Direct synthesis of methyl 2-diazo-4-aryl-3-butenoates and their application to the enantioselective synthesis of 4-aryl-4-(1-naphthyl)-2-butenoates

Article abstract of DOI:10.1016/j.tetasy.2006.01.023

An improved one-flask synthesis of various methyl 2-diazo-4-aryl and 4-heteroaryl-3-butenoates, precursors to donor/acceptor substituted carbenoids, is described. Their Rh₂(S-DOSP)₄ catalyzed reaction with 1-acetoxy-3,4-dihydronaphth

Full text of DOI:10.1016/j.tetasy.2006.01.023

Tetrahedron: Asymmetry 17 (2006) 665–673
Direct synthesis of methyl 2-diazo-4-aryl-3-butenoates
and their application to the enantioselective synthesis
of 4-aryl-4-(1-naphthyl)-2-butenoates
Huw M. L. Davies,* Jaemoon Yang and James R. Manning
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260-3000, USA
Received 6 January 2006; accepted 20 January 2006
Available online 20 March 2006
Dedicated to Jack Halpern on the occasion of his 80th birthday
Abstract—An improved one-flask synthesis of various methyl 2-diazo-4-aryl and 4-heteroaryl-3-butenoates, precursors to donor/
acceptor substituted carbenoids, is described. Their Rh2(S-DOSP)4 catalyzed reaction with 1-acetoxy-3,4-dihydronaphthalene,
via a combined C–H activation/Cope rearrangement pathway followed by elimination of acetic acid affords a highly enantioselective
(98–99% ee) entry to methyl 4-aryl- and 4-heteroaryl-4-(1-naphthyl)-2-butenoates.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
4-phenyl-4-(1-naphthyl)-3-butenoate 3 (Scheme 1).4d In
order to broaden the utility of this chemistry to potential
pharmaceutical targets, the ready availability of a range
of aryl- and heteroarylvinyldiazoacetates would be
highly desirable. Herein, we report a one-flask synthesis
of a series of arylvinyldiazoacetates, the majority of
which have not been prepared before. Furthermore,
we illustrate through the synthesis of 4-aryl-4-(1-naph-
thyl)-2-butenoates the range of functionality that is
compatible with the combined C–H activation/Cope
rearrangement chemistry.
Recently, carbenoid chemistry has become an attractive
means for intermolecular functionalization of unacti-
vated C–H bonds.1–3 The metal-catalyzed decomposi-
tion of diazo compounds generates reactive carbenoid
intermediates that are capable of undergoing insertions
into C–H bonds.1 A major challenge of such transfor-
mations is controlling the reactivity of the carbenoid
species, such that selective functionalization of the sub-
strate can occur. An effective way to accomplish this is
through the use of diazo compounds that contain both
electron donating and electron accepting substituents.1
On metal-catalyzed decomposition they generate
donor/acceptor-substituted carbenoids that are highly
chemoselective. Methyl arylvinyldiazoacetates are a very
useful class of precursors to these donor/acceptor carb-
enoids. Their importance has been further increased by
the discovery of the combined C–H activation/Cope
rearrangement as a highly diastereoselective and enan-
tioselective transformation.4 An example of the utiliza-
tion of this chemistry is the dirhodium tetrakis-
(N-(dodecylbenzenesulfonyl)prolinate) [Rh2(S-DOSP)4]
catalyzed reaction of methyl styryldiazoacetate 1 with
1-acetoxy-3,4-dihydronaphthalene 2 to form methyl
2. Results and discussion
The existing protocol for the synthesis of arylvinyldi-
azoacetates usually begins from the arylcarboxaldehyde
and requires three discrete steps, a Wittig reaction to
generate the 4-arylbutenoic acid, an esterification step
and a diazo transfer step.5 In addition, tedious extrac-
tions and chromatographic purifications at two stages
are required. The synthesis of the arylvinyldiazoacetates
would be much more convenient if a one-flask procedure
was developed and only a single chromatographic
purification was required in the final step. In order to
explore the possibility of developing a one-flask proce-
dure, 3,4-dimethoxybenzaldehyde 4a was used as a mod-
el substrate. After considerable experimentation, THF
was found to be the optimum solvent for compatibility
*
Corresponding author. Tel.: +1 716 645 6800x2186; fax: +1 716 645
6547; e-mail: hdavies@acsu.buffalo.edu
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.01.023

666
H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
Ph
CO2Me
CO2Me
OAc
N2
Rh2(S-DOSP)4
DMB, 0 oC
+
Ph
1
2
3
85% yield, 99.6% ee
Scheme 1. Previous example of the enantioselective synthesis of methyl 4-(1-naphthyl)-4-phenylbutenoate.
with the three reaction steps. The reaction of 4a with
Wittig reagent 5 using an excess of potassium t-butoxide
as base generated the potassium butenoate 6a, which
was then directly methylated with dimethyl sulfate to
form the methyl butenoate 7a. p-Acetamidobenz-
enesulfonyl azide (p-ABSA)6 and DBU were then
added to the reaction mixture to form the arylvinyl-
diazoacetate 8a. The overall yield for the three step
sequence was 63% and 8a was formed in a >20:1 E:Z
isomer ratio (Scheme 2).
heteroatoms such as the thiophene 8k–m, pyridine 8n,
and benzothiophene 8p derivatives. Even so, if the het-
eroatom is reasonably protected as in the case of the
5-substituted thiophenes 8l and 8m, butenoates 9l and
9m can be formed in good yield and very high enantio-
selectivity. Furan derivative 8i failed to form any of the
butenoate 9i, but this is unsurprising because furans
are highly reactive toward carbenoid intermediates.7
Once again, if the furan is sterically protected as in the
5-chloro derivative 8j, the corresponding butenoate 9j
can be formed in 45% yield. Striking examples that illus-
trate the selectivity of the combined C–H activation/
Cope rearrangement are the successful reactions with
the indole derivatives 8g and 8h.
Having established that the one-flask protocol was effec-
tive, the synthesis of various methyl arylvinyldiazoace-
tate derivatives was undertaken (Table 1). Styryldiazo-
acetates 8a–e with a range of phenyl substituents were
formed in 46–65% yield. The reaction could also be ex-
tended to naphthyl 8f, indole 8g and 8h, furan 8i and 8j,
thiophene 8k–m, pyridine 8n, benzofuran 8o, and benzo-
thiophene 8p derivatives to form the arylvinyldiazoace-
tates in 17–64% yield. In all cases, a high preference
for the formation of the (E)-isomer was observed, and
in cases where significant traces of the (Z)-isomer
were present, it was readily removed by column
chromatography.
