was effected by chromatography,
and/or recrystallization.
Gen er a l Meth od B: Gen er a l P r oced u r e for th e Ti(IV)-
P r om oted Rea ction s of Styr en es w ith 1,4-Ben zoqu in on e
Mon oim id es. TiCl4 was added to a solution of Ti(OiPr)4 in
CH2Cl2 at 0 °C to rt. After stirring for 5-15 min, this mixture,
or neat TiCl4, was added to a solution of the imide in CH2Cl2
maintained at -78 °C followed, after 5-15 min, by the styrene,
either neat or as a solution in CH2Cl2. The reaction mixture
was stirred at -78 °C until no imide was present by TLC,
generally 15-60 min unless otherwise stated and then quenched
by the addition of saturated aqueous sodium bicarbonate. The
resulting mixture was filtered through Celite, the Celite was
rinsed with CH2Cl2, and the filtrate was extracted with CH2-
Cl2. The extracts were washed with water and brine, dried
(Na2SO4), and concentrated. Purification was effected by
chromatography, and/or recrystallization.
N -[(2R *,3R *)-2,3-Dih yd r o-7-m e t h oxy-2-(4-m e t h oxy-
p h en yl)-3-m et h ylb en zofu r a n -5-yl]b en zen esu lfon a m id e
(5a ). According to general method A, (E)-4-propenylanisole
(30 µL, 0.20 mmol) was added to a solution of BF3‚Et2O (29
µL, 0.23 mmol) and monoimide 2 (50 mg, 0.18 mmol) in CH2-
Cl2 (10 mL). Workup and chromatography (1:1:8 to 2:2:6 CH2-
Cl2:Et2O:hexanes) of the crude yellow oil afforded 8a (6 mg,
8%) and 5a (70 mg, 91%). Physical and spectral properties of
5a , a white solid, mp 160-161 °C (Et2O/CH2Cl2/hexanes); Rf

9304 J . Org. Chem., Vol. 61, No. 26, 1996
Engler et al.
(d, J ) 8.5 Hz, 2H), 7.54 (apparent t, J ) 7.5, 1H), 7.41
(apparent t, J ) 7.9, 2H), 7.36-7.29 (m, 6H), 6.94 (bs, 1H),
6.93 (dd, J ) 1.9, 8.6, 1H), 6.85 (d, J ) 8.6, 1H), 6.57 [H-6
(bs)], 6.42 [H-4 (bs)], 6.38 [N-H (s)], 5.09 (d, J ) 9.3, 1H), 5.05
(s, 2H), 3.88 (s, 3H), 3.86 (s, 3H), 3.37 (dq, J ) 6.8, 9.3, 1H),
1.27 (d, J ) 6.8, 3H); 13C NMR (125 MHz) 149.2, 149.1, 146.5,
143.0, 138.9, 136.6, 133.9, 132.8, 132.3, 129.3, 128.9, 128.5,
128.0, 127.5, 127.4, 119.2, 112.6, 110.9 (2C), 109.5, 93.6, 71.1,
56.0 (2C), 45.4, 17.5; HRMS m/ z 532.1790 (M+ + 1) (calcd for
C30H29NO6S - 532.1794).
N-[(2R*,3R*)-2,3-Dih yd r o-7-ben zyloxy-3-m eth yl-2-(3,4-
m eth ylen edioxyph en yl)ben zofu r an -5-yl]ben zen esu lfon a-
m id e (6c). According to general method A, (E)-1,2-(methyl-
enedioxy)-4-propenylbenzene (45 µL, 0.31 mmol) was added
to a solution of BF3‚Et2O (21 µL, 0.17 mmol) and monoimide
3 (50 mg, 0.14 mmol) in CH2Cl2 (10 mL). Workup and
chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the
crude yellow oil afforded 9c (6 mg, 8.2%) and 6c (53 mg, 73%).
Physical and spectral properties of 6c, a white solid, mp 119-
120 °C (Et2O/hexanes); Rf 0.25 (3:3:4 Et2O:CH2Cl2:hexane); 1H
NMR (500 MHz) 7.66 (d, 2H, J ) 8.0), 7.53 (apparent t, 1H, J
) 7.4), 7.42- 7.26 (m, 7H), 6.86 (d, 1H, J ) 1.5), 6.83 (dd, 1H,
J ) 1.5, 8.0), 6.77 (d, 1H, J ) 8.0), 6.73 (s, 1H, NH), 6.59 (d,
1H, J ) 1.5), 6.41 (d, 1H, J ) 1.5), 5.95 (s, 2H), 5.06 (d, 1H, J
) 9.5), 5.05 (s, 2H), 3.29 (apparent quintet, 1H), 2.18 (s, 3H),
1.25 (d, 3H, J ) 6.5 Hz); 13C NMR (125 MHz) 147.9, 147.6,
146.3, 142.8, 138.7, 136.6, 133.9, 133.7, 132.8, 129.4, 128.8,
128.5, 127.9, 127.5, 127.3, 120.0, 112.5, 110.8, 108.0, 106.6,
101.1, 93.3, 71.0, 45.6, 17.7; HRMS m/ z 515.1375 (M+) (Calcd
for C29H25NO6S 515.1403).
Compound 9c was identified by spectral comparison to that
isolated from the Ti(IV)-promoted reaction, see below.
N-[(2R*,3R*)-2,3-Dih yd r o-2-(3,4-d im et h oxyp h en yl)-7-
isob u t oxy-3-m e t h ylb e n zofu r a n -5-yl]b e n ze n e su lfon a -
m id e (7b). According to general method A, (E)-1,2-dimethoxy-
4-propenylbenzene (59 µL, 0.35 mmol) was added to a solution
of BF3‚Et2O (25 µL, 0.20 mmol) and monoimide 4 (50 mg, 0.19
mmol) in CH2Cl2 (10 mL). Workup and chromatography (1:
1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the crude yellow oil
afforded 10b (8 mg, 10%) and 7b (70 mg, 89%). Physical and
spectral properties of 7b, a white solid, mp 138-139 °C (CH2-
Cl2/Et2O/hexanes); Rf 0.25 (3:3:4 Et2O:CH2Cl2:hexanes); 1H
NMR (500 MHz) 7.76 (d, 2H, J ) 7.5), 7.55 (t, 1H, J ) 7.4),
7.45 (t, 2H, J ) 7.5), 6.93 (d, 1H, J ) 1.7), 6.91 (dd, 1H, J )
8.2, 1.7), 6.83 (d, 1H, J ) 8.2), 6.75 (s, 1H, NH), 6.50 (d, 1H,
J ) 1.0), 6.41 (d, 1H, J ) 1.0), 5.08 (d, 1H, J ) 9.2), 3.87 (s,
3H), 3.85 (s, 3H), 3.66 (m, 2H), 3.33 (apparent quintet, 1H),
2.00 (septet, 1H, J ) 6.7), 1.26 (d, 3H, J ) 6.8), 0.95 (d, 3H, J
) 6.7); 0.94 (d, 3H, J ) 6.7); 13C NMR (125 MHz) 149.1, 146.4,
143.6, 138.9, 133.6 132.8, 132.6, 129.3, 128.9, 127.4, 119.0,
112.3, 110.9, 110.4, 109.3, 93.3, 75.6, 55.9 (2C), 45.6, 28.0, 19.2,
19.2, 17.6 (one quaternary sp2-C signal is not apparent). Anal.
Calcd for C27H31NO6S: C, 65.17; H, 6.28; N, 2.81. Found: C,
65.00; H, 6.40; N, 2.50.
Compound 10b was identified by spectral comparison to the
product isolated from the Ti(IV)-promoted reaction, see below.
