Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of trans-vinylcyclopropane-enes

Article abstract of DOI:10.1021/ja8008715

Vinylcyclopropane (VCP) has been well applied as a five-carbon component, rather than a three-carbon component, in transition-metal catalyzed cycloadditions. Here we demonstrate a Rh(I)-catalyzed [3 + 2] reaction of trans-VCP-enes, where VCP acts as a three-carbon synthon to furnish five-membered carbocycles. This novel cycloaddition is efficient in generating bicyclic cyclopentanes in good yields from simple and easily prepared substrates. When cis-VCP-ene is used as the substrate, VCP acts as a five-carbon unit to give a [5 + 2] cycloadduct. Rationalization of the [3 + 2] and [5 + 2] cycloadditions of VCP-enes has been proposed. Copyright

Full text of DOI:10.1021/ja8008715

Published on Web 05/14/2008
Rh(I)-Catalyzed Intramolecular [3 + 2] Cycloaddition of
trans-Vinylcyclopropane-enes
Lei Jiao, Siyu Ye, and Zhi-Xiang Yu*
Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education, College of Chemistry, Peking UniVersity, Beijing 100871, China
Received February 4, 2008; E-mail: yuzx@pku.edu.cn
Scheme 1
Developing methods to synthesize five-membered carbocycles
has been intensively pursued by the synthetic community.1 One
spectacular achievement in this regard is witnessed by many [3 +
2] cycloadditions between various three-carbon and two-carbon
components.2 Among these three-carbon synthons, cyclopropane,
a highly strained ring system expected to act as an efficient two-
electron three-carbon synthon, has attracted tremendous attention.
To date, various cyclopropane derivatives substituted with a wide
range of activating functional groups have been successfully used
in [3 + 2] cycloadditions.1c For example, cyclopropyl ketones2g,h
and alkylidenecyclopropanes2j have been shown to participate in
several transition-metal catalyzed [3 + 2] cycloadditions. In
contrast, vinylcyclopropanes (VCP) are less employed in the
transition-metal catalyzed [3 + 2] cycloaddition, possibly because
of the preference of VCP to act as a five-carbon component in the
[5 + x] cycloadditions.3 Previous reports of VCPs as three-carbon
units are only limited to those with one or two electron-withdrawing
activating groups on the cyclopropane ring.4 Therefore, discovering
new cycloaddition reactions in which unactivated VCP acts as a
three-carbon unit will advance the cyclopropane chemistry. Herein,
we wish to report a novel and unexpected Rh(I)-catalyzed intramo-
lecular [3 + 2] cycloaddition of unactivated VCP-enes for the
construction of bicyclic five-membered rings, where VCPs act as
three-carbon synthons.
Table 1. Optimization Studies on the [3 + 2] Cycloadditiona
entry CO (atm)
catalyst (mol %)
T (°C)
solvent
T (h) yield (%)b
1
2
3
4
5
0.2c
1.0
0
0
0
5% [Rh(CO)2Cl]2
5% [Rh(CO)2Cl]2
5% [Rh(CO)2Cl]2
10% RhCl(PPh3)3
10% RhCl(PPh3)3 +
10% AgOTf
5% [Rh(CO)2Cl]2
5% [Rh(CO)2Cl]2 +
10% AgOTf
80 dioxane 23
80 dioxane 17
80 dioxane 17
80 dioxane 23
80 dioxane 23
59
28d
77
13d
21e
6
7
0
0
110 toluene
50 toluene 10
5.5
83
62
a Racemic VCP-ene 1 was used. b Isolated yields. c Reaction run with
0.2 atm CO + 0.8 atm N2. d Recovered 52% of 1. e Recovered 31% of 1.
We recently demonstrated that ene-vinylcyclopropane (ene-VCP),
which has an alkene tethered to the vinyl position of VCP, undergoes
a Rh(I)-catalyzed two-component [(5 + 2) + 1] cycloaddition with
CO to furnish bicyclic cyclooctenones (Scheme 1).5 We envisioned
that, it might be an interesting extension to employ a new type of
substrate, VCP-ene, which has an alkene tethered to the cyclopropane
ring of VCP, in the [(5 + 2) + 1] cycloaddition to construct a bridged
bicyclic cyclooctenone structure (Scheme 1). This hypothesis was tested
with tosylamide-tethered VCP-ene 1 under the optimal [(5 + 2) + 1]
cycloaddition conditions (0.2 atm CO, [Rh(CO)2Cl]2 as catalyst,
dioxane as solvent, 80 °C).5 However, instead of the expected bridged
[(5 + 2) + 1] cycloadduct, a symmetric bicyclic 5,5-ring compound
2 was obtained (Table 1), which was speculated to be generated via a
[3 + 2] cycloaddition between alkene and cyclopropane moieties
without incorporation of CO and the vinyl group of VCP.
Realizing that this unexpected result represents an important example
where unactivated VCP participates in the [3 + 2] cycloaddition as a
three-carbon component, we decided to further develop this reaction
