Rh2(S-PTAD)4-catalyzed asymmetric cyclopropenation of aryl alkynes

Article abstract of DOI:10.1016/j.tet.2011.04.029

Rh₂(S-PTAD)₄ is an effective catalyst for the asymmetric cyclopropenation of aryl alkynes using a siloxyvinyldiazoacetate as the carbenoid precursor. Upon deprotection of the silyl protecting group, highly enantioenriched cyclopropen

Full text of DOI:10.1016/j.tet.2011.04.029

Tetrahedron 67 (2011) 4313e4317
Contents lists available at ScienceDirect
Tetrahedron
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Rh2(S-PTAD)4-catalyzed asymmetric cyclopropenation of aryl alkynes
*
John F. Briones, Huw M.L. Davies
Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Rh2(S-PTAD)4 is an effective catalyst for the asymmetric cyclopropenation of aryl alkynes using
a siloxyvinyldiazoacetate as the carbenoid precursor. Upon deprotection of the silyl protecting group,
highly enantioenriched cyclopropenes bearing geminal acceptor groups can be accessed. These cy-
clopropenes undergo regioselective rhodium(II)-catalyzed ring expansion to furans.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 20 March 2011
Received in revised form 7 April 2011
Accepted 11 April 2011
Available online 16 April 2011
Keywords:
Asymmetric cyclopropenation
Cyclopropenes
Donor/acceptor carbenoids
Dirhodium catalysis
Siloxyvinyldiazoacetate
1. Introduction
can be achieved.6 In contrast, the asymmetric synthesis of
cyclopropenes containing two acceptor groups by the carbenoid
Cyclopropenes are important synthetic targets1 because of their
broad utility as intermediates in organic synthesis and their oc-
currence in a variety of natural products.2e4 One of the most gen-
erally useful methods for the synthesis of cyclopropenes is the
metal catalyzed reaction of diazo compounds 1 with alkynes 2
(Scheme 1). These reactions proceed via metal carbenoid in-
termediates 3, which then cyclopropenate the alkynes to form 4.
approach is less developed.7,8 High asymmetric induction has
only been achieved when one of the acceptor groups is a cyano
group.9,10 In this paper we describe an indirect method for the
asymmetric synthesis of cyclopropenes 7 bearing two carbonyl
acceptor groups by reaction of siloxyvinyldiazoacetate 5 with
alkynes 6 (Scheme 2).11
O
O
OTBS
R
1. Rh2(S-PTAD)4
MeO
R
CO2Me
X
Y
X
Y
X
Y
2
Rh(II)
2. TBAF
N2
Rh
N2
R
R
5
6
7
1
3
4
Scheme 1. Rhodium-catalyzed cyclopropenation.
Scheme 2. Synthesis of cyclopropenes bearing two acceptor groups.
The reactivity of metal carbenoids is greatly influenced by the
nature of the substituents on the carbenoid. Consequently, re-
views of metal carbenoids often classify the carbenoids into three
distinct groups, the acceptor carbenoids, the acceptor/acceptor
carbenoids and the donor/acceptor carbenoids. Rhodium-
catalyzed asymmetric intermolecular cyclopropenation5 with
acceptor- and donor/acceptor carbenoids are now well-
established processes, and high levels of asymmetric induction
A further objective of this study is to illustrate the interplay
between diazoacetoacetate 9 and siloxyvinyldiazoacetate 5, which
is readily formed from 9.12 Nitrogen extrusion from 9 generates
the acceptor/acceptor carbenoid 10, whereas 5 generates the do-
nor/acceptor carbenoid 8. Acceptor/acceptor carbenoids are highly
electrophilic intermediates, whereas the reactivity of donor/ac-
ceptor carbenoids is greatly modulated by the influence of the
donor group.5a,13 Hence, it is possible to use 5 as a surrogate for 9
when the high reactivity of the acceptor/acceptor carbenoid 9,
precludes its successful utilization in
(Scheme 3).
a particular reaction
* Corresponding author. E-mail address: hmdavie@emory.edu (H.M.L. Davies).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.029

4314
J.F. Briones, H.M.L. Davies / Tetrahedron 67 (2011) 4313e4317
OTBS
CO2Me
O
O
Rh
Rh
O
O
H
OMe
N2
N2
N
SSO2
N
O
O
Rh
Rh
H
O
5
9
N
O
Rh(II)
Rh(II)
R
R
OTBS
CO2Me
O
O
4
R=C11-13H23-27
Rh2 S-DOSP)4
4
OMe
Rh2(S-NTTL)4
Rh
Rh
(
8
10
Scheme 3. Relationship between 5 and 9.
R
N
O
O
Rh
Rh
H
R
N
O
O
H
H
O
2. Results and discussion
Rh
Rh
O
One of the challenges of conducting cyclopropenation reactions
with the diazoacetoacetate 9 is the tendency of this system to react
via zwitterionic intermediates, leading to two different reaction
pathways.14 This type of behavior has been reported in the rhodium
acetate-catalyzed reaction of 11 with phenylacetylene 6a, which
instead of forming the cyclopropene 12 generated the furan 14
(Scheme 4).15 The formation of 14 could, in principle, arise from
a zwitterionic intermediate 13 formed directly from the reaction of
the carbenoid with the alkyne or by ring-opening of an initially
formed cyclopropene 12.
O
O
N
R
H
H
4
2
R = SO2-2,4,6-triiPrC6H2
Rh2(S-BiTISP)2
Rh2(S-PTADD)4
(R = adamantyl)
(R = tBu)
Rh2(S-PTTL))
4
Fig. 1. Structures of chiral dirhodium catalysts Rh2(S-DOSP)4, Rh2(S-PTAD)4, Rh2(S-
NTTL)4, Rh2(S-PTTL)4, and Rh2(S-biTISP)2.