N-[(2R*,3R*)-2,3-Dih yd r o-7-isobu toxy-3-m eth yl-2-(3,4-
m eth ylen edioxyph en yl)ben zofu r an -5-yl]ben zen esu lfon a-
m id e (7c). According to general method A, (E)-1,2-(methyl-
enedioxy)-4-propenylbenzene (33 µL, 0.23 mmol) was added
to a solution of BF3‚Et2O (15 µL, 0.12 mmol) and monoimide
4 (33 mg, 0.10 mmol) in CH2Cl2 (10 mL). Workup and
chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the
crude yellow oil afforded 7c (24 mg, 48%) as a white solid, mp
104-106 °C (Et2O/hexanes); Rf 0.30 (3:3:4 Et2O/CH2Cl2/hex-
anes); 1H NMR (500 MHz) 7.74 (d, 2H, J ) 7.4), 7.55 (apparent
t, 1H, J ) 7.4), 7.45 (apparent t, 2H, J ) 7.4), 6.87 (d, 1H, J
) 1.0), 6.83 (dd, 1H, J ) 1.0, 8.0), 6.77 (d, 1H, J ) 8.0), 6.54
(s, 1H, NH), 6.48 (d, 1H, J ) 1.7), 6.38 (b s, 1H) [a COSY
spectrum revealed that the 6.48 and 6.38 signals were
coupled], 5.92 (s, 2H), 5.06 (d, 1H, J ) 8.9), 3.66 (m, 2H), 3.29
(apparent quintet, 1H), 2.01 (septet, 1H, J ) 6.7), 1.26 (d, 3H,
J ) 6.7), 0.96 (d, 3H, J ) 6.7); 0.95 (d, 3H, J ) 6.7); 13C NMR
(125 MHz) 147.9, 147.6, 146.3, 143.6, 138.9, 134.2, 133.4, 132.8,
129.2, 128.9, 127.4, 120.0, 112.4, 110.6, 108.1, 106.6, 101.1,
93.1, 75.6, 45.7, 28.0, 19.21, 19.17, 17.8. Anal. Calcd for
C26H27NO6S: C, 64.84; H, 5.65; N, 2.91. Found: C, 64.78; H,
5.80; N, 2.80.
(2R*,3R*)-1-(Ben zen esu lfon yl)-2,3-d ih yd r o-5-h yd r oxy-
6-m eth oxy-2-(4-m eth oxyp h en yl)-3-m eth ylin d ole (8a ). Ac-
cording to general method B, (E)-4-propenylanisole (30 µL, 0.20
mmol) was added to a solution of a mixture of TiCl4 (20 µL,
0.18 mmol) and Ti(OiPr)4 (108 µL, 0.365 mmol) in CH2Cl2 (0.5
mL) and monoimide 2 (50 mg, 0.18 mmol) in CH2Cl2 (10 mL).
Workup and chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:
hexanes) of the crude yellow oil afforded 8a (58 mg, 76%) and
5a (10 mg, 13%). Physical and spectral properties of 8a , a
white solid, mp 67-68 °C (Et2O/hexanes); Rf 0.30 (3:3:4 Et2O:
1
CH2Cl2:hexanes); H NMR (500 MHz) 7.71 (d, 2H, J ) 7.5),
7.54 (t, 1H, J ) 7.5), 7.42 (apparent t, 3H), 7.22 (d, 1H, J )
8.7), 6.83 (d, 1H, J ) 8.7), 6.58 (s, 1H), 5.56 (s, 1H), 4.56 (d,
1H, J ) 3.0), 3.98 (s, 3H), 3.78 (s, 3H), 2.95 (dq, 1H, J ) 3, 7),
0.65 (d, 3H, J ) 7.0); 13C NMR (125 MHz) 159.0, 146.4, 143.3,
137.4, 134.9, 133.6, 133.0, 128.9, 128.4, 127.3, 126.9, 114.0,
110.0, 100.4, 72.7, 56.4, 55.3, 45.8, 21.8. Anal. Calcd for
C
23H23NO5S: C, 64.92; H, 5.45; N, 3.29. Found: C, 65.17; H,
5.48; N, 2.98.
(2R *,3R *)-1-(B e n ze n e s u lfo n y l)-2,3-d ih y d r o -2-(3,4-
d im e t h oxyp h e n yl)-5-h yd r oxy-6-m e t h oxy-3-m e t h ylin -
d ole (8b). According to general method B, (E)-1,2-dimethoxy-
4-propenylbenzene (134 µL, 0.794 mmol) was added to a
solution of a mixture of TiCl4 (200 µL, 1.81 mmol) and Ti(OiPr)4
(537 µL, 1.81 mmol) in CH2Cl2 (0.5 mL) and monoimide 2 (100
mg, 0.361 mmol) in CH2Cl2 (10 mL). Workup and chroma-
tography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the crude
yellow oil afforded 8b (146 mg, 89%) as a white solid, mp 178-
179 °C (Et2O/hexanes); Rf 0.22 (3:3:4 CH2Cl2:Et2O:hexanes);
1H NMR (500 MHz) 7.70 (d, 2H, J ) 7.9), 7.53 (t, 1H, J ) 7.5),
7.42 (m, 3H), 6.86 (dd, 1H, J ) 2.0, 8.3), 6.78 (m, 2H), 6.58 (s,
1H), 5.50 (s, 1H, OH), 4.55 (d, 1H, J ) 3.2), 3.99 (s, 3H), 3.85
(s, 3H), 3.82 (s, 3H), 2.98 (dq, 1H, J ) 7.0, 3.2), 0.68 (d, 3H, J
) 7.0); 13C NMR (125 MHz) 149.1, 148.6, 146.4, 143.3, 137.4,
135.2, 133.6, 133.1, 128.9, 128.3, 127.3, 118.0, 111.1, 109.9,
109.0, 100.3, 72.9, 56.4, 55.9, 55.89, 45.7, 21.8. Anal. Calcd
for C24H25NO6S: C, 63.28; H, 5.53; N, 3.08. Found: C, 62.90;
H, 5.60; N, 2.90.
(2R*,3R*)-1-(Ben zen esu lfon yl)-2,3-d ih yd r o-5-h yd r oxy-
6-m et h oxy-3-m et h yl-2-[3,4-(m et h ylen ed ioxy)p h en yl]in -
d ole (8c). According to general method B, (E)-1,2-(methyl-
enedioxy)-4-propenylbenzene (52 µL, 0.36 mmol) was added
to a solution of a mixture of TiCl4 (50 µL, 0.46 mmol) and
Ti(OiPr)4 (269 µL, 0.908 mmol) in CH2Cl2 (0.5 mL) and
monoimide 2 (50 mg, 0.18 mmol) in CH2Cl2 (10 mL). Workup
and chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of
the crude yellow oil afforded 8c (58 mg, 73%) as a white solid,
mp 166-167 °C (MeOH/hexanes); Rf 0.30 (3:3:4 Et2O:CH2Cl2:
1
hexanes); H NMR (500 MHz) 7.71 (d, 2H, J ) 7.9), 7.54 (t,
1H, J ) 7.4), 7.42 (m, 3H), 6.80-6.72 (m, 3H), 6.57 (s, 1H),
5.91 (s, 2H), 5.57 (s, 1H), 4.50 (d, 1H, J ) 3.0), 3.98 (s, 3H),
2.92 (dq, 1H, J ) 7, 3), 0.64 (d, 3H, J ) 7.0); 13C NMR (125
MHz) 147.8, 147.0, 146.4, 143.3, 137.2, 136.7, 133.5, 133.1,
128.9, 128.2, 127.2, 119.1, 109.9, 108.1, 106.2, 101.0, 100.4,
72.9, 56.4, 45.9, 21.8. Anal. Calcd for C23H21NO6S: C, 62.86;
H, 4.82; N, 3.19. Found: C, 62.52; H, 5.00; N, 3.00.
(2R*,3R*)-1-(Ben zen esu lfon yl)-2,3-d ih yd r o-5-h yd r oxy-
6-m eth oxy-3-m eth yl-2-(4-m eth ylp h en yl)in d ole (8d ). Ac-
cording to general method B, (E)-1-methyl-4-propenylbenzene
(26 mg, 0.20 mmol) was added to a solution of TiCl4 (179 µL,
1.62 mmol) and monoimide 2 (50 mg, 0.18 mmol) in CH2Cl2
(10 mL). Workup and chromatography (1:1:8 CH2Cl2:Et2O:
hexanes) of the crude brown oil afforded 8d (55 mg, 74%) as a
white solid, mp 139-140 °C (Et2O/hexanes); Rf 0.40 (3:3:4
1
Et2O:CH2Cl2:hexanes); H NMR (500 MHz) 7.22 (d, 2H, J )
7.4), 7.54 (t, 1H, J ) 7.4), 7.43 (m, 3H), 7.20 (d, 2H, J ) 8.0),
7.10 (d, 2H, J ) 8.0), 6.57 (s, 1H), 5.51 (s, 1H, NH), 4.56 (d,
1H, J ) 3.0), 3.99 (s, 3H), 2.96 (dq, 1H, J ) 7.0, 3.0), 2.28 (s,
3H), 0.66 (d, 3H, J ) 7.0); 13C NMR (125 MHz) 146.3, 143.3,
139.7, 137.3, 137.2, 133.6, 133.0, 129.3, 128.9, 128.3, 127.3,
125.6, 109.9, 100.4, 72.9, 56.4, 45.9, 21.9, 21.1. Anal. Calcd
for C23H23NO4S: C, 67.46; H, 5.66; N, 3.42. Found: C, 67.10;
H, 6.00; N, 3.02.

