Lewis Acid Catalyzed Nucleophilic Ring Opening and 1,3-Bisfunctionalization of Donor-Acceptor Cyclopropanes with Hydroperoxides: Access to Highly Functionalized Peroxy/(α-Heteroatom Substituted)Peroxy Compounds

Article abstract of DOI:10.1021/acs.joc.8b02561

The Lewis acid catalyzed ring opening reaction of Donor-Acceptor (D-A) cyclopropanes with alkyl hydroperoxides is reported to furnish various peroxycarbonyls and 1,3-haloperoxygenated compounds in good to excellent yields. This method adds another instanc

Full text of DOI:10.1021/acs.joc.8b02561

Subscriber access provided by YORK UNIV
Article
Lewis Acid Catalyzed Nucleophilic Ring Opening and 1,3-Bisfunctionalization
of Donor-Acceptor Cyclopropanes with Hydroperoxides: Access to Highly
Functionalized Peroxy/(#-Heteroatom Substituted)Peroxy Compounds
Kuldeep Singh, Tishya S Bera, Vandana Jaiswal, Subrata
Biswas, Biplab Mondal, Dinabandhu Das, and Jaideep Saha
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 19 Dec 2018
Downloaded from http://pubs.acs.org on December 19, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 40
The Journal of Organic Chemistry
Lewis Acid Catalyzed Nucleophilic Ring Opening and 1,3-Bisfunctionalization of Donor-
Acceptor Cyclopropanes with Hydroperoxides: Access to Highly Functionalized Peroxy/(α-
Heteroatom Substituted)Peroxy Compounds
1
2
3
4
5
6
7
8
9
Kuldeep Singh†,Tishya S. Bera†,Vandana Jaiswal†, Subrata Biswas†, Biplab Mondal†, Dinabandhu
Das‡, and Jaideep Saha*†
†Division of Molecular Synthesis & Drug Discovery, Centre of Biomedical Research (CBMR), SGPGIMS
Campus. Raebareli Road, Lucknow 226014, Uttar Pradesh. India.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
‡School of Physical Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
ABSTRACT:The Lewis acid catalyzed ring opening reaction of Donor-Acceptor (D-A)
cyclopropanes with alkyl hydroperoxides is reported to furnish various peroxycarbonyls and 1,3-
haloperoxygenated compounds in good to excellent yields. This method adds another instance to
scarcely reported noncyclilizing 1,3-bisfunctionalization of D-A cyclopropanes with two different
functional groups and is relied on the dual role of peroxide as nucleophile and oxidant through an
orchestrated reaction sequence. The products obtained including α-heterosubstituted peroxy
compounds,
are
amenable
to
useful
synthetic
elaboration
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 40
1
2
INTRODUCTION
3
4
5
6
7
8
9
Donor-Acceptor (D-A) cyclopropanes have emerged as versatile three carbon building blocks
in modern organic synthesis.1 Myriad of catalytic methodologies have been developed engaging D-A
cyclopropanes in various reactions including nucleophilic ring opening processes, [3+n]
cycloadditions and rearrangements. In the ring-opening reactions, generally the nucleophilic addition
first occurs at the emerging positively charged centre at C3 adjacent to the donor group, and the
ensuing negative charge at C1 is being neutralized through capture of a proton. Different amines,
phenols, thiols, carboxylic acids, azide, electron-rich arenes and indoles have been employed to
realize this chemistry (Scheme 1A, left panel) with the assistance of a either Lewis or BrØnsted acid
as catalyst.2,3 On the facet of this conventional ring opening processes to open chain structures, few
elegant strategies have emerged recently that promoted 1,3-bisfunctionalization through concomitant
functionalization of C1 with non-proton electrophiles (Scheme 1A, right panel).4 Although
promising, the underlying challenges with this particular reaction avenue lie in finding, either a
suitable single reagent that formally bears E+ and Nu- components within self or a pair of (non-self
reacting) nucleophile and electrophile, which can engage themselves compatibly and synchronously
with the activation process of D-A cyclopropane. These constrains in fact mostly contributed to the
dearth of such transformations.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Our Strategy and Early Precedents On Ring-Opening Reactions of D-A Cyclopropanes
and Synthesis of Peroxycarbonyls
2
ACS Paragon Plus Environment

Page 3 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
In this context, Sparr and Gilmour led the seminal work on 1,3-dichlorination of aldehyde-
substituted cyclopropanes.4a Subsequently, Werz disclosed the use of Willgerodt’s reagent (PhICl2)
and sulfenyl/selenyl halides for 1,3-dichlorination and halochalcogenation4b-d of D-A cyclopropanes,
respectively. These methods utilized a single reagent for the desired bisfunctionalization step. Studer
reported the use of distinct electrophilic and nucleophilic reagents to realize arylamination and
aminobromination in a multicomponent fashion.4e-f Despite of these recent developments,
simultaneous introduction of two different functional groups at the two reactive centres of D-A
cyclopropane to open chain form is largely remained as an unmet challenge.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Structurally distinct classes of peroxide bearing skeletons have received considerable
attention in recent years due to their potential biological activities (Figure 1) and uses in the
downstream synthetic transformations to important derivatives.5-8 Of particular significance are the
different peroxycarbonyls7 and α-heteroatom substituted peroxides.5,7 While there has been a growing
interest to exploit the synthetic benefits of peroxycarbonyls, reported protocols for their preparation
to date are mostly centered on transition metal catalyzed carboperoxidation of olefins6b-h via radical
processes, which in many cases, suffer from poor yields and limited substrate scope.
Figure 1. Natural products and bioactive molecules bearing peroxy group as pharmacophore
O
HO
Me
H
HO
N
MeO
N
H
O
O
O
N
O
H
Me
Me
N
O
O
O
O
Artemisinin
HO
Verruculogen
tBu
4
O
O
O
N
S
S
N
O
O
O
N
OH
tBu
HO
H
O
O
Dioxetanone
Anti-cancer agent
Anti-malarial agent
Conceptually, addition of hydroperoxides to D-A cyclopropanes or aminocyclopropanes could
enable the assembly of aforementioned peroxy-compounds which however previously reported to be
unsuccessful.6f Use of peroxide as nucleophile is somewhat tempered due to their oxidizing
properties. On the upside, we envisaged that the oxidative property might be leveraged for the in situ
generation of an electrophilic species (X+), to be captured at C1. Thus, the overall process would
constitute a unified approach to transform D-A cyclopropanes into the acyclic bisfunctionalized
derivatives. In fact, such process would be much desired over a stepwise 1,3-functionalization
method for practical aspects.9 We herein report a catalytic, highly efficient and general strategy for
the synthesis of various γ-peroxycarbonyls (some bearing the α-“N” orα-“O”-peroxy moiety) via
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 40
1
2
addition of hydroperoxides to activated D-A cyclopropanes and furthermore this process can be
3
4
telescoped for the subsequent α-halogenation (C1 functionalization).
5
6
7
RESULTS AND DISCUSSION
8
9
We first decided to explore the feasibility of the ring-opening of D-A cyclopropanes with alkyl
hydroperoxides before stepping into 1,3-difunctionalizations. We commenced the study with
cyclopropane 1a (1.0 equiv) and tert-butylhydroperoxide (2a; 2.0 equiv) in presence of various
catalysts and solvents (Table 1, see Supporting Information for more details). Use of BrØnsted acids
proved to be completely ineffective for the transformation (not shown in Table 1). We next turned
our attention to various metal Lewis acids. First we examined nickel(II) catalysts, which however
didn’t provide any desired product in our case (entries 1-2). Pleasingly, changing the Lewis acid to
Sc(OTf)3, desired product 3aa was obtained, albeit in low yield (entry 3).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization of the Hydroperoxide Additiona
CO2Me
CO2Me
p
Tol
cat
p
Tol
tBuOOH
+
CO2Me
CO2Me
tBuOO
solvent
H
2a
1a
3aa
Entry
Cat.
[mol%] TBHP[equiv.] Solvent Conc[M]b Yield[%]c
1
2
3
4
5
6
7
8
9
Ni(ClO4)2.6H2O
NiCl2
10
10
10
10
10
10
10
10
10
10
10
10
5
2.0
2.0
2.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
10
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
2.0
2.0
2.0
0
0
Sc(OTf)3
Sc(OTf)3
Sn(OTf)2
Yb(OTf)3
In(OTf)3
MgI2
20
N.Dd
0
0
25
0
Bi(OTf)3
0
10 Cu(OTf)2
11 Sc(OTf)3
12 Sc(OTf)3
13 Sc(OTf)3
14 Sc(OTf)3
0
5
DCM
DCM
DCM
73
62e
71
10
20
10
4
ACS Paragon Plus Environment

Page 5 of 40
The Journal of Organic Chemistry
1
2
3
4
aReaction conditions: 1a (1.0 equiv), 2a (2-10 equiv), cat (10-20 mol%), solvent (0.2-2.0 M), reaction time (2 h).
b
c
Reactions were carried out at room temperature. Concentration of 1a in the particular reaction solvent. Yields of the
d
isolated products. N.D = Not Determined (the product was mixed with unknown impurity).eReaction time was 20 h.
5
6
7
8
9
Increasing the equivalents of TBHP (5 equiv) in the reaction significantly improved the conversion
(ca. 50%), however in this case, the desired product was contaminated with an inseparable impurity
(entry 4). Several other Lewis acids (e.g., Sn(OTf)2, Yb(OTf)3, In(OTf)3, MgI2, Bi(OTf)3, Cu(OTf)2
etc.) were screened, which were largely ineffective for this reaction (entries 5-10). At this stage,
Sc(OTf)3 was chosen as the most promising catalyst for further optimization studies. Subsequently,
other parameters such as solvent (entry 11), catalyst loading and temperature were varied (see SI for
details), which in fact didn’t prove beneficial. Gratifyingly, adding 10 equivalents of TBHP and
maintaining a higher concentration of substrate in DCM (2.0 M), a clean conversion of 3aa was
reproducibly obtained with 73% yield (entry 12). While lower loading of the catalyst slowed down
the reaction (entry 13), higher catalyst loading (20 mol%) did not show any further improvement in
the yield (71%, entry 14).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
With the optimized conditions in hand, we subsequently investigated the scope of this transformation
(Scheme 2). Variation in the ester moieties (3ba-3ca) or even use of diketone (3da) or ketoester
moiety (3ea-3fa) was well tolerated.10 Next, the electronic and steric effects of substituted aryl
groups as the donor moiety on D-A cyclopropanes were examined.
Scheme 2. Scope of Hydroperoxide Addition to D-A Cyclopropanes
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 40
1
2
3
4
Reaction conditions: cyclopropane (1 equiv), peroxide (10 equiv), Sc(OTf)3 (10 mol %), DCM (2.0 M). Yields of isolated
products are given. a20 mol % catalyst was used. bReaction was done at 0 oC. cpTsOH (1 equiv.), MeOH.
5
6
7
8
9
Presence of different weak and strong electron donating groups (3ga-3ka) or halogen substitution
(3ma-3na) didn’t show any marked difference in reactivity, and afforded the products in good to
excellent yields (70-91%) except the o-OMe substituted compound (3la), which could be correlated
to steric effects. Donor groups having extended π-framework (3oa-3pa) or heterocyclic moieties
(3qa-3ra) were successfully employed in our methodology. We also evaluated indole-derived D-A
cyclopropanes in the reaction. While the N-methyl protected compound was deteriorated in the
reaction (not shown in the scheme), N-tosyl protected congener provided the desired product (3sa) in
very high yield (83%), indicating that electron-donating substituent on indole nitrogen would not be
tolerated. Promising biological activities of the α-hetero substituted peroxy compounds prompted us
to examine D-A amino cyclopropanes bearing N-phthaloyl, N-succinimidyl and N-maleimido donor
moieties in the reaction. To our satisfaction, products 3ta-3va were obtained in good to excellent
yields (77-94%). Use of tetrahydropyranyl (THP) hydroperoxide in the reaction was also successful
(3gb, 3rb and 3tb). Importantly, 3tb could serve as the surrogates for free hydroperoxide;
deprotection of THP group resulted in the formation of 3tc in 64% yield. Furthermore, the
methodology also allowed addition of p-peroxyquinol which afforded more complex 3ad in
moderate yield. A gram scale preparation of 3aa furnished 74% yield, highlighting the practicability
of the current method.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. 1,3-Bromoperoxygenation With Different Brominating Agents
CO2Me
CO2Me
Sc(OTf)3
Ph
Ph
TBAB or NBS
tBuOOH
CO2Me
+
tBuOO
Br
CO2Me
2a
1g
with TBAB, 5ga’ (58%)
with NBS, 5ga’ (92%)
Intrigued by the remarkable success achieved on ring-opening peroxidation at C3, we next pursued
direct 1,3-halogenation-peroxidation in presence of hydroperoxide and appropriate halogenating
agent. We first considered the avenue to generate the desired electrophile in situ through an
umpolung process with the aid of TBHP. Thus, tetrabutylammonium bromide (TBAB) was chosen
first to affect C1 bromination of 1g subsequent to peroxide addition at C3 (Scheme 3). To our
delight, the concept of umpolung halide11 worked quite neatly and afforded 5ga’ in 58% yield. Use
of N-bromosuccinimide (NBS) however displayed much higher reactivity, providing 5ga’
6
ACS Paragon Plus Environment