Table 1
O
O
Ph
Reaction of methyl diazoacetoacetate 9 and phenylacetylene 6a using different
O
CH3
,
b
Rh(II) catalystsa
Ph
6a
OEt
N2
11
Rh2(OAc)4
CO2Et
14
Entry
Catalystc
Solvent
Temp (ꢁC)
% Yield
% ee
7a
15
Ph
O
O
1
2
3
4
5
6
Rh2(Oct)4
Rh2(Oct)4
Rh2(S-PTAD)4
Rh2(S-PTAD)4
Rh2(S-DOSP)4
Rh2(S-DOSP)4
DCM
DCM
DCM
DCM
Pentane
Pentane
23
ꢀ45
23
d
97
24
9
d
17
d
d
d
<5
<5
7
61
74
66
73
69
O
CO2Et
EtO
Ph
ꢀ45
23
12
13
ꢀ45
11
a
Scheme 4. Proposed mechanism for the Rh(II)-catalyzed formation of furan 14.
Reaction conditions: 0.5 mmol scale of 6a used, reaction time: 3 h.
Diazoacetate 15 (2 equiv) used.
b
c
Catalyst (2 mol %) loading.
In order to explore whether it would be possible to conduct an
asymmetric cyclopropenation of phenylacetylene with diazo-
acetoacetate 9, a series of reactions were conducted, varying the
catalyst and solvent. When Rh2(Oct)4 was used as catalyst, only the
furan product 15 was formed as seen in the 1H NMR of the crude
reaction mixture. The product was isolated in 97% yield and the
structure of 15 was confirmed by X-ray crystallography.16 In an
attempt to isolate a cyclopropene product 7a, the reaction was
conducted at ꢀ45 ꢁC. Indeed, 1H NMR analysis of the crude reaction
showed a mixture of cyclopropene 7a and the furan 14.
deprotection of the silyl protecting group. Several chiral catalysts
were also surveyed for this particular reaction to form cyclo-
propene 16 and the results are shown in Table 2.
Table 2
Reaction of siloxyvinyldiazoacetate 5 and phenylacetylene using different Rh(II)
,b
catalystsa
Different reactivity was observed when chiral dirhodium com-
plexes, Rh2(S-DOSP)4, and Rh2(S-PTAD)4, were used as catalysts
(Fig. 1). In these cases, the cyclopropene product 7a was formed as
the major product in about 70% yield in reactions conducted at
room temperature. The cyclopropenes, however, were formed in
very poor enantiomeric excess for both catalysts even when the
reaction was conducted at ꢀ45 ꢁC (Table 1).
Entry
Catalystc
Solvent
% Yield
% eed
1
2
3
4
5
Rh2(R-DOSP)4
Rh2(S-PTAD)4
Rh2(S-NTTL)4
Rh2(S-PTTL)4
Rh2(S-BiTISP)2
Pentane
DCM
DCM
DCM
Pentane
41
93
93
91
43
ꢀ51
94
88
90
58
Since enantiomerically enriched cyclopropenes could not be
directly accessed using diazo compound 9 as carbenoid precursor,
we turned our attention to siloxyvinyldiazoacetate 5 because in
principle, the cyclopropenyl ketone could be accessed upon
a
Reaction conditions: 0.5 mmol scale of 6a used, reaction time: 2 h.
Diazoacetate 5 (2 equiv) used.
Catalyst (2 mol %) loading.
b
c
d
Negative ee value means opposite sense of enantioinduction.

J.F. Briones, H.M.L. Davies / Tetrahedron 67 (2011) 4313e4317
4315
The prolinate-based catalyst Rh2(R-DOSP)4 and the bridged cat-
alyst Rh2(S-BiTISP)2 both performed poorly in terms of yield and
enantioselectivity. Excellent yields and enantioselectivities were
obtained using the structurally related catalysts Rh2(S-NTTL)4 and
Rh2(S-PTTL)4. All of the catalysts gave the same sense of enantioin-
duction as Rh2(S-PTAD)4. These results are consistent with previous
studies on asymmetric reactions with siloxyvinyldiazoacetate 5. We
have reported that Rh2(S-PTAD)4 was a very effective catalyst in
asymmetric tandem cyclopropanation/Cope rearrangement re-
actions with 5.17 Muller had observed that Rh2(S-NTTL)4 is better
than Rh2(S-DOSP)4 in intermolecular cyclopropanation with silox-
yvinyldiazoacetate 5. The absolute configuration of the cyclo-
ring expansion of the cyclopropenyl ketones to furans was in-
vestigated. Cyclopropene 7a in DCM was stirred in the presence of
Rh2(Oct)4 at 23 ꢁC (Scheme 5).1H NMR analysis of the crude reaction
mixture after 2 h showed small amounts of furan product. After 48 h
of stirring proton NMR analysis showed near complete conversion of
the cyclopropene to the furan product. The product was isolated by
flash chromatography and the pure furan product was obtained in
86% yield. In the absence of Rh2(Oct)4, the cyclopropene did not
undergo ring expansion to the corresponding furan. This result
demonstrates that indeed the cyclopropene undergoes a Rh(II)-
catalyzed rearrangement to the furan product. However, the rear-
rangement is slower than
a
typical rhodium-catalyzed
propene 16 was not rigorously determined and was tentatively
cyclopropenation, which means the reaction between diazo-
acetoacetate 9 and phenylacetylene 6a is more likely to undergo
a mechanism involving zwitterionic intermediates instead of
a rearrangement of an initially formed cyclopropene (Scheme 5).