Reactions of Styrenyl Systems with Benzoquinone Monoimides
J . Org. Chem., Vol. 61, No. 26, 1996 9305
(2R*,3R*)-2-(4-Acetoxyp h en yl)-1-(ben zen esu lfon yl)-2,3-
d ih yd r o-5-h yd r oxy-6-m eth oxy-3-m eth ylin d ole (8e). Ac-
cording to general method B, (E)-1-acetoxy-4-propenylbenzene
(32 mg, 0.18 mmol) in CH2Cl2 (2 mL) was added to a solution
of TiCl4 (79 µL, 0.72 mmol) and monoimide 2 (50 mg, 0.18
mmol) in CH2Cl2 (10 mL). Workup and chromatography (1:
1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the crude brown oil
afforded 8e (15 mg, 18%) as a white solid, mp 136-137 °C
(Et2O/hexanes); Rf 0.11 (3:3:4 Et2O:CH2Cl2:hexanes); 1H NMR
(500 MHz) 7.70 (d, 2H, J ) 7.5), 7.54 (t, 1H, J ) 7.4), 7.43
(apparent t, 3H), 7.31 (d, 2H, J ) 8.6), 7.01 (d, 2H, J ) 8.5),
6.56 (s, 1H), 5.51 (s, 1H, OH), 4.60 (d, 1H, J ) 3), 3.99 (s, 3H),
2.97 (dq, 1H, J ) 3, 7), 2.28 (s, 3H), 0.64 (d, 3H, J ) 7); 13C
NMR (125 MHz) 169.4, 150.0, 146.4, 143.4, 140.1, 137.2, 133.4,
133.2, 129.0, 128.2, 127.3, 126.8, 121.7, 110.0, 100.4, 72.4, 56.5,
(1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the crude yellow oil
afforded 10b (80 mg, 64%) and 7b (4 mg, 3%). Physical and
spectral properties of 10b, a white solid, mp 142-143 °C (CH2-
Cl2/Et2O/hexanes); Rf 0.34 (3:3:4 Et2O:CH2Cl2:hexanes); 1H
NMR (500 MHz) 7.70 (d, 2H, J ) 7.5), 7.53 (t, 1H, J ) 7.4),
7.42 (apparent t, 3H), 6.86 (dd, 1H, J ) 8.5, 1.7), 6.78 (m, 2H),
6.59 (s, 1H), 5.56 (s, 1H, OH), 4.54 (d, 1H, J ) 3.1), 3.90 (m,
2H), 3.84 (s, 3H), 3.81 (s, 3H), 2.97 (dq, 1H, J ) 3.1, 7.0), 2.16
(m, 1H), 1.08 (d, 3H, J ) 6.7), 1.07 (d, 3H, J ) 6.7), 0.67 (d,
3H, J ) 7.0); 13C NMR (125 MHz) 149.1, 148.5, 145.8, 143.4,
137.3, 135.2, 133.5, 133.1, 128.9, 128.2, 127.3, 118.0, 110.1,
109.8, 109.0, 101.1, 75.6, 72.9, 55.9 (2C), 45.8, 28.3, 21.9, 19.3
(2C). Anal. Calcd for C27H31NO6S: C, 65.17; H, 6.28; N, 2.81.
Found: C, 64.80; H, 6.40; N, 2.70.
Compound 7b was identified by spectral comparison to the
product isolated from the BF3‚Et2O-promoted reaction, see
above.
45.8, 22.0, 21.1; HRMS m/ z 453.1251 (M+) (Calcd for C24H23
-
NO6S 453.1246)
(2R*,3R*)-1-(Ben zen esu lfon yl)-2,3-d ih yd r o-5-h yd r oxy-
6-m et h oxy-3-m et h yl-2-p h en ylin d ole (8f). According to
general method B, trans-â-methylstyrene (39 µL, 0.30 mmol)
was added to a solution of TiCl4 (33 µL, 0.30 mmol) and
monoimide 2 (75 mg, 0.27 mmol) in CH2Cl2 (10 mL). Workup
and chromatography (2:2:6 CH2Cl2:Et2O:hexanes) of the crude
yellow oil afforded 8f (80 mg, 75%) as a white solid, mp 169-
171°C (Et2O/hexanes); Rf 0.15 (3:3:4 Et2O:CH2Cl2:hexanes); 1H
NMR (500 MHz) 7.72 (d, 2H, J ) 7.9), 7.55 (t, 1H, J ) 7.4),
7.44 (apparent t, 3H), 7.30 -7.23 (m, 5H), 6.57 (s, 1H), 5.52
(s, 1H, OH), 4.60 (d, 1H, J ) 3.0), 4.00 (s, 3H), 2.97 (dq, 1H, J
) 7.0, 3.0), 0.66 (d, 3H, J ) 7.0); 13C NMR (125 MHz) 145.4,
143.4,142.6, 137.2, 133.6, 133.1, 128.9, 128.6, 128.3, 127.6,
127.3, 125.6, 110.0, 100.0, 73.0, 56.4, 45.9, 22.0. Anal. Calcd
for C22H21NO4S: C, 66.81; H, 5.35; N, 3.54. Found: C, 66.43;
H, 5.68; N, 3.20.
(2R*,3R*)-1-(Ben zen esu lfon yl)-2,3-d ih yd r o-5-h yd r oxy-
6-isobu toxy-3-m eth yl-2-[3,4-(m eth ylen ed ioxy)p h en yl]in -
d ole (10c). According to general method B, (E)-1,2-(methyl-
enedioxy)-4-propenylbenzene (15 µL, 0.10 mmol) was added
to a solution of a mixture of TiCl4 (26 µL, 0.24 mmol) and
Ti(OiPr)4 (70 µL, 0.24 mmol) in CH2Cl2 (0.5 mL) and monoim-
ide 4 (15 mg, 0.047 mmol) in CH2Cl2 (10 mL). Workup and
chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the
crude yellow oil afforded 10c (21 mg, 93%) as a white solid,
mp 132-133 °C (Et2O/hexanes); Rf 0.5 (3:3:4 Et2O:CH2Cl2:
hexanes); 1H NMR (500 MHz) 7.71 (d, 2H, J ) 7.5), 7.54
(apparent t, 1H), 7.45-7.40 (m, 3H), 6.79-6.72 (m, 3H), 6.58
(s, 1H), 5.91 (s, 2H), 5.56 (s, 1H, OH), 4.49 (s, 1H, J ) 2.8),
3.93 (m, 2H), 2.91 (dq, 1H, J ) 2.8, 7.0), 2.18 (septet, 1H, J )
7.0), 1.09 (d, 3H, J ) 7.0), 1.08 (d, 3H, J ) 7.0), 0.63 (d, 3H, J
) 7.0); 13C NMR (75 MHz) 148.3, 147.5, 146.3, 143.9, 137.8,
137.2, 133.9, 133.5, 129.3, 128.5, 127.7, 119.5, 110.3, 108.6,
106.7, 101.7, 101.4, 76.2, 73.4, 46.4, 28.7, 22.3, 19.7 (2C). Anal.
Calcd for C26H27NO6S: C, 64.84; H, 5.65; N, 2.91. Found: C,
65.20; H, 5.50; N, 2.80.
(2R*,3R*)-1-(Ben zen esu lfon yl)-6-ben zyloxy-2,3-dih ydr o-
5-h yd r oxy-2-(3,4-d im eth oxyp h en yl)-3-m eth ylin d ole (9b).