Page 7 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
in excellent yield (92%). Importantly, in the absent of TBHP, reaction between peroxy-addition
product 3ga and NBS didn’t give rise to 5ga’, which indicates the synergistic effects between
reaction components and reagents in the overall transformation. The malonate proton signal at δ 3.55
ppm in 3ga was absent in 5ga’, which confirmed the site selective bromination at C1 in the later
compound. This was additionally analysed and confirmed by 2D-NMR studies. Subsequently, we
examined the scope of this 1,3-bisfunctionalization with various D-A cyclopropanes (Scheme 4).
Akin to peroxidation-bromination, chlorination and iodination could also be achieved with NCS and
NIS in reasonable yields (5gb’-5gc’). Anticipating that the acceptor groups might play crucial roles
during the C1 functionalization step, various diesters (5aa’-5ac’, 5ba’-5ca’and 5wa’) ketoesters and
diketone (5ea’, 5xa’-5ya’ and 5db’) were evaluated. In fact, all the compounds underwent smooth
transformation, indicating a broad choice for the adjacent acceptor groups that could be
accommodated in D-A cyclopropanes for our method. During the 1,3-haloperoxygenation process,
no significant difference in reactivity was found between electron donating (5ha’-5hb’, 5za’, 5lb’)
and halogen substituted compounds (5ma’,5na’and 5nc’); desired products were isolated in good to
high yields (61-86%).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Scope of 1,3-Halo-Peroxygenation
EWG1
O
X
EWG1
Sc(OTf)3
EWG2
tBuOOH
X
R1
+
+
N
EWG2
O
CH2Cl2
R1
tBu
O
1
2a
4a’-c’
O
5
X= Br, Cl, I
——————————————————————————————————————————
CO2Me
CO2R
X
X
CO2Me
CO2R’
O
O
tBu
tBu
Ph
O
O
p-Tol
5gb’ X= Cl (64%)
5gc’ X= I (57%)
5aa’ R= R’= Me, X= Br (71%)
5ab’ R= R’= Me, X= Cl (66%)
5ab’
5ac’ R= R’= Me, X= I (72%)
5ba’ R= R’= Et, X= Br (68%)
COR’
X
5ca’ R= Me, R’= 4-MeC6H4, X= Br (60%, dr = 1:1)
5wa’R= Me, R’= Ph, X= Br (59%, dr = 5:1)
R
O
tBu
X
CO2Me
CO2Me
Ph
O
CO2Me
X
5ea’ R’= Ph, R= CO2Me, X= Br (63%, dr= 1.5:1)
5xa’ R’= Ph, R= CO2Et, X= Br (59%, dr= 1.5:1)
5ya’ R’= CH3,R= CO2Et, X= Br (64%, dr= 1:1)
5db’ R’= Ph, R= COPh, X= Cl (65%)
CO2Me
naph
O
O
S
O
tBu
O
X
tBu
5ra’ X= Br (64%)
5rb’ X=Cl (66%)
5oa’ X= Br 62%)
5ob’ X= Cl (72%)
CO2Me
X
CO2Me
CO2Me
CO2Me
X
O
CO2Me
O
Br
tBu
O
R
CO2Me
O
N
R
O
O
5ha’ R= p-iPr, X= Br (62%)
5hb’ R= p-iPr, X= Cl (69%)
5za’ R= p-OAc, X= Br (74%)
5lb’ R= o-OMe, X= Cl (61%)
5ma’R= p-F, X = Br (72%)
5na’ R= p-Cl, X= Br (86%)
5nc’ R= p-Cl, X= I (65%)
tBu
O
O
Me
R
5ta’ R= phthalimide, X= Br (77%)
5tc’ R= phthalimide, X= I (65%)
5ua’ R= succinamide, X= Br (69%)
5ub’ R= succinamide, X= Cl (71%)
6
7
R= H, (62%, dr = 25:1)
R= Cl, (73%, dr = 10:1)
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 40
1
2
3
4
Reaction conditions: D-A cyclopropane (1 equiv), 2 (10.0 equiv), Sc(OTf)3 (10 or 20 mol %), NXS (1.5 equiv, X = Br,
Cl, I), DCM (2.0 M). aReaction was performed at 0 oC.
5
6
7
8
9
Use of naphthyl-substituted compound afforded smooth transformation (5oa’-5ob’), whereas
reaction with thienyl donor was not site selective; additional ring halogenation was obtained in both
the cases (5ra’-5rb’). Different amino cyclopropanes reacted consistently with halogenating agents
furnishing halogenated α-amino peroxy products (5ta’-5tc’, 5ua’-5ub’). Apart from TBHP,
methylcyclohexyl hydroperoxide also provided the desired bis-functionalized compounds (6-7) in
good yields.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 5.Hydroperoxide Addition to Substituted α-Cyclopropylketones
tBuOO
a.
R
50 mol% Sc(OTf)3
10 equiv. TBHP
p-Tol
R
tBuOO
DCM, rt, 3 h
O
p-Tol
O
tBuOO
p-Tol
O
8a R= H
8b R= p-OMe
8c R= 3,4,5-tri-OMe
with 8a, 9 (0%)
with 8b, 9 (70%)
with 8c, 9 (35%)
(9’ not observed)
------------------------------------------------------------------------------------------------------------------------
b.
OMe
Br
OOtBu
OOtBu
OOtBu
tBuOO
tBuOO
tBuOO
O
O
O
9a’(59%)
9b’(72%)
9c’(66%)
OOtBu
S
OOtBu
tBuOO
tBuOO
O
O
9e’(56%)
9d’(70%)
At this juncture, hydroperoxide addition to D-A cyclopropanes, bearing a single ketone functional
group as acceptor, was evaluated (Scheme 5). This class of DAC exhibits different reactivity and not
widely been used in catalytic cyclopropane methodologies. Initially, we employed 8a-8c under the
optimized reaction conditions (using 10 mol% Sc(OTf)3), which however failed to give any
hydroperoxide addition product. With 8b, two-fold increase in catalyst loading provided a new
compound in 10% yield, which was characterized to be ageminal bisperoxide 9 (see SI for details).
Surprisingly, no trace of the product 9’ was observed by MS and NMR analysis. With 8b itself, the
yield of 9 could be significantly improved,after few optimization trials, to 70% with 50 mol%
loading of the catalyst (Scheme 5a). Reaction with 8c furnished the same product 9 (35%) under the
reaction condition, which infers that both 8b and 8c were transformed into the same intermediate
during the reaction course. Different aromatic moieties adjacent to ketone were well tolerated in the
reaction, including a α-tetralone derivative, providing 9a’-9e’ in good yields (Scheme 5b).
Notably, this trait of D-A cyclopropane peroxidation reaction should prove beneficial for the easy
assembly of moderately functionalized geminal bisperoxides,5c,7c-d which could lend themselves for
8
ACS Paragon Plus Environment

Page 9 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
further synthetic elaboration. Since the aromatic donor moiety was lost during this transformation, an
initial TBHP addition to D-A cyclopropane followed by a Hock-type rearrangement12 involving 1,2-
aryl migration could be speculated, forming the crucial intermediate II (Scheme 6). At this stage,
sequential TBHP addition and phenol elimination steps (via III) could proceed to deliver the final
products.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 6. Proposed Mechanism for Geminal bisperoxide Formation
tBu
O
Ar1
H
Ar1OH
HOOtBu
O
Ar2
Ar2
1,2-aryl
O
O
O
O
9
O
Ar1
Ar2
O
O
I
Ar1
LA
migration
HOOtBu
II
III
tBu
We next explored the synthetic versatility of the synthesized mono-peroxy and 1,3-
haloperoxygenated compounds through an array of distinct chemical transformations (Scheme 7).
Scheme 7. Follow-up Reactions
Reagents and conditions: (a)(i) 20 mol%DBU, CH3CN(ii) PhNHNH2, MeOH, reflux; (b) H2, 20% Pd(OH)2/C, MeOH, rt; (c) β-
naphthol, TfOH, DCM; (d) AIBN (cat), AllylBu3Sn, benzene, reflux; (e) NaN3, DMF, rt; (f) 1-methoxy-4-vinylbenzene, Pd(OAc)2,
Xantphos, Cs2CO3, benzene; (g) 2-bromophenol, KF, DMF, rt; (h) Et3N, DCM, rt.
In the event, compound 3aa was converted to tetrahydropyridazine derivative 10 (52%) in an one-pot
two-step synthesis procedure. The reaction proceeded via Kornblum-DelaMare rearrangement13 to a
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 40
1
2
3
4
5
6
7
8
ketone by catalytic DBU and subsequent cyclization by reaction with phenylhydrazine. Notably,
such scaffold is present in different natural products and biologially active compounds.14
Hydrogenolysis of 3aa with Pd(OH)2 on carbon provided lactone 11 in 72% (dr =1:1) yield. To tap
the potential of Hock-type rearrangement with the synthesized peroxycarbonyls, 3aa was treated
with β-naphthol in presence of TfOH, which resulted in the formation of 14H-dibenzo[a,j]xanthenes
(12) in 63% yield.15 We next performed some follow-up reactions with halo-peroxygenated product,
5ga’, aiming for the selective functionalization of C-Br bond. In this course, radical allylation and
substitution reaction with NaN3 were performed with 5ga’, which delivered the respective products,
13 (76%) and 14 (88%) in high yields. Heck coupling of 5ga’ with 1-methoxy-4-vinylbenzene
afforded 15 in moderate yield (35%) as an inseparable mixture of cis and trans (1:3) isomer.16
Simultaneous functionalizations at C1 and C3 were affected by treating 5ga’ with 2-bromophenol
and KF, which rendered aroylmethylidene 16 (58%). Importantly, this class of compounds have been
reported to access from D-A nitrocyclopropanes17 and the present reaction alludes a viable
alternative. Treatment of 5ga’ with triethylamine triggered similar bisfunctionalization, furnishing 17
in 60% yield.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 8. (a) Stereospecific Peroxidation-bromination of Entiomerically Pure Cyclopropane (S)-1g;
(b) Proposed Reaction Mechanism for 1,3- Haloperoxygenation.
CO2Me
a.
Br
Sc(OTf)3 (20 mol%)
TBHP, NBS
CO2Me
CO2Me
CO2Me
Ph
O
CH2Cl2, rt
tBu
Ph
O
(S)-1g
(> 99% ee)
(R)-5ga’
(72%, > 99% ee)
------------------------------------------------------------------------------------------------------------------------
b.
MeO
Ph
O
O
t
MeO
BuOO
[Br ]
B
MeO
MeO
O
tBuOOH
ScIIILn
(S)-1g
O
Ph
O
A
N
Br OR
[Br
]
MeO
ScIIILn
(R)-5ga’
O
Ph
O
O
tBuOO
Br
OMe
C
(S)-1g
To gain insights into the reaction mechanism, we next investigated the stereospecificity of the 1,3-
bisfunctionalization process by using enantiopure cyclopropane (S)-1g (> 99% ee) under
optimized conditions (Scheme 8a). The reaction proceeded with complete stereospecificity providing
5ga’ in 72% yield. This result suggests that the initial ring-opening step with peroxide occurs via a
SN2 reaction.
10
ACS Paragon Plus Environment

