C-O versus C-C bond cleavage: Selectivity control in Lewis acid catalyzed chemodivergent cycloadditions of aryl oxiranyldicarboxylates with aldehydes, and theoretical rationalizations of reaction pathways

Article abstract of DOI:10.1002/chem.201201453

A clean break: Lewis acid catalyzed chemodivergent [3+2] cycloadditions of aryl oxiranyldicarboxylates with aldehydes are revealed, in which the C-C or C-O bond cleavage of oxiranes can be controlled by the use of Ni(ClO ₄)₂ or Sn(OTf)₂ catalysts (see scheme). Possible reaction pathways for these transformations are demonstrated by theoretical calculations. Copyright

Full text of DOI:10.1002/chem.201201453

COMMUNICATION
DOI: 10.1002/chem.201201453
À
À
C O Versus C C Bond Cleavage: Selectivity Control in Lewis Acid
Catalyzed Chemodivergent Cycloadditions of Aryl Oxiranyldicarboxylates
with Aldehydes, and Theoretical Rationalizations of Reaction Pathways
Zuliang Chen,[a] Ziqi Tian,[b] Jieming Zhang,[a] Jing Ma,*[b] and Junliang Zhang*[a]
Oxiranes have attracted significant attention mainly as
a result of being useful as building blocks for the synthesis
of organic structures, their ease of preparation, and their
propensity for strain-induced ring-opening reactions. The
in the presence of different Lewis acids (LAs). In mode I,
the oxiranyldicarboxylate 1 could be activated by coordina-
tion of the sp3-O of oxirane and one of the carboxylate
oxygen atoms (sp2-O) to a Lewis acid. Alternatively, in
mode II another Lewis acid may activate the oxiranyldicar-
boxylates by association with two carboxylate oxygen atoms
(sp3-O). These two coordination modes may result in two
different ring opening pathways of the epoxide motif, that is,
dominant chemistry of oxiranes is ring opening reactions by
[1,2]
À
À
C O bond cleavage,
with C C bond cleavage as a notable
exception.[3,4]
Due to their unique catalytic activity, selectivity, and reac-
tivity under mild conditions, Lewis acids have been devel-
oped as an essential tool for synthetic transformations, and
have been widely used in the synthesis of natural products
and medicinal compounds.[5] Each Lewis acid has character-
istic features, thus a systematic screening of different Lewis
acids is often unavoidable. To optimize this time-consuming
screening process, a fundamental understanding and classifi-
cation of Lewis acids is expected to help address this issue.
Herein, we report the chemodivergent 1,3-dipoplar cycload-
dition of aryl oxiranyldicarboxylates with aldehydes, in
À
À
C O or C C bond breakage, respectively, that are then
trapped by an aldehyde, leading to two chemodivergent cy-
cloadducts, 3 and 4 (Scheme 1).
À
À
which the C C or C O bond cleavage of oxirane can be
controlled by the appropriate choice of Lewis acid. Diver-
gent synthesis from the same starting material(s) is an inter-
esting, but challenging task that has attracted many chemists
in past years.[6] The mechanism of these transformations
have also been computationally studied and, furthermore,
these findings may be applied to the classification of Lewis
acid into subgroups based on their catalytic activity, chemo-
selectivity, and stereoselectivity.
Scheme 1. Proposed routes for the oxirane bond cleavage reactions.