According to general method B, (E)-1,2-dimethoxy-4-prope-
nylbenzene (31 µL, 0.19 mmol) was added to a solution of a
mixture of TiCl4 (23 µL, 0.21 mmol) and Ti(OiPr)4 (126 µL,
0.425 mmol) in CH2Cl2 (0.5 mL) and monoimide 3 (30 mg,
0.085 mmol) in CH2Cl2 (10 mL). Workup and chromatography
(2:2:6 CH2Cl2:Et2O:hexanes) of the crude yellow oil afforded
9b (45 mg, 100%) as a white solid, mp 76-77 °C (Et2O/
N-[(6a S*,11a S*)-6,6a ,11a -Tr ih yd r o-3,10-d im eth oxy-6H-
b e n zofu r o[3,2-c][1]b e n zop yr a n -8-yl]b e n ze n e su lfon a -
m id e (13). According to general method A, 7-methoxy-2H-
chromene (11, 170 mg, 1.05 mmol) was added to a solution of
BF3‚OEt2 (140 µL, 1.14 mmol) and monoimide 2 (278 mg, 1.00
mmol) in CH2Cl2 (5 mL). Workup and chromatography (2:3:5
to 2:4:4 CH2Cl2:Et2O:hexanes) furnished 13 (384 mg, 87%) as
a white solid, mp 112-114 °C (CH2Cl2/Et2O/hexanes); Rf 0.28
(2:3:5 CH2Cl2:Et2O:hexanes); 1H NMR (500 MHz) 7.72 (d, J )
7.3 Hz, 2H), 7.55 (apparent t, J ) 7.5, 1H), 7.44 [overlapping
d (J ) 8.5, 1H) and apparent t (J ) 7.5, 2H)], 6.82 (s, 1H),
6.60 (dd, J ) 2.5, 8.5, 1H), 6.54 (d, J ) 1.8, 1H), 6.52 (d, J )
1.8, 1H), 6.43 (d, J ) 2.5, 1H), 5.53 (d, J ) 6.9, 1H), 4.12 (dd,
J ) 4.7, 11, 1H), 3.77 (s, 3H), 3.72 (s, 3H), 3.58 (apparent t, J
) 11, 1H), 3.53-3.48 (m, 1H); 13C NMR (125 MHz) 161.1,
156.5, 146.5, 144.6, 138.7, 133.0, 132.2, 129.5, 128.9, 128.5,
127.4, 113.2, 111.7, 109.5, 109.2, 101.5, 78.8, 66.0, 56.0, 55.3,
40.4. Anal. Calcd for C23H21NO6S: C, 62.85; H, 5.10; N, 3.18.
Found: C, 63.10; H, 5.10; N, 3.28.
1
hexanes); Rf 0.18 (2:2:6 Et2O:CH2Cl2:hexanes); H NMR (500
MHz) 7.52-7.33 (m, 11H), 6.86 (dd, 1H, J ) 1.9, 8.2), 6.78 (m,
2H), 6.59 (s, 1H), 5.61 (s, 1H, OH), 5.26 (s, 2H), 4.53 (d, 1H, J
) 3.4), 3.85 (s, 3H), 3.81 (s, 3H), 2.97 (dq, 1H, J ) 3.4, 7.0),
0.67 (d, 3H, J ) 7.0); 13C NMR (125 MHz) 149.1, 148.6, 145.0,
143.5, 137.2, 136.1, 135.2, 133.5, 132.9, 128.8 (2C), 128.6,
128.4, 127.9, 127.2, 118.0, 111.1, 110.2, 109.0, 101.8, 73.0, 71.2,
55.9 (2C), 45.7, 21.8; HRMS m/ z 531.1707 (M+) (Calcd for
C30H29NO6S - 531.1716).
(2R*,3R*)-1-(Ben zen esu lfon yl)-6-(ben zyloxy)-2,3-d ih y-
d r o-5-h yd r oxy-3-m eth yl-2-[3,4-(m eth ylen ed ioxy)p h en yl]-
in d ole (9c). According to general method B, (E)-1,2-(meth-
ylenedioxy)-4-propenylbenzene (45 µL, 0.31 mmol) was added
to a solution of a mixture of TiCl4 (78 µL, 0.71 mmol) and
Ti(OiPr)4 (211 µL, 0.712 mmol) in CH2Cl2 (0.5 mL) and
monoimide 3 (50 mg, 0.14 mmol) in CH2Cl2 (10 mL). Workup
and chromatography (1:1:8 to 2:2:6 Et2O:CH2Cl2:hexanes) of
the crude yellow oil afforded 9c (49 mg, 67%) as a white solid,
mp 177-178 °C (Et2O/hexanes); Rf 0.30 (3:3:4 Et2O:CH2Cl2:
hexanes); 1H NMR (500 MHz) 7.54-7.33 (m, 11H), 6.80-6.73
(m, 3H), 6.58 (s, 1H), 5.91 (s, 2H), 5.63 (s, 1H), 5.25 (s, 2H),
4.48 (d, 1H, J ) 3.2), 2.92 (dq, 1H, J ) 3.2, 7.0), 0.64 (d, 3H,
J ) 7.0); 13C NMR (125 MHz) 147.8, 147.0, 145.1, 143.5, 137.0,
136.7, 136.1, 133.4, 133.0, 128.82, 128.80, 128.45, 128.44,
128.0, 127.2, 119.1, 110.2, 108.1, 106.2, 101.8, 101.0, 72.9, 71.1,
45.9, 21.8; HRMS m/ z 515.1421 (M+) (Calcd for C29H25NO6S
515.1403).
N-[(6a S*,11a S*)-10-(Ben zyloxy)-6,6a ,11a -t r ih yd r o-3-
m e t h oxy-6H -b e n zofu r o[3,2-c][1]b e n zop yr a n -8-yl]b e n -
zen esu lfon a m id e (14). According to general method A,
7-methoxy-2H-chromene (11, 50 mg, 0.31 mmol) in CH2Cl2 (1
mL) was added to a solution of BF3‚OEt2 (30 µL, 0.24 mmol)
and monoimide 3 (68 mg, 0.19 mmol) in CH2Cl2 (4 mL).
Workup and chromatography (2:3:5 to 3:2:5 CH2Cl2:Et2O:
hexanes) gave 14 (89 mg, 91%) as a white foam, mp 93-95
1
°C; Rf 0.26 (3:2:5 CH2Cl2:Et2O:hexanes); H NMR (500 MHz)
7.60 (d, J ) 7.8, 2H), 7.54 (apparent t, J ) 7.3, 7.6, 1H), 7.47
(d, J ) 8.6, 1H), 7.40 (apparent t, J ) 7.8, 2H), 7.34-7.29 (m,
5H), 6.62 (dd, J ) 2.4, 8.6, 1H), 6.54 (d, J ) 1.9, 1H), 6.52 (d,
J ) 1.9, 1H), 6.44 (d, J ) 2.4, 1H), 6.30 (bs, 1H), 5.54 (d, J )
7.0, 1H), 5.03 (ABq, J ) 12, ∆ν)15 Hz, 2H), 4.13 (dd, J ) 5.0,
11, 1H), 3.78 (s, 3H), 3.59 (apparent t, J ) 11, 1H), 3.53-3.48
(m, 1H); 13C NMR (125 MHz) 161.1, 156.5, 147.0, 143.5, 138.6,
136.4, 133.0, 132.2, 129.3, 129.0, 128.9, 128.5, 128.0, 127.5,
127.3, 113.6, 112.0, 111.8, 109.2, 101.5, 78.7, 71.2, 65.9, 55.4,
40.4; HRMS m/ z 515.1402 (calcd for C29H25NO6S 515.1403).
(2R *,3R *)-1-(B e n ze n e s u lfo n y l)-2,3-d ih y d r o -2-(3,4-
d im et h oxyp h en yl)-5-h yd r oxy-6-isob u t oxy-3-m et h ylin -
dole (10b). According to general method B, (E)-1,2-dimethoxy-
4-propenylbenzene (93 µL, 0.64 mmol) was added to a solution
of a mixture of TiCl4 (138 µL, 1.26 mmol) and Ti(OiPr)4 (373
µL, 1.26 mmol) in CH2Cl2 (0.5 mL) and monoimide 4 (80 mg,
0.25 mmol) in CH2Cl2 (10 mL). Workup and chromatography

9306 J . Org. Chem., Vol. 61, No. 26, 1996
Engler et al.