Page 11 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
We also performed 45Sc NMR experiments (see Supporting Information for details) for the reaction,
which indicates the possibility for the presence of alkylperoxy-scandium species in the catalytic
cycle.18
Taken together, the literature reports and our observations, the following mechanism is suggested for
the formation of halo-peroxygenated product 5ga’ from 1g (Scheme 8b). Coordination of
cyclopropane 1g with Sc-Lewis acid generates A, which then suffers a SN2 attack by hydroperoxide
and leads to ring-opened intermediate B. Malonate unit of the intermediate subsequently reacts with
a highly electrophilic Br+ species generated from NBS or TBAB by TBHP11,19 and provides C.
Finally, exchange of the Sc-Lewis acid between C and 1g leads to the final product 5ga’, and
regenerates A.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CONCLUSIONS
In summary, we have developed an operationally simple and efficient strategy for the ring-opening
and bis-functionalization of D-A cyclopropanes with hydroperoxides and halogenating agents. This
is the first example for assembly of highly functionalized γ-peroxycarbonyls via ionic process, which
provides a general platform to access this class of compounds, including α-heterosubstituted peroxy
compounds of biological relevance, and is distinct from the radical approaches reported earlier. The
products formed through this methodology offer interesting opportunities for synthetic elaborations
as illustrated with selected transformations.
EXPERIMENTAL SECTION
Genral Information. Unless otherwise noted, all reactions were conducted with oven or flame-dried
glassware and maintaining an inert (under nitrogen or argon) atmosphere. Solvents were dried
according to standard procedures and all reagents/catalysts were purchased commercially and used
without any further purification. Reactions were monitored by TLC, using Merck silica gel 60 F 254
plates. The plates were visualized under UV light (254 nm) or by using 10% ethanolic
phosphomolybdic acid (PMA) or 1% aqueous KMnO4 or iodine. Flash column chromatography was
1
13
performed using silica gel (230-400 mesh). H and C NMR spectra were recorded on Avance III,
1
Bruker 400 MHz and 100 MHz spectrometers respectively using CDCl3 or DMSO-d6. H NMR
chemicals shift are expressed in ppm (δ) relative to δ = 7.26 for CDCl3 and δ = 2.50 for DMSO-d6.
13C NMR chemical shift are expressed in ppm (δ) relative to δ = 77.16 for CDCl3 and δ = 39.51 for
45
DMSO-d6 resonance. Sc NMR spectra were recorded on Avance III, Bruker 400 MHz (97 MHz)
spectrometer and are reported in ppm using Sc(OTf)3 in CD3CN as external standard (-2.5 ppm). FT-
IR experiments were performed on PerkinElmer Spectrum Version 10.03.08. HRMS and Electron
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 40
1
2
3
4
5
6
7
8
Spray Ionization (ESI) (m/z) spectra were recorded on Agilent Technologies 6530 Accurate- Mass
Q-TOF LC/MS. Enantiomeric excess (ee) was measured by HPLC analysis with chiral stationary
phase. Donor-Acceptor cyclopropanes (1a, 1g-1h, 1i, 1m-1r),20 1b,4b 1d,3g 1e,21 1j,22 1k,23 1l,24 1s,25
1t-1v,26 1x-1y,27 1z,28 are known compounds and prepared according to the reported methods.
Donor-Acceptor cyclopropanes with monocarbonyl acceptor group 8a-8c, 8ba’, 8bb’, 8bc’ and 8be’
are known and were prepared according to the previous reports.29 Tetrahydropyranyl (THP)
hydroperoxide,30 methylcyclohexyl hydroperoxide30 and p-peroxyquinol31 were prepared following
thereported literature procedures. Spectroscopic data of these compounds were matched to the
published data.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Caution: Although we have experienced no hazards in our experiments with peroxides, but due to
explosive nature of the peroxides, any preparative work with these peroxy compounds should be
carried out in the fume hood equipped with a blast shield.
p-Tolyl 1-benzoyl-2-phenylcyclopropane-1-carboxylate (1f): Compound 1e was transformed into
mono-acid (1e-COOH) according to literature procedure32 and used directly for the next reaction
(see Scheme S1 in Supporting Information). To a solution of compound 1e-COOH (0.050 g, 0.18
mmol) in dry dichloromethane (2.0 M) under argon were added DCC (0.047 g, 0.22 mmol), p-cresol
(0.022g, 0.20 mmol) and DMAP (1 mg) and the reaction mixture was stirred at room temperature for
12 h. Upon completion of the reaction (TLC controlled) solvent was removed under reduced pressure
and the crude residue was purified by silica gel column chromatography (5:95 EtOAc:Hexanes as
1
eluent) to give 1f as colorless oil in 80% (0.055 g) isolated yield. Rf 0.5 (1:9 EtOAc:Hexanes); H
NMR (400 MHz, CDCl3) δ 8.05-8.03 (m, 2H), 7.65-7.61 (m, 1H), 7.55-7.52 (m, 2H), 7.45-7.43 (m,
2H), 7.40-7.33 (m, 3H), 6.91 (d, J = 8.3 Hz, 2H), 6.01 (d, J = 8.5 Hz, 2H), 3.84 (t, J = 8.6 Hz, 1H),
13
2.62 (dd, J = 8.2, 5.0 Hz, 1H), 2.21 (s, 3H), 1.84 (dd, J = 9.0, 4.9 Hz, 1H); C NMR (100 MHz,
CDCl3) δ 194.6, 169.1, 137.2, 135.0, 133.1, 132.8, 129.2, 128.7, 128.6, 128.4, 128.2, 128.0, 127.4,
127.3, 52.3, 42.4, 30.8, 20.2; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C24H20NaO3 379.1310;
Found 379.1311.
1-Methyl 1-(p-tolyl) 2-(p-tolyl) cyclopropane-1,1-dicarboxylate (1c): Compound 1c was prepared
from cyclopropane 1a (0.32g, 1.1 mmol) following the similar procedure as shown for compound 1f
1
and was obtained in 60% yield (0.24g) as colorless oil. Rf 0.60 (1:5 EtOAc: Hexanes); H NMR
(400 MHz, CDCl3) δ7.42-7.38 (m, 2H), 7.27-7.23 (m, 1H), 7.16-7.10 (m, 6H), 3.46 (s, 3 H), 3.34 (t,
J = 8.7 Hz, 1 H), 2.34-2.31 (m, 4H), 1.89 (dd, J = 9.3, 5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
168.9, 167.1, 148.6, 137.4, 135.9, 131.3, 130.1, 129.1, 128.6, 121.2, 52.6, 37.4, 33.0, 21.3, 21.0,
19.9; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C20H20NaO4 347.1259, Found 347.1232.
12
ACS Paragon Plus Environment

Page 13 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
1-Methyl 1-phenyl 2-(p-tolyl) cyclopropane-1,1-dicarboxylate (1w): Compound 1w was prepared
from cyclopropane 1a (0.32g, 1.1 mmol)following similar procedure as shown for compound 1f
1
(Scheme S1) and was obtained in 70% overall yield (0.220g). Rf 0.35 (1:10 EtOAc:Hexanes); H
NMR (400 MHz, CDCl3) δ 7.42-7.38 (m, 2H), 7.27 – 7.23 (m, 1H), 7.16 – 7.10 (m, 6H), 3.46 (s,
8
9
13
3H), 3.34 (t, J = 8.7 Hz, 1H), 2.34 – 2.31 (m, 4H), 1.88 (dd, J = 9.3, 5.2 Hz, 1H); C NMR (100
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
MHz, CDCl3) δ 168.7, 167.0, 150.8, 137.4, 131.3, 129.6, 129.1, 128.6, 126.2, 121.6, 52.6, 37.4, 33.0,
21.3, 20.0; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C19H18NaO4 333.1103, Found 333.1092.
(2-(4-Methoxyphenyl)cyclopropyl)(thiophen-2-yl)methanone (8bdʹ): Following the literature
procedure29,compound 8db’ was prepared from the corresponding chalcone (0.5 g, 2 mmol) and
1
obtained as colorless oil in 75% (0.4 g) isolated yield. Rf 0.65 (1:4 EtOAc:Hexanes); H NMR (400
MHz, CDCl3) δ 7.79-7.78 (m, 1H), 7.64-7.63 (m, 1H), 7.14-7.09 (m, 3H), 6.87-6.84 (m, 2H), 3.80 (s,
3H), 2.72-2.67 (m, 2H), 1.87 (ddd, J = 8.6, 5.6, 4.2 Hz, 1H), 1.50 (ddd, J = 7.9, 7.0, 4.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 191.1, 158.6, 145.1, 133.6, 132.4, 131.8, 128.3, 127.6, 114.1, 55.5, 30.0,
29.3, 18.8; HRMS (ESI-TOF) m/z: [M+H]+ calculated for C15H15O2S 259.0793, Found 259.0816.
General procedure for ring-opening peroxidation of D-A cyclopropanes with tert-butyl
hydroperoxide (TBHP): To a solution of cyclopropane 1 (50-100 mg) in dry dichloromethane (2.0
M) under argon was added tert-butyl hydroperoxide (10 equiv. 5-6 M solution in decane). Sc(OTf)3
(10 or 20 mol%) was then added to the solution and the reaction mixture was stirred at room
temperature. The reaction was monitored by thin layer chromatography (TLC) until the
disappearence of the starting materials (2-4 h) was observed. Next, the reaction mixture was diluted
with DCM (2 mL), washed with water (2 mL) and brine (2 mL) and the organic layer was dried over
anhydrous Na2SO4. Solvents were removed under reduced pressure (bath temperatuer 30 oC) and the
crude product was purified by flash column chromatography to obtain the peroxy products (3aa-
3va).
Dimethyl-2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)malonate (3aa): Following the general
procedure, D-A cyclopropane 1a (0.100g, 0.40 mmol) was transformed into peroxy compound 3aa
and purified by silica gel column chromatography (using 5: 95 EtOAc: Hexanes as eluent) to give
the title compound as colorless oil in 73% (0.100g) yield. Rf 0.8 (1:4 EtOAc: Hexanes); FT-IR (ν
cm-1): 3400, 2979, 2954, 1754, 1738, 1436, 1363, 1198, 1154, 1062, 1023, 816; 1H NMR (400 MHz,
CDCl3) δ 7.22 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 4.87 (dd, J = 8.4, 5.5 Hz, 1H), 3.72 (s,
3H), 3.71 (s, 3H), 3.60 (dd, J = 8.1, 6.6 Hz, 1H), 2.51-2.43 (m, 1H), 2.34 (s, 3H), 2.32-2.28 (m, 1H),
13
1.18 (s, 9H); C NMR (100 MHz, CDCl3) δ169.6 (2), 137.7, 137.2, 129.1, 126.9, 83.2, 80.4, 52.7,
52.6, 48.8, 34.5, 26.5, 21.3; HRMS (ESI-TOF) m/z: [M+H]+ calculated for C18H26NaO6 361.1627,
Found 361.1644.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 40
1
2
3
4
5
6
7
Diethyl 2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)malonate (3ba): Following the general procedure,
D-A cyclopropane 1b (0.100 g, 0.36 mmol) was transformed into peroxy compound 3ba and purified
by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent) to give the title compound as
1
colorless oil in 77% (0.102 g) isolated yield. Rf 0.65 (1:4 EtOAc: Hexanes); H NMR (400 MHz,
8
9
CDCl3) δ 7.22 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 4.88 (dd, J = 8.4, 5.6 Hz, 1H), 4.22-4.14
(m, 4H), 3.55 (dd, J = 8.2, 6.6 Hz, 1H), 2.45 (ddd, J = 15.0, 8.5, 6.6 Hz, 1H), 2.34 (s, 3H), 2.32-2.26
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
(m, 1H), 1.26 (t, J = 7.1 Hz, 6H), 1.18 (s, 9H); C NMR (100 MHz, CDCl3) δ 169.3, 169.2, 137.7,
137.4, 19.1, 126.9, 83.2, 80.4, 61.6, 61.5, 49.2, 34.5, 26.5, 21.3, 14.1; HRMS (ESI-TOF) m/z:
[M+Na]+ calculated for C20H30NaO6 389.1940, Found 389.1911.
1-Methyl-3-(p-tolyl) 2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)malonate (3ca): Following the
general procedure, D-A cyclopropane 1c (0.090 g, 0.27 mmol) was transformed into peroxy
compound 3ca and purified by silica gel column chromatography (5: 95 EtOAc: Hexanes as eluent)
to give the title compound as colorless oil in 60% (0.069g) isolated yield (dr = 1:1). Rf 0.8 (1:4
1
EtOAc: Hexanes); H NMR (400 MHz, CDCl3) δ 7.25-7.23 (m, 4H), 7.17-7.14 (m, 8H), 6.95-6.93
(m, 4H), 4.95-4.99 (m, 2H), 3.86 (dd, J = 8.9, 6.0 Hz, 1H), 3.78 (s, 3H), 3.77 (s, 3H), 3.75-3.73 (m,
13
1H), 2.65-2.60 (m, 2H), 2.46-2.37 (m, 2H), 2.34 (br s, 12H), 1.20 (s, 9H), 1.19 (s, 9H); C NMR
(100 MHz, CDCl3) δ 169.6, 169.5, 168.0 (2), 148.4 (2), 138.0, 137.9, 137.2, 137.0, 135.9, 130.1,
129.3, 129.2, 127.0, 126.9, 121.1 (2), 83.3, 83.2, 80.6 (2), 52.9 (2), 49.1 (2), 34.7, 34.4, 26.6 (2),
21.3, 21.0; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C24H30NaO6 437.1940, Found 437.1954.
2-(2-(tert-Butylperoxy)-2-phenylethyl)-1,3-diphenylpropane-1,3-dione (3da): Following the
general procedure (20 mol % Sc(OTf)3 was used in this case), D-A cyclopropane 1d (0.050 g, 0.15
mmol) was transformed into peroxy compound 3da and purified by silica gel column
chromatography (1: 9 EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 79%
(0.050g) isolated yield. Rf 0.6 (1:9 Acetone: Hexanes); 1H NMR (400 MHz, CDCl3) δ 8.03-8.00 (m,
2H), 7.89-7.86 (m, 2H), 7.61-7.52 (m, 2H), 7.49-7.39 (m, 5H), 7.36-7.34 (m, 3H), 7.33-7.29 (m, 1H),
13
5.64 (dd, J = 7.8, 5.2 Hz, 1H), 5.02 (dd, J = 8.5, 5.1 Hz, 1H), 2.62-2.51 (m, 2H), 1.16 (s, 9H); C
NMR (100 MHz, CDCl3) δ 196.1, 195.7, 140.7, 136.2, 135.7, 133.7, 133.5, 129.0, 128.9, 128.6,
128.5, 128.1, 127.0, 83.8, 80.6, 53.3, 34.8, 26.6; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C27H28NaO4 439.1885, Found 439.1892.
Methyl 2-benzoyl-4-(tert-butylperoxy)-4-phenylbutanoate (3ea): Following the general procedure
(20 mol % Sc(OTf)3 was used), D-A cyclopropane 1e (0.060 g, 0.21 mmol) was transformed into
peroxy compound 3ea and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as
eluent) to give the title compound as colorless oil in 63% (0.050g) yield (dr = 1:1). Rf 0.65 (1:5
1
EtOAc: Hexanes); H NMR (400 MHz, CDCl3) δ 8.00-7.95 (m, 4H), 7.61-7.56 (m, 2H), 7.49-7.44
(m, 4H), 7.36-7.27 (m, 10H), 5.01-4.97 (m, 1H), 4.93 (dd, J = 8.2, 5.4 Hz, 1H), 4.73-4.70 (m, 1H),
14
ACS Paragon Plus Environment