The mechanism of the transformation is considered to
be a combined C–H activation/Cope rearrangement to
form 10, followed by elimination of acetic acid and gen-
eration of butenoate 9 (Fig. 1). The combined C–H acti-
vation/Cope rearrangement has been shown to be highly
enantioselective (generally, >96% ee)4 and the stereo-
chemical outcome has been consistent with the model
shown in Figure 1.4d In this model, the catalyst is config-
ured in a D2-symmetric arrangement with two blocking
groups as shown. The substrate approaches from the
front and over the vinyl part of the carbenoid to give
the initial C–H activation/Cope rearrangement interme-
diate 10. In our previous studies, aryl compounds
related to 10 were prone to a retro-Cope rearrange-
ment,4d,e but in this case elimination of acetic acid
occurs preferentially to form 9. The current studies show
that the enantioselectivity in the combined C–H activa-
tion/Cope rearrangement is virtually independent of the
nature of the aryl substituent in the methyl arylvinyldi-
With a variety of arylvinyldiazoacetates in hand, the
next step was to test their reactivity in the C–H activa-
tion/Cope rearrangement reaction with 1-acetoxy-3,4-
dihydronaphthalene (Table 2). This reaction was very
favorable with the majority of substrates resulting in
the formation of the 4-aryl-4-(1-naphthyl)butenoates in
high yield (79–90%) and exceptionally high enantioselec-
tivity (P98% ee). Exceptions to this general trend were
in the case of heterocycles containing very nucleophilic
Ph3P+(CH2)2CO2H Cl- 5
O
Me2SO4 (2 eq)
rt, 15 h
MeO
MeO
MeO
MeO
(1.2 eq)
CO2K
H
6a
KOt-Bu (2.6 eq)
THF, rt, 2 h
4a
in the flask
N2
DBU (2 eq)
p-ABSA (1.5 eq)
MeO
MeO
MeO
CO2Me
CO2Me
0 oC, 2 h
7a
in the flask
MeO
8a
(63% yield)
Scheme 2. One-pot synthesis of arylvinyldiazoacetate.

H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
667
Table 1. One-flask, three-step synthesis of methyl arylvinyldiazoace-
tates
Table 2. C–H Activation chemistry of arylvinyldiazoacetates
Ar
CO2Me
OAc
Rh2(S-DOSP)4
(0.5 mol%)
N2
CO2Me
P+
Ph3 (CH2)2CO2H Cl-
N2
KOt-Bu, THF; Me2SO4;
+
hex-tol, rt
ArCHO
Ar
CO2Me
Ar
then DBU, p-ABSA
2
8
9
Producta
Ar
Yield (%)
ee (%)
Product
Ar
Yield (%)
8a
63
9a
92
99.5
MeO
MeO
OMe
OMe
9b
9c
79
82
99.4
99.1
8b
8c
59
65
Br
Br
MeO
MeO
9d
79
>98
Cl
Cl
8d
46
Cl
Cl
9e
9f
90
89
98.5
Ph
8e
8f
49
55
Ph
>98
9g
9h
82
82
>98
>98
N
Boc
8g
49
Br
N
Boc
N
Boc
Br
9i
0
45
14
88
66
8h
8i
17
69
O
N
Boc
9j
99.6
Cl
O
S
O
9k
9l
ND
S
8j
46
62
Cl
O
99.5
Cl
8k
S
9m
99.3
Ph
S
8l
54
50
33
Cl
S
S
9n
9o
9p
0
60
20
N
8m
8n
Ph
99.1
O
S
ND
N
a Reaction conducted at 23 ꢁC with 8 (2 equiv) added over 1 h to a
stirred solution of 2 (1 equiv) and Rh2(S-DOSP)4 (0.5 mol %) and
then stirred overnight. The yield represents isolated yield after
chromatography except for 9k, which represents an NMR deter-
mined conversion. The enantiomeric excess for some of the products
could not be reported to three significant figures due to excessive
peak broadening during the chiral HPLC analysis.
8o
8p
30
30
O
S

668
H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
Rh
δ−
H
Rh
Ar
CO2Me
Ar
AcO
CO2Me
C-H/Cope
Ar
AcO
CO2Me
+ H
H
δ
H
9
10
Figure 1. Predictive stereochemical model for Rh2(S-DOSP)4-catalyzed reaction.
azoacetates because 9 is formed in P98% ee in all cases.
On the basis of this model, the predicted configuration
for 9 is as drawn. Supporting evidence that this predic-
tion was correct was obtained by comparing the specific
rotation of 3 derived from the reactions of 1 and 2 with
the material obtained from the reaction of 8f with 1,3-
cyclohexadiene.4a
4.2. (E)-Methyl 2-diazo-4-(3,4-dimethoxyphenyl)but-3-
enoate 8a
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 2:1) to give 8a as a red solid (0.825 g,
63% yield), Rf 0.29 (pentane–diethyl ether, 2:1); FTIR
(neat): 2079, 1702, 1514, 1246 cmꢀ1
;
1H NMR
(500 MHz, CDCl3): d 6.91 (d, J = 2.0 Hz, 1H), 6.88
(dd, J = 8.2, 2.0 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H),
6.30 (d, J = 16.5 Hz, 1H), 6.14 (d, J = 16.5 Hz, 1H),
3.91 (s, 3H), 3.89 (s, 3H), 3.86 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 165.2 (C), 148.7 (C), 148.0 (C),
129.5 (C), 122.6 (CH), 118.5 (CH), 110.7 (CH), 108.2
(CH), 107.8 (CH), 55.31 (CH3), 55.27 (CH3), 51.7
(CH3), missing carbon attributed to C@N2; LC–MS
(ESI) m/z (relative intensity): 235.0 (100), 263.1
([M+H]+, 81). Anal. Calcd for C13H14N2O4: C, 59.54;
H, 5.38. Found: C, 59.60; H, 5.37.
3. Conclusion
In conclusion, we have developed a very convenient one-
flask protocol for the synthesis of a wide variety of aryl
and heteroarylvinyldiazoacetates, which requires only
one purification step. The reactivity of these diazo com-
pounds with 1-acetoxy-3,4-dihydronaphthalene through
a combined C–H activation/Cope rearrangement path-
way has been explored. The corresponding 4-aryl-4-
(1-naphthyl)butenoates were obtained in P98% ee.
These studies demonstrate that a variety of heterocyclic
systems are compatible with the chemistry of the donor/
acceptor substituted rhodium carbenoids.
4.3. (E)-Methyl 2-diazo-4-(4-bromophenyl)but-3-
enoate 8b
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 10:1) to give 8b as a red solid (0.829 g,
59% yield), Rf 0.36 (petroleum ether–diethyl ether,
9:1); FTIR (neat): 3010, 2953, 2845, 2078, 1705,
4. Experimental
4.1. General procedure for preparation of the
vinyldiazoacetates 8
1626 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.43 (d,
;
J = 8.5 Hz, 2H), 7.21 (d, J = 8.5 Hz, 2H), 6.48 (d,
J = 16.5 Hz, 1H), 6.13 (d, J = 16.5 Hz, 1H), 3.85 (s,
3H); 13C NMR (75 MHz, CDCl3): d 165.2 (C), 135.6
(C), 131.7 (CH), 127.2 (CH), 121.6 (CH), 120.6 (C),
112.1 (CH), 52.2 (CH3), missing carbon attributed to
C@N2; HRMS (EI) calcd for C11H9N2O2Br 279.9847,
found 279.9824.
A solution of potassium tert-butoxide (1.46 g, 13 mmol)
in THF (14 mL) was added at 0 ꢁC via syringe into a
mixture of the aldehyde (5 mmol) and 2-carboxyethyltri-
phenylphosphonium chloride (2.22 g, 6.0 mmol)4a in
THF (12 mL) over 15 min. The reaction mixture was
stirred for a further 15 min at 0 ꢁC and then 2 h at ambi-
ent temperature under argon. Dimethyl sulfate (1.26 g,
10 mmol) was then added at ambient temperature and
the mixture stirred for a further 15 h under argon. The
mixture was then cooled in an ice bath and DBU
(1.52 g, 10 mmol) slowly added followed by p-ABSA
(1.80 g, 7.5 mmol), which was added in several portions
at 0 ꢁC over 5 min. After stirring for 2 h at 0 ꢁC under
argon, the solvent was removed in vacuo and the residue
diluted with cold water (10 mL), CH2Cl2 (20 mL), and
saturated NH4Cl (20 mL). The organic layer was
washed once with saturated NH4Cl, dried over MgSO4,
filtered, and then concentrated. Purification of product 8
was performed by flash chromatography on silica gel or
neutral alumina using a pentane/diethyl ether solvent
system.