18
€
assigned based on the results reported by Muller and co-workers
and our previous work on rhodium-catalyzed cyclopropenation
with alkynes and styryldiazoacetates.6e The optimized conditions
for the one-pot cyclopropenation/deprotection of arylacetylenes
was found to be slow addition of the diazo compound (over 2 h) to
a dichloromethane solution of Rh2(S-PTAD)4 (2 mol %) and the al-
kyne at ꢀ45 ꢁC. The silyl protecting group can be removed in situ by
adding excess amount of TBAF after complete addition of the diaz-
oacetate solution to the reaction mixture. Under the optimized
conditions, the substrate scope of the cyclopropenation reactionwas
investigated. Various aromatic acetylenes were used as trapping
agent (Table 3) and results showed that the reaction is generally
compatible with substituted arylacetylenes 6 affording cyclo-
propenyl ketones 7 in moderate to excellent yields (77e94% yield)
and excellent enantioselectivities (93e99% ee). Clean cyclo-
propenation and no benzylic CeH insertion were observed using
p-ethylethynylbenzene (entry 4) and TBS-protected o-ethy-
nylbenzylalcohol (entry 12) as substrates, which showed that
cyclopropenation can occur in a highly selective manner. Selective
monoyclopropenation of diynes in the case of was also possible
(entries 9 and 10). Electron rich arylacetylenes, such as p-ethynyla-
nisole and 2-ethynylnaphthalene also afforded highly enantiopure
cyclopropenes, however, these products were too unstable for full
characterization and are not included in the table.19 The absolute
configuration of the cyclopropene 7 was not rigorously determined
O
O
O
CH3
Ph
Rh2(Oct)4
MeO
Ph
DCM, rt, 48h
86% yield
CO2Me
7a
15
Scheme 5. Rh(II)-catalyzed rearrangement of cyclopropenes 7a to furan 15.
3. Conclusion
In summary, siloxyvinyldiazoacetates were found to be effective
carbenoid precursors for highly enantioselective Rh2(S-PTAD)4-
catalyzed cyclopropenation reactions with arylacetylenes. A new
class of optically active cyclopropenes with quaternary carbon
bearing germinal acceptor groups is now readily accessible.
Cyclopropenyl ketone was also found to undergo a regioselective
Rh(II)-catalyzed ring expansion to furans.
4. Experimental section
4.1. General
€
and was tentativelyassigned based on the results reported by Muller
and co-workers18 and our previous work on rhodium-catalyzed
cyclopropenation with alkynes and styryldiazoacetates.6e With the
cyclopropenyl ketones in hand, the feasibility of Rh(II)-catalyzed
General methods for spectral and analytical procedures and
X-ray crystallographic data for 15 are described in Supplementary
data.
4.2. General procedure for Rh(II)-catalyzed decompositions of
methyl diazoacetoacetate 9 in the presence of
phenylacetylene
Table 3
Rh2(S-PTAD)4-catalyzed cyclopropenation of various alkynes and silox-
ylvinyldiazoacetate 5a
,
b
A mixture of alkyne (0.5 mmol) and Rh2(Oct)4 (0.01 mmol) was
dissolved in 1 mL of dichloromethane and stirred at indicated
temperature under an atmosphere of argon. Diazoacetoacetate 9
(1.0 mmol) in 10 mL dichloromethane was then added to the re-
action mixture via syringe pump over 2 h. After the complete ad-
dition, the reaction mixture was stirred for additional 1 h and the
reaction mixture was concentrated in vacuo. The residue was pu-
rified on silica using 10:1 hexane/diethyl ether followed by 1:1
hexane/EtOAc as eluents to give the desired product/s.
Entry
R
Product
% Yield
ee %
1
2
3
4
5
6
7
8
H
o-Me
p-Me
p-Et
P-tBu
P-Br
p-Ph
m-CF3
p-Ethynyl
m-Ethynyl
p-F, m-Me
o-CH2OTBS
7a
7b
7c
7d
7e
7f
7g
7h
7i
83
80
86
90
87
92
88
94
85
88
77
94
98
98
93
97
98
95
98
93
94
97
97
99
4.3. General procedure for Rh(II)-catalyzed decompositions of
siloxyvinyldiazoacetate 5 in the presence of acetylenes
9
A mixture of alkyne 6 (0.5 mmol) and Rh2(S-PTAD)4 (0.01 mmol)
was dissolved in 1 mL of dichloromethane and stirred at ꢀ45 ꢁC
10
11
12
7j
7k
7l
under an atmosphere of argon. Siloxyvinyldiazoacetate
5
a
(1.0 mmol) in 10 mL dichloromethane was then added to the re-
action mixture via syringe pump over 2 h. After the complete
Reaction conditions: 0.5 mmol of alkyne, 1.0 mmol of TBAF used.
Diazoacetate 5 (2 equiv) used.
b

4316
J.F. Briones, H.M.L. Davies / Tetrahedron 67 (2011) 4313e4317
addition, the reaction mixture was stirred for additional 20 min
followed by addition of TBAF (1.0 mmol) in one portion. The re-
action mixture was further stirred at 23 ꢁC followed by aqueous
work-up. The organic layer was dried over MgSO4, filtered, and
concentrated. The residue was purified on silica using 10:1 hexane/
diethyl ether followed by 1:1 hexane/EtOAc as eluents to afford the
desired cyclopropenyl ketones.