To test our hypothesis, dimethyl-3-para-tolyloxirane-2,2-
dicarboxylate (1a) and benzaldehyde 2a were subjected to
During the course of our research into developing new
oxirane chemistry,[4,7] we hypothesized that oxiranyldicar-
boxylates 1 might undergo two different reaction pathways
a solution of YACHTUNGTERNU(NG OTf)3 (5 mol%) in CH2Cl2 with 4 ꢀ molecu-
lar sieves at room temperature, yielding cycloadduct 3a
À
(through C O bond cleavage of oxirane) and cycloadduct
À
4a (through C C bond cleavage of oxirane) in 26 and 66%
[a] Z. Chen,+ J. Zhang, Prof. Dr. J. Zhang
Shanghai Key Laboratory of Green Chemistry and
Chemical Processes
yield, respectively (see the Supporting Information,
Table S1, entry 1). After many attempts, the best reaction
À
conditions for C O bond cleavage were found to be the use
Department of Chemistry, East China Normal University
3663 N. Zhongshan Road, Shanghai 200062 (P.R. China)
Fax : (+86)21-6223-5039
of Sn
A
À
ditions A; Table S1, entry 36). In sharp contrast, C C bond
cleavage to give oxirane product 4a occurred exclusively in
excellent yield and diastereoselectivity when the reactions
E-mail: jlzhang@chem.ecnu.edu.cn
[b] Z. Tian,+ Prof. Dr. J. Ma
Institute of Theoretical and Computational Chemistry
Key Laboratory of Mesoscopic Chemistry of MOE
School of Chemistry & Chemical Engineering, Nanjing University
22 Hankou Road, Nanjing, 210093 (P.R. China)
E-mail: majing@nju.edu.cn
were performed in the presence of NiACTHUNTGRNEG(UN ClO4)2·6H2O (Table
S1, entries 37–39), and toluene was found to be the best sol-
vent for this case (conditions B; Table S1, entry 39).
Based on the results shown in Table S1 (see the Support-
ing Information), these Lewis acids can be classified into
several groups based on their efficiency as follows: A, active
(yieldꢀ50%); B or C, weak (10%ꢁyieldꢁ50%) or inac-
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201201453.
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

Table 1. The reaction of various oxiranes 1 and benzaldehyde 2a.[a]
tive (yieldꢁ10%). According to their selectivity, Lewis
À
acids in group A were further divided into A-1 (C O
À
bond cleavage selectivity, 3a/4aꢀ2:1), A-2 (C C bond
cleavage selectivity, 4a/3aꢀ2:1) and A-3 (neutral). Simi-
À
larly, Lewis acids in group B were divided into B-1 (C O
À
bond cleavage selectivity, 3a/4aꢀ2:1), B-2 (C C bond
cleavage selectivity, 4a/3aꢀ2:1) and B-3 (neutral). The
results listed in Table S1 in the Supporting Information
show that most Lewis acids are classified into group A
(active) (Table S1, entries 1–2, 4–5, 11, 13–26, and 28–32).
Entry
1
Conditions
t [h]
Yield [%][b]
cis/trans[c]
1
2
1a
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
1
6
7
40
12
72
1
7
1
23
3
27
1
3a (83)
4a (91)
3b (72)
4b (93)
3c (59)
4c (84)
3d (83)
4d (90)
3e (68)
4e (80)
3 f (64)
4 f (87)
3g (86)
4g (95)
3h (81)
4h (90)
4:1
47:1
3.3:1
50:1
2:1
25:1
3.3:1
10:1
2.7:1
5:1
2.7:1
>99:1
1.6:1
33:1
3:1
Moreover, Fe
(OTf)2, Bi(OTf)3, Y
(ClO4)3·6H2O, Yb(ClO4)3·6H2O, La
(ClO4)3·xH2O, Hg(ClO4)2·6H2O, Zn(ClO4)2·6H2O, and In-
(ClO4)3·8H2O are classified into group A-1; Y(OTf)3, Gd-
(OTf)3, Yb(OTf)3, Ni(ClO4)2·6H2O, and Cu(ClO4)2·6H2O
are classified into group A-2. Group A-3 Lewis acids in-
clude Sc(OTf)3, Al(OTf)3, Mg(ClO4)2·6H2O, and Al-
(ClO4)3·9H2O. None of the Lewis acids are classified into
group B-1; Ce(OTf)3 (Table S1, entry 3) is classified into
group B-2; and Zn(OTf)2 and Cu(OTf)2 (Table S1, en-
tries 10 and 12) are classified into group B-3. The reac-
tion proceeded slowly when La(OTf)3, Mg(OTf)2, Ni-
(OTf)2, AgOTf, or AgClO4·H2O was used as the catalyst,
A
N
G
ACHTUNGRTENN(UNG OTf)2, Sn-
A
E
N
ACHTUNGTRENNUNG
3[d,e]
4
1b
1c
1d
1e
1 f
1g
1h
A
R
ACHTUNGTRENNUNG
5[d,e]
6[e,f]
7
A
R
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
E
N
ACHTUNGTRENNUNG
8[e,g]
9[e]
10[h]
11
A
R
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
12
13
14
15
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
11
1
16
A
ACHTUNGTRENNUNG
16
20:1
ACHTUNGTRENNUNG
[a] 1 (0.5 mmol), 2a (0.55 mmol), catalyst (5 mol%) and activated 4 ꢀ
and these catalysts are classified into group C (Table S1,
entries 6–9, 33).