4.4. (E)-Methyl 2-diazo-4-(4-methoxyphenyl)but-3-
enoate 8c
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 8c as a red solid (0.754 g,
65% yield), Rf 0.23 (pentane–diethyl ether, 9:1); FTIR
(neat): 3041, 3009, 2956, 2834, 2072, 1694 cmꢀ1 1H
;
NMR (500 MHz, CDCl3): d 7.29 (d, J = 8.8 Hz, 2H),
6.86 (d, J = 8.8 Hz, 2H), 6.29 (d, J = 16.0 Hz, 1H),
6.14 (d, J = 16.0 Hz, 1H), 3.84 (s, 3H), 3.80 (s, 3H);
13C NMR (75 MHz, CDCl3): d 165.8 (C), 158.8 (C),
129.6 (C), 127.0 (CH), 122.7 (CH), 114.1 (CH), 108.5
(CH), 55.2 (CH3), 52.2 (CH3), missing carbon attributed
to C@N2; HRMS (EI) calcd for C12H12N2O3 232.0848,
found 232.0867.

H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
669
4.5. (E)-Methyl 2-diazo-4-(3,4-dichlorophenyl)but-3-
enoate 8d
(CH), 114.4 (CH), 110.5 (CH), 83.6 (C), 52.0 (CH3),
27.9 (CH3), missing carbon attributed to C@N2; HRMS
(EI) calcd for C18H19N3O4 341.1370, found 341.1369.
Anal. Calcd for C18H19N3O4: C, 63.33; H, 5.61. Found:
C, 63.57; H, 5.77.
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 10:1) to give 8d as a red solid (0.623 g,
46% yield), Rf 0.30 (petroleum ether–diethyl ether,
9:1); FTIR (neat): 3051, 3000, 2954, 2149, 2086,
4.9. tert-Butyl-3-((E)-3-(methoxycarbonyl)-3-diazoprop-
1-enyl)-5-bromo-1H-indole-1-carboxylate 8h
1697 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.41 (d,
;
J = 2.0 Hz, 1H), 7.35 (d, J = 8.5 Hz, 1H), 7.16 (dd,
J = 8.5, 2.0 Hz, 1H), 6.48 (d, J = 16.5 Hz, 1H), 6.10
(d, J = 16.5 Hz, 1H), 3.86 (s, 3H); 13C NMR
(125 MHz, CDCl3): d 164.9 (C), 136.8 (C), 132.6 (C),
130.35 (CH), 130.28 (C), 127.2 (CH), 124.7 (CH),
120.1 (CH), 113.6 (CH), 52.3 (CH3), missing carbon
attributed to C@N2; HRMS (EI) calcd for
C11H8N2O2Cl2 269.9963, found 269.9972.
Purified via flash chromatography (neutral alumina,
pentane–diethyl ether, 9:1) to give 8h as a pink solid
(0.357 g, 17% yield), Rf 0.37 (pentane–diethyl ether,
5:1); FTIR (CH2Cl2): 2079, 1736, 1710, 1450,
1371 cmꢀ1 1H NMR (500 MHz, CDCl3): d 8.05 (m,
;
1H), 7.85 (d, J = 2.0 Hz, 1H), 7.59 (s, 1H), 7.43 (dd,
J = 8.5, 2.0 Hz, 1H), 6.46 (d, J = 16.5 Hz, 1H), 6.27
(d, J = 16.5 Hz, 1H), 3.88 (s, 3H), 1.67 (s, 9H); 13C
NMR (75 MHz, CDCl3): d 165.4 (C), 149.0 (C), 134.5
(C), 129.9 (C), 127.5 (CH), 123.3 (CH), 122.1 (CH),
117.8 (C), 116.7 (CH), 116.3 (C), 113.5 (CH), 111.5
(CH), 84.2 (C), 52.2 (CH3), 28.1 (CH3), missing carbon
attributed to C@N2; LC–MS (ESI) m/z (relative inten-
sity): 447.9 (100), 441.9 ([M+Na]+, 57.1); HRMS (ESI)
calcd for C18H18NaBrN3O4 442.0373, found 442.0375.
4.6. (E)-Methyl 2-diazo-4-(4-biphenyl)but-3-enoate 8e
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 8e as a red solid (0.677 g,
49% yield), Rf 0.32 (pentane–diethyl ether, 5:1); FTIR
(neat): 3020, 2947, 2072, 1699 cmꢀ1
;
1H NMR
(500 MHz, CDCl3): d 7.61–7.56 (m, 4H), 7.46–7.43 (m,
4H), 7.36–7.33 (m, 1H), 6.53 (d, J = 16.3 Hz, 1H), 6.24
(d, J = 16.3 Hz, 1H), 3.87 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 165.3 (C), 140.4 (C), 139.5 (C), 135.7 (C),
128.6 (CH), 127.2 (CH), 126.7 (CH), 126.1 (CH), 122.4
(CH), 111.1 (CH), 52.2 (CH3), one missing carbon
attributed to C@N2, the other to accidental equivalence;
HRMS (EI) m/z calcd for [C17H14N2O2]+ (M+):
278.1050, found 278.1053.
4.10. (E)-Methyl 2-diazo-4-(furan-2-yl)but-3-enoate 8i
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 19:1) to give 8i as a red oil (0.662 g, 69%
yield); Rf 0.54 (pentane–diethyl ether, 9:1); FTIR (neat)
1
2080, 1707 cmꢀ1; H NMR (500 MHz, CDCl3): d 7.34
(d, J = 1.5 Hz, 1H), 6.39–6.35 (m, 2H), 6.16 (d,
J = 3.5 Hz, 1H), 6.12 (d, J = 16 Hz, 1H), 3.83 (s, 3H);
13C NMR (75 MHz, CDCl3): d 165.3 (C), 152.7 (C),
141.9 (CH), 111.7 (CH), 111.4 (CH), 109.6 (CH), 106.8
(CH), 52.2 (CH3), missing carbon attributed to C@N2;
HRMS (EI) calcd for C9H8N2O3 192.0535, found
192.0529.
4.7. (E)-Methyl 2-diazo-4-(naphthalen-3-yl)but-3-enoate
8f
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1–7:1) to give 8f as a red solid (0.697 g,
55% yield), Rf 0.31 (pentane–diethyl ether, 9:1); FTIR
(neat): 3057, 3020, 2946, 2120, 2093, 1705 cmꢀ1
;
1H
4.11. (E)-Methyl 2-diazo-4-(5-chlorofuran-2-yl)but-
3-enoate 8j
NMR (500 MHz, CDCl3): d 7.80–7.78 (m, 3H), 7.69
(s, 1H), 7.60 (dd, J = 9.0, 1.8 Hz, 1H), 7.47–7.41 (m,
2H), 6.60 (d, J = 16.5 Hz, 1H), 6.36 (d, J = 16.5 Hz,
1H), 3.88 (s, 3H); 13C NMR (75 MHz, CDCl3): d
165.4 (C), 134.2 (C), 133.5 (C), 132.5 (C), 128.2 (CH),
127.8 (CH), 127.5 (CH), 126.2 (CH), 125.6 (CH), 125.3
(CH), 122.99 (CH), 122.95 (CH), 111.3 (CH), 52.1
(CH3), missing carbon attributed to C@N2; HRMS
(EI) calcd for C15H12N2O2 252.0899, found 252.0899.