3139, 2952, 1720, 1693, 1275, 1229, 820 cmꢀ1; ESI-HRMS: (MþH) m/
z, found: 231.0976; calcd (C14H15O3): 231.1016; HPLC: ODH, 10% i-
PrOH/hexane, 1 ml minꢀ1, UV 254 nm, tR: 10.6 min (major), 11.3 min
(minor), 98% ee with Rh2(S-PTAD)4; [
a
]
þ11.8 (c 1.0, CHCl3).
D23
4.3.6. Methyl (R)-1-acetyl-2-(4-ethylphenyl)cycloprop-2-enecarbox-
ylate (7d). Purification by silica gel chromatography eluting with
hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7d in 90%
yield (109 mg) as a yellow oil. Rf 0.42 (hexane/EtOAc 8:2); 1H NMR
4.3.1. Methyl 2-methyl-5-phenylfuran-3-carboxylate (15). Purification
by silica gel chromatography eluting with hexane/Et2O (10:1) affor-
ded as white solid. Mp 55e57 ꢁC; Rf 0.72 (hexane/EtOAc 8:2); 1H
(400 MHz, CDCl3):
d
7.50 (d, J¼6.8 Hz, 2H), 7.26 (d, J¼8.8 Hz, 2H),
6.85 (s, 1H), 3.71 (s, 3H), 2.68 (q, J¼7.2 Hz, 2H), 2.22 (s, 3H), 1.25 (t,
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) 206.4 (C), 172.1 (C), 147.7
(CH), 130.6 (CH), 128.8 (CH), 121.5 (C), 113.3 (C), 95.1 (CH), 52.4
(CH3), 40.7 (C), 29.1 (CH2), 28.1 (CH3), 15.5 (CH3); IR (neat) 3140,
2966, 1723, 1694, 1276, 1230, 837 cmꢀ1; ESI-HRMS: (MþH) m/z,
found: 245.1133; calcd (C15H17O3): 245.1172; HPLC: ADH, 2% i-PrOH/
hexane, 1 ml minꢀ1, UV 254 nm, tR: 37.4 min (major), 40.2 min
NMR (400 MHz, CDCl3):
d
7.59 (d, J¼7.2 Hz, 2H), 7.34 (t, J¼7.2 Hz, 2H),
7.23 (t, J¼7.2 Hz, 1H), 6.84 (s, 3H), 3.80 (s, 3H), 2.60 (s, 3H); 13C NMR
(100 MHz, CDCl3): 164.6 (C), 158.9 (C), 151.9 (C), 130.2 (C), 128.9 (CH),
127.8 (CH), 123.8 (CH), 115.3 (C), 105.6 (CH), 51.5 (CH3), 14.0 (CH3); IR
(neat) 2951, 1715, 1614, 1440, 1230, 1096, 907, 729, 690 cmꢀ1; ESI-
HRMS: (MþH) m/z, found: 217.0820; calcd (C13H13O3): 217.0858;
(minor), 97% ee with Rh2(S-PTAD)4; [
a]
þ7.8 (c 1.0, CHCl3).
D23
4.3.2. Methyl (R)-1-(1-((tert-butyldimethylsilyl)oxy)vinyl)-2-phenyl-
cycloprop-2-enecarboxylate (16). Purification by silica gel chroma-
tography eluting with hexane/Et2O (10:1) afforded 16 in 93% yield
(154 mg) as a yellowish oil. Rf 0.74 (hexane/EtOAc 8:2); 1H NMR
4.3.7. Methyl (R)-1-acetyl-2-(4-(tert-butyl)phenyl)cycloprop-2-ene-
carboxylate (7e). Purification by silica gel chromatography eluting
with hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7e in
87% yield (118 mg) as a yellow oil. Rf 0.45 (hexane/EtOAc 8:2); 1H
(400 MHz, CDCl3): d 7.60 (m, 2H), 7.38 (m, 3H), 6.95 (s, 1H), 4.29 (d,
J¼0.4 Hz, 1H), 4.17 (d, J¼0.4 Hz,1H), 3.67 (s, 3H), 0.88 (s, 9H), 0.16 (s,
6H); 13C NMR (100 MHz, CDCl3): 174.3 (C), 158.9 (C), 130.4 (CH),
130.1 (CH), 128.9 (CH), 125.6 (C), 117.3 (C), 99.4 (CH), 90.6 (CH), 52.2
(CH3), 25.7 (CH3), ꢀ4.6 (CH3) (CH3); IR (neat) 2951, 2929, 2857,
1725, 1623, 1297, 1242, 1056, 1013, 832, 696 cmꢀ1; ESI-HRMS:
(MþH) m/z, found: 330.1610; calcd (C19H26O3Si): 330.1651; HPLC:
ADH, 1% i-PrOH/hexane, 1 ml minꢀ1, UV 254 nm, tR: 21.1 min (mi-
nor), 26.3 min (major), 94% ee with Rh2(S-PTAD)4.
NMR (400 MHz, CDCl3):
d
7.53 (d, J¼8.4 Hz, 2H), 7.47 (d, J¼8.4 Hz,
2H), 6.83 (s, 1H), 3.71 (s, 3H), 2.22 (s, 3H), 1.33 (s, 9H); 13C NMR
(100 MHz, CDCl3) 206.4 (C), 172.1 (C), 154.5 (CH), 130.3 (CH), 126.3
(CH),121.3 (C),113.2 (C), 95.2 (CH), 52.4 (CH3), 40.7 (C), 35.2 (C), 31.3
(CH3), 28.1 (CH3); IR (neat) 3139, 2957, 1721, 1696, 1270, 1229,
838 cmꢀ1
;
ESI-HRMS: (MþH) m/z, found: 273.1446; calcd
(C17H21O3): 273.1484; HPLC: ADH, 10% i-PrOH/hexane, 1 ml minꢀ1
UV 254 nm, tR: 10.8 min (major), 13.1 min (minor), 98% ee with
Rh2(S-PTAD)4; [
þ4.8 (c 1.0, CHCl3).