N-[(6a S*,11a S*)-10-Isob u t oxy-3-m et h oxy-6,6a ,11a -t r i-
h ydr oben zofu r o[3,2-c][1]ben zopyr an -8-yl]ben zen esu lfon a-
m id e (15). According to general method A, 7-methoxy-2H-
chromene (11, 29 mg, 0.18 mmol) was added to a solution of
BF3‚Et2O (26 µL, 0.21 mmol) and monoimide 4 (53 mg, 0.17
mmol) in CH2Cl2 (10 mL). Workup and chromatography (1:
1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the crude yellow oil
afforded 15 (66 mg, 81%) and 21 (2 mg, 2%). Physical and
spectral properties of 15, a white solid, mp 171-173 °C (CH2-
Cl2/Et2O/hexanes); Rf 0.10 (1:4 EtOAc:hexanes); 1H NMR (500
MHz) 7.70 (d, 2H, J ) 7.5), 7.50 (t, 1H, J ) 7.5), 7.47-7.43
(m, 3H), 6.62 (dd, 1H, J ) 8.5, 2.5), 6.52 (d, 1H, J ) 2.0), 6.48
(d, 1H, J ) 2.0), 6.46 (s, 1H, NH), 6.43 (d, 1H, J ) 2.5), 5.52
(d, 1H, J ) 7.0), 4.13 (dd, 1H, J ) 11.0, 5.0), 3.78 (s, 3H), 3.64
(d, 2H, J ) 6.7), 3.59 (dd, 1H, J ) 11.0, 11.0), 3.49 (m, 1H),
2.00 (m, 1H), 0.95 (d, 6H, J ) 6.7); 13C NMR (125 MHz) 161.1,
156.5, 146.9, 144.2, 138.7, 132.9, 132.2, 129.2, 128.9, 128.7,
127.4, 113.3, 111.9, 111.3, 109.1, 101.5, 78.5, 75.6, 65.9, 55.3,
40.4, 28.0, 19.2. Anal. Calcd for C26H27NO6S: C, 64.84; H,
5.65; N, 2.91. Found: C, 64.85; H, 5.90; N, 2.99.
Compound 21 was identified by spectral comparison to the
product isolated from the Ti(IV)-promoted reaction, see below.
N-[(6a S*,11a S*)-3,10-Dim eth oxy-5-(4-tolu en esu lfon yl)-
6,6a ,11,11a -tetr a h yd r oben zofu r o[3,2-c][1]qu in olin e-8-yl]-
ben zen esu lfon a m id e (16). According to general method A,
a 3.4:1 mixture of dihydroquinoline 12 and its 5-methoxy
isomer (70 mg, 0.22 mmol) in CH2Cl2 (2 mL) was added to a
solution of BF3‚Et2O (27 µL, 0.21 mmol) and monoimide 2 (45
mg, 0.162 mmol) in CH2Cl2 (10 mL). Workup and chroma-
tography (5:95 to 10:90 EtOH:CH2Cl2) of the crude yellow oil
afforded 16 (67 mg, 70%) as a white solid, mp 166-168 °C
(CH2Cl2/Et2O/hexanes); Rf 0.07 (1:4 EtOAc:hexanes); 1H NMR
(500 MHz) 7.70 (d, 2H, J ) 7.5), 7.57 (t, 1H, J ) 7.5), 7.48 (m,
5H), 7.27 (d, 1H, J ) 3.0), 7.19 (d, 2H, J ) 7.5), 6.82 (dd, 1H,
J ) 2.5, 8.5), 6.47 (d, 1H , J ) 2.0), 6.43 (d, 1H, J ) 2.0), 6.27
(s, 1H, NH), 5.16 (d, 1H, J ) 8.1), 4.18 (dd, 1H, J ) 5.5, 14.0),
3.82 (s, 3H), 3.70 (s, 3H), 3.20 (m, 1H), 3.02 (dd, 1H, J ) 11.5,
14.0), 2.38 (s, 3H); 13C NMR (125 MHz) 159.9, 146.0, 144.3,
144.1, 138.7, 137.6, 136.7, 133.0, 131.4, 129.8, 129.7, 129.1,
129.0, 127.4, 127.0, 119.3, 113.2, 113.0, 109.2, 109.1, 79.4, 56.0,
55.5, 47.6, 40.3, 21.5. Anal. Calcd for C30H28N2O7S2: C, 60.79;
H, 4.76; N, 4.73. Found: C, 60.80; H, 4.68; N, 4.50.
14.0), 3.82 (s, 3H), 3.58 (d, 2H, J ) 6.6), 3.19 (m, 1H), 2.98
(dd, 1H, J ) 14.0, 11.7), 2.40 (s, 3H), 1.97 (m, 1H), 0.92 (d,
6H, J ) 6.7); 13C NMR (125 MHz) 159.8, 146.4, 144.1, 143.8,
138.7, 137.5, 136.7, 132.9, 131.2, 129.8, 129.5, 129.2, 128.9,
127.4, 127.0, 120.0, 113.3, 112.9, 111.0, 109.2, 78.9, 75.5, 55.5,
47.6, 40.3, 28.0, 21.5, 19.1; HRMS m/ z 635.1876 (M + 1) (Calcd
C33H35N2S2O7 635.1886).
(6a S*,11a S*)-11-(Ben zen esu lfon yl)-3,9-d im et h oxy-8-
h yd r oxy-6,6a ,11,11a -tetr a h yd r o[1]ben zop yr a n o[4,3-b]in -
d ole (19). According to general method B, 7-methoxy-2H-
chromene (11, 32 mg, 0.20 mmol) was added to a solution of a
mixture of TiCl4 (20 µL, 0.18 mmol) and Ti(OiPr)4 (107 µL,
0.361 mmol) in CH2Cl2 (0.5 mL) and monoimide 2 (50 mg, 0.18
mmol) in CH2Cl2 (10 mL). Workup and chromatography (1:
1:8 CH2Cl2:Et2O:hexanes) of the crude yellow oil afforded 19
(38 mg, 48%) as a white solid, mp > 250 °C (dec) (Et2O); Rf
0.38 (2:2:6 CH2Cl2:Et2O:hexanes); 1H NMR (DMSO-d6, 500
MHz) 8.95 (s, 1H), 7.70-7.62 (m, 3H), 7.54-7.48 (m, 3H), 6.94
(s, 1H), 6.68 (s, 1H), 6.62-6.60 (dd, 1H, J ) 8.5, 2.5), 6.18 (d,
1H, J ) 2.5), 5.53 (d, 1H, J ) 8.5 Hz), 4.41 (dd, 1H, J ) 1.5,
12), 3.98 (dd, 1H, J ) 12, 2.4), 3.75 (s, 3H), 3.65 (s, 3H), 2.86
(bd, 1H, J ) 8.5); 13C NMR (DMSO-d6, 125 MHz) 159.6, 156.5,
147.5, 145.1, 137.5, 133.5, 132.4, 131.4, 129.3, 127.0, 125.6,
114.0, 110.7, 109.0, 103.8, 100.9, 63.9, 59.8, 55.8, 55.1 (one
signal is buried under residual solvent signals). Anal. Calcd
for C23H21NO6S: C, 62.86; H, 4.82; N, 3.19. Found: C, 62.64;
H, 4.80; N, 3.16.
N-[(6a S*,11a S*)-9-(Ben zyloxy)-6,6a ,11,11a -tetr a h yd r o-
3-m eth oxy-11-(ben zen esu lfon yl)[1]ben zop yr a n o[4,3-b]in -
d ole-8-ol (20). According to general method B, 7-methoxy-
2H-chromene (11, 28 mg, 0.17 mmol) was added to a solution
of a mixture of TiCl4 (39 µL, 0.35 mmol) and Ti(OiPr)4 (101
µL, 0.34 mmol) in CH2Cl2 (0.5 mL) and monoimide 3 (50 mg,
0.14 mmol) in CH2Cl2 (10 mL). Workup and chromatography
(2:2:6 to 2:3:5 CH2Cl2:Et2O:hexanes) of the crude yellow oil
afforded 20 (37 mg, 51%) as a white solid, mp 196-197 °C
(EtOAc/hexanes); Rf 0.39 (2:4:4 CH2Cl2:Et2O:hexanes); 1H
NMR (500 MHz) 7.71 (d, J ) 8.7, 2H), 7.55-7.32 (m, 10H),
7.27 (s, 1H), 6.71 (s, 1H), 6.61 (dd, J ) 2.6, 8.7, 1H), 6.20 (d,
J ) 2.5, 1H), 5.62 (s, 1H), 5.37 (d, J ) 8.4, 1H), 5.12 (ABq, J
) 11, ∆ν)43 Hz, 2H), 4.33 (dd, J ) 1.9, 12, 1H), 4.03 (dd, J )
2.4, 12, 1H), 3.70 (s, 3H), 2.81 (bd, J ) 8.3, 1H); 13C NMR (125
MHz) 160.2, 156.6, 145.5, 144.6, 137.9, 135.8, 133.9, 133.0,
132.0, 129.0, 128.8, 128.5, 128.2, 127.0, 126.0, 113.3, 109.5,
109.2, 105.3, 101.2, 71.3, 64.2, 60.1, 55.2, 40.1. Anal. Calcd
for C29H25NO6S: C, 67.56; H, 4.90; N, 2.72. Found: C, 67.50;
H, 5.10; N, 2.60.