Purified via flash chromatography (neutral alumina,
pentane–diethyl ether, 19:1) to give 8j as a red solid
(0.522 g, 46% yield), Rf 0.47 (pentane–diethyl ether,
9:1); FTIR (neat) 2954, 2084, 1708, 1632, 1339 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d 6.36 (d, J = 16.2 Hz,
1H), 6.14 (s, 2H), 6.06 (d, J = 16.2 Hz, 1H), 3.85 (s,
3H); 13C NMR (75 MHz, CDCl3): d 165.2 (C), 152.3
(C), 135.8 (C), 110.7 (CH), 110.2 (CH), 108.6 (CH),
108.0 (CH), 52.2 (CH3), missing carbon attributed to
C@N2; HRMS (EI) calcd for C9H7ClN2O3 226.0140,
found 226.0141.
4.8. tert-Butyl 3-((E)-3-(methoxycarbonyl)-3-diazoprop-
1-enyl)-1H-indole-1-carboxylate 8g
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 8g as a red solid (0.840 g,
49% yield), Rf 0.26 (pentane–diethyl ether, 9:1); FTIR
4.12. (E)-Methyl 2-diazo-4-(thiophen-2-yl)but-3-
enoate 8k
1
(neat) 2079, 1734 cmꢀ1; H NMR (500 MHz, CDCl3):
d 8.17 (m, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H),
7.35 (t, J = 7.5 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 6.52
(d, J = 16.5 Hz, 1H), 6.32 (d, J = 16.5 Hz, 1H), 3.87
(s, 3H), 1.67 (s, 9H); 13C NMR (75 MHz, CDCl3): d
165.4 (C), 149.2 (C), 135.7 (C), 128.1 (C), 124.6 (CH),
122.8 (CH), 122.6 (CH), 119.4 (CH), 118.3 (C), 115.2
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 19:1) to give 8k as a red solid (0.644 g,
62% yield), Rf 0.41 (pentane–diethyl ether, 9:1); FTIR
1
(neat) 2080, 1703 cmꢀ1; H NMR (500 MHz, CDCl3):
d 7.15 (d, J = 5.0 Hz, 1H), 6.95 (dd, J = 5.0, 3.5 Hz,
1H), 6.90 (d, J = 3.5 Hz, 1H), 6.42 (d, J = 16 Hz, 1H),

670
H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
6.27 (d, J = 16 Hz, 1H), 3.85 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 165.3 (C), 142.1 (C), 127.4 (CH),
124.5 (CH), 124.1 (CH), 116.7 (CH), 110.4 (CH), 52.2
(CH3), missing carbon attributed to C@N2; HRMS
(EI) calcd for C9H8N2O2S 208.0301, found 208.0307.
(neat): 2083, 1709, 1688, 1339 cmꢀ1 1H NMR
;
(500 MHz, CDCl3): d 7.49 (d, J = 7.6 Hz, 1H), 7.43 (d,
J = 7.9 Hz, 1H), 7.24 (t, J = 7.0 Hz, 1H), 7.18 (t,
J = 7.0 Hz, 1H), 6.72 (d, J = 16.0 Hz, 1H), 6.50 (s,
1H), 6.28 (d, J = 16.0 Hz, 1H), 3.88 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 165.0 (C), 154.8 (C), 154.5 (C),
129.1 (C), 124.2 (CH), 122.8 (CH), 120.6 (CH), 113.3
(CH), 111.3 (CH), 110.7 (CH), 103.3 (CH), 52.3
(CH3), missing carbon attributed to C@N2; LRMS
(EI) m/z (relative intensity): 155.0 (100), 242.0 ([M]+,
28.5); HRMS (EI) m/z calcd for [C13H10N2O3]+
(M+): 242.0686, found 242.0691. Anal. Calcd for
C13H10N2O3: C, 64.46; H, 4.16. Found: C, 64.74; H,
4.17.
4.13. (E)-Methyl 2-diazo-4-(5-chlorothiophen-2-yl)but-
3-enoate (8l)
Purified via flash chromatography (neutral alumina,
pentane–diethyl ether, 20:1) to give 8l as an orange solid
(0.656 g, 54% yield), Rf 0.36 (pentane–diethyl ether, 9:1);
FTIR (neat): 2083, 1705 cmꢀ1 1H NMR (500 MHz,
;
CDCl3):
d
6.75 (d, J = 3.5 Hz, 1H), 6.65 (d,
J = 3.5 Hz, 1H), 6.29 (d, J = 16 Hz, 1H), 6.14 (d,
J = 16 Hz, 1H), 3.85 (s, 3H); 13C NMR (125 MHz,
CDCl3): d 164.9 (C), 140.9 (C), 128.2 (C), 126.4 (CH),
123.5 (CH), 116.0 (CH), 110.7 (CH), 52.1 (CH3), missing
carbon attributed to C@N2; HRMS (EI) calcd for
C9H7ClN2O2S 241.9911, found 241.9908.
4.17. (E)-Methyl 2-diazo-4-(benzo[b]thiophen-3-yl)but-3-
enoate (8p)
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 8p as a red solid (0.382 g,
30% yield), Rf 0.30 (pentane–diethyl ether, 5:1); FTIR
4.14. (E)-Methyl 2-diazo-4-(5-phenylthiophen-2-yl)but-
3-enoate 8m
(neat): 2080, 1699, 1230 cmꢀ1 1H NMR (500 MHz,
;
CDCl3): d 7.89–7.85 (m, 2H), 7.43–7.36 (m, 3H),
6.57–6.48 (m, 2H), 3.88 (s, 3H); 13C NMR (125 MHz,
CDCl3): d 165.3 (C), 140.2 (C), 137.0 (C), 133.2
(C), 124.4 (CH), 124.1 (CH), 122.7 (CH), 121.5 (CH),
120.7 (CH), 115.1 (CH), 112.3 (CH), 52.1 (CH3),
missing carbon attributed to C@N2; HRMS (EI) m/z
calcd for [C13H10N2O2S]+ (M+): 258.0457, found
258.0466.
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 8m as a pink solid (0.714 g,
50% yield), Rf 0.33 (pentane–diethyl ether, 5:1); FTIR
(neat): 2090, 1708, 1437, 1260 cmꢀ1
;
1H NMR
(500 MHz, CDCl3): d 7.59 (d, J = 7.5 Hz, 2H), 7.37
(appt. t, J = 8.0 Hz, 2H), 7.27 (t, J = 8.0 Hz, 1H), 7.17
(d, J = 4.0 Hz, 1H), 6.85 (d, J = 4.0 Hz, 1H), 6.38 (d,
J = 16.0 Hz, 1H), 6.28 (d, J = 16.0 Hz, 1H), 3.84 (s,
3H); 13C NMR (125 MHz, CDCl3): d 165.2 (C), 142.7
(C), 141.5 (C), 134.0 (C), 128.7 (CH), 127.3 (CH),
125.7 (CH), 125.3 (CH), 123.3 (CH), 116.7 (CH), 110.1
(CH), 52.2 (CH3), missing carbon attributed to C@N2;
HRMS (EI) m/z calcd for [C15H12N2O2S]+ (M+):
284.0614, found 284.0619.