,
a]
D23
4.3.3. Methyl
(R)-1-acetyl-2-phenylcycloprop-2-enecarboxylate
(7a). Purification by silica gel chromatography eluting with hex-
ane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7a in 83% yield
(90 mg) as a yellow oil. Rf 0.30 (hexane/EtOAc 8:2); 1H NMR
4.3.8. Methyl (R)-1-acetyl-2-(4-bromophenyl)cycloprop-2-enecarbox-
ylate (7f). Purification by silica gel chromatography eluting with
hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7f in 92% yield
(137 mg) as a yellow oil. Rf 0.38 (hexane/EtOAc 8:2); 1H NMR
(400 MHz, CDCl3): d 7.59 (m, 2H), 7.42 (m, 3H), 6.98 (s, 1H), 3.69 (s,
3H), 2.22 (s, 3H); 13C NMR (100 MHz, CDCl3) 206.1 (C), 172.0 (C),
130.9 (CH), 130.4 (CH), 129.2 (CH), 124.1 (C), 113.3 (C), 96.5 (CH),
52.3 (CH3), 40.7 (C), 28.1 (CH3); IR (neat) 3139, 2952, 1721, 1693,
1274, 1229, 697 cmꢀ1; ESI-HRMS: (MþH) m/z, found: 217.0820;
calcd (C13H13O3): 217.0858; HPLC: ADH, 10% i-PrOH/hexane,
1 ml minꢀ1, UV 254 nm, tR: 10.6 min (major), 11.3 min (minor), 98%
(400 MHz, CDCl3):
d
7.55 (d, J¼8.4 Hz, 2H), 7.41 (d, J¼8.4 Hz, 2H), 6.93
(s,1H), 3.69 (s, 3H), 2.22 (s, 3H); 13C NMR (100 MHz, CDCl3) 205.9 (C),
171.8 (C), 132.6 (CH), 131.8 (CH), 125.5 (C), 123.1 (C), 112.5 (C), 97.2
(CH), 52.5 (CH3), 40.6 (C), 28.3 (CH3); IR (neat) 3141, 2951, 1721, 1694,
1273, 1227, 827 cmꢀ1; ESI-HRMS: (MþH) m/z, found: 294.9925;
calcd (C13H12BrO3): 294.9964; HPLC: ADH, 10% i-PrOH/hexane,
1 ml minꢀ1, UV 254 nm, tR: 18.3 min (major), 20.9 min (minor), 95%
ee with Rh2(S-PTAD)4; [
a]
þ10.9 (c 1.0, CHCl3).
D23
ee with Rh2(S-PTAD)4; [
a]
D23
þ16.9 (c 1.0, CHCl3).
4.3.4. Methyl (R)-1-acetyl-2-(o-tolyl)cycloprop-2-enecarboxylate
(7b). Purification by silica gel chromatography eluting with hexane/
Et2O (10:1) then hexane/EtOAc (1:1) afforded 7b in 80% yield (92 mg)
a as yellow oil. Rf 0.33 (hexane/EtOAc 8:2); 1H NMR (400 MHz, CDCl3):
4.3.9. Methyl (R)-2-([1,10-biphenyl]-4-yl)-1-acetylcycloprop-2-ene-
carboxylate (7g). Purification by silica gel chromatography eluting
with hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7g in 88%
yield (129 mg) as a yellow oil. Rf 0.33 (hexane/EtOAc 8:2); 1H NMR
d
7.40 (d, J¼7.6 Hz, 1H), 7.30 (m, 3H), 6.99 (s, 1H), 3.71 (s, 3H), 2.52 (s,
3H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) 206.2 (C), 172.0 (C), 140.5
(CH), 131.2 (CH), 130.9 (CH), 130.6 (CH), 126.5 (CH), 123.0 (C), 112.4 (C),
98.1 (CH), 52.3 (CH3), 39.8 (C), 28.1 (CH3), 20.2 (CH3); IR (neat) 3138,
2953, 2853, 1720, 1694, 1273, 1208, 723 cmꢀ1; ESI-HRMS: (MþH) m/z,
found: 231.0976; calcd (C14H15O3): 231.1016; HPLC: ADH, 10% i-PrOH/
hexane, 1 ml minꢀ1, UV 254 nm, tR: 8.6 min (major), 9.8 min (minor),
(400 MHz, CDCl3): d 7.64 (m, 4H), 7.57 (m, 2H), 7.42 (m, 2H), 7.37 (m,
1H), 6.93 (s,1H), 3.72 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3)
206.2 (C), 172.0 (C), 143.8 (CH), 140.2 (CH), 130.9 (CH), 129.2 (CH),
128.3 (CH),127.9 (CH),127.4 (CH),122.9 (C),113.1 (C), 96.3 (CH), 52.4
(CH3), 40.8 (C), 28.2 (CH3); IR (neat) 3139, 3030, 2951, 1721, 1693,
1274,1229, 843, 696 cmꢀ1; ESI-HRMS: (MþH) m/z, found: 293.1133;
calcd (C19H17O3): 293.1172; HPLC: ADH, 10% i-PrOH/hexane,
1 ml minꢀ1, UV 254 nm, tR: 23.2 min (major), 27.5 min (minor), 98%
98% ee with Rh2(S-PTAD)4; [
a
]
þ6.8 (c 1.0, CHCl3).