molecular sieves (100 mg) in solvent (5 mL) at room temperature. Condi-
tions A: Sn
[b] Isolated yield. [c] Determined by 1H NMR spectroscopic analysis of
the crude reaction mixture. [d] 10 mol% of Sn(OTf)2. [e] 2.0 equivalents
of 2a. [f] The reaction was conducted at 508C and 20 mol% Ni-
CAHUTNGTREN(NUG OTf)2, CH2Cl2; Conditions B: NiHCATUNGTNERN(UGN ClO4)2·6H2O, toluene.
Interestingly, the group 3 metal triflates (Sc
(OTf)3) are both active, whereas the lanthanide triflates
show different activities and selectivities. With the in-
ACHTUNGRTEN(NUNG OTf)3 and
AHCTUNGTRENNUNG
YACHTUNGTRENNUNG
(ClO4)2·6H2O was used. [g] The reaction was conducted at À108C.
crease in metal atomic number, the lanthanide triflates [h] Trace amounts of 3e were obtained.
have a tendency to bind to the carbonyl sp2-O of the oxir-
À
ane 1a, leading to C C bond cleavage as the predomi-
nant reaction pathway (Table S1, entries 3–5). On the other
hand, the Group 13–15 metal triflates are all active (Table
S1, entries 13–15, 17, and18), and Lewis acids such as Al-
methoxy group was complete within 7 h (Table 1, entry 8).
The ortho methoxy substitutent significantly decreases the
diastereoselectivity for the NiII-catalyzed transformation,
which is not the case for the SnII-catalyzed reaction (Table 1,
entries 9 and 10). Gratifyingly, the dicarboxylates can be
switched to ethyl or allyl esters to give the desired products
in high yields (Table 1, entries 13–16).
ACHTUNGTRENNUNG(OTf)3, GaACHTUNGTRENNUNG(OTf)3, and InACTHUNGTREN(UNNG OTf)3 have a tendency to selec-
tively bind to the ether sp3-O of the oxirane 1a, leading to
À
C O bond cleavage. In some cases, metal perchlorates are
much more active than metal triflates (Table S1, entry 6 vs.
entry 24; entry 7 vs. entry 19; entry 8 vs. entry 26), indicating
that the anion also plays an important role in the activity of
the Lewis acid.
