Angewandte
Chemie
DOI: 10.1002/anie.201201367
Synthetic Methods
Catalytic Ring Expansion of Vinyl Oxetanes: Asymmetric Synthesis of
Dihydropyrans Using Chiral Counterion Catalysis**
Boying Guo, Gregg Schwarzwalder, and Jon T. Njardarson*
As a part of our program aimed at developing new ring-
expansion reactions from strained heterocyclic precursors[1]
we are exploring vinyl oxetanes as potential candidates. We
were particularly eager to learn if our success with the ring
expansion of vinyl oxiranes to 2,5-dihydrofurans using [Cu-
(hfacac)2] could be translated into an equivalent transforma-
tion for vinyl oxetanes (Scheme 1). Given the allylic nature of
the system and the favorable release of strain energy, vinyl
cases d-lactones were formed.[5] The scope and yield of their
cascade reaction, which was developed using classic palla-
dium chemistry and relies on a superior leaving group to that
in our ether ring expansion, was reasonable but limited to
a few enals; enones were found to be poor substrates.
We selected vinyl oxetane 1 as our model substrate. It is
readily accessible by a nucleophilic addition to a commercially
available b-chloro carbonyl precursor[6] and it has a phenyl
group that we postulated would aid oxetane bond breaking
and stabilization of a cationic intermediate. When 1 was
subjected to the standard catalytic [Cu(hfacac)2] conditions
we used for the vinyl oxiranes,[1a] ring expansion to 3,6-
dihydro-2H-pyran 2 did indeed occur after prolonged heating
at 1508C, albeit in poor yield (Table 1, entry 1). The
Table 1: Catalyst screening for vinyl oxetane ring expansion.
Entry Catalyst
mol% Solvent T [8C] t [h] % Conv.
Scheme 1. Proposed catalytic ring expansion of vinyl oxetanes.
1
2
3
4
5
6
7
8
[Cu(hfacac)2]
5
5
5
5
5
5
1
5
5
5
5
1
1
1
1
1
toluene
THF
THF
THF
THF
CH2Cl2
CH2Cl2
THF
THF
THF
150
RT
RT
RT
RT
5
10
10
10
2.5
0.05
0.5
10
10
10
10
0.5
0.5
0.5
0.5
0.5
5
15
0
0
Cu(OAc)2
Cu(TFA)2
CuI
oxetanes seemed like perfect ring-expansion candidates.
Furthermore, we predicted that a broader range of catalysts
would be competent for this new ring-expansion reaction
because the competing 1,2-hydride shift pathway we needed
to overcome for the vinyl oxirane ring expansion is less likely
to occur for the vinyl oxetanes.
In general, vinyl oxetanes have received limited attention,
where the few published studies have focused on nucleophilic
ring openings[2] of vinyl oxetanes and insertions of hetero-
atoms[3] into the oxetane.[4] There is only one report in the
literature of a related lactonic vinyl oxetane ring expansion
(Scheme 1). In 2000, when trying to expand the scope of their
cationic-palladium-mediated b-lactone synthesis to include
conjugated aldehydes Hattori et al. realized that in many
0
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
[Pd(hfacac)2]
[PdCl2(CH3CN)2]
[Ni(hfacac)2]
[Zn(hfacac)2]
Mg(OTf)2
Ni(OTf)2
Zn(OTf)2
Bi(OTf)2
TfOH
99
99
99
15
56
0
RT
À78
RT
9
RT
RT
RT
10
11
12
13
14
15
16
17
18
19
20
THF
0
0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
À78
À78
À78
À78
À78
À78
À78
À78
À78
15
35
88
99
63
17
0
p-TsOH
TFA
AcOH
10
10
10
10
5
5
72
=
(EtO)2P O(OH)
67
[*] B. Guo, Prof. J. T. Njardarson
Department of Chemistry and Biochemistry, University of Arizona
1306 E. University Blvd., Tucson, AZ 85721 (USA)
E-mail: njardars@email.arizona.edu
detrimental hydride shift pathway is presumably a far less
likely competing path for vinyl oxetanes than vinyl oxiranes,
therefore we decided to evaluate other stable readily
available catalysts. Metal(II) triflates were the most effective
catalysts and dichloromethane the best solvent. Copper(II)
triflate (Table 1, entries 5–7) proved to be a remarkably well-
suited catalyst for the ring expansion, thus affording the
desired product (2) both rapidly and quantitatively using only
1 mol% of catalyst at À788C. These results prompted us to
G. Schwarzwalder
Department of Chemistry and Chemical Biology
Cornell University, Baker Laboratory
Ithaca, NY 14853-1301 (USA)
[**] We thank the NSF (CHE-0848324) and the University of Arizona for
financial support.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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