Page 15 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
4.66-4.63 (m, 1H), 3.70 (s, 3H), 3.65 (s, 3H), 2.58-2.45 (m, 4H), 1.18 (s, 9H), 1.10 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 195.1, 194.9, 170.2, 170.1, 140.5, 136.1, 135.7, 133.7 (2), 129.0, 128.9, 128.8
(2), 128.4 (2), 128.0, 126.9 (2), 83.5, 83.3, 80.5, 52.7, 52.6, 50.8, 50.4, 34.8 (2), 26.5, 26.4; HRMS
(ESI-TOF) m/z: [M+Na]+ calculated for C22H26NaO5 ([M+Na]+): 393.1678, Found 393.1642.
p-Tolyl-2-benzoyl-4-(tert-butylperoxy)-4-phenylbutanoate(3fa): Following the general procedure,
D-A cyclopropane 1f (0.080 g, 0.22 mmol) was transformed into peroxy compound 3fa and purified
by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent) to give the title compound as
colorless oil in 51% (0.051g) isolated yield (dr = 1.2:1). Rf 0.6 (1:4 EtOAc: Hexanes); 1H NMR (400
MHz, CDCl3) δ8.06 (d, J = 7.3 Hz, 2H), 8.01 (d, J = 7.3 Hz, 1.5H), 7.64-7.59 (m, 2H), 7.53-7.47 (m,
4H), 7.40-7.29 (m, 9H), 7.16-7.10 (m, 3.5H), 6.92 (d, J = 8.4 Hz, 2H), 6.83 (d, J = 8.4 Hz, 1.5H),
5.11 (dd, J = 9.2, 4.3 Hz, 1H), 5.04 (dd, J = 7.9, 5.8 Hz, 1H), 4.98 (dd, J = 9.2, 4.6 Hz, 1H), 4.76 (t, J
= 7.0 Hz, 1H), 2.75-2.61 (m, 1H), 2.61-2.46 (m, 3H), 2.33 (s, 3H), 2.31 (s, 2H), 1.24 (s, 9H), 1.14 (s,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
6H); C NMR (100 MHz, CDCl3) δ 195.1, 194.7, 168.8, 168.6, 148.5, 148.4, 140.5, 140.3, 135.8,
135.6, 133.9, 133.8, 130.0 (2), 129.1, 129.0, 128.9, 128.6, 128.5, 128.2, 128.1, 127.0, 126.9, 121.1,
121.0, 83.5, 83.4, 80.6 (2), 51.3, 50.8, 35.0, 34.6, 26.7, 26.5 21.0 (2); HRMS (ESI-TOF) m/z:
[M+Na]+ calculated for C28H30NaO5 469.1991, Found 469.1992.
Dimethyl-2-(2-(tert-butylperoxy)-2-phenylethyl)malonate (3ga): Following the general procedure
(20 mol % Sc(OTf)3 was used), D-A cyclopropane 1g (0.100 g, 0.42 mmol) was transformed into
peroxy compound 3ga and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as
eluent) to give the title compound as colorless oil in 84% (0.115g) isolated yield. Rf 0.6 (1:4 EtOAc:
1
Hexanes); H NMR (400 MHz, CDCl3) δ7.26-7.18 (m, 5H), 4.83 (dd, J = 8.6, 5.3 Hz, 1H), 3.64 (s,
3H), 3.63 (s, 3H), 3.55 (dd, J = 8.3, 6.4 Hz, 1H), 2.38 (ddd, J = 14.9, 8.6, 6.4 Hz, 1H), 2.30-2.23 (m,
13
1H), 1.10 (s, 9H); C NMR (100 MHz, CDCl3) δ 169.6, 169.5, 140.3, 128.4, 128.0, 126.9, 83.2,
80.5, 52.7, 52.6, 48.7, 34.5, 26.4; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C17H24NaO6
347.1471, Found 347.1468.
Dimethyl-2-(2-(tert-butylperoxy)-2-(4-isopropylphenyl)ethyl)malonate (3ha): Following the
general procedure, D-A cyclopropane 1h (0.100 g, 0.36 mmol) was transformed into peroxy
compound 3ha and purified by silica gel column chromatography (15: 95 Et2O: Hexanes as eluent)
to give the title compound as colorless oil in 68% (0.090g) isolated yield. Rf 0.3 (1:4 Et2O: Hexanes);
1H NMR (400 MHz, CDCl3) δ 7.24 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.2 Hz, 2H), 4.88 (dd, J = 8.3,
5.5 Hz, 1H), 3.71 (s, 3H), 3.70 (s, 3H), 3.61 (dd, J = 8.2, 6.5 Hz, 1H), 2.94-2.84 (m, 1H), 2.48 (ddd,
J = 14.7, 8.3, 6.5 Hz, 1H), 2.37-2.30 (m, 1H), 1.24 (d, J = 6.9 Hz, 6H), 1.18 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 169.7, 169.6, 148.6, 137.5, 126.9, 126.5, 83.2, 80.5, 52.7, 52.6, 48.8, 34.5, 39.9,
26.5, 24.1; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C20H30NaO6 389.1940, Found 389.1911.
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 40
1
2
Dimethyl-2-(2-(tert-butylperoxy)-2-(4-methoxyphenyl)ethyl)malonate (3ia): This reaction was
3
4
o
set up according to the general procedure, except the temperature of the reaction was kept at 0 C
5
6
7
throughout. Thus, D-A cyclopropane 1i (0.100 g, 0.38 mmol) was transformed into peroxy
compound 3ia and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent) to
8
9
1
give the title compound as colorless oil in 73% (0.098g) yield. Rf 0.7 (1:4 EtOAc: Hexanes); H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (400 MHz, CDCl3) δ 7.24 (d, J = 8.6 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 4.84 (dd, J = 8.3, 5.7
Hz, 1H), 3.78 (s, 3H), 3.71 (s, 3H), 3.69 (d, J = 4.9 Hz, 3H), 3.57 (dd, J = 8.0, 6.7 Hz, 1H), 2.49
13
(ddd, J = 14.9, 8.3, 6.7 Hz, 1H), 2.35–2.24 (m, 1H), 1.16 (s, 9H); C NMR (100 MHz, CDCl3) δ
169.6 (2), 159.5, 132.2, 128.3, 113.8, 82.9, 80.4, 55.3, 52.7, 52.6, 48.8, 34.3, 26.5; HRMS (ESI-
TOF) m/z: [M+Na]+ calculated forC18H26NaO7 377.1576, mass found 377.1550.
Diethyl-2-(2-(tert-butylperoxy)-2-(3,4-dimethoxyphenyl)ethyl)malonate (3ja): This reaction was
o
set up according to the general procedure, except the temperature of the reaction was kept at 0 C
throughout. Thus, D-A cyclopropane 1j (0.100 g, 0.31 mmol) was transformed into peroxy
compound 3ja and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent) to
1
give the title compound as colorless oil in 70% (0.090g) yield. Rf 0.6 (1:4 EtOAc: Hexanes); H
NMR (400 MHz, CDCl3) δ 6.86-6.79 (m, 2H), 6.80 (d, J = 8.7 Hz, 1H), 4.83 (dd, J = 8.3, 5.7 Hz,
1H), 4.19-4.14 (m, 4H), 3.86 (s, 3H), 3.84 (s, 3H), 3.50 (dd, J = 8.0, 6.8 Hz, 1H), 2.48 – 2.38 (m,
13
1H), 2.26 (ddd, J = 14.1, 8.1, 5.7 Hz, 1H), 1.26-1.22 (m, 6H), 1.16 (s, 9H), C NMR (100 MHz,
CDCl3) δ 169.2 (2), 148.9, 148.8, 132.9, 119.4, 110.9, 109.9, 83.1, 80.2, 80.4, 61.5 (2), 55.9 (2),
49.1, 34.3, 26.5, 14.1; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C21H32NaO8 435.1995,
Found 435.2005.
Dimethyl-2-(2-(tert-butylperoxy)-2-(3,4,5-trimethoxyphenyl)ethyl)malonate (3ka): Following
the general procedure, D-A cyclopropane 1k (0.100 g, 0.30 mmol) was transformed into peroxy
compound 3ka and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent)
1
to give the title compound as colorless oil in 91% (0.116g) yield. Rf 0.6 (1:4 EtOAc: Hexanes); H
NMR (400 MHz, CDCl3) δ 6.53 (s, 2H), 4.82 (dd, J = 8.5, 5.3 Hz, 1H), 3.84 (s, 6H), 3.81 (s, 3H),
3.72 (s, 3H), 3.71 (s, 3H), 3.60 (dd, J = 8.3, 6.4 Hz, 1H), 2.42-2.35 (m, 1H), 2.34 -2.24 (m, 1H), 1.18
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 169.6 (2), 153.2, 137.6, 136.1, 103.7, 83.3, 80.6, 60.9, 56.2,
52.7 (2), 48.7, 34.7, 26.5; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C20H30NaO9 437.1788,
Found 437.1821.
Dimethyl-2-(2-(tert-butylperoxy)-2-(2-methoxyphenyl)ethyl)malonate (3la): This reaction was
o
set up according to the general procedure, except the temperature of the reaction was kept at 0 C
throughout. Thus, D-A cyclopropane 1l (0.100 g, 0.37 mmol) was transformed into peroxy
compound 3la and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent) to
1
give the title compound as colorless oil in 59% (0.080g) yield. Rf 0.5 (1:4 EtOAc: Hexanes); H
16
ACS Paragon Plus Environment