With optimal reaction conditions in hand, the oxirane sub-
strate scope was examined for this Lewis acid catalyzed, se-
lective, 1,3-dipolar cycloaddition (Table 1). In general, the
We next studied the scope of this reaction by variation of
the aldehyde component (Table 2). The data in Table 2
shows that the reaction of an aldehyde 2 that contains an
electron-donating or electron-withdrawing group at the para
position of the phenyl ring proceeded smoothly to provide
the corresponding cycloadducts in 82–95% yield (Table 2,
entries 1–6). Furthermore, polysubstituted benzaldehyde 2e
and the heterocyclic aldehyde furfural (2 f) were also com-
patible, giving the desired products in 70–96% yield
(Table 2, entries 7–10). Finally, the reactions of aliphatic al-
dehydes 2g–2i produced the corresponding cycloadducts in
73–95% yield with moderate to good diastereoselectivities
(Table 2, entries 11–18). The structure and the relative ste-
reochemistry of the products were established by X-ray crys-
tallographic analysis of the cis isomers of 3a and 4j (see the
Supporting Information, Figure S1).[8]
À
C O bond cleavage products 3 are obtained exclusively in
high yields with moderate diastereoselectivities from cataly-
À
sis with Sn
(OTf)2; whereas C C bond cleavage products 4
are obtained with high to excellent yields in the presence of
NiACHTUNGTRENNUNG
(ClO4)2 (5 mol%). However, the NiII-catalyzed reaction is
much slower than the corresponding SnII-catalyzed reaction.
Introduction of an electron-donating group on the phenyl
ring of the oxirane accelerates the reaction rate. For exam-
ple, the reaction of oxirane 1c containing a weakly electron-
withdrawing chloride group required 3 days for full conver-
sion under reaction conditions B (Table 1, entry 6). In con-
trast, the reaction of oxirane 1d with an electron-donating
Synthetic applications of 1,3-dioxolane 4 have been show-
cased by the selective transformations of the representative
&
2
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Chemodivergent Cycloadditions
COMMUNICATION
Table 2. The reaction of 1a and various aldehydes 2.
(DFT) studies by using oxirane 1a and benzaldehyde 2a as
the model substrates, with SnACHTNUTRGENNUG(OTf)2 and NiACHTUNGTERN(NUGN ClO4)2 as the re-
spective catalysts (see the Supporting Information for all de-
tails).[10–12] Both Sn
bond cleavages favor SN2 stepwise pathways through an anti
attack. Figure 1 shows that the metal anions are coordinated
to the sp3-oxygen of the oxirane and one of the carbonyl
(OTf)2- and Ni
N
À
À
groups, forming the intermediate IM1 on the C O cleavage
pathway. The interaction between the anion and the sp3-O
Entry
2
Conditions
t [h]
Yield [%][a]
cis/trans[b]
À
weakens the C O bond of the oxirane, and nucleophilic
À
attack on the oxirane from the back of this C O bond
1
2
3
4
5
2b
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
1
10
1
22
1
60
1
18
1
22
1
26
1
11
1
16
1
3i (84)
4i (95)
3j (82)
4j (86)
3k (82)
4k (85)
3l (74)
4l (96)
3m (70)
4m (88)
3n (83)
4n (95)
3o (81)
4o (73)
3p (80)
4p (79)
3q (78)
4q (77)
4.5:1
>99:1
1:1.1
25:1
1:1.7
10:1
3.8:1
>99:1
1:1
À
occurs via transition state TS1. Subsequently the C C bond
of the IM2 oxirane, which has a gauche conformation, ro-
2c
2d
2e
2 f
2g
2h
2i
À
tates by 1208 to form IM3. The newly formed C O bond
then rotates to allow ring closure into a heterocyclic inter-
mediate, IM4. From IM2 to IM3 there are two possible rota-
tion directions with a similar energy barrier (8 kcalmolÀ1).
The different rotation directions from IM3 to IM4 lead to
the cis- and trans-isomers.[13] Finally, the catalyst is released
and the product is formed. The rate-determining step is the
6[c]
7
8
9
10
11
12
13
14
15
16
17
18
2:1
1:1.6
8.3:1
1:1.5
8.3:1
1:1
16:1
2.3:1
6.2:1
À
SN2 step from IM1-2a to TS1, in which the old C O bond is
À
cleaved and the new C O bond is going to be formed. The
single bond rotations, including the steps from IM2 to TS2
and IM3 to TS3, are important for controlling the stereose-
lectivity of the reactions (see Figure 2).