4.18. General procedure for preparation of the 4-aryl-4-
(1-naphthyl)butenoates 9
A solution of 8 (1.0 mmol) in toluene (14 mL) and hex-
anes (1 mL) was added via a syringe pump over 30 min
into a green solution of 3,4-dihydro-1-naphthalenyl ace-
tate 2 (0.094 g, 0.5 mmol) and Rh2(S-DOSP)4 (10 mg,
0.005 mmol) in toluene (0.5 mL) and hexanes (1.5 mL).
After stirring for at least 12 h at rt under argon, the
crude reaction mixture was concentrated in vacuo and
purified by flash chromatography on silica gel using a
pentane/diethyl ether solvent system to give 9.
4.15. (E)-Methyl 2-diazo-4-(pyridin-3-yl)but-3-enoate 8n
Purified via flash chromatography (neutral alumina,
pentane–diethyl ether, 2:1) to give 8n as a red solid
(0.335 g, 33% yield), Rf 0.20 (pentane–diethyl ether,
2:1 · 2); FTIR (neat): 2085, 1702, 1252 cmꢀ1
;
1H
4.19. (S,E)-Methyl 4-(3,4-dimethoxyphenyl)-4-(naphtha-
len-5-yl)but-2-enoate 9a
NMR (400 MHz, CD3OD): d 8.42 (d, J = 2.4 Hz, 1H),
8.23 (dd, J = 4.8, 0.8 Hz, 1H), 7.83 (d, J = 8.0 Hz,
1H), 7.29 (dd, J = 8.0, 4.8 Hz, 1H), 6.63 (d,
J = 16.8 Hz, 1H), 6.34 (d, J = 16.8 Hz, 1H), 3.76 (s,
3H); 13C NMR (75 MHz, CDCl3): d 164.3 (C), 147.4
(CH), 147.2 (CH), 132.0 (C), 131.3 (CH), 122.9 (CH),
118.5 (CH), 113.3 (CH), 51.8 (CH3), missing carbon
attributed to C@N2; HRMS (ESI) m/z calcd for
[C10H10N3O2]+ (M+H)+: 204.0768, found 204.0761.
Anal. Calcd for C10H9N3O2: C, 59.11; H, 4.46. Found:
C, 58.90; H, 4.48.
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 3:2) to give 9a as a solid (0.166 g, 92%
yield); mp 47–55 ꢁC; Rf 0.33 (pentane–diethyl ether,
25
2:1); ½aꢁD ¼ þ33:6 (c 1.80, CHCl3); FTIR (neat): 1719,
1515, 1265 cmꢀ1 1H NMR (500 MHz, CD3OD): d
;
7.91 (m, 1H), 7.78 (m, 1H), 7.71 (d, J = 8.5 Hz, 1H),
7.44 (dd, J = 16.5, 6.5 Hz, 1H), 7.38–7.32 (m, 3H),
7.20 (d, J = 7.0 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.69
(d, J = 2.0 Hz, 1H), 6.61 (dd, J = 8.0, 2.0 Hz, 1H),
5.59 (d, J = 6.0 Hz, 1H), 5.53 (dd, J = 16.0, 1.5 Hz,
1H), 3.70 (s, 3H), 3.615 (s, 3H), 3.612 (s, 3H); 13C
NMR (75 MHz, CDCl3): d 166.9 (C), 150.6 (CH),
149.2 (C), 148.0 (C), 137.2 (C), 134.1 (C), 133.4 (C),
131.5 (C), 128.9 (CH), 127.9 (CH), 126.35 (CH),
126.26 (CH), 125.6 (CH), 125.3 (CH), 123.8 (CH),
122.9 (CH), 121.0 (CH), 112.1 (CH), 111.2 (CH), 55.8
4.16. (E)-Methyl 2-diazo-4-(benzofuran-2-yl)but-3-
enoate 8o
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 8:1) to give 8o as a red solid (0.363 g,
30% yield), Rf 0.31 (pentane–diethyl ether, 5:1); FTIR

H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
671
25
(CH3), 51.5 (CH3), 49.0 (CH), missing carbon attributed
yield); Rf 0.24 (pentane–diethyl ether, 9:1); ½aꢁD
¼
to accidental equivalence of two of the methoxy groups;
HRMS (EI) calcd for C23H22O4 362.1513, found
362.1520; HPLC analysis: 99.5% ee (Chiralcel OD-H,
10% i-PrOH in hexanes, 1.0 mL/min, k = 254 nm,
tR = 13.8 min, major; tR = 21.2 min, minor). Anal.
Calcd for C23H22O4: C, 76.22; H, 6.12. Found: C,
75.83; H, 6.33.
þ37:7 (c 4.88, CHCl3); FTIR (neat): 1723 cmꢀ1
;
1H
NMR (500 MHz, CD3OD): d 7.98 (m, 1H), 7.92 (m,
1H), 7.88 (d, J = 8.0 Hz, 1H), 7.56–7.46 (m, 5H), 7.36
(d, J = 2.0 Hz, 1H), 7.34 (d, J = 7.0 Hz, 1H), 7.15 (dd,
J = 8.5, 2.0 Hz, 1H), 5.81 (d, J = 6.5 Hz, 1H), 5.70
(dd, J = 16.0, 1.5 Hz, 1H), 3.75 (s, 3H); 13C NMR
(125 MHz, CDCl3): d 166.4 (C), 148.9 (CH), 141.2 (C),
135.8 (C), 134.0 (C), 132.8 (C), 131.1 (C), 131.0 (C),
130.6 (CH), 130.5 (CH), 129.0 (CH), 128.4 (CH), 128.1
(CH), 126.5 (CH), 126.4 (CH), 125.8 (CH), 125.3
(CH), 123.6 (CH), 123.3 (CH), 51.6 (CH3), 48.4
(CH); HRMS (EI) calcd for C21H16Cl2O2 370.0522,
found 370.0528; HPLC analysis: >98% ee (Chiralcel
OD-H, 5% i-PrOH in hexanes, 0.8 mL/min, k =
254 nm, tR = 14.3 min, major; 34.0 min, minor). Anal.
Calcd for C21H16Cl2O2: C, 67.94; H, 4.34. Found: C,
68.07; H, 4.51.
4.20. (S,E)-Methyl 4-(4-bromophenyl)-4-(naphthalen-5-
yl)but-2-enoate 9b
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9b as a yellow solid (0.151 g,
79% yield); mp 45–47 ꢁC; Rf 0.36 (pentane–diethyl ether,
25
9:1); ½aꢁD ¼ þ24:5 (c 0.80, CHCl3); FTIR (neat):
1
1719 cmꢀ1; H NMR (500 MHz, CD3OD): d 7.88–7.86
(m, 1H), 7.80–7.78 (m, 1H), 7.23 (d, J = 7.5 Hz, 1H),
7.43 (dd, J = 15.5, 6.5 Hz, 1H), 7.38–7.33 (m, 5H),
7.19 (d, J = 7.5 Hz, 1H), 7.03 (d, J = 8.5 Hz, 2H), 5.65
(d, J = 6.5 Hz, 1H), 5.55 (dd, J = 15.5, 1.5 Hz, 1H),
3.62 (s, 3H); 13C NMR (75 MHz, CDCl3): d 166.7 (C),
149.7 (CH), 140.0 (C), 136.4 (C), 134.1 (C), 131.8
(CH), 131.2 (C), 130.5 (CH), 129.0 (CH), 128.2 (CH),
126.5 (CH), 126.4 (CH), 125.7 (CH), 125.3 (CH), 123.6
(CH), 123.4 (CH), 121.0 (C), 51.6 (CH3), 48.8 (CH);
HRMS (EI) calcd for C21H17BrO2 380.0406, found
380.0402; HPLC analysis: 99.4% ee (Chiralcel OD-H,
5% i-PrOH in hexanes, 0.8 mL/min, k = 254 nm,
tR = 12.1 min, major; tR = 27.0 min, minor). Anal.