(6a S*,11a S*)-11-(Ben zen esu lfon yl)-8-h yd r oxy-9-isobu -
toxy-3-m eth oxy-6,6a ,11,11a -tetr a h yd r o[1]ben zop yr a n o-
[4,3-b]in dole (21). According to general method B, 7-methoxy-
2H-chromene (11, 50 mg, 0.31 mmol) was added to a solution
of a mixture of TiCl4 (36 µL, 0.33 mmol) and Ti(OiPr)4 (101
µL, 0.340 mmol) in CH2Cl2 (0.5 mL) and monoimide 4 (70 mg,
0.22 mmol) in CH2Cl2 (10 mL). Workup and chromatography
(1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of the crude yellow oil
afforded 21 (60 mg, 57%) as a white solid, mp 194-196 °C
(CH2Cl2/Et2O/hexanes); Rf 0.15 (1:4 EtOAc:hexanes); 1H NMR
(500 MHz) 7.70 (d, 1H, J ) 8.5), 7.61 (d, 2H, J ) 8.0), 7.55 (t,
1H, J ) 8), 7.40 (t, 2H, J ) 8), 7.14 (s, 1H), 6.70 (s, 1H), 6.60
(dd, 1H, J ) 8.5, 2.5), 6.19 (d, 1H, J ) 2.5), 5.60 (s, 1H, OH),
5.35 (d, 1H, J ) 8.2), 4.31 (dd, 1H, J ) 12, 1.5), 4.02 (dd, 1H,
J ) 12, 2.4), 3.88 (dd, 1H, J ) 8.9, 6.6), 3.74 (dd, 1H, J ) 8.9,
6.6), 3.70 (s, 3H), 2.79 (b d, 1H, J ) 8.2), 2.11 (m, 1H), 1.04 (d,
3H, J ) 6.8), 1.02 (d, 3H, J ) 6.8); 13C NMR (125 MHz) 160.2,
156.5, 146.1, 144.5, 138.0, 133.9, 133.1, 132.0, 129.1, 127.1,
125.5, 113.3, 109.5, 108.8, 104.8, 101.1, 75.5, 64.2, 60.1, 55.2,
40.1, 28.2, 19.2. Anal. Calcd for C26H27NO6S: C, 64.84; H,
5.65; N, 2.91. Found: C, 64.50; H, 5.80; N, 2.68.
N-[(6a S*,11a S*)-10-(Ben zyloxy)-3-m et h oxy-5-(4-t olu -
en esu lfon yl)-6,6a ,11,11a -tetr a h yd r oben zofu r o[3,2-c][1]-
qu in olin e-8-yl]ben zen esu lfon a m id e (17). According to
general method A, a 3.4:1 mixture of dihydroquinoline 12 and
its 5-methoxy isomer (110 mg, 0.35 mmol) in CH2Cl2 (2 mL)
was added to a solution of BF3‚Et2O (40 µL, 0.33 mmol) and
monoimide 3 (86 mg, 0.24 mmol) in CH2Cl2 (10 mL). Workup
and chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of
the crude yellow oil afforded 17 (86 mg, 53%) as a white solid,
mp 88-90 °C (CH2Cl2/Et2O/hexanes); Rf 0.14 (1:4 EtOAc:
1
hexanes); H NMR (300 MHz) 7.60-7.16 (m, 16H), 6.81 (dd,
1H, J ) 8.4, 2.4), 6.56 (s, 1H, NH), 6.53 (d, 1H, J ) 1.8), 6.45
(d, 1H, J ) 1.8), 5.10 (d, 1H, J ) 8.1), 4.96 (s, 2H), 4.18 (dd,
1H, J ) 5.4, 13.8), 3.81 (s, 3H), 3.16 (m, 1H), 2.96 (dd, 1H, J
) 13.8, 11.7), 2.36 (s, 3H); 13C NMR (75 MHz) 159.7, 146.3,
144.0, 143.0, 138.5, 137.4, 136.6, 136.2, 132.8, 131.2, 129.7,
129.4, 128.8, 128.3, 127.9, 127.3, 127.1, 126.9, 119.3, 113.1,
113.05, 111.4, 109.0, 79.0, 70.9, 55.4, 47.4, 40.1, 21.4 (one sp2-C
signal is not visible). Anal. Calcd for C36H32N2O7S2: C, 64.65;
H, 4.82; N, 4.19. Found: C, 64.55; H, 5.00; N, 4.10.
N-[(6a S*,11a S*)-10-Isobu toxy-3-m eth oxy-5-(4-tolu en e-
su lfon yl)-6,6a ,11,11a -t e t r a h yd r ob e n zofu r o[3,2-c][1]-
qu in olin e-8-yl]ben zen esu lfon a m id e (18). According to
general method A, a 2.5:1 mixture of dihydoquinoline 12 and
its 5-methoxy isomer (122 mg, 0.386 mmol) in CH2Cl2 (2 mL)
was added to a solution of BF3‚Et2O (37 µL, 0.29 mmol) and
monoimide 4 (80 mg, 0.25 mmol) in CH2Cl2 (10 mL). Workup
and chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of
the crude brown oil afforded 18 (46 mg, 29%) as a white solid,
mp 108-109 °C (Et2O/hexanes); Rf 0.08 (2:2:6 Et2O:CH2Cl2:
hexanes); 1H NMR (500 MHz) 7.71 (dd, 2H, J ) 1.2, 8.4), 7.55
(t, 1H, J ) 7.3), 7.48-7.39 (m, 6H), 7.26 (d, 1H, J ) 2.3) 7.19
(d, 1H, J ) 8.2), 6.83 (dd, 1H, J ) 2.6, 8.6), 6.75 (broad s, 1H,
NH), 6.47 (s, 2H), 5.09 (d, 1H, J ) 8.2), 4.21 (dd, 1H, J ) 5.6,
(6a S*,11a S*)-11-(Ben zen esu lfon yl)-9-(ben zyloxy)-8-h y-
d r oxy-3-m et h oxy-5-(4-t olu en esu lfon yl)-6,6a ,11,11a -t et -
r a h yd r oin d olo[3.2-c][1]qu in olin e (23). According to gen-
eral method B, a 3:1 mixture of dihydroquinoline 12 and its
5-methoxy isomer (63 mg, 0.20 mmol) in CH2Cl2 (2 mL) was
added to a solution of a mixture of TiCl4 (28 µL, 0.26 mmol)
and Ti(OiPr)4 (77 µL, 0.26 mmol) in CH2Cl2 (0.5 mL) and
monoimide 3 (55 mg, 0.16 mmol) in CH2Cl2 (10 mL). Workup

Reactions of Styrenyl Systems with Benzoquinone Monoimides
J . Org. Chem., Vol. 61, No. 26, 1996 9307
and chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of
the crude brown oil afforded 23 (50 mg, 48%) and 17 (27 mg,
26%). Physical and spectral properties of 23, a white solid,
mp 143-144 °C (MeOH); Rf 0.21 (3:3:4 Et2O:CH2Cl2:hexanes);
1H NMR (500 MHz) 7.77 (d, 1H, J ) 8.7), 7.51 (t, 1H, J ) 7.3),
7.46-7.36 (m, 6H), 7.29-7.25 (m, 4H), 7.21 (d, 2H, J ) 8.0),
7.14 (d, 2H, J ) 7.8), 7.05 (d, 1H, J ) 2.3), 6.82 (dd, 1H, J )
2.3, 8.7), 6.52 (s, 1H), 5.61 (s, 1H, OH), 5.16 (ABq, 2H, J )
11.5, ∆υ ) 18 Hz), 4.41 (d, 1H, J ) 9.6), 4.21 (dd, 1H, J ) 7.0,
14.1), 3.77 (s, 3H), 3.44 (dd, 1H, J ) 8.0, 14.1), 3.18 (m, 1H),
2.47 (s, 3H); 13C NMR (125 MHz) 159.3, 145.3, 144.8, 143.7,
138.0, 137.0, 136.8, 135.7, 133.4, 133.2, 130.1, 129.7, 128.8,
128.7, 128.6, 128.0, 127.6, 127.1, 121.8, 113.1, 109.9, 109.2,
104.6, 71.2, 60.7, 55.5, 47.4, 41.8, 21.6. Anal. Calcd for
(2R *,3R *)-1-(B e n ze n e s u lfo n y l)-2,3-d ih y d r o -5,6-d i-
m eth oxy-2-(4-m eth oxyp h en yl)-3-m eth ylin d ole (34).