2j
72
À
[a] Isolated yield. [b] Determined by 1H NMR spectroscopic analysis of
the crude reaction mixture. [c] Two equivalents of 2d were used.
In contrast, on the C C bond cleavage pathways the
anions are coordinated to the two carbonyl groups of oxir-
ane 1a to form IM5. The IM5,
which has a six-membered-ring
structure, is energetically more
favorable than the IM1. The
variation of the natural bond
orbital (NBO) charges (see the
Supporting
Information,
Table S2 for details) of oxirane
shows that the polarity of the
À
À
C C bond increases. The C C
bond is weakened and cleaved
by thermal ring opening to gen-
erate a carbonyl ylide inter-
mediate, IM6 (the polar zwitter-
ionic intermediate). This reacts
with the aldehyde via a [3+2]
cycloaddition pathway,[14] step-
ping from IM6 to IM7 in
Figure 1, and this step is pre-
Scheme 2. Examples of synthetic applications of the bond cleavage reaction by using a 1,3-dioxolane, 4.
compound 4l (Scheme 2). This 1,3-dioxolane (4l) underwent
a highly selective Krapcho decarboxylation[9] to afford tri-
substituted 1,3-dioxolane 5 in 56% yield as a single isomer.
This compound then underwent further reduction upon
treatment with NaBH4 in methanol, yielding a trisubstituted
1,3-dioxolane 6 in 76% yield. Gratifyingly, the sterically less
hindered ester of 4l can be selectively reduced by treatment
with NaBH4 in methanol, affording a 1,3-dioxolane 7 in
82% yield as a single isomer.
dicted to be the rate-determining step and to determine the
distereoselectivity of the reaction.[15] Electron-rich aldehydes
are expected to react faster if the key step is IM6 to IM7 (nu-
cleophilic attack of the oxygen lone pair on the aldehyde on
the complex IM6), and this theoretical prediction has been
corroborated by the experimental results [Eq. (1)].
To gain some insight into the mechanistic issues raised
during this study, we carried out density functional theory
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

J. Zhang, J. Ma et al.
Figure 2. Geometries of the key transition states in the cleavage reaction.
Figure 1. The Gibbs free energy profiles (DG298 in units of kcalmolÀ1 at
À
À
298 K) of the reaction pathways for C O and C C bond cleavage cata-
lyzed by a) Sn(OTf)2 and b) Ni(ClO4)2 in CH2Cl2 solution (by using
a PCM solvent model, e=8.9).
N
ACHTUNGTRENNUNG
À
overall than the C O cleavage pathway (Figure 1b, black
À
line). Thus, the C C cleavage is favored when Ni
A
used as the catalyst. This is also in agreement with experi-
mental results (see the Supporting Information; Table S1,
entries 26 and 27).
When SnACHTUNGTRENNUNG(OTf)2 is used as the catalyst (Figure 1a), the ac-
À
À
tivation energies of the C O and C C bond cleavages are
5.0 and 10.8 kcalmolÀ1, respectively, and the energy barrier
In summary, we have developed a method for the Lewis
acid catalyzed chemodivergent cycloaddition of aryl oxira-
À1
À
from IM6 to TS5 is 14.6 kcalmol . This indicates that the C
O bond cleavage is a more favorable reaction pathway than
the C C bond cleavage, and is consistent with the experi-
mental results (see the Supporting Information; Table S1,
À
À
nyldicarboxylates with aldehydes in which the C C or C O
bond cleavage of oxiranes can be controlled by the use of
À
a NiACHTUNGTRENNU(G ClO4)2 or SnCAHTUNGRTNEN(UNG OTf)2 catalyst, respectively. DFT calcula-
entry 17). In contrast, the energy barriers of the Ni
G
tions support the proposed mechanism of these two reaction
pathways. These chemodivergent transformations may be
used as a probe to classify the Lewis acids into subgroups,
which will make a fundamental contribution to this field.