Calcd for C21H17BrO2: C, 66.16; H, 4.49. Found: C,
65.94; H, 4.49.
4.23. (S,E)-Methyl 4-(4-biphenyl)-4-(naphthalen-5-yl)but-
2-enoate 9e
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 9e as a yellow solid (0.125 g,
66% yield), mp 53–55 ꢁC; Rf 0.21 (pentane–diethyl ether,
25
5:1); ½aꢁD ¼ þ2:4 (c 3.02, CHCl3); FTIR (CDCl3): 3028,
2948, 1721, 1652 cmꢀ1; H NMR (400 MHz, CDCl3): d
1
8.04 (m, 1H), 7.93–7.85 (m, 2H), 7.69–7.29 (m, 14H),
5.80–5.73 (m, 2H), 3.78 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 166.8 (C), 150.3 (CH), 140.5 (C), 139.9 (C),
139.8 (C), 137.0 (C), 134.1 (C), 131.4 (C), 129.1 (CH),
128.9 (CH), 128.7 (CH), 127.9 (CH), 127.4 (CH), 127.2
(CH), 126.9 (CH), 126.5 (CH), 126.3 (CH), 125.6
(CH), 125.3 (CH), 123.7 (CH), 123.0 (CH), 51.5
(CH3), 49.0 (CH); LRMS (ESI) m/z (relative intensity):
379.1 ([M+H]+, 70); HPLC analysis: 98.5% ee (Chiralcel
OD-H, 10% i-PrOH in hexanes, 0.9 mL/min, k =
254 nm, tR = 13.0 min, major; tR = 21.9 min, minor).
Anal. Calcd for C27H22O2: C, 85.69; H, 5.86. Found:
C, 85.46; H, 5.89.
4.21. (S,E)-Methyl 4-(4-methoxyphenyl)-4-(naphthalen-5-
yl)but-2-enoate 9c
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9c as an oil (0.136 g, 82%
25
yield); Rf 0.15 (9:1 pentane–diethyl ether); ½aꢁD
¼
þ35:1 (c 1.51, CHCl3); FTIR (neat): 1722, 1510,
1251 cmꢀ1; H NMR (500 MHz, CD3OD): d 7.89 (d,
1
J = 7.5 Hz, 1H), 7.77 (m, 1H), 7.71 (d, J = 8.5 Hz,
1H), 7.44 (dd, J = 16.5, 6.5 Hz, 1H), 7.36–7.31 (m,
3H), 7.18 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 8.5 Hz,
2H), 6.76 (d, J = 8.5 Hz, 2H), 5.58 (d, J = 6.5 Hz, 1H),
5.50 (dd, J = 16, 1.5 Hz, 1H), 3.66 (s, 3H), 3.61 (s,
3H); 13C NMR (75 MHz, CDCl3): d 166.9 (C), 158.5
(C), 150.8 (CH), 137.4 (C), 134.1 (C), 132.9 (C), 131.4
(C), 129.8 (CH), 128.8 (CH), 127.8 (CH), 126.3 (CH),
126.2 (CH), 125.6 (CH), 125.3 (CH), 123.8 (CH), 122.8
(CH), 114.1 (CH), 55.2 (CH3), 51.5 (CH3), 48.6 (CH);
HRMS (EI) calcd for C22H20O3 332.1407, found
332.1411; HPLC analysis: 99.1% ee (Chiralcel OD-H,
10% i-PrOH in hexanes, 0.8 mL/min, k = 254 nm,
tR = 11.1 min, major; tR = 19.9 min, minor). Anal.
Calcd for C22H20O3: C, 79.50; H, 6.06. Found: C,
79.64; H, 6.23.
4.24. (S,E)-Methyl 4-(naphthalen-3-yl)-4-(naphthalen-5-
yl)but-2-enoate 9f
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9f as a solid (0.156 g,
89% yield); mp 85–86 ꢁC; Rf 0.27 (pentane–diethyl ether,
25
9:1); ½aꢁD ¼ þ6:9 (c 0.64, CHCl3); FTIR (neat): 1722
cmꢀ1
; d 7.99 (d,
1H NMR (500 MHz, CDCl3):
J = 8.0 Hz, 1H), 7.88–7.74 (m, 5H), 7.67–7.63 (m, 2H),
7.48–7.41 (m, 5H), 7.33–7.29 (m, 2H), 5.81 (d,
J = 6.0 Hz, 1H), 5.67 (dd, J = 16.0, 1.6 Hz, 1H), 3.73
(s, 3H); 13C NMR (75 MHz, CDCl3): d 166.9 (C),
150.2 (CH), 138.5 (C), 136.9 (C), 134.1 (C), 133.5
(C), 132.4 (C), 131.5 (C), 128.9 (CH), 128.4 (CH),
128.0 (CH), 127.8 (CH), 127.6 (CH), 127.4 (CH), 127.1
(CH), 126.7 (CH), 126.3 (CH), 126.2 (CH), 125.9
(CH), 125.7 (CH), 125.4 (CH), 123.8 (CH), 123.3
(CH), 51.5 (CH3), 49.5 (CH); HRMS (EI) calcd for
C25H20O2 352.1458, found 352.1463; HPLC analysis:
>98% ee (Chiralcel OD-H, 5% i-PrOH in hexanes,
0.8 mL/min, k = 254 nm, tR = 14.9 min, major; tR =
21.4 min, minor).
4.22. (S,E)-Methyl 4-(3,4-dichlorophenyl)-4-(naphthalen-
5-yl)but-2-enoate 9d
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9d as an oil (0.146 g, 79%

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H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
4.25. tert-Butyl 3-((R,E)-3-(methoxycarbonyl)-1-(naph-
thalen-5-yl)allyl)-1H-indole-1-carboxylate 9g
7.39 (dd, J = 16.0, 6.0 Hz, 1H), 7.30 (d, J = 7.6 Hz,
1H), 6.08 (d, J = 3.6 Hz, 1H), 6.00 (d, J = 3.6 Hz,
1H), 5.77 (dd, J = 16.0, 1.6 Hz, 1H), 5.63 (d,
J = 6.0 Hz, 1H), 3.73 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 166.6 (C), 153.3 (C), 146.5 (CH), 135.8
(C), 134.1 (C), 134.0 (C), 131.1 (C), 129.0 (CH),
128.5 (CH), 126.5 (CH), 126.3 (CH), 125.8 (CH),
125.4 (CH), 123.6 (CH), 123.1 (CH), 110.6 (CH),
107.0 (CH), 51.6 (CH3), 43.2 (CH); HRMS (EI) calcd
for C19H15ClO3 326.0704, found 326.0705; HPLC
analysis: 99.6% ee (Chiralcel OD-H, 5% i-PrOH in hex-
anes, 0.8 mL/min, k = 254 nm, tR = 8.8 min, major;
tR = 14.6 min, minor).