A
slurry of phenol 8a (80 mg, 0.19 mmol) and K2CO3 (31 mg,
0.23 mmol) in acetone (2 mL) at rt was treated with methyl
iodide (12 µL, 0.20 mmol) and (nBu)4N+ I- (3 mg, 0.009 mmol).
The reaction mixture was refluxed under nitrogen for 24 h,
cooled to rt, and then poured into water (5 mL). CH2Cl2 (5
mL) was added, and the aqueous layer was separated and
extracted with CH2Cl2 (3 × 5 mL). The combined extracts
were washed with H2O (20 mL), brine (20 mL), dried (Na2-
SO4), and concentrated. Chromatography of the resultant pale
yellow solid (2:2:6 Et2O:CH2Cl2:hexanes) afforded 34 (63 mg,
76%) as a white crystalline solid, mp 133-134 °C (Et2O/CH2-
Cl2/hexanes); Rf 0.16 (3:3:4 Et2O:CH2Cl2:hexanes); 1H NMR
(500 MHz) 7.71 (d, 2H, J ) 7.6), 7.53 (t, 1H, J ) 7.4), 7.43 (m,
3H), 7.20 (d, 2H, J ) 8.7), 6.83 (d, 2H, J ) 8.7), 6.52 (s, 1H),
4.57 (d, 1H, J ) 3), 3.98 (s, 3H), 3.81 (s, 3H), 3.78 (s, 3H), 2.97
(dq, 1H, J ) 3, 7), 0.68 (d, 3H, J ) 7); 13C NMR (125 MHz)
159.0, 149.1, 146.8, 137.3, 134.9, 134.2, 133.0, 128.9, 127.3,
126.9, 114.0, 107.2, 100.9, 72.8, 56.3, 56.2, 55.3, 46.0, 21.9 (one
quaternary sp2-C signal is not apparent). Anal. Calcd for
C24H25NO5S: C, 65.58; H, 5.73; N, 3.19. Found: C, 65.40; H,
5.40; N, 2.90.
(2R *,3R *)-1-(B e n ze n e s u lfo n y l)-2,3-d ih y d r o -2-(3,4-
d im eth oxyp h en yl)-6-m eth oxy-3-m eth ylin d ol-5-yl Tr iflu -
or om eth a n esu lfon a te (35). To a solution of phenol 8b (90
mg, 0.20 mmol) and pyridine (0.16 mL, 2.0 mmol) in CH2Cl2
(5 mL) at -78 °C was added trifluoromethanesulfonic anhy-
dride (0.13 mL, 0.79 mmol). The reaction mixture was stirred
for 15 min at -78 °C and poured into water (10 mL), and CH2-
Cl2 (10 mL) was added. The aqueous layer was separated and
extracted with CH2Cl2 (3 × 5 mL). The combined CH2Cl2
extracts were washed with saturated aqueous sodium bicar-
bonate (20 mL), 10% aqueous hydrochloric acid (20 mL), brine
(20 mL), dried (Na2SO4), and concentrated. Chromotagraphy
(1:1:8 CH2Cl2:Et2O:hexanes) of the crude brown oil afforded
35 (80 mg, 69%) as a white solid, mp 64-65 °C (Et2O/hexanes);
Rf 0.35 (3:3:4 CH2Cl2:Et2O:hexanes); 1H NMR (500 MHz) 7.68
(d, 2H, J ) 7.5), 7.56 (t, 1H, J ) 7.5), 7.53 (s, 1H), 7.44 (t, 2H,
J ) 7.5), 6.88 (s, 1H), 6.83 (dd, 1H, J ) 1.8, 8.3), 6.78 (d, 1H,
J ) 8.3), 6.69 (d, 1H, J ) 1.8), 4.67 (d, 1H, J ) 3.9), 3.99 (s,
3H), 3.86 (s, 3H), 3.78 (s, 3H), 3.07 (dq, 1H, J ) 3.9, 7.0), 0.88
(d, 3H, J ) 7.0); 13C NMR (125 MHz) 151.5, 149.1, 148.8, 141.7,
137.6, 135.2, 133.9, 133.5, 129.0, 127.4, 127.1, 119.3 (q, J C-F
) 320) 118.4, 118.2, 111.0, 108.9, 100.8, 73.7, 56.6, 55.9, 55.8,
45.1, 21.4; HRMS m/ z 587.0920 (M+) (Calcd for C25H24NO8S2F3
587.0895).
C
36H32N2O7S2: C, 64.65; H, 4.82; N, 4.41. Found: C, 62.39;
H, 5.10; N, 4.08.
Compound 17 was identified by spectral comparison to the
product isolated from the BF3‚Et2O-promoted reaction, see
above.
(6a S*,11a S*)-11-(Ben zen esu lfon yl)-8-h yd r oxy-9-isobu -
toxy-3-m eth oxy-5-(4-tolu en esu lfon yl)-6,6a,11,11a-tetr ah y-
d r oin d olo[3.2-c][1]qu in olin e (24). According to general
method B, a 3:1 mixture of dihydroquinoline 12 and its
5-methoxy isomer (29 mg, 0.092 mmol) in CH2Cl2 (2 mL) was
added to a solution of a mixture of TiCl4 (13 µL, 0.12 mmol)
and Ti(OiPr)4 (34 µL, 0.12 mmol) in CH2Cl2 (0.5 mL) and
monoimide 4 (22 mg, 0.069 mmol) in CH2Cl2 (10 mL). Workup
and chromatography (1:1:8 to 2:2:6 CH2Cl2:Et2O:hexanes) of
the crude brown oil afforded 24 (24 mg, 55%) and 18 (16 mg,
37%). Physical and spectral properties of 24, a white solid,
mp 204-205 °C (MeOH); Rf 0.12 (2:2:6 Et2O:CH2Cl2:hexanes);
1H NMR (500 MHz) 7.77 (d, 1H, J ) 8.7), 7.55 (apparent t,
1H, J ) 7.2), 7.38 (d, 2H, J ) 8.3), 7.35-7.30 (m, 4H), 7.20 (d,
2H, J ) 8.2), 7.15 (s, 1H), 7.04 (d, 1H, J ) 2.6), 6.81 (dd, 1H,
J ) 2.6, 8.7), 6.53 (s, 1H), 5.57 (s, 1H, OH), 4.44 (d, 1H, J )
9.6), 4.20 (dd, 1H, J ) 6.9, 14.1), 3.88 (dd, 1H, J ) 6.6, 9.0),
3.75 (m, 4H), 3.47 (dd, 1H, J ) 7.8, 14.1), 3.17 (m, 1H), 2.46
(s, 3H), 2.13 (m, 1H), 1.05 (d, 3H, J ) 6.2), 1.04 (d, 3H, J )
6.2); 13C NMR (125 MHz) 159.3, 146.0, 144.6, 143.7, 138.0,
137.0, 136.9, 133.4, 133.2, 130.1, 129.7, 128.8, 127.2 (2C),
121.7, 113.0, 109.6, 109.0, 104.0, 75.6, 60.7, 55.4, 47.3, 41.8,
28.2, 21.6, 19.2 (2C), (one sp2-C signal is not visible). Anal.
Calcd for C33H34N2O7S2: C, 62.44; H, 5.40; N, 4.41. Found:
C, 62.39; H, 5.10; N, 4.08.
Compound 18 was identified by spectral comparison to the
product isolated from the BF3‚Et2O-promoted reaction, see
above.