À
À
catalyzed C O and C C bond cleavages are 12.6 and
13.9 kcalmolÀ1, respectively (Figure 1b). This seems to be
a more kinetically favorable reaction pathway for the C O
À
À
cleavage than the C C cleavage; however, the C C cleav-
age pathway (Figure 1b, gray line) is much less endothermic
&
4
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Chemodivergent Cycloadditions
COMMUNICATION
gler, C. Wolf, Org. Lett. 2009, 11, 4724; d) L. Liu, J. Zhang, Angew.
Chem. 2009, 121, 6209; Angew. Chem. Int. Ed. 2009, 48, 6093; e) Y.
Zhang, F. Liu, J. Zhang, Chem. Eur. J. 2010, 16, 6146; f) G. Zhou, J.
Zhang, Chem. Commun. 2010, 46, 6593; g) G. Lu, T. Yoshino, H.
Morimoto, S. Matsunaga, M. Shibasaki, Angew. Chem. 2011, 123,
4474; Angew. Chem. Int. Ed. 2011, 50, 4382; h) Z. Wang, Z. Yang,
D. Chen, X. Liu, L. Lin, X. Feng, Angew. Chem. 2011, 123, 5030;
Angew. Chem. Int. Ed. 2011, 50, 4928.
Acknowledgements
Financial support from the NSFC (20972054, 20825312), the Ministry of
Education of China, and the 973 Program (2011CB808600) is greatly ap-
preciated.
Keywords: cleavage
reactions
·
chemoselectivity
·
[7] J. Feng, J. Zhang, J. Am. Chem. Soc. 2011, 133, 7304.
cycloaddition · Lewis acids · oxiranes
[8] CCDC-823611 (3a) and CCDC-823612 (4j) contain the supplemen-
tary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
[1] a) R. E. Parker, N. S. Isaacs, Chem. Rev. 1959, 59, 737; b) E. N. Ja-
cobsen, Acc. Chem. Res. 2000, 33, 421; c) I. Vilotijevic, T. F. Jamison,
Angew. Chem. 2009, 121, 5352; Angew. Chem. Int. Ed. 2009, 48,
5250; d) C. J. Morten, J. A. Byers, A. R. V. Dyke, I. Vilotijevic, T. F.
Jamison, Chem. Soc. Rev. 2009, 38, 3175.
[9] A. P. Krapcho, J. F. Weimaster, J. Org. Chem. 1980, 45, 4105.
[10] Gaussian 09, Revision B01, M. J. Frisch, G. W. Trucks, H. B. Schle-
gel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V.
Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X.
Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Son-
nenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J.
Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox,
J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W.
Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A.
Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, ꢇ.
Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian,
Inc., Wallingford CT, 2009.
[2] For Lewis acid catalyzed [3+2] cycloadditions of simple oxiranes
À
with ketones or aldehydes by C O bond cleavage, see: a) R. P. Han-
zlik, M. Leinwetter, J. Org. Chem. 1978, 43, 438; b) D. Torok, J. Fig-
ueroa, W. Scott, J. Org. Chem. 1993, 58, 7274; c) Z. Zhu, J. Espen-
son, Organometallics 1997, 16, 3658; d) R. D. Adams, T. S. Barnard,
K. Brosius, J. Organomet. Chem. 1999, 582, 358; e) J. R. Vyvyan,
J. A. Meyer, K. D. Meyer, J. Org. Chem. 2003, 68, 9144; f) A. Proco-
pio, R. Dalpozzo, A. De Nino, L. Maiuolo, M. Nardi, B. Russoa,
Adv. Synth. Catal. 2005, 347, 1447; g) P. Krasik, M. Bohemier-Ber-
nard, Q. Yu, Synlett 2005, 854; h) J. M. Concellꢂn, J. R. Suꢃrez, S.