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 9g as a white solid (0.181 g,
82% yield), mp 91–94 ꢁC; Rf 0.19 (pentane–diethyl
25
ether, 5:1); ½aꢁD ¼ þ2:3 (c 3.02, CHCl3); FTIR (neat):
2980, 1728, 1371, 1157 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): d 8.12 (m, 1H), 8.02 (m, 1H), 7.89 (m, 1H),
7.79 (d, J = 8.0 Hz, 1H), 7.57–7.47 (m, 3H), 7.39 (m,
1H), 7.32–7.24 (m, 4H), 7.16–7.12 (m, 1H), 5.82 (d,
J = 6.4 Hz, 1H), 5.74 (dd, J = 15.8, 1.4 Hz, 1H), 3.70
(s, 3H), 1.65 (s, 9H); 13C NMR (75 MHz, CDCl3): d
166.8 (C), 149.7 (C), 148.6 (CH), 135.7 (C), 134.1
(C), 131.3 (C), 129.5 (C), 129.0 (CH), 128.0 (CH),
126.4 (CH), 126.2 (CH), 125.7 (CH), 125.4 (CH),
124.6 (CH), 123.2 (CH), 123.0 (CH), 122.6 (CH),
120.9 (C), 119.4 (CH), 115.3 (CH), 83.9 (C), 51.5
(CH3), 40.3 (CH), 28.1 (CH3), two missing carbons
attributed to accidental equivalence; LCMS (ESI) m/z
(relative intensity): 464.0 ([M+Na]+, 100.0); HPLC
analysis: >98% ee (Chiralcel OD-H, 20% i-PrOH in
hexanes, 0.8 mL/min, k = 254 nm, tR = 6.5 min, major;
17.5 min, minor). Anal. Calcd for C28H27NO4: C,
76.17; H, 6.16; N, 3.17. Found: C, 75.83; H, 6.23; N,
3.08.
4.28. (R,E)-Methyl 4-(5-chlorothiophen-2-yl)-4-(naphtha-
len-5-yl)but-2-enoate 9l
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9l as an oil (0.151 g,
88% yield); Rf 0.24 (pentane–diethyl ether, 9:1);
25
½aꢁD ¼ þ69:8 (c 1.25, CHCl3); FTIR (neat): 1723 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
d
7.97–7.87 (m,
2H), 7.83 (d, J = 8.0 Hz, 1H), 7.51–7.44 (m, 4H), 7.36
(d, J = 6.8 Hz, 1H), 6.75 (d, J = 4.0 Hz, 1H), 6.59
(d, J = 4.0 Hz, 1H), 5.83 (dd, J = 15.6, 1.6 Hz, 1H),
5.73 (d, J = 6.0 Hz, 1H), 3.75 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 166.5 (C), 148.5 (CH), 143.1
(C), 136.0 (C), 134.1 (C), 131.0 (C), 129.2 (C), 129.0
(CH), 128.6 (CH), 126.6 (CH), 126.0 (CH), 125.9
(CH), 125.8 (CH), 125.5 (CH), 125.3 (CH), 123.3
(CH), 123.2 (CH), 51.6 (CH3), 44.6 (CH); HRMS (EI)
calcd for C19H15ClO2S 342.0476, found 342.0471;
HPLC analysis: 99.5% ee (Chiralcel OD-H, 5% i-PrOH
in hexanes, 0.8 mL/min, k = 254 nm, tR = 10.4 min,
major; tR = 22.6 min, minor). Anal. Calcd for
C19H15ClO2S: C, 66.56; H, 4.41. Found: C, 66.34; H,
4.69.
4.26. tert-Butyl 3-((R,E)-3-(methoxycarbonyl)-1-(naph-
thalen-5-yl)allyl)-5-bromo-1H-indole-1-carboxylate 9h
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9h as a yellow solid (0.213 g,
82% yield), mp 94–96 ꢁC; Rf 0.13 (pentane–diethyl ether,
25
10:1); ½aꢁD ¼ þ27:9 (c 4.14, CHCl3); FTIR (neat): 1729,
1
1450, 1372 cmꢀ1; H NMR (500 MHz, CDCl3): d 7.94
(m, 2H), 7.89 (m, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.49
(m, 3H), 7.40 (m, 3H), 7.27 (d, J = 7.3 Hz, 1H), 7.19
(s, 1H), 5.73 (d, J = 5.8 Hz, 1H), 5.68 (dd, J = 15.6,
1.2 Hz, 1H), 3.70 (s, 3H), 1.61 (s, 9H); 13C NMR
(75 MHz, CDCl3): d 166.7 (C), 149.3 (C), 148.2 (CH),
135.2 (C), 134.5 (C), 134.2 (C), 131.3 (C), 129.1 (CH),
128.3 (CH), 127.6 (CH), 126.5 (CH), 126.1 (CH), 125.9
(C), 125.8 (CH), 125.4 (CH), 123.3 (CH), 123.2 (CH),
122.0 (CH), 120.2 (C), 116.9 (CH), 116.1 (C), 84.5 (C),
51.6 (CH3), 40.1 (CH), 28.1 (CH3), missing carbon
attributed to accidental equivalence; LCMS (ESI) m/z
(relative intensity): 541.9 ([M+Na]+, 85.6); HRMS
(ESI) calcd for C28H26BrNO4Na 542.0937, found
542.0940; HPLC analysis: >98% ee (Chiralcel OD-H,
15% i-PrOH in hexanes, 0.9 mL/min, k = 254 nm,
tR = 5.9 min, major; 15.6 min, minor). Anal. Calcd for
C28H26BrNO4: C, 64.62; H, 5.04. Found: C, 64.88; H,
5.27.
4.29. (R,E)-Methyl 4-(naphthalen-5-yl)-4-(5-phenylthio-
phen-2-yl)but-2-enoate 9m
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 9m as an oily brown
solid (0.126 g, 66% yield), Rf 0.20 (pentane–diethyl
25
ether, 5:1); ½aꢁD ¼ þ18:9 (c 1.32, CHCl3); FTIR
(CHCl3): 3061, 2951, 1719, 1271 cmꢀ1
;
1H NMR
(500 MHz, CDCl3): d 8.04–8.02 (m, 1H), 7.90–7.88
(m, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.58–7.46 (m, 6H),
7.43–7.41 (m, 1H), 7.33 (t, J = 8.0 Hz, 2H), 7.25–7.22
(m, 1H), 7.16 (d, J = 3.5 Hz, 1H), 6.79 (d, J = 3.5 Hz,
1H), 5.88–5.83 (m, 2H), 3.75 (s, 3H); 13C NMR
(125 MHz, CDCl3): d 166.7 (C), 149.1 (CH), 143.77
(C), 143.75 (C), 136.6 (C), 134.1 (C), 134.0 (C), 131.1
(C), 128.9 (CH), 128.8 (CH), 128.4 (CH), 127.3 (CH),
127.2 (CH), 126.5 (CH), 126.1 (CH), 125.8 (CH),
125.5 (CH), 125.4 (CH), 123.4 (CH), 123.0 (CH), 122.7
(CH), 51.6 (CH3), 44.6 (CH); LRMS (EI) m/z
(relative intensity): 385.1 ([M+H]+, 100.0); HRMS
(ESI) m/z calcd for [C25H20O2SNa]+ (M+Na)+:
407.1076, found 407.1082; HPLC analysis: 99.3% ee
(Chiralcel OD-H, 5% i-PrOH in hexanes, 0.9 mL/min,
k = 254 nm, tR = 14.8 min, major; tR = 27.9 min,
minor).