1-(B e n ze n e s u lfo n y l)-5,6-d im e t h o x y -2-(4-m e t h o x y -
p h en yl)-3-m eth ylin d ole (36a ). To a solution of 34 (35 mg,
0.080 mmol) in dry benzene (3 mL) was added DDQ (23.5 mg,
0.104 mmol), and the mixture was stirred for 20 h at rt. The
mixture was filtered, concentrated, and the residue was
dissolved in ether (20 mL), washed with 10% aqueous NaOH
solution (15 mL), dried (Na2SO4), and concentrated. Chroma-
tography (1:1:8 Et2O:CH2Cl2:hexanes) afforded 36a (25 mg,
72%) as a white solid, mp >190 °C dec (Et2O/hexanes); Rf 0.17
(3:3:4 Et2O:CH2Cl2:hexanes); 1H NMR (500 MHz) 7.91 (s, 1H),
7.44 (t, 1H, J ) 7.4), 7.34 (d, 2H, J ) 7.5), 7.26-7.21 (m, 4H),
6.95 (d, 2H, J ) 8.5), 6.80 (s, 1H), 4.04 (s, 3H), 3.93 (s, 3H),
3.88 (s, 3H), 1.99 (s, 3H); 13C NMR (125 MHz) 159.4, 147.9,
147.4, 137.7, 135.4, 133.2, 132.5, 131.2, 128.5, 126.6, 125.0,
123.8, 119.6, 112.8, 100.3 (2C), 56.4, 56.1, 55.2, 9.6; HRMS
m/ z 437.1326 (M+) (Calcd for C24H23NO5S 437.1297).
(1R*,5R*,6R*,7R*)-3-Hydr oxy-6-m eth yl-7-ph en ylbicyclo-
[3.2.1]oct-3-en e-2,8-dion e (33a). According to general method
B, trans-â-methylstyrene (26 µL, 0.20 mmol) was added to a
solution of a mixture of TiCl4 (20 µL, 0.181 mmol) and Ti(OiPr)4
(161 µL, 0.542 mmol) in CH2Cl2 (0.5 mL) and 3 (63.7 mg, 0.181
mmol) in CH2Cl2 (10 mL). The reaction was warmed gradually
to rt until finished (16 h). Workup and chromatography (1:
1:8 CH2Cl2:Et2O:hexanes) of the crude yellow oil afforded 33a
(18 mg, 41%) as a pale yellow oil which was identified by
comparison of spectral data to that reported.2a
(1R *,5R *,6R *,7R *)-3-H y d r o x y -6-m e t h y l-7-(3-m e t h -
oxyp h en yl)-bicyclo[3.2.1]oct-3-en e-2,8-d ion e (33b). Ac-
cording to general method B, (E)-3-propenylanisole (15 mg,
0.100 mmol) was added to a solution of a mixture of TiCl4 (33
µL, 0.30 mmol) and Ti(OiPr)4 (89 µL, 0.30 mmol) in CH2Cl2
(0.5 mL) and monoimide 3 (35 mg, 0.10 mmol) in CH2Cl2 (10
mL). The reaction was warmed gradually to rt until finished
(16 h). Workup and chromatography (1:1:8 to 2:2:6 CH2Cl2/
Et2O/hexanes) of the crude yellow oil afforded 33b (13 mg,
48%) as a light yellow oil; Rf 0.16 (3:3:4 Et2O:CH2Cl2:hexanes);
1H NMR (500 MHz) 7.20 (t, 1H, J ) 8.0), 6.78 (dd, 1H, J )
2.4, 8.0), 6.75 (d, 1H, J ) 8.5), 6.64 (bd, 1H, J ) 8.0), 6.60 (bs,
1H), 5.91 (s, 1H, OH), 3.86 (dd, 1H, J ) 1.8, 7.0), 3.77 (s, 3H),
3.21 (t, 1H, J ) 7), 3.06 (dd, 1H, J ) 1.8, 8.5), 2.56 (apparent
quintet, 1H), 1.26 (d, 3H, J ) 7.0); 13C NMR (125 MHz) 199.1,
191.5, 159.8, 149.9, 139.4, 129.8, 120.5, 119.6, 114.4, 112.8,
55.1, 54.2, 49.3, 42.3, 21.4, 12.0; HRMS m/ z 272.1049 (M+)
(Calcd for C16H16O4 272.1049).
1-(Ben zen esu lfon yl)-2-(3,4-d im eth oxyp h en yl)-6-m eth -
oxy-3-m eth ylin d ol-5-yl Tr iflu or om eth a n esu lfon a te (36b).
To a solution of 35 (65 mg, 0.11 mmol) in dry benzene (6 mL)
was added DDQ (65 mg, 0.29 mmol), and the mixture was
stirred for 24 h at 70 °C. The mixture was worked up as
described for 36a . Chromatography (1:1:8 Et2O:CH2Cl2:hex-
anes) afforded 36b (47 mg, 70%) as a white solid, mp 186-
1
187 °C (Et2O); Rf 0.39 (3:3:4 CH2Cl2:Et2O:hexanes); H NMR
(500 MHz) 8.08 (s, 1H), 7.50 (t, 1H, J ) 7.3), 7.35 (m, 4H),
7.26 (s, 1H), 6.87 (d, 1H, J ) 8.2), 6.73 (dd, 1H, J ) 1.9, 8.2),
6.70 (d, 1H, J ) 1.9), 4.06 (s, 3H), 3.96 (s, 3H), 3.82 (s, 3H),
1.98 (s, 3H); 13C NMR (125 MHz) 149.4, 149.3, 147.9, 138.2,
136.8, 136.7, 136.4, 133.7, 128.8, 126.8, 124.4, 124.2, 122.8,

9308 J . Org. Chem., Vol. 61, No. 26, 1996
Engler et al.
118.8 (q, J C-F ) 315), 118.5, 115.0, 112.3, 110.0, 101.0, 56.8,
55.9 (2C), 9.4. Anal. Calcd for C25H22NO8S2F3: C, 51.28; H,
3.79; N, 2.39. Found: C, 51.33; H, 3.53; N, 2.18.
55.9 (2C), 55.8, 9.5 (one sp2-C signal is not apparent); HRMS
m/ z 437.1307 (M+) (Calcd for C24H23NO5S 437.1297).
1-(Ben zen esu lfon yl)-2-(3,4-d im eth oxyp h en yl)-6-m eth -
oxy-3-m eth ylin d ole (36c). To triflate 36b (40 mg, 0.068
mmol) in DMF (0.35 mL) at rt was added palladium(II) acetate
trimer (9.7 mg, 0.14 mmol) followed by 1,1′-bis(diphenylphos-
phino)ferrocene (20 mg, 0.036 mmol), triethylamine (194 µL,
1.40 mmol), and a 90% aqueous formic acid solution (0.05 mL).
The mixture was heated at 90 °C for 24 h and then cooled,
and water (0.6 mL) was added followed by EtOAc (4 mL). The
aqueous layer was separated and extracted with EtOAc (3 ×
4 mL). The combined extracts were washed with saturated
aqueous ammonium chloride, saturated aqueous sodium bi-
carbonate, and water (5 mL each), dried (Na2SO4), and
concentrated. Chromatography (1:1:8 CH2Cl2:Et2O:hexanes)
of the crude brown oil afforded 36c (25 mg, 84%) as a white
solid, mp 149-150 °C (Et2O/hexanes); Rf 0.38 (3:3:4 Et2O:CH2-
Ack n ow led gm en t. Financial support for this re-
search was provided by the National Science Foundation
(CHE-9116576, OSR-9255223, and OSR-9550487) and
the University of Kansas General Research Fund. TAE
gratefully acknowledges a fellowship from the Alfred P.
Sloan Foundation. We thank Ms. Cynthia Scheibe for
help with initial experiments employing styrene 1a .
Su p p or tin g In for m a tion Ava ila ble: Full experimental
procedures for preparation of styrenes 1e/g, licarin B, and
eupomatenoids-1 and -12; IR and mass spectral data for all
new products; copies of 1H and 13C NMR spectra of new
compounds lacking combustion analytical data (49 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
1
Cl2:hexanes); H NMR (500 MHz) 7.91 (d, 1H, J ) 2.2), 7.45
(t, 1H J ) 7.4), 7.40 (d, 2H, J ) 7.5), 7.29 (m, 3H), 6.93 (dd,
1H, J ) 2.2, 8.5), 6.89 (d, 1H, J ) 8.1), 6.81 (m, 2H), 3.96 (s,
3H), 3.94 (s, 3H), 3.85 (s, 3H), 2.00 (s, 3H). 13C NMR (125
MHz) 158.1, 149.1, 147.8, 138.2, 135.2, 133.3, 128.5, 126.8,
125.5, 124.0, 123.9, 119.4, 119.3, 115.0, 112.9, 109.9, 100.7,
J O9617068