Garcꢄa-Granda, M. R. Dꢄaz, Org. Lett. 2005, 7, 247; i) F. Benfatti, G.
Cardillo, L. Gentilucci, A. Tolomelli, M. Monari, F. Piccinelli, Adv.
Synth. Catal. 2007, 349, 1256.
À
[11] The B3LYP functional was used for geometry optimizations, with
the standard 6-31+G[d] basis sets for the light elements, and
LANL2DZ basis sets containing the pseudo potential for metal
atoms. The stabilities of the wavefunctions were tested and the com-
pounds that contained Ni favoured triplet ground states, thus the un-
restricted methods were employed. Frequency calculations were per-
formed to test the obtained stationary points, intermediates (IM)
and transition states (TS), and to find their thermochemical correc-
tions. The solvent effects from dichloromethane (e=8.9) were inves-
tigated by using a polarized continuum model (PCM) at the opti-
mized gas phase structures. The molecular cavities were built up
using a UFF model. The Gibbs free energies in the solution were
[3] For C C bond cleavage of oxiranes under thermal conditions, see:
a) R. Huisgen, Angew. Chem. 1977, 89, 589; Angew. Chem. Int. Ed.
Engl. 1977, 16, 572, and references therein; b) P. De March, R. Huis-
gen, J. Am. Chem. Soc. 1982, 104, 4952; c) C. Bemaus, J. Font, P. de
March, Tetrahedron 1991, 47, 7713; d) C. Yoakim, W. W. Ogilvie, N.
Goudreau, J. Naud, B. Hachꢅ, J. A. OꢆMeara, M. G. Cordingley, J.
Archambault, P. W. White, Bioorg. Med. Chem. Lett. 2003, 13, 2539;
e) G. W. Wang, H. T. Yang, P. Wu, C. B. Miao, Y. Xu, J. Org. Chem.
2006, 71, 4346; f) G. Bentabed-Ababsa, A. Derdour, T. Roisnel,
J. A. Sꢃez, L. R. Domingo, F. Mongin, Org. Biomol. Chem. 2008, 6,
3144.
À
[4] For catalytic C C bond cleavage of oxiranes, see: a) T. Wang, J.
obtained by employing the following equation: DGsol =DGgas
(DEsolÀDEgas).
+
Zhang, Chem. Eur. J. 2011, 17, 86; b) Z. Chen, L. Wei, J. Zhang,
Org. Lett. 2011, 13, 1170; c) T. Wang, C. Wang, J. Zhang, Chem.
Commun. 2011, 47, 5578; d) R. Liu, M. Zhang, J. Zhang, Chem.
Commun. 2011, 47, 12870; e) J. Zhang, Z. Chen, H. Wu, J. Zhang,
Chem. Commun. 2012, 48, 1817.
[12] For some theoretical reports on [3+2] cycloaddition reactions, see:
a) J. Zhang, W. Shen, M. Li, Eur. J. Org. Chem. 2007, 4855; b) G.
Bentabed-Ababsa, A. Derdour, T. Roisnel, J. A. Sꢃez, P. Pꢅrez, E.
Chamorro, L. R. Domingo, F. Mongin, J. Org. Chem. 2009, 74, 2120;
c) W. Benchouk, S. M. Mekelleche, M. Aurell, L. R. Domingo, Tetra-
hedron 2009, 65, 4644; d) L. R. Domingo, J. A. Sꢃez, J. Org. Chem.
2011, 76, 373; e) V. V. Diev, R. R. Kostikov, R. Gleiter, A. P. Mol-
chanov, J. Org. Chem. 2006, 71, 4066.