D23
D23
4.3.5. Methyl
(R)-1-acetyl-2-(p-tolyl)cycloprop-2-enecarboxylate
ee with Rh2(S-PTAD)4; [
a
]
þ1.6 (c 1.0, CHCl3).
(7c). Purification by silica gel chromatography eluting with hexane/
Et2O (10:1) then hexane/EtOAc (1:1) afforded 7c in 86% yield (99 mg)
as a yellow oil. Rf 0.36 (hexane/EtOAc 8:2); 1H NMR (400 MHz,
4.3.10. Methyl (R)-1-acetyl-2-(3-(trifluoromethyl)phenyl)cycloprop-
2-enecarboxylate (7h). Purification by silica gel chromatography
eluting with hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded
7h in 94% yield (138 mg) as a yellow oil. Rf 0.42 (hexane/EtOAc
CDCl3):
d
7.44 (d, J¼8.0 Hz, 2H), 7.23 (d, J¼8.0 Hz, 2H), 6.82 (s, 1H),
3.68 (s, 3H), 2.36 (s, 3H), 2.18 (s, 3H); 13C NMR (100 MHz, CDCl3)
206.4 (C), 172.1 (C), 141.5 (CH), 130.5 (CH), 129.9 (CH), 121.3 (C), 113.3
(C), 95.1 (CH), 52.3 (CH3), 40.7 (C), 28.1 (CH3), 21.8 (CH3); IR (neat)
8:2); 1H NMR (400 MHz, CDCl3):
d
7.86 (s, 1H), 7.75 (d, J¼7.6 Hz,
1H), 7.79 (d, J¼8.0 Hz, 1H), 7.59 (t, J¼7.6 Hz, 2H), 7.08 (s, 1H), 3.74

J.F. Briones, H.M.L. Davies / Tetrahedron 67 (2011) 4313e4317
4317
(s, 3H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) 205.7 (C), 171.6 (C),
Acknowledgements
133.5 (CH), 132.0 (C, q, J¼130.4 Hz), 129.9 (CH), 127.4 (CH), 127.0
(CH), 125.1 (C), 112.1 (C), 98.6 (CH), 52.5 (CH3), 40.7 (C), 28.4 (CH3);
IR (neat) 3139, 2952, 1721, 1693, 1274, 1229, 697 cmꢀ1; ESI-HRMS:
(MþH) m/z, found: 285.0694; calcd (C14H11F3O3): 285.0733; HPLC:
ADH, 10% i-PrOH/hexane, 1 ml minꢀ1, UV 254 nm, tR: 4.5 min
Support of this work by the National Science Foundation (CHE-
0750273) is gratefully acknowledged. We thank Kenneth I Hard-
castle for the X-ray crystallographic structure determination
(major), 7.1 min (minor), 98% ee with Rh2(S-PTAD)4; [
1.0, CHCl3).
a
]
þ1.7 (c
D23
Supplementary data
Detailed experimental for the compounds, X-raycrystallographic
data for 15, HPLC traces for all chiral compounds and 1H NMR and 13
C
4.3.11. Methyl (R)-1-acetyl-2-(3-ethynylphenyl)cycloprop-2-enecarbo-
xylate (7i). Purification by silica gel chromatography eluting with
hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7i in 88% yield
(106 mg) as a yellow oil. Rf 0.41 (hexane/EtOAc 8:2); 1H NMR
NMR spectra forall newcompoundsaredescribed in Supplementary
data. Supplementary dataassociated with this article can be found in
online version at doi:10.1016/j.tet.2011.04.029.
(400 MHz, CDCl3):
d
7.69 (t, J¼1.6 Hz, 1H), 7.55 (m, 2H), 7.41 (t,
J¼7.6 Hz, 1H), 6.98 (s, 1H), 3.73 (s, 3H), 3.15 (s, 1H), 2.27 (s, 3H), 2.18 (s,
3H); 13C NMR (100 MHz, CDCl3) 205.9 (C), 171.8 (C), 134.3 (CH), 133.8
(CH), 130.6 (CH), 129.3 (CH), 124.5 (C), 123.5 (C), 112.5 (C), 97.5 (CH),
82.5 (C), 78.8 (CH), 52.5 (CH3), 40.7 (C), 28.4 (CH3); IR (neat) 3284,
3142, 2952, 1721,1694,1274,1224,1045, 799 cmꢀ1; ESI-HRMS: (MþH)
m/z, found: 217.0820; calcd (C13H13O3): 217.0858; HPLC: ADH, 10% i-
PrOH/hexane, 1 ml minꢀ1, UV 254 nm, tR: 10.6 min (major), 11.3 min
References and notes
1. (a) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003,103, 977;
(b) Djerassi, C.; Doss, G. A. New J. Chem.1990,14, 713; (c) Salaun, J. Curr. Med. Chem.
1995, 2, 511; (d) Salaun, J. Top. Curr. Chem. 2000, 207,1; (e) Faust, R. Angew. Chem.,
Int. Ed. 2001, 40, 2251; (f) Baird, M. S.; Dale, C. M.; Lyotollis, W.; Simpson, M. J.
Tetrahedron Lett. 1992, 33, 1521; (g) Baird, M. S.; Grehan, B. J. Chem. Soc., Perkin
Trans. 1 1993, 1547; (h) Doss, G. A.; Djerassi, C. J. Am. Chem. Soc. 1988, 110, 8124.
2. (a) Donaldson, W. A. Tetrahedron 2001, 57, 8589; (b) Wessjohann, L. A.; Brandt,
W.; Thieman, T. Chem. Rev. 2003, 103, 1625; (c) Brackmann, F.; De Meijere, A.