Page 17 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
NMR (400 MHz, CDCl3) δ 7.33 (d, J = 6.2 Hz, 1H), 7.19 - 7.15 (m, 1H), 6.89 (t, J = 7.4 Hz, 1H),
6.77 (d, J = 8.2 Hz, 1H), 5.30 (dd, J = 7.3, 5.6 Hz, 1H), 3.73 (s, 3H), 3.64 (s, 3H), 3.61 (s, 3H), 3.52
13
(t, J = 7.2 Hz, 1H), 2.40 - 2.28 (m, 2H), 1.13 (s, 9H); C NMR (100 MHz, CDCl3) δ 169.8, 169.7,
156.5, 128.7, 128.6, 127.3, 120.6, 110.4, 80.4, 77.6, 55.4, 52.6 (2), 48.6, 33.3, 26.5; HRMS (ESI-
TOF) m/z: [M+Na]+ calculated for C18H26NaO7 377.1576, Found 377.1554.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dimethyl-2-(2-(tert-butylperoxy)-2-(4-fluorophenyl)ethyl)malonate (3ma): Following the
general procedure (20 mol % Sc(OTf)3 was used in this case), D-A cyclopropane 1m (0.100 g, 0.39
mmol) was transformed into peroxy compound 3ma and purified by silica gel column
chromatography (1: 9 EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 72%
(0.098g) yield. Rf 0.6 (1:4 EtOAc: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.31-7.28 (m, 2H), 7.02
(t, J = 8.7 Hz, 2H), 4.87 (dd, J = 8.7, 5.2 Hz, 1H), 3.72 (s, 6H), 3.60 (dd, J = 8.3, 6.4 Hz, 1H), 2.42
13
(ddd, J = 15.0, 8.7, 6.4 Hz, 1H), 2.33-2.26 (m, 1H), 1.16 (s, 9H); C NMR (100 MHz, CDCl3) δ
169.5 (2), 162.6 (d, J = 245.8 Hz), 136.2 (d, J = 3.2 Hz), 128.6 (d, J = 8.1 Hz), 115.3 (d, J = 21.4
Hz), 82.6, 80.6, 52.8, 52.7, 48.7, 34.5, 26.5; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C17H23FNaO6 365.1376, Found 365.1341.
Dimethyl-2-(2-(tert-butylperoxy)-2-(4-chlorophenyl)ethyl)malonate (3na): Following the general
procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1n (0.100 g, 0.37 mmol) was
transformed into peroxy compound 3na and purified by silica gel column chromatography (1: 9
EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 90% (0.120g) yield. Rf
0.65 (1:4 EtOAc: Hexanes); 1H NMR (400 MHz, CDCl3) δ 1H NMR (400 MHz, CDCl3) δ 7.35-7.33
(m, 2H), 7.31-7.29 (m, 2H), 4.91 (dd, J = 8.7, 5.1 Hz, 1H), 3.76 (s, 3H), 3.75 (s, 3H), 3.64 (dd, J =
8.4, 6.3 Hz, 1H), 2.46-2.38 (m, 1H), 2.6-2.29 (m, 1H), 1.20 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
169.5, 169.4, 139.1, 133.7, 128.6, 128.3, 82.5, 80.6, 52.8, 52.7, 48.7, 34.5, 26.5; HRMS (ESI-TOF)
m/z: [M+Na]+ calculated for C17H23ClNaO6 381.1081, Found 381.1078.
Dimethyl 2-(2-(tert-butylperoxy)-2-(naphthalen-2-yl)ethyl)malonate (3oa): Following the
general procedure (20 mol% Sc(OTf)3 was used), D-A cyclopropane 1o (0.100 g, 0.35 mmol) was
transformed into peroxy compound 3oa and purified by silica gel column chromatography (5:95
EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 81% (0.107g) yield. Rf 0.8
1
(1:4 EtOAc: Hexanes); H NMR (400 MHz, CDCl3) δ 7.86-7.80 (m, 4H), 7.52-7.45 (m, 3H), 5.11
(dd, J = 8.5, 5.3 Hz, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 3.69 (dd, J = 8.2, 6.5 Hz, 1H), 2.57 (ddd, J =
14.9, 8.6, 6.5 Hz, 1H), 2.48-2.41 (m, 1H), 1.21 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 169.6, 169.5,
137.8, 133.3, 133.2, 128.2, 128.1, 127.7, 126.1, 126.0, 126.0 (2), 124.6, 83.4, 80.5, 52.7, 52.6, 48.7,
34.5, 26.5; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C21H26NaO6 397.1627, Found 397.1621.
Dimethyl (E)-2-(2-(tert-butylperoxy)-4-phenylbut-3-en-1-yl)malonate (3pa): Following the
general procedure, D-A cyclopropane 1p (0.080 g, 0.31 mmol) was transformed into peroxy
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 40
1
2
3
4
5
6
7
compound 3pa and purified by silica gel column chromatography (1:9 Et2O: Hexanes as eluent) to
give the title compound as colorless oil in 63% (0.068g) yield. Rf 0.4 (1:4 Et2O: Hexanes); 1H NMR
(400 MHz, CDCl3) δ 7.32-7.31 (m, 2H), 7.25-7.21 (m, 2H), 7.18-7.14 (m, 1H), 6.50 (d, J = 16.0 Hz,
1H), 6.05 (dd, J = 16.0, 7.6 Hz, 1H), 4.47-4.42 (m, 1H), 3.64 (s, 3H), 3.63 (s, 3H), 3.61 – 3.55 (m,
8
9
13
1H), 2.32-2.16 (m, 2H), 1.15 (s, 9H); C NMR (100 MHz, CDCl3) δ 169.7, 169.6, 136.5, 133.1,
128.6, 128.0, 127.9, 126.7, 80.2, 80.5, 52.7 (2), 48.4, 32.6, 26.5; HRMS (ESI-TOF) m/z: [M+Na]+
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
calculated for C19H26NaO6 373.1627, Found 373.1613.
Dimethyl-2-(2-(tert-butylperoxy)-2-(furan-2-yl)ethyl)malonate (3qa): This reaction was set up
o
according to the general procedure, except the temperature of the reaction was kept at 0 C
throughout. Thus, D-A cyclopropane 1q (0.100 g, 0.44 mmol) was transformed into peroxy
compound 3qa and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent)
to give the title compound as colorless oil in 57% (0.080g) yield. Rf 0.65 (1:4 EtOAc: Hexanes); 1H
NMR (400 MHz, CDCl3) δ 7.37-7.36 (m, 1H), 6.33-6.31 (m, 2H), 4.91 (dd, J = 8.5, 5.8 Hz, 1H),
3.72 (s, 3H), 3.71 (s, 3H), 3.61 (dd, J = 8.1, 6.6 Hz, 1H), 2.60 (ddd, J = 15.0, 8.5, 6.6 Hz, 1H), 2.41
13
(ddd, J = 14.2, 8.2, 5.8 Hz, 1H), 1.11 (s, 9H); C NMR (100 MHz, CDCl3) δ 169.5, 169.4, 152.4,
142.5, 110.3, 109.2, 80.6, 76.2, 52.7 (2), 48.5, 30.8, 26.3; HRMS (ESI-TOF) m/z: [M+Na]+
calculated for C15H22NaO7 337.1263, Found 337.1254.
Dimethyl-2-(2-(tert-butylperoxy)-2-(thiophen-2-yl)ethyl)malonate (3ra):Following the general
procedure, D-A cyclopropane 1r (0.100 g, 0.42 mmol) was transformed into peroxy compound 3ra
and purified by silica gel column chromatography (1: 9 EtOAc: Hexanes as eluent) to give the title
compound as colorless oil in 80% (0.110g) yield. Rf 0.7 (1:4 EtOAc: Hexanes); 1H NMR (400 MHz,
CDCl3) δ 7.20 (dd, J = 4.9, 1.1 Hz, 1H), 6.95 (br d, J = 3.0 Hz, 1H), 6.91-6.88 (m, 1H), 5.08 (dd, J =
8.4, 5.7 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 3H), 3.60 (dd, J = 8.1, 6.6 Hz, 1H), 2.55 (ddd, J = 15.0, 8.5,
13
6.6 Hz, 1H), 2.37 (ddd, J = 14.1, 8.2, 5.7 Hz, 1H), 1.10 (s, 9H); C NMR (100 MHz, CDCl3) δ
169.5, 169.4, 142.7, 126.5, 126.0, 125.5, 80.7, 78.6, 52.7 (2), 48.7, 34.3, 26.4; HRMS (ESI-TOF)
m/z: [M+Na]+ calculated for C15H22NaO6S 353.1035, Found 353.1010.
Dimethyl-2-(2-(tert-butylperoxy)-2-(1-tosyl-1H-indol-3-yl)ethyl)malonate (3sa): Following the
general procedure, D-A cyclopropane 1s (0.050 g, 0.11 mmol) was transformed into peroxy
compound 3sa and purified by silica gel column chromatography (15:85 EtOAc: Hexanes as eluent)
1
to give the title compound as colorless oil in 83% (0.050g) yield. Rf 0.3 (1:4 EtOAc: Hexanes); H
NMR (400 MHz, CDCl3) δ 7.96-7.94 (m, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.65-7.63 (m, 1H), 7.56 (s,
1H), 7.32-7.28 (m, 1H), 7.24-7.19 (m, 3H), 5.16 (dd, J = 8.7, 5.0 Hz, 1H), 3.71 (s, 6H), 3.67 (dd, J =
8.6, 6.1 Hz, 1H), 2.60 (ddd, J = 14.8, 8.8, 6.1 Hz, 1H), 2.52-2.53 (m, 1H), 2.32 (s, 3H), 1.12 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 169.6, 169.5, 145.1, 135.4, 135.2, 129.3, 127.0, 124.9, 124.5, 123.4,
18
ACS Paragon Plus Environment

Page 19 of 40
The Journal of Organic Chemistry
1
2
3
4
121.5, 120.6, 113.8, 80.5, 76.6, 52.8, 52.7, 48.7, 32.7, 26.4, 21.7; HRMS (ESI-TOF) m/z: [M+Na]+
calculated for C26H31NNaO8S 540.1668, Found 540.1680.
5
6
7
8
Dimethyl-2-(2-(tert-butylperoxy)-2-(1,3-dioxoisoindolin-2-yl)ethyl)malonate (3ta): Following
the general procedure (20 mol% Sc(OTf)3 was used), D-A cyclopropane 1t (0.100 g, 0.33 mmol) was
transformed into peroxy compound 3ta and purified by silica gel column chromatography (3:7
EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 77% (0.100g) yield. Rf 0.3
(4:6 EtOAc: Hexanes); FT-IR (ν cm-1): 3400, 2979, 1721, 1364, 1328; 1H NMR (400 MHz, CDCl3)
δ 7.87 (dd, J = 5.4, 3.1 Hz, 2H), 7.74 (dd, J = 5.5, 3.0 Hz, 2H), 5.87 (dd, J = 8.0, 6.4 Hz, 1H), 3.74
(s, 3H), 3.72 (s, 3H), 3.55 (t, J = 7.5 Hz, 1H), 3.02-2.95 (m, 1H), 2.67 (ddd, J = 14.3, 7.6, 6.4 Hz,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
1H), 1.12 (s, 9H); C NMR (100 MHz, CDCl3) δ 168.8 (2), 167.6, 134.5, 131.8, 123.8, 81.8, 81.4,
53.0, 48.5, 29.0, 26.3; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C19H23NNaO8 416.1321,
Found 416.1327.
Dimethyl 2-(2-(tert-butylperoxy)-2-(2,5-dioxopyrrolidin-1-yl)ethyl)malonate (3ua): Following
the general procedure (20 mol% Sc(OTf)3 was used), D-A cyclopropane 1u (0.100 g, 0.39 mmol)
was transformed into peroxy compound 3ua and purified by silica gel column chromatography (3:7
EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 94% (0.127g) yield. Rf
0.35 (4:6 EtOAc: Hexanes);1H NMR (400 MHz, CDCl3) δ 5.67 (dd, J = 8.3, 6.0 Hz, 1H), 3.71 (s,
3H), 3.70 (s, 3H), 3.45 (dd, J = 7.9, 7.0 Hz, 1H), 2.84 (ddd, J = 15.1, 8.3, 6.9 Hz, 1H), 2.67 (br s,
4H), 2.47 (ddd, J = 14.3, 8.1, 6.0 Hz, 1H), 1.13 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.5, 168.7,
82.2, 81.4, 52.9 (2), 48.3, 28.4, 28.6, 26.2; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C15H23NNaO8 368.1321, Found 368.1306.
Dimethyl-2-(2-(tert-butylperoxy)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)malonate
(3va): Following the general procedure (20 mol% Sc(OTf)3 was used), D-A cyclopropane 1v (0.100
g, 0.39 mmol) was transformed into peroxy compound 3va and purified by silica gel column
chromatography (3: 7 EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 86%
1
(0.117g) yield. Rf 0.35 (4:6 EtOAc: Hexanes); H NMR (400 MHz, CDCl3) δ 6.72 (br s, 2H), 5.65
(dd, J = 8.3, 6.2 Hz, 1H), 3.73 (s, 6H), 3.48-3.51 (m, 1H), 2.92-2.84 (m, 1H), 2.54 (ddd, J = 14.4,
13
7.8, 6.2 Hz, 1H), 1.13 (s, 9H); C NMR (100 MHz, CDCl3) δ 170.1, 168.8, 168.7, 134.6, 81.3 (2),
53.0 (2), 48.4, 28.9, 26.3; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C15H21NNaO8 366.1165,
Found 366.1181.
Ring-opening peroxidation of D-A cyclopropanes with tetrahydropyranyl (THP)
hydroperoxide: Preparation of compound 3gb: Cyclopropane 1g (0.200g, 0.85 mmol) was
dissolved in a mixture of dry DCM and cyclohexane (1.6 mL, 1:3, v/v) under argon. To this solution
was added a solution of 2-hydroperoxytetrahydro-2H-pyran (2.0 equiv in 0.4 mL cyclohexane) and
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 40
1
2
3
4
5
6
7
8
Sc(OTf)3 (42 mg, 0.085 mmol). The reaction mixture was stirred for 4 h at room temperature. After
completion of the reaction (monitored by TLC), reaction was diluted with DCM (5 mL) and
successively washed with water (5 mL) and brine (5 mL). The combined organic layer was dried
over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified by
silica gel column chromatography (using 15: 85 EtOAc: Hexanes as eluent) to afford 3gb (0.213 g,
71 %) as colorless oil (dr = 1:1). Rf 0.65 (1:4 EtOAc: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.38-
7.36 (m, 5H), 7.34-7.28 (m, 5H), 5.15-5.08 (m, 2H), 5.07-5.02 (m, 2H), 3.94-3.88 (m, 1H), 3.73 (s,
3H), 3.72 (s, 3H), 3.71 (s, 3H), 3.71 (s, 3H), 3.65-3.48 (m, 3H), 2.51-2.53 (m, 1H), 2.40–2.29(m,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
3H), 1.72-1.38 (m, 14H). C NMR (100 MHz, CDCl3) δ 169.6, 169.5 (2), 140.4, 139.9, 128.5 (2),
128.2, 126.9, 126.7, 101.8, 100.5, 84.4, 83.5, 62.6, 62.3, 52.7 (2), 48.7 (2), 34.2, 33.8, 27.9, 27.7,
25.2, 25.1, 19.6, 19.5; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C18H24NaO7 375.1420,
Found 375.1436.
Dimethyl-2-(2-(((R)-tetrahydro-2H-pyran-2-yl)peroxy)-2-(thiophen-2-yl)ethyl)malonate (3rb):
Compound 3rb was prepared from cyclopropane 1r (0.100g, 0.42 mmol), following similar
procedure as shown for compound 3gb and was obtained in 61% yield (0.091g) as colorless oil (dr =
1:1). Rf 0.55 (1:4 EtOAc: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.30-7.28 (m, 2H), 7.07 (d, J =
3.5 Hz, 2H), 6.99-6.97 (m, 2H), 5.38-5.29 (m, 2H), 5.05-5.01 (m, 2H), 3.94-3.80 (m, 2H), 3.75 (s,
6H), 3.74 (s, 6H), 3.72-3.68 (m, 2H), 3.60-3.52 (m, 2H), 2.72-2.41 (m, 4H), 1.67-1.65 (m, 3H), 1.60-
13
1.46 (m, 9H); C NMR (100 MHz, CDCl3) δ 169.5, 139.4, 143.2, 142.2, 126.7 (2), 126.4, 126.2,
126.0, 125.8, 101.8, 100.9, 79.7, 79.0, 62.6, 62.4, 52.8 (2), 48.6, 34.1, 33.7, 27.9, 27.8, 25.2, 19.6
(2); HRMS (ESI-TOF) m/z: [M+Na]+ calculated C16H22NaO7S 381.0984, Found 381.0950.
Dimethyl-2-(2-(1,3-dioxoisoindolin-2-yl)-2-(((R)-tetrahydro-2H-pyran-2-yl)
peroxy)ethyl)malonate (3tb): Compound 3tb was prepared from cyclopropane 1t (0.100g, 0.33
mmol), following similar procedure as shown for compound 3gb and was obtained in 79% yield
1
(0.110 g) as colorless oil (dr = 1:1). Rf 0.3 (1:4 EtOAc: Hexanes); H NMR (400 MHz, CDCl3) δ
7.87-7.84 (m, 4H), 7.75-7.71 (m, 4H), 6.10 (dd, J = 9.2, 5.1 Hz, 1H), 5.96 (dd, J = 8.4, 6.0 Hz, 1H),
5.12-5.10 (m, 1H), 5.00-4.98 (m, 1H), 3.98-3.92 (m, 1H), 3.72-3.71 (m, 12H), 3.68 (dd, J = 8.9, 5.9
Hz, 1H), 3.59-3.54 (m, 2H), 3.35-3.29 (m, 1H), 3.23-3.18 (m, 1H), 3.05-2.92 (m, 2H), 2.67-2.53 (m,
2H), 1.61-1.46 (m, 7H), 1.42-1.31 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 169.9, 168.8, 168.7,
167.7, 167.5, 134.5, 134.2, 132.0, 131.8, 123.7, 123.5, 101.9, 101.7, 83.2, 82.0, 77.4, 63.3, 62.5, 52.9
(3), 48.3 (2), 29.4, 29.1, 27.8, 27.5, 25.1, 24.8, 20.2, 19.2; HRMS (ESI-TOF) m/z: [M+Na]+
calculated for C20H23NNaO9 444.1271, Found 444.1314.
Dimethyl-2-(2-(1,3-dioxoisoindolin-2-yl)-2-hydroperoxyethyl)malonate (3tc): p-Toluenesulfonic
acid (0.028 g, 0.16 mmol) was added to a solution of cyclopropane 3tb (0.070 g, 0.16 mmol) in dry
methanol (1 mL, 0.16 M) under argon and the reaction mixture was stirred at room temperature for
20
ACS Paragon Plus Environment