[5] For reviews on Lewis acid catalyzed reactions, see: a) Selectivities in
Lewis Acid Promoted Reactions (Ed.: D. Schinzer), Kluwer Aca-
demic Publishers, Dordrecht, 1989; b) R. W. Marshman, Aldrichimi-
ca Acta 1995, 28, 77; c) M. Santelli, J. M. Pons in Lewis Acids and
Selectivity in Organic Synthesis (Eds: M. Santelli, J. M. Pons), CRC
Press, Boca Raton, 1996; d) H. Yamamoto in Lewis Acid Reagents:
[13] By using SnACHTNUTRGNEUNG(OTf)2, the energy barrier from IM3 to the trans transi-
tion state is 3.9 kcalmolÀ1, compared with 3.2 kcalmolÀ1 for the cis
transition state. The ratio of cis to trans product is 3.3:1, which is
close to the experimental result.
A
Practical Approach (Ed.: H. Yamamoto), Oxford University
Press, Oxford, 1999; e) S. Kobayashi, Eur. J. Org. Chem. 1999, 15;
f) H. Yamamoto in Lewis Acids in Organic Synthesis, Vol. 1–2 (Ed.:
H. Yamamoto), Wiley-VCH, Weinheim, 2000; g) S. Kobayashi, M.
Sugiura, H. Kitagawa, W. W. L. Lam, Chem. Rev. 2002, 102, 2227;
h) C.-Y. Wang, Z.-F. Xi, Chem. Soc. Rev. 2007, 36, 1395; i) G. Barto-
li, M. Locatelli, P. Melchiorre, L. Sambri, Eur. J. Org. Chem. 2007,
2037; j) R. Dalpozzo, G. Bartoli, L. Sambri, P. Melchiorre, Chem.
Rev. 2010, 110, 3501; k) S. Antoniotti, V. Dalla, E. DuÇach, Angew.
Chem. 2010, 122, 8032; Angew. Chem. Int. Ed. 2010, 49, 7860; l) S.
Kobayashi, Y. Yamashita, Acc. Chem. Res. 2011, 44, 58.
À
[14] Because the potential energy surface is quite flexible when the C1
O2 bond (see Figure 2) has recently formed, it is difficult to locate
a minimum between TS5 and IM7. We propose that the cycloaddi-
tion is stepwise, as there is an obvious intermediate with one small
imaginary frequency on the optimizing path from TS5 to IM7.
[15] By using NiACHTUNTRGNEUNG(ClO4)2, the cycloaddition energy barriers for trans and
cis products are 15.4 and 9.1 kcalmolÀ1, respectively. This result indi-
cates that there may be a small amount of trans product in the di-
chloromethane solution, which is consistent with the experimental
results.
[6] For selected recent examples of changing the selectivity by use of
Lewis acids, see: a) H. Y. Kim, H.-J. Shih, W. E. Knabe, K. Oh,
Angew. Chem. 2009, 121, 7556; Angew. Chem. Int. Ed. 2009, 48,
7420; b) H. Y. Kim, K. Oh, Org. Lett. 2009, 11, 5682; c) K. Y. Span-
Received: April 27, 2012
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

J. Zhang, J. Ma et al.
Cycloaddition Reactions
Z. Chen, Z. Tian, J. Zhang, J. Ma,*
J. Zhang* ...................... &&&& — &&&&
À
À
C O Versus C C Bond Cleavage:
Selectivity Control in Lewis Acid
Catalyzed Chemodivergent Cycloaddi-
tions of Aryl Oxiranyldicarboxylates
with Aldehydes, and Theoretical
Rationalizations of Reaction Pathways
A clean break: Lewis acid catalyzed
chemodivergent [3+2] cycloadditions
of aryl oxiranyldicarboxylates with
aldehydes are revealed, in which the
anes can be controlled by the use of
NiACTHUNTGRENNGU(ClO4)2 or SnCAHTUNGTREN(NUGN OTf)2 catalysts (see
scheme). Possible reaction pathways
for these transformations are demon-
strated by theoretical calculations.
À
À
C C or C O bond cleavage of oxir-
&
6
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!