Chem. Rev. 2007, 107, 4493; (d) Kalfoken, R.; Brandau, S.; Wibbeling, B.; Hoppe,
D. Angew. Chem., Int. Ed. 2004, 43, 6667; (e) Kunz, R. K.; McMillan, D. W. C. J. Am.
Chem. Soc. 2005, 127, 3240; (f) Johnasson, C. C. C.; Bremeyer, N.; Ley, S. V.; Owen,
D. R.; Smith, S. C.; Gaunt, M. J. Angew. Chem., Int. Ed. 2006, 45, 6024.
3. Khoury, P. R.; Goddard, J. D.; Tam, W. Tetrahedron 2004, 60, 8103.
4. (a) Noyori, R. Science 1990, 248,1194; (b) Stammer, C. H. Tetrahedron 1990, 46, 2231;
(c) Shimamoto, K.; Ohfune, Y. Tetrahedron Lett. 1990, 31, 4049; (d) Lee, M.; Lee, D.;
Zhao, Y.; Newton, M. G.; Chun, M. W.; Chu, C. K. Tetrahedron Lett. 1995, 36, 3499.
5. (a) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861; (b) Davies, H.
M. L.; Bruzinski, P. R.; Lake, D. H.; Kong, N.; Fall, M. J. J. Am. Chem. Soc. 1996, 118,
6897; (c) Davies, H. M. L. Eur. J. Org. Chem. 1999, 2459; (d) Hu, W.; Timmons, D.
J.; Doyle, M. P. Org. Lett. 2002, 4, 901.
(minor), 98% ee with Rh2(S-PTAD)4; [
a
]
þ6.8 (c 1.0, CHCl3).
D23
4.3.12. Methyl (R)-1-acetyl-2-(4-ethynylphenyl)cycloprop-2-enecar-
boxylate (7j). Purification by silica gel chromatography eluting with
hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7j in 85% yield
(102 mg) as a yellow oil. Rf 0.45 (hexane/EtOAc 8:2); 1H NMR
(400 MHz, CDCl3):
d
7.54 (app t, J¼8.8 Hz, 4H), 7.00 (s, 1H), 3.72 (s,
3H), 3.23 (s, 1H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3) 205.9 (C),
171.8 (C), 132.9 (CH), 130.3 (CH), 124.7 (C), 124.3 (C), 112.7 (C), 97.6
(CH), 83.0 (C), 79.9 (CH), 52.5 (CH3), 40.7 (C), 28.3 (CH3), 21.8 (CH3);
IR (neat) 3293, 3142, 2953, 1723, 1694, 1274, 1230, 907, 727 cmꢀ1
;
6. (a) Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.; Lynch, V.; Simonsen, S. H.;
Ghosh, J. J. Am. Chem. Soc. 1993, 115, 9968; (b) Doyle, M. P.; Protopova, M.; Muller,
P.; Ene, D.; Shapiro, E. A. J. Am. Chem. Soc. 1994, 116, 8492; (c) Lou, Y.; Horikawa,
M.; Kloser, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 1994, 126, 8916; (d)
Davies, H. M. L.; Lee, G. H. Org. Lett. 2004, 6, 1233; (e) Briones, J. F.; Hansen, J.;
Hardcastle, K. I.; Autschbach, J.; Davies, H. M. L. J. Am. Chem. Soc. 2010, 132, 17211.
7. Charette has reported stereoselective cyclopropanation utilizing nitro/acetate-
nitro/acetophenone- cyano/acetamide-, and keto/acetamide-substituted carbe-
noids. (a) Wurz, R. P.;Charette, A. B. Org. Lett. 2003, 5, 2327;(b)Moreau,B.; Charette,
A. B. J. Am. Chem. Soc. 2005, 127, 16014; (c) Wurz, R. P.; Charette, A. B. J. Org. Chem.
2004, 69, 1262; (d) Marcoux, D.; Azzi, S.; Charette, A. B. J. Am. Chem. Soc. 2009, 131,
6970; (e) Lindsay, V. N. G.; Lin, W.; Charette, A. B. J. Am. Chem. Soc. 2009,131,16383;
(f) Marcoux, D.; Goudreau, S. R.; Charette, A. B. J. Org. Chem. 2009, 74, 8939; (g)
Marcoux, D.; Lindsay, V. N. G.; Charette, A. B. Chem. Commun. 2010, 46, 910.
8. Zhang has reported the use of chiral cobalt(II) porphyrin complexes to syn-
thesize cyclopropanes from acceptor/acceptor-substituted diazo reagents in
a highly enantio- and diasetereo-selective fashion: (a) Zhu, S.; Ruppel, J. V.; Lu,
H.; Wojtas, L.; Zhang, X. P. J. Am. Chem. Soc. 2008, 130, 5042; (b) Chen, Y.;
Ruppel, J. V.; Zhang, X. P. J. Am. Chem. Soc. 2007, 129, 12074; (c) Chen, Y.; Zhang,
X. P. J. Org. Chem. 2007, 72, 5931; (d) Zhu, S.; Perman, J. A.; Zhang, X. P. Angew.
Chem., Int. Ed. 2008, 47, 8460.