Page 21 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
12 h. Upon completion of the reaction as determined by the disappearence of starting material, the
reaction solvent was removed under reduced pressure and the crude product was purified by flash
silica gel column chromatography (using 2:3 EtOAc: Hexanes as eluent) to obtain 3tc as colorless
oil in 64% yield (0.036g). Rf 0.25 (3:7 EtOAc: Hexanes); 1H NMR (400 MHz, CDCl3) δ 9.33 (br s,
1H), 7.87 (dd, J = 5.5, 3.0 Hz, 2H), 7.75 (dd, J = 5.5, 3.1 Hz, 2H), 5.91 (dd, J = 8.8, 5.4 Hz, 1H),
3.75 (s, 3H), 3.73 (s, 3H), 3.59 (t, J = 7.3 Hz, 1H), 3.12-3.04 (m, 1H), 2.61-2.54 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 169.3, 168.9, 167.8, 134.7, 131.7, 123.9, 83.9, 53.1, 48.5, 29.0; HRMS (ESI-
TOF) m/z: [M+Na]+ calculated for C15H15NNaO8 360.0695, Found 360.0660.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dimethyl-2-(2-((1-methyl-4-oxocyclohexa-2,5-dien-1-yl)peroxy)-2-(p-tolyl)ethyl)malonate
(3ad):To a solution of cyclopropane 1a (0.150g, 0.6 mmol) in dry dichloromethane (3.0 mL) under
argon was added 4-hydroperoxy-4-methylcyclohexa-2,5-dien-1-one (0.527g, 2.1 mmol). Sc(OTf)3
(10 mol%) was then added to the solution and the reaction mixture was stirred at room temperature
for 4 h. Upon completion of the reaction (TLC controlled), the solvent was removed under reduced
pressure and the crude product was purified by flash silical gel column chromatography (using 1:9
EtOAc: Hexanes as eluent) to obtain the peroxy products (3ad) as colorless oil in 55% overall yield
1
(0.130g). Rf 0.35 (1:4 EtOAc: Hexanes); H NMR (400 MHz, CDCl3) δ 7.20 -7.14 (m, 4H), 6.82
(dd, J = 10.1, 3.0 Hz, 1H), 6.67 (dd, J = 10.1, 3.0 Hz, 1H), 6.23-6.16 (m, 2H), 4.91 (dd, J = 8.9, 5.3
Hz, 1H), 3.71 (s, 3H), 3.68 (s, 3H), 3.44 (dd, J = 8.4, 6.3 Hz, 1H), 2.34 (s, 3H), 2.32-2.20 (m, 2H),
13
1.26 (s, 3H) ; C NMR (100 MHz, CDCl3) δ 185.4, 169.4 (2), 150.6, 150.3, 138.3, 136.4, 129.5,
129.2 (2), 127.0, 84.2, 77.7, 52.8, 52.7, 48.5, 33.9, 23.2, 21.3; HRMS (ESI-TOF) m/z: [M+Na]+
calculated for C21H24NaO7 411.1420, Found 411.1417.
Scale Up Experiment: In a flame dried Schlenk tube, cyclopropane 1a (1.0 g, 4.0 mmol) was
dissolved in dry DCM (2 mL) and to this solution was slowly added tert-butyl hydroperoxide (8.0
mL, 5-6 M solution in decane) under argon. Sc(OTf)3 (0.2 g, 0.04 mmol) was then added in portions
and the resulting mixture was stirred at room temperature under argon for 3h. After completion (TLC
controlled) the reaction was diluted with DCM (10 mL), washed with water (5 mL) and brine (5 mL)
and the organic layer was dried over anhydrous Na2SO4. Solvents were removed under reduced
pressure (bath temperatuer 30 oC) and the crude product was purified by flash column
chromatography (using 5: 95 EtOAc: Hexanes as eluent) to obtain the peroxy compound 3aa (1.0 g,
74%) as colorless oil.
General procedure for 1,3-haloperoxygenation of D-A cyclopropanes with tert-butyl
hydroperoxide (TBHP): Preparation of compounds 5. To a solution of cyclopropane 1 (50-100
mg) in dry dichloromethane (2.0 M) under argon was added tert-butyl hydroperoxide (2a) (10 equiv.
5-6 M solution in decane). Sc(OTf)3 (10 or 20 mol%) was then added to the solution and the reaction
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 40
1
2
3
4
5
6
7
8
mixture was stirred at room temperature for 45-75 minutes. Next, the reaction mixture was cooled to
0 oC and was added 1.5 equiv. of halogenating agent (4aʹ-4cʹ, N-halosuccinamide, NXS, X = Br, Cl,
I) in one portion. The reaction was continued for another 2-3 h at room temperature. Upon
completion (TLC controlled), the reaction was quenched with saturated NaHCO3 solution and
extracted in DCM (5 mL x 2). Organic layer was dried (Na2SO4) and concentrated in vacuo (bath
9
o
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
temperatuer 30 C). The crude residue was purified by flash silica gel column chromatography to
obtain the haloperoxygenated products 5.
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-phenylethyl)malonate (5gaʹ): Following the general
procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1g (0.100g, 0.42 mmol) was
transformed into bromo-peroxy compound 5gaʹ and purified by silica gel column chromatography
(4:96 EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 92% (0.158g) yield.
Rf 0.25 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.35-7.30 (m, 5H), 5.23-5.20 (m, 1H),
3.84 (s, 3H), 3.58 (s, 3H), 2.97 (dd, J = 15.4, 8.2 Hz, 1H), 2.67 (dd, J = 15.4, 4.4 Hz, 1H), 1.13 (s,
13
9H); C NMR (100 MHz, CDCl3) δ 167.1, 166.7, 140.0, 128.3 (2), 127.7, 82.7, 80.5, 60.4, 54.1,
53.9, 42.9, 26.6; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C17H23BrNaO6 425.0576, Found
425.0565.
Dimethyl 2-(2-(tert-butylperoxy)-2-phenylethyl)-2-chloromalonate (5gbʹ): Following the general
procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1g (0.100g, 0.42 mmol) was
transformed into chloro-peroxy compound 5gbʹ and purified by silica gel column chromatography
(4:96 EtOAc: Hexanes as eluent) to give the title compound as colorless oil in 64% (0.098g) yield.
Rf 0.5 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.35-7.29 (m, 5 H), 5.20 (dd, J = 8.3, 4.8
Hz, 1H), 3.85 (s, 3H), 3.60 (s, 3 H), 2.98 (dd, J = 15.3, 8.3 Hz, 1H), 2.64 (dd, J = 15.3, 4.8 Hz, 1H),
13
1.12 (s, 9H); C NMR (100 MHz, CDCl3) δ 166.9, 166.8, 140.1, 128.3 (2), 127.7, 81.5, 80.6, 68.4,
54.0, 53.9, 42.3, 26.6. HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C17H23ClNaO6 381.1081,
Found 381.1102.
Dimethyl-2-(2-(tert-butylperoxy)-2-phenylethyl)-2-iodomalonate (5gcʹ): Following the general
procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1g (0.100g, 0.42 mmol) was
transformed into iodo-peroxy compound 5gcʹ and purified by silica gel column chromatography
(4:96 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 57% (0.110 g) yield. Rf
1
0.45 (1:9 Et2O: Hexanes); H NMR (400 MHz, CDCl3) δ 7.35-7.29 (m, 5H), 5.14 (dd, J = 8.0, 4.8
Hz, 1H), 3.81 (s, 3H), 3.57 (s, 3H), 2.80 (dd, J = 15.5, 8.0 Hz, 1H), 2.60 (dd, J = 15.5, 4.8 Hz, 1H),
13
1.14 (s, 9H); C NMR (100 MHz, CDCl3) δ 168.7, 167.9, 140.1, 128.3 (2), 127.7, 85.1, 80.5, 54.2,
53.9, 44.6, 41.7, 26.7; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C17H23INaO6 473.0437,
Found 473.0433.
22
ACS Paragon Plus Environment

Page 23 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)malonate (5aaʹ): Following the
general procedure, D-A cyclopropane 1a (0.100g, 0.40 mmol) was transformed into bromo-peroxy
compound 5aaʹ and purified by silica gel column chromatography (6:94 Et2O: Hexanes as eluent) to
give the title compound as colorless oil in 71% (0.120 g) yield. Rf 0.4 (1:4 Et2O: Hexanes); FT-IR (ν
8
9
1
cm-1): 3400, 2925, 1747, 1514, 1364, 1260, 1073, 817; H NMR (400 MHz, CDCl3) δ 7.24 (d, J =
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8.1 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 5.18 (dd, J = 7.9, 4.9 Hz, 1H), 3.84 (s, 3H), 3.58 (s, 3H), 2.98
(dd, J = 15.4, 8.0 Hz, 1H), 2.66 (dd, J = 15.4, 4.9 Hz, 1H), 2.34 (s, 3H), 1.13 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 167.2, 166.8, 138.0, 137.0, 129.0, 127.7, 82.6, 80.5, 60.5, 54.1, 53.9, 42.8, 26.6,
21.3; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C18H25BrNaO6 439.0732, Found 439.0706.
Dimethyl 2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)-2-chloromalonate (5abʹ): Following the
general procedure, D-A cyclopropane 1a (0.100g, 0.40 mmol) was transformed into chloro-peroxy
compound 5abʹ and purified by silica gel column chromatography (4:96 EtOAc: Hexanes as eluent)
1
to give the title compound as colorless oil in 66% (0.099 g) yield. Rf 0.4 (1:9 Et2O: Hexanes); H
NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 5.16 (dd, J = 8.1, 4.9
Hz, 1H), 3.85 (s, 3H), 3.58 (s, 3H), 2.98 (dd, J = 15.3, 8.2 Hz, 1H), 2.62 (dd, J = 15.3, 4.9 Hz, 1H),
13
2.34 (s, 3H), 1.12 (s, 9H); C NMR (100 MHz, CDCl3) δ 166.9, 166.8, 138.0, 136.9, 129.0, 127.7,
81.3, 80.5, 68.4, 54.0, 53.8, 42.2, 26.6, 21.3; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C18H25ClNaO6 395.1237, Found 395.1267.
Dimethyl 2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)-2-iodomalonate (5acʹ):Following the general
procedure, D-A cyclopropane 1a (0.100 g, 0.40 mmol) was transformed into iodo-peroxy compound
5acʹ and purified by silica gel column chromatography (4:96 Et2O: Hexanes as eluent) to give the
1
title compound as colorless oil in 72% (0.135 g) yield. Rf 0.55 (1:9 Et2O: Hexanes); H NMR (400
MHz, CDCl3) δ 7.24 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 5.10 (dd, J = 7.8, 5.0 Hz, 1H),
3.81 (s, 3H), 3.56 (s, 3H), 2.80 (dd, J = 15.4, 7.9 Hz, 1H), 2.58 (dd, J = 15.5, 4.9 Hz, 1H), 2.34 (s,
13
3H), 1.14 (s, 9H); C NMR (100 MHz, CDCl3) δ 168.7, 168.0, 138.0, 137.0, 129.0, 127.8, 85.0,
80.5, 54.2, 53.9, 44.5, 41.9, 26.7, 21.4; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C18H25INaO6 487.0594, Found 487.0602.
Diethyl 2-bromo-2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)malonate (5baʹ): Following the general
procedure, D-A cyclopropane 1b (0.100 g, 0.36 mmol) was transformed into bromo-peroxy
compound 5baʹ and purified by silica gel column chromatography (6:94 EtOAc: Hexanes as eluent)
to give the title compound as colorless oil in 68% (0.110 g) yield. Rf 0.7 (1:4 EtOAc: Hexanes); 1H
NMR (400 MHz, CDCl3) δ 7.24 (d, J = 8.1 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 5.18 (dd, J = 8.0, 4.9
Hz, 1H), 4.34-4.25 (m, 2H), 4.07-4.93 (m, 2H), 2.96 (dd, J = 15.4, 8.0 Hz, 1H), 2.65 (dd, J = 15.4,
13
4.9 Hz, 1H), 2.33 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H), 1.13 (s, 9H); C NMR
(100 MHz, CDCl3) δ 166.6, 166.2, 137.9, 137.2, 128.9, 127.6, 82.6, 80.4, 63.1, 63.0, 61.2, 42.7,
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 40
1
2
3
4
26.6, 21.3, 14.0, 13.7; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C20H29BrNaO6 467.1045,
Found 467.1019.
5
6
1-Methyl-3-(p-tolyl)
2-bromo-2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)malonate
(5caʹ):
Following the general procedure, D-A cyclopropane 1c (0.100 g, 0.36 mmol) was transformed into
bromo-peroxy compound 5caʹ and purified by silica gel column chromatography (6:94 Et2O:
Hexanes as eluent) to give the title compound as mixture of diastereomers in 60% (0.091 g) yield (dr
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
= 1:1). Rf 0.5 (1:9 Et2O: Hexanes); H NMR (400 MHz, CDCl3) δ 7.30-7.27 (m, 4H), 7.19-7.14 (m,
8H), 7.10 – 7.00 (m, 2H), 7.06-7.04 (m, 2H), 5.28-5.25 (m, 2H), 3.91 (s, 3H), 3.65 (s, 3H), 3.13-3.05
13
(m, 2H), 2.82-2.72 (m, 2H), 2.35 (br s, 9H), 2.33 (s, 3H), 1.14 (s, 1H), 1.12 (s, 9H); C NMR (100
MHz, CDCl3) δ 167.0, 166.5, 165.6, 164.8, 148.7, 148.3, 138.1, 137.2, 136.9, 136.2, 130.1, 130.0,
129.1, 127.7 (2), 120.9, 120.6, 82.8, 82.5, 80.8, 80.6, 60.7, 60.6, 54.3, 54.0, 43.0, 42.9, 26.7 (2), 21.4
(2), 21.1, 21.0; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C24H29BrNaO6 515.1045, Found
515.1020
1-Methyl 3-phenyl 2-bromo-2-(2-(tert-butylperoxy)-2-(p-tolyl)ethyl)malonate (5waʹ) :Following
the general procedure, D-A cyclopropane 1w (0.060g, 0.19 mmol) was transformed into bromo-
peroxy compound 5waʹ and purified by silica gel column chromatography (4:96 Et2O: Hexanes as
eluent) to give the title compound as mixture of diastereomers in 59% (0.055 g) yield (dr = 5:1). Rf
0.4 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.42-7.34 (m, 3H), 7.32-7.28 (m, 4H), 7.27-
7.21 (m, 2H), 7.19-7.17 (m, 2H), 6.98-6.95 (m, 2H), 5.32 (s, 0.17 H), 5.29 (dd, J = 8.4, 4.4 Hz, 1H),
3.94 (s, 3H), 3.69 (s, 0.6H), 3.15-3.09 (m, 1.2H), 2.35-2.75 (m, 1.2H), 2.38 (s, 0.6H), 2.37 (s, 3H),
13
1.16 (s, 9H), 1.14 (s, 2H); C NMR (100 MHz, CDCl3) δ 166.4, 165.4, 150.5, 138.1, 137.2, 136.9,
136.6, 129.6 (2), 129.2, 129.1, 127.7, 127.6, 126.6, 126.5, 121.2, 120.9, 82.7, 82.5, 80.8, 80.6, 60.6,
60.5, 54.3, 54.1, 43.1, 42.9, 26.7 (2), 21.4 (2); HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C23H27BrNaO6 501.0889, Found 501.0866.
Methyl 2-benzoyl-2-bromo-4-(tert-butylperoxy)-4-phenylbutanoate (5eaʹ): Following the
general procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1e (0.080 g, 0.28 mmol) was
transformed into bromo-peroxy compound 5eaʹ and purified by silica gel column chromatography
(4:96 Et2O: Hexanes as eluent) to give the title compound as semi solid in 63% (0.081 g) yield (dr =
1.5:1). Rf 0.65 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 8.02-8.00 (m, 2H), 7.95-7.93 (m,
1H), 7.55-7.52 (m, 2H), 7.43-7.29 (m, 12H), 5.36 (dd, J = 9.5, 2.8 Hz, 1H), 5.19 (t, J = 6.0 Hz,
0.6H), 3.70 (s, 3H), 3.26 (s, 2H), 3.20 (dd, J = 15.4, 5.7 Hz, 0.7H), 3.03-2.91 (m, 2H), 2.80 (dd, J =
13
15.9, 2.8 Hz, 1H), 1.10 (s, 9H), 1.09 (s, 6H); C NMR (100 MHz, CDCl3) δ 188.6, 188.0, 168.1,
141.0, 139.4, 133.8, 133.6, 135.5, 133.4 (2), 129.6, 129.5, 128.6, 128.5, 128.4, 128.3 (2), 128.1,
127.6, 82.9, 82.2, 80.4, 64.9, 64.6, 54.1, 53.6, 43.8, 43.0, 26.6 (2); HRMS (ESI-TOF) m/z: [M+Na]+
calculated for C22H25BrNaO5 471.0783, Found 471.0818.
24
ACS Paragon Plus Environment