to a practical synthetic approach to bicyclic five-memberd ring systems.
We systematically optimized the reaction conditions for this new [3
+ 2] cycloaddition using substrate 1. It was found that, even under
higher CO pressure, no CO-incorporated product was detected and
only [3 + 2] cycloadduct 2 was obtained (Table 1, entry 2). Without
CO atmosphere, the [3 + 2] reaction proceeded well (Table 1, entry
3). Wilkinson’s catalyst could also catalyze this reaction, but was less
efficient (Table 1, entries 4 and 5). Toluene as solvent was found to
be better than 1,4-dioxane, producing cycloadduct 2 in 83% yield
(Table 1, entry 6). Notably, Rh(I)+ species (generated through
[Rh(CO)2Cl]2 + AgOTf) as catalyst was proved to be more active
and thus allow the reaction to run at lower temperature (Table 1, entry
7). In all cases, the [3 + 2] cycloadduct 2 was obtained as a single
diastereomer. When ene-cyclopropane 3 was submitted to the opti-
mized conditions, the [3 + 2] cycloaddition could not occur and the
substrate remained intact, highlighting the importance of the vinyl
substitution in the [3 + 2] cycloaddition (Table 1).
A series of VCP-ene substrates was tested under the optimized
reaction conditions to explore the substrate scope of this [3 + 2]
cycloaddition (Table 2). The results indicated that this cycloaddition
reaction is tolerant of different substitution on the VCP and ene
moieties. Alkyl and aryl substituents on the vinyl functionality of VCP
furnished the corresponding [3 + 2] cycloadducts in moderate to good
yields (Table 2, entries 1 to 4). Alkyl substituent on ene moiety gave
the cycloadduct with an additional stereocenter (Table 2, entry 5), and
methyl substitution on cyclopropane moiety provided a similar
cycloadduct (Table 2, entry 6). Bicyclic cycloadduct with a quaternary
carbon could also be produced in a good yield from 1-methyl-
substituted VCP-ene 16 (Table 2, entry 7). Interestingly, VCP-ene 18
with a special bicyclic VCP moiety afforded a linear-triquinane-like
tricyclic [3 + 2] cycloadduct 19 in a good yield (Table 2, entry 8).
Other tether in VCP-ene substrate, such as ether functionality, is also
tolerated in this [3 + 2] cycloaddition (Table 2, entry 4). However,
the VCP-ene substrates with an internal substitution on the ene moiety,
an elongated tether (for 6,5-ring formation), or a carbon-tether failed
to undergo the [3 + 2] cycloaddition.
Reaction of cis-substituted VCP-ene 20 was examined to see
whether its [3 + 2] cycloaddition would produce a cycloadduct with
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10.1021/ja8008715 CCC: $40.75  2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Rh(I)-Catalyzed [3 + 2] Cycloaddition Reactionsa
Scheme 4. Plausible Mechanism of the [3 + 2] Cycloaddition
a Racemic substrates were used. Condition A: 5 mol % [Rh(CO)2Cl]2 as
catalyst, toluene as solvent, substrate concentration 0.025 M. Condition B: 5
mol % [Rh(CO)2Cl]2 + 10 mol % AgOTf as catalyst, toluene as solvent,
substrate concentration 0.025 M. Isolated yields are reported. b Confirmed
by X-ray crystallographic analysis. c dr ) 7:1.
where C1′ and C5 are in close proximity. Thus, the final reductive
elimination leads to the formation of C1′-C5 bond to produce the [5
+ 2] cycloadduct, instead of the unfavorable formation of C1′-C3
bond to give the [3 + 2] cycloadduct.
In conclusion, we have described the first examples of an Rh(I)-
catalyzed intramolecular [3 + 2] cycloaddition of VCP-enes, demon-
strating that vinylcyclopropanes without electron-withdrawing activa-
tion groups can act as three-carbon synthons in transition-metal
catalyzed cycloadditions. The present methodology provides an ef-
ficient and diastereoselective approach to fused five-membered ring
systems. Further studies of this reaction (scope, mechanism, and
application) are underway.
Scheme 2. Reaction of a cis-VCP-ene
Scheme 3. Chirality Transfer in the [3 + 2] Cycloaddition
Acknowledgment. We thank Peking University, the Natural
Science Foundation of China (20521202 and 20672005), and the
Ministry of Education of China (108001) for financial support, Dr.
Wenxiong Zhang for X-ray crystallographic analysis, and Ms. Qian
Li for experimental assistance.
Supporting Information Available: Experimental details. This
material is available free of charge via the Internet at http://pubs.acs.org.
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