ESI-HRMS: (MþH) m/z, found: 241.0820; calcd (C15H13O3): 241.0859;
HPLC: ADH, 10% i-PrOH/hexane, 1 ml minꢀ1, UV 254 nm, tR: 17.9 min
(major), 19.3 min (minor), 93% ee with Rh2(S-PTAD)4; [
1.0, CHCl3).
a
]
þ2.1 (c
D23
4.3.13. Methyl (R)-1-acetyl-2-(4-fluoro-3-methylphenyl)cycloprop-2-
enecarboxylate (7k). Purification by silica gel chromatography elut-
ing with hexane/Et2O (10:1) then hexane/EtOAc (1:1) afforded 7k in
77% yield (96 mg) as a yellow oil. Rf 0.39 (hexane/EtOAc); 1H NMR
(400 MHz, CDCl3):
d
7.44 (d, J¼8.0 Hz, 2H), 7.23 (d, J¼8.0 Hz, 2H),
6.82 (s, 1H), 3.68 (s, 3H), 2.36 (s, 3H), 2.18 (s, 3H); 13C NMR (100 MHz,
CDCl3) 206.1 (C), 171.9 (C), 164.1 (C), 161.6 (C), 133.7 (CH), 129.9 (CH,
J¼35.2 Hz), 126.3 (C, J¼72.8 Hz), 120.1 (C), 116.1 (CH, 94.4 Hz), 112.5
(C), 95.5 (CH), 52.4 (CH3), 40.8 (C), 28.2 (CH3), 14.6 (CH3); IR (neat)
3139, 2955,1719,1693,1274,1229, 697 cmꢀ1; ESI-HRMS: (MþH) m/z,
found: 249.0882; calcd (C14H13FO3): 249.0921; HPLC: ADH, 10% i-
PrOH/hexane, 1 ml minꢀ1, UV 254 nm, tR: 17.8 min (major), 20.2 min
9. For seminal work on asymmetric cyclopropenation bearing an ester and tri-
fluoromethyl groups see: Muller, P.; Grass, S.; Shahi, S. P.; Bernardinelli, G.
Tetrahedron 2004, 60, 4755.
10. Uehara, M.; Suematsu, H.; Yasutomi, Y.; Katsuki, T. J. Am. Chem. Soc. 2011, 133,
170; Cui, X.; Xu, X.; Lu, H.; Zhu, S.; Wojtas, L.; Zhang, X. P. J. Am. Chem. Soc. 2011,
133, 3304.
(minor), 97% ee with Rh2(S-PTAD)4; [
a
]
þ7.9 (c 1.0, CHCl3).
D23
4.3.14. Methyl (R)-1-acetyl-2-(2-(((tert-butyldimethylsilyl)oxy)-
methyl)-phenyl)cycloprop-2-enecarboxylate (7l). Purification by silica
gel chromatography eluting with hexane/Et2O (10:1) then hexane/
EtOAc (1:1) afforded 7l in 94% yield (169 mg) as a yellow oil. Rf 0.69
11. For the Rh(II)-catalyzed synthesis of racemic cyclopropenes bearing geminal
carbonyl groups using carbomethoxy iodonium yilides see: Batsila, C.; Kostakis,
G.; Hadjarapoglou, L. P. Tetrahedron Lett. 2002, 43, 5997.
12. Davies, H. M. L.; Ahmed, G.; Churchill, M. R. J. Am. Chem. Soc. 1996, 118, 10774.
13. (a) Davies, H. M. L. J. Mol. Catal. A 2002, 189, 125; (b) Davies, H. M. L.; Hansen, T.;
Churchill, M. R. J. Am. Chem. Soc. 2000, 122, 3063; (c) Davies, H. M. L.; Manning,
J. R. Nature 2008, 451, 417.
14. Davies, H. M. L.; Antoulinakis, E. G. Org. React. 2001, 57, 1.
15. Davies, H. M. L.; Romines, K. Tetrahedron 1988, 44, 11.
16. The crystal structure of 16 has been deposited at the Cambridge Crystallo-
graphic Data Centre, and the deposition number CCDC 817354 has been
allocated.
(hexane/EtOAc); 1H NMR (400 MHz, CDCl3):
d
7.68 (d, J¼7.6 Hz, 1H),
7.48 (t, J¼7.6 Hz, 1H), 7.31e7.43 (m, 2H), 6.95 (s, 1H), 4.98 (s, 2H), 3.72
(s, 3H), 2.25 (s, 3H), 0.98 (s, 9H), 0.14 (s, 6H); 13C NMR (100 MHz,
CDCl3) 206.0 (C), 171.9 (C), 143.4 (CH), 131.1 (CH), 130.9 (CH), 127.4
(CH), 126.5 (CH), 120.5 (C), 111.1 (C), 98.6 (CH), 62.7 (CH2), 52.4 (CH3),
39.9 (C), 28.2 (CH3), 26.1 (CH3), 18.6 (C), ꢀ5.1 (CH3); IR (neat) 3139,
2954, 2885, 2856, 1724, 1693, 1254, 1122, 1079, 837, 757 cmꢀ1; ESI-
HRMS: (MþH) m/z, found: 217.0820; calcd (C13H13O3): 217.0858;
HPLC: ASH, 10% i-PrOH/hexane, 0.7 ml minꢀ1, UV 254 nm, tR: 8.4 min
17. Reddy, R. P.; Davies, H. M. L. J. Am. Chem. Soc. 2007, 129, 10312.
€
18. Muller, P.; Bernardinelli, G.; Allenbach, Y. F.; Ferri, M.; Flack, H. D. Org. Lett.
2004, 6, 1725.
19. Cyclopropenes bearing the keto and ester groups slowly decompose on
standing at room temperature over a period of months and should be stored at
ꢀ20 ꢁC to avoid decomposition.
(major),10.3 min (minor), 99% ee with Rh2(S-PTAD)4; [
CHCl3).
a
]
þ7.2 (c 1.0,
D23