Page 25 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Ethyl-2-benzoyl-2-bromo-4-(tert-butylperoxy)-4-phenylbutanoate (5xaʹ): Following the general
procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1x (0.060 g, 0.20 mmol) was
transformed into bromo-peroxy compound 5xaʹ and purified by silica gel column chromatography
(4:96 Et2O: Hexanes as eluent) to give the title compound as semi solid in 59% (0.056 g) yield (dr =
1.5:1). Rf 0.65 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 8.03-8.01 (m, 2H), 7.96-7.94 (m,
1H), 7.58-7.50 (m, 2H), 7.42-7.29 (m, 12H), 5.36 (dd, J = 9.4, 2.9 Hz, 1H), 5.19 (t, J = 5.9 Hz,
0.7H), 4.24-4.10 (m, 2H), 3.82-3.73 (m, 0.7H), 3.61-3.53 (m, 1H), 3.21 (dd, J = 15.4, 5.7 Hz, 0.7H),
2.99-2.89 (m, 2H), 2.80 (dd, J = 15.9, 3.0 Hz, 1H), 1.11 (s, 9H), 1.08 (s, 6H), 1.00 (t, J = 7.1 Hz,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
3H), 0.83 (t, J = 7.1 Hz, 2H); C NMR (100 MHz, CDCl3) δ 188.9, 188.3, 167.5, 167.4, 141.2,
139.7, 134.0, 133.9,133.4, 133.3, 129.7, 129.6, 128.5, 128.4, 128.3, 128.2, 128.1, 127.5, 82.9, 82.3,
80.5, 80.4, 65.4, 64.9, 63.4, 63.1, 43.8, 43.0, 26.6 (2), 13.7, 13.4; HRMS (ESI-TOF) m/z: [M+Na]+
calculated for C23H27BrNaO5 485.0940, Found 485.0956.
Ethyl 2-acetyl-2-bromo-4-(tert-butylperoxy)-4-phenylbutanoate (5yaʹ): Following the general
procedure, D-A cyclopropane 1y (0.100g, 0.43 mmol) was transformed into bromo-peroxy
compound 5yaʹ and purified by silica gel column chromatography (4:96 EtOAc: Hexanes as eluent)
to give the title compound as colorless oil in 64% (0.111 g) yield (dr = 1:1). Rf 0.6 (1:4 Et2O:
Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.34-7.28 (m, 10H), 5.20-5.14 (m, 2H), 4.33-4.27 (m, 2H),
4.11-4.03 (m, 1H), 4.00-3.92 (m, 1H), 2.93 (dd, J = 15.5, 8.4 Hz, 1H), 2.82 (dd, J = 15.7, 9.6 Hz,
1H), 2.63 (dd, J = 15.5, 4.6 Hz, 1H), 2.55 (dd, J = 15.7, 3.4 Hz, 1H), 2.46 (s, 3H), 2.32 (s, 3H), 1.33
13
(t, J = 7.1 Hz, 3H), 1.21 (t, J =7.1, 3H), 1.10 (s, 9H), 1.07 (s, 9H); C NMR (100 MHz, CDCl3) δ
197.1, 196.1, 167.3, 166.8, 140.8, 134.0, 128.3 (2), 128.1, 127.8, 127.4, 82.7, 82.6, 80.4, 67.5, 67.3,
63.4, 63.1, 42.3, 42.2, 26.9, 26.6, 25.1, 14.0, 13.7; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C18H25BrNaO5 423.0783, Found 423.0779.
2-(2-(tert-Butylperoxy)-2-phenylethyl)-2-chloro-1,3-diphenylpropane-1,3-dione
(5dbʹ):
Following the general procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1d (0.100 g,
0.30 mmol) was transformed into chloro-peroxy compound 5dbʹ and purified by silica gel column
chromatography (3:97 Et2O: Hexanes as eluent) to give the title compound as semi solid in 65%
1
(0.089 g) yield. Rf 0.65 (1:9 Et2O: Hexanes); H NMR (400 MHz, CDCl3) δ 7.92-7.89 (m, 4H),
7.49-7.43 (m, 2H), 7.37-7.27 (m, 9H), 5.26 (dd, J = 8.7, 3.1 Hz, 1H), 3.28 (dd, J = 15.8, 8.7 Hz, 1H),
3.04 (dd, J = 15.8, 3.2 Hz, 1H), 0.86 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 191.6, 191.0, 140.8,
134.3, 134.1, 133.6, 133.4, 130.1, 130.0, 128.5, 128.2, 128.0, 127.5, 81.0, 80.1, 78.2, 44.9, 26.4;
HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C27H27ClNaO4 473.1496, Found 473.1502.
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-(4-isopropylphenyl)ethyl)malonate
(5haʹ):Following the general procedure, D-A cyclopropane 1h (0.100 g, 0.36 mmol) was
transformed into bromo-peroxy compound 5haʹ and purified by silica gel column chromatography
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 40
1
2
3
4
5
6
7
8
(4:96 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 62% (0.100 g) yield. Rf
0.6 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.27-7.25 (m, 2H), 7.19 (d, J = 8.1 Hz, 2H),
5.18 (dd, J = 7.6, 5.2 Hz, 1H), 3.83 (s, 3H), 3.53 (s, 3H), 3.00 (dd, J = 15.4, 7.7 Hz, 1H), 2.93-2.86
(m, 1H), 2.68 (dd, J = 15.4, 5.2 Hz, 1H), 1.24 (d, J = 6.9 Hz, 6H), 1.14 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 167.1, 166.8, 149.0, 137.1, 127.8, 126.4, 82.7, 80.6, 60.6, 54.1, 53.8, 42.7, 34.0, 26.6, 24.1
(2); HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C20H29BrNaO6 469.1025, Found 469.1000.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dimethyl-2-(2-(tert-butylperoxy)-2-(4-isopropylphenyl)ethyl)-2-chloromalonate
(5hbʹ):
Following the general procedure, D-A cyclopropane 1h (0.100 g, 0.36 mmol) was transformed into
chloro-peroxy compound 5hbʹ and purified by silica gel column chromatography (4:96 Et2O:
Hexanes as eluent) to give the title compound as colorless oil in 69% (0.100 g) yield. Rf 0.4 (1:4
1
Et2O: Hexanes); H NMR (400 MHz, CDCl3) δ 7.26-7.24 (m, 2H), 7.19 (d, J = 8.1 Hz, 2H), 5.17
(dd, J = 7.8, 5.2 Hz, 1H), 3.84 (s, 3H), 3.53 (s, 3H), 3.00 (dd, J = 15.2, 7.8 Hz, 1H), 2.93-2.86 (m,
13
1H), 2.64 (dd, J = 15.2, 5.2 Hz, 1H), 1.23 (d, J = 6.9 Hz, 6H), 1.13 (s, 9H); C NMR (100 MHz,
CDCl3) δ 166.8 (2), 149.0, 137.1, 127.7, 126.3, 81.4, 80.5, 68.4, 54.0, 53.8, 42.1, 34.0, 26.6, 24.1 (2);
HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C20H29ClNaO6 423.1550, Found 423.1555.
Dimethyl 2-(2-(4-acetoxyphenyl)-2-(tert-butylperoxy)ethyl)-2-bromomalonate (5zaʹ): Following
the general procedure, D-A cyclopropane 1z (0.070 g, 0.23 mmol) was transformed into bromo-
peroxy compound 5zaʹ and purified by silica gel column chromatography (6:94 EtOAc: Hexanes as
eluent) to give the title compound as colorless oil in 74% (0.082 g) yield. Rf 0.5 (1:4 EtOAc:
Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 8.5 Hz, 2H), 7.06 (d, J = 8.6 Hz, 2H), 5.21 (dd,
J = 8.0, 4.9 Hz, 1H), 3.83 (s, 3H), 3.60 (s, 3H), 2.95 (dd, J = 15.4, 8.0 Hz, 1H), 2.65 (dd, J = 15.4,
13
4.9 Hz, 1H), 2.29 (s, 3H), 1.13 (s, 9H); C NMR (100 MHz, CDCl3) δ 169.5, 167.0, 166.7, 150.6,
137.6, 128.8, 121.5, 82.1, 80.7, 60.3, 54.2, 54.0, 42.9, 26.6, 21.3; HRMS (ESI-TOF) m/z: [M+Na]+
calculated for C19H25BrNaO8 483.0631, Found 483.0630..
Dimethyl-2-(2-(tert-butylperoxy)-2-(2-methoxyphenyl)ethyl)-2-chloromalonate (5lbʹ): This
reaction was set up according to the general procedure, except the temperature of the reaction was
o
kept at 0 C throughout. Thus, D-A cyclopropane 1l (0.100 g, 0.37 mmol) was transformed into
chloro-peroxy compound 5lbʹ and purified by silica gel column chromatography (1:9 Et2O: Hexanes
as eluent) to give the title compound as colorless oil in 61% (0.090 g) yield. Rf 0.65 (3:7 Et2O:
1
Hexanes); H NMR (400 MHz, CDCl3) δ 7.43-7.41 (m, 1H), 7.29-7.25 (m, 1H), 6.99-6.96 (m, 1H),
6.88 (dd, J = 8.2, 0.6 Hz, 1H), 5.71 (dd, J = 8.9, 4.2 Hz, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.67 (s, 3H),
13
2.88 (dd, J = 15.3, 8.9 Hz, 1H), 2.71 (dd, J = 15.3, 4.2 Hz, 1H), 1.17 (s, 9H); C NMR (100 MHz,
CDCl3) δ 167.2, 166.8, 156.9, 128.9, 128.4, 128.2, 120.4, 110.7, 80.4, 75.7, 68.5, 55.6, 53.9, 53.8,
41.2, 26.6; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C18H25ClNaO7 411.1187, Found
411.1150.
26
ACS Paragon Plus Environment