4.27. (R,E)-Methyl 4-(5-chlorofuran-2-yl)-4-(naphthalen-
5-yl)but-2-enoate 9j
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9j as a yellow solid
(0.073 g, 45% yield); Rf 0.26 (pentane–diethyl ether,
25
9:1); ½aꢁD ¼ þ26:9 (c 0.87, CHCl3); FTIR (neat):
1
1719 cmꢀ1; H NMR (500 MHz, CDCl3): d 7.94–7.87
(m, 2H), 7.82 (d, J = 7.6 Hz, 1H), 7.53–7.43 (m, 3H),

H. M. L. Davies et al. / Tetrahedron: Asymmetry 17 (2006) 665–673
673
4.30. (R,E)-Methyl 4-(benzofuran-2-yl)-4-(naphthalen-
5-yl)but-2-enoate 9o
Acknowledgements
Financial support of this work by the National Science
Foundation (CHE-0350536) is gratefully acknow-
ledged.
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 9:1) to give 9o as a yellow oily solid
(0.102 g, 60% yield), Rf 0.15 (pentane–diethyl ether,
25
10:1); ½aꢁD ¼ ꢀ33:5 (c 0.94, CHCl3); FTIR (neat):
1723, 1655, 1454, 1272, 1170 cmꢀ1
;
1H NMR
References
(500 MHz, CDCl3): d 8.00 (m, 1H), 7.90 (m, 1H), 7.84
(d, J = 8.2 Hz, 1H), 7.54–7.43 (m, 6H), 7.36 (d,
J = 7.3 Hz, 1H), 7.25 (m, 1H), 7.20 (m, 1H), 6.44 (s,
1H), 5.83 (m, 2H), 3.74 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 166.6 (C), 156.9 (C), 155.0 (C), 146.4 (CH),
134.2 (C), 134.1 (C), 131.2 (C), 129.0 (CH), 128.5
(CH), 128.3 (C), 126.6 (CH), 126.5 (CH), 125.8 (CH),
125.5 (CH), 124.0 (CH), 123.8 (CH), 123.2 (CH), 122.8
(CH), 120.8 (CH), 111.2 (CH), 105.4 (CH), 51.6
(CH3), 43.7 (CH); LRMS (EI) m/z (relative intensity):
342.2 ([M]+, 100.0); HRMS (EI) m/z calcd for
[C23H18O3]+ 342.1250, found 342.12509; HPLC analy-
sis: 99.1% ee (Chiralcel OD-H, 15% i-PrOH in hexanes,
0.8 mL/min, k = 254 nm, tR = 12.7 min, major; tR =
11.3 min, minor). Anal. Calcd for C23H18O3: C, 80.68;
H, 5.30. Found: C, 80.44; H, 5.37.
1. For recent reviews on C–H activation by carbenoid-induced
C–H insertion, see: (a) Davies, H. M. L.; Loe, O. Synthesis
2004, 2595; (b) Davies, H. M. L.; Beckwith, R. E. J. Chem.
Rev. 2003, 103, 2861.
2. For selected reviews on other methods for C–H activation,
see: (a) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97,
2879; (b) Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698;
(c) Arndsten, B. A.; Bergman, R. G. Science 1995, 270,
1970; (d) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem.
Res. 2001, 34, 633; (e) Ritleng, V.; Sirlin, C.; Pfeffer, M.
Chem. Rev. 2002, 102, 1731; (f) Kakiuchi, F.; Chatani, N.
Adv. Synth. Catal. 2003, 345, 1077.
3. For recent examples of catalytic C–H functionalization, see:
(a) O’Malley, S. J.; Tan, K. L.; Watzke, A.; Bergman, R.
G.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 13496; (b)
Dangel, B. D.; Godula, K.; Youn, S. W.; Sezen, B.; Sames,
D. J. Am. Chem. Soc. 2002, 124, 11856; (c) Wehn, P. M.;
DuBois, J. J. Am. Chem. Soc. 2002, 124, 12950; (d) Waltz,
K. M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 11358;
(e) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2004, 126, 9542; (f) Davies, H. M. L.; Jin, Q. Org. Lett.
2004, 6, 1769.
4.31. (R,E)-Methyl 4-(benzo[b]thiophen-3-yl)-4-(naphtha-
len-5-yl)but-2-enoate 9p
Purified via flash chromatography (silica gel, pentane–
diethyl ether, 7:1) to give 9p as a yellow oil (0.036 g,
4. (a) Davies, H. M. L.; Stafford, D. G.; Hansen, T. Org. Lett.
1999, 1, 233; (b) Davies, H. M. L.; Stafford, D. G.; Hansen,
T.; Churchill, M. R.; Keil, K. M. Tetrahedron Lett. 2000,
41, 2035; (c) Davies, H. M. L.; Jin, Q. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5472; (d) Davies, H. M. L.; Jin, Q. J. Am.
Chem. Soc. 2004, 126, 10862; (e) Davies, H. M. L.;
Beckwith, R. E. J. J. Org. Chem. 2004, 69, 9241; (f) Davies,
H. M. L.; Walji, A. M. Angew. Chem., Int. Ed. 2005, 44,
1733; (g) Davies, H. M. L.; Jin, Q. Org. Lett. 2005, 7, 2293;
(h) Davies, H. M. L.; Manning, J. R. J. Am. Chem. Soc.
2006, 128, 1060.
5. (a) Ozaki, F.; Matsukara, M.; Kabasawa, Y.; Ishibashi, K.;
Ikemori, M.; Hamano, S.; Minami, N. Chem. Pharm. Bull.
1992, 40, 2735; (b) Davies, H. M. L.; Clark, T. J.; Smith, H.
D. J. Org. Chem. 1991, 56, 3817.
6. Baum, J. S.; Shook, D. A.; Davies, H. M. L.; Smith, H. D.
Synth. Commun. 1987, 17, 1709.
20% yield), Rf 0.23 (pentane–diethyl ether, 5:1);
25
½aꢁD ¼ þ4:0 (c 1.70, CHCl3); FTIR (neat): 3061, 2948,
1
1720, 1269 cmꢀ1; H NMR (500 MHz, CDCl3): d 7.96
(d, J = 8.0 Hz, 1H), 7.91–7.87 (m, 2H), 7.80 (d,
J = 8.0 Hz, 1H), 7.59–7.54 (m, 2H), 7.51–7.46 (m, 2H),
7.40–7.33 (m, 2H), 7.29 (t, J = 7.50 Hz, 1H), 7.23 (d,
J = 7.0 Hz, 1H), 7.02 (s, 1H), 5.97 (d, J = 6.0 Hz, 1H),
5.66 (dd, J = 15.8, 1.3 Hz, 1H), 3.71 (s, 3H); 13C
NMR (75 MHz, CDCl3): d 166.7 (C), 148.6 (CH),
140.7 (C), 137.9 (C), 135.80 (C), 135.76 (C), 134.1 (C),
131.4 (C), 129.0 (CH), 128.1 (CH), 126.6 (CH), 126.3
(CH), 125.8 (CH), 125.5 (CH), 124.9 (CH), 124.5
(CH), 124.2 (CH), 123.4 (CH), 123.2 (CH), 122.9
(CH), 122.0 (CH), 51.6 (CH3), 43.0 (CH); LRMS (EI)
m/z (relative intensity): 359.1 ([M+H]+, 30); HRMS
(ESI) m/z calcd for [C23H18O2SNa]+ (M+Na)+:
381.0920, found 381.0934.
7. Davies, H. M. L.; Ahmed, G.; Churchill, M. R. J. Am.
Chem. Soc. 1996, 118, 10774.