Page 27 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-(4-fluorophenyl)ethyl)malonate (5maʹ): Following
the general procedure (20 mol % Sc(OTf)3 was used), D-A cyclopropane 1m (0.100 g, 0.39 mmol)
was transformed into bromo-peroxy compound 5maʹ and purified by silica gel column
chromatography (4:96 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 72%
(0.121 g) yield. Rf 0.4 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.33-7.30 (m, 2H), 7.02
(t, J = 8.7 Hz, 2H), 5.19 (dd, J = 8.3, 4.7 Hz, 1H), 3.83 (s, 3H), 3.62 (s, 3H), 2.93 (dd, J = 15.4, 8.3
Hz, 1H), 2.63 (dd, J = 15.4, 4.7 Hz, 1H), 1.11 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 167.1, 166.6,
162.6 (d, J = 246.3 Hz), 135.9 (d, J = 3.2 Hz), 129.3 (d, J = 8.2 Hz), 115.1 (d, J = 21.4 Hz), 81.9,
80.6, 60.2, 54.1, 53.9, 42.9, 26.6; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C17H22BrFNaO6
([M+Na]+): 443.0481, Found 443.0441.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-(4-chlorophenyl)ethyl)malonate (5naʹ):Following
the general procedure, using 20 mol % Sc(OTf)3, D-A cyclopropane 1n (0.100 g, 0.37 mmol) was
transformed into bromo-peroxy compound 5naʹ and purified by silica gel column chromatography
(4:96 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 86% (0.141 g) yield. Rf
0.5 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.33-7.27 (m, 4H), 5.19 (dd, J = 8.5, 4.5 Hz,
1H), 3.84 (s, 3H), 3.64 (s, 3H), 2.90 (dd, J = 15.5, 8.5 Hz, 1H), 2.62 (dd, J = 15.5, 4.5 Hz, 1H), 1.12
13
(s, 9H); C NMR (100 MHz, CDCl3) δ 167.2, 166.6, 138.8, 134.0, 129.0, 128.5, 82.0, 80.7, 60.1,
54.1, 54.0, 43.0, 26.6; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C17H22BrClNaO6 459.0186,
Found 459.0190.
Dimethyl-2-(2-(tert-butylperoxy)-2-(4-chlorophenyl)ethyl)-2-iodomalonate (5ncʹ):Following the
general procedure, using 20 mol % Sc(OTf)3, D-A cyclopropane 1n (0.100 g, 0.37 mmol) was
transformed into iodo-peroxy compound 5ncʹ and purified by silica gel column chromatography
(8:92 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 65% (0.118 g) yield. Rf
0.5 (1:4 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.31-7.28 (d, J = 1.5 Hz, 4H), 5.12 (dd, J =
8.4, 4.5 Hz, 1H), 3.81 (s, 3H), 3.62 (s, 3H), 2.71 (dd, J = 15.5, 8.4 Hz, 1H), 2.55 (dd, J = 15.5, 4.5
Hz, 1H), 1.12 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.7, 167.7, 138.9, 133.9, 129.0, 128.5, 84.3,
80.7, 54.3, 54.0, 44.7, 41.3, 26.7; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C17H22ClINaO6
507.0047, Found 507.0036.
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-(naphthalen-2-yl)ethyl)malonate (5oaʹ):Following
the general procedure, using 20 mol % Sc(OTf)3, D-A cyclopropane 1o (0.060 g, 0.21 mmol) was
transformed into bromo-peroxy compound 5oaʹ and purified by silica gel column chromatography
(4:96 EtOAc: Hexanes as eluent) to give the title compound as semi solid in 62% (0.059 g) yield. Rf
0.5 (1:9 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.86-7.80 (m, 4H), 7.51-7.41 (m, 3H), 5.39
(dd, J = 8.2, 4.7 Hz, 1H), 3.86 (s, 3H), 3.52 (s, 3H), 3.05 (dd, J = 15.5, 8.2 Hz, 1H), 2.75 (dd, J =
15.5, 4.7 Hz, 1H), 1.14 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 167.2, 166.8, 137.6, 133.4,
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 40
1
2
3
4
133.2,128.2 (2), 127.8, 127.0, 126.3, 126.2, 125.2, 82.9, 80.7, 60.4, 54.2, 53.9, 43.0, 26.7; HRMS
(ESI-TOF) m/z: [M+Na]+ calculated for C21H25BrNaO6 475.0732, Found 475.0741.
5
6
7
8
Dimethyl 2-(2-(tert-butylperoxy)-2-(naphthalen-2-yl)ethyl)-2-chloromalonate (5obʹ):Following
the general procedure, using 20 mol % Sc(OTf)3, D-A cyclopropane 1o (0.100 g, 0.35 mmol) was
transformed into chloro-peroxy compound 5obʹ and purified by silica gel column chromatography
(4:96 Et2O: Hexanes as eluent) to give the title compound as semi solid in 72% (0.104 g) yield. Rf
0.6 (1:4 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.86-7.79 (m, 4H), 7.51-7.47 (m, 3H), 5.39
(dd, J = 8.4, 4.7 Hz, 1H), 3.88 (s, 3H), 3.53 (s, 3H), 3.06 (dd, J = 15.3, 8.4 Hz, 1H), 2.72 (dd, J =
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
15.3, 4.7 Hz, 1H), 1.14 (s, 9H); C NMR (100 MHz, CDCl3) δ 166.9, 166.8, 137.6, 133.4, 133.2,
128.2, 127.8, 126.9, 126.3, 126.2, 125.1, 81.5, 80.7, 68.4, 54.1, 53.9, 42.4, 26.6; HRMS (ESI-TOF)
m/z: [M+Na]+ calculated for C21H25ClNaO6 431.1227, Found 431.1251.
Dimethyl-2-bromo-2-(2-(5-bromothiophen-2-yl)-2-(tert-butylperoxy)ethyl)malonate
o
(5raʹ):Following the general procedure (reaction was performed at 0 C), D-A cyclopropane 1r
(0.100 g, 0.41 mmol) was transformed into bromo-peroxy compound 5raʹ and purified by silica gel
column chromatography (4:96 Et2O: Hexanes as eluent) to give the title compound as colorless oil
1
in 64% (0.130 g) yield. Rf 0.4 (2:3 Et2O: Hexanes); H NMR (400 MHz, CDCl3) δ 6.91(d, J = 3.8
Hz, 1H), 6.81 d, J = 4.0 Hz, 1H), 5.37 (dd, J = 8.2, 4.6 Hz, 1H), 3.83 (s, 3H), 3.70 (s, 3H), 3.03 (dd, J
13
= 15.4, 8.2 Hz, 1H), 2.75 (dd, J = 15.4, 4.7 Hz, 1H), 1.14 (s, 9H); C NMR (100 MHz, CDCl3) δ
167.1, 166.5, 144.6, 129.2, 127.0, 112.8, 81.0, 78.0, 60.0, 54.2, 54.0, 42.7, 26.6; HRMS (ESI-TOF)
m/z: [M+Na]+ calculated for C15H20Br2NaO6S 508.9245, Found 508.9245.
Dimethyl-2-(2-(tert-butylperoxy)-2-(5-chlorothiophen-2-yl)ethyl)-2-chloromalonate
(5rbʹ):
o
Following the general procedure (reaction was performed at 0 C), D-A cyclopropane 1r (0.100 g,
0.41 mmol) was transformed into chloro-peroxy compound 5rbʹ and purified by silica gel column
chromatography (4:96 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 66%
(0.110 g) yield. Rf 0.6 (1:4 Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 6.85 (d, J = 3.5 Hz, 1H),
6.76 (d, J = 3.8 Hz, 1H), 5.31 (dd, J = 8.4, 4.5 Hz, 1H), 3.83 (s, 3H), 3.70 (s, 3H), 3.00 (dd, J = 15.2,
13
8.5 Hz, 1H), 2.69 (dd, J = 15.2, 4.6 Hz, 1H), 1.12 (s, 9H); C NMR (100 MHz, CDCl3) δ 166.7,
166.4, 141.6, 130.4, 126.0, 125.4, 81.0, 76.6, 68.0, 54.1, 54.0, 42.0, 26.5; HRMS (ESI-TOF) m/z:
[M+Na]+ calculated for C15H20Cl2NaO6S 421.0255, Found 421.0275.
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-(1,3-dioxoisoindolin-2-yl)ethyl)malonate
(5taʹ):Following the general procedure, D-A cyclopropane 1t (0.100 g, 0.33 mmol) was transformed
into bromo-peroxy compound 5taʹ and purified by silica gel column chromatography (25:75 Et2O:
Hexanes as eluent) to give the title compound as colorless oil in 77% (0.120 g) yield. Rf 0.35 (40:60
1
1
Et2O: Hexanes); H NMR (400 MHz, CDCl3) δ H NMR (400 MHz, CDCl3) δ 7.88-7.87 (m, 2H),
7.76-7.74 (m, 2H), 6.18-6.15 (m, 1H), 3.84 (br s, 3H), 3.73 (br s, 3H), 3.52-3.46 (m, 1H), 3.03-2.98
28
ACS Paragon Plus Environment

Page 29 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
(m, 1H), 1.10 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 167.3, 166.9, 166.2, 134.5, 131.7 123.8, 81.4,
81.2, 59.2, 54.3, 54.2, 38.6, 26.3; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C19H22BrNNaO8
494.0426, Found 494.0396.
Dimethyl
2-(2-(tert-butylperoxy)-2-(1,3-dioxoisoindolin-2-yl)ethyl)-2-iodomalonate
8
9
(5tcʹ):Following the general procedure, D-A cyclopropane 1t (0.100 g, 0.33 mmol) was transformed
into iodo-peroxy compound 5tcʹ and purified by silica gel column chromatography (15:85 Et2O:
Hexanes as eluent) to give the title compound as semi solid in 65% (0.112 g) yield. Rf 0.35 (1:4
Et2O: Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.90-7.87 (m, 2H), 7.77-7.73 (m, 2H), 6.10 (dd, J =
7.7, 4.4 Hz, 1H), 3.82 (s, 3H), 3.72 (s, 3H), 3.36 (dd, J = 15.7, 7.7 Hz, 1H), 2.97 (dd, J = 15.6, 4.4
Hz, 1H), 1.10 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.5, 168.0, 167.5, 134.5, 132.8, 123.8, 83.4,
81.4, 54.4, 54.2, 40.5, 39.3, 26.4; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C19H22INNaO8
542.0288, Found 542.0296.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dimethyl-2-bromo-2-(2-(tert-butylperoxy)-2-(2,5-dioxopyrrolidin-1-yl)ethyl)malonate
(5uaʹ):Following the general procedure, D-A cyclopropane 1u (0.100 g, 0.39 mmol) was
transformed into bromo-peroxy compound 5uaʹ and purified by silica gel column chromatography
(8:92 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 69% (0.115 g) yield. Rf
0.4 (40:60 EtOAc: Hexanes); 1H NMR (400 MHz, CDCl3) δ 5.96 (dd, J = 8.0, 4.1 Hz, 1H), 3.80 (s,
3H), 3.76 (s, 3H), 3.35 (dd, J = 15.7, 8.1 Hz, 1H), 2.80 (dd, J = 15.7, 4.1 Hz, 1H), 2.67 (br s, 4H),
1.12 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.2, 166.9, 166.0, 81.6, 81.4, 59.0, 54.3, 54.2, 37.9,
28.0, 26.3; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C15H22BrNNaO8 446.0426, Found
446.0427.
Dimethyl-2-(2-(tert-butylperoxy)-2-(2,5-dioxopyrrolidin-1-yl)ethyl)-2-chloromalonate
(5ubʹ):Following the general procedure, D-A cyclopropane 1u (0.100 g, 0.39 mmol) was
transformed into bromo-peroxy compound 5ubʹ and purified by silica gel column chromatography
(8:92 Et2O: Hexanes as eluent) to give the title compound as colorless oil in 71% (0.106 g) yield. Rf
0.4 (40:60 EtOAc: Hexanes); 1H NMR (400 MHz, CDCl3) δ 5.96 (dd, J = 8.0, 4.3 Hz, 1H), 3.81 (s,
3H), 3.77 (s, 3H), 3.34 (dd, J = 15.5, 8.0 Hz, 1H), 2.78 (dd, J = 15.5, 4.3 Hz, 1H), 2.68 (br s, 4H),
13
1.13 (s, 9H); C NMR (100 MHz, CDCl3) δ 176.3, 166.6, 166.1, 81.5, 80.4, 67.5, 54.2 (2), 37.2,
28.0, 26.3; HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C15H22ClNNaO8 402.0932, Found
402.0923
Synthesis of Peroxy-Halogenated Compounds 6 and 7:
Dimethyl-2-bromo-2-(2-((1-methylcyclohexyl)peroxy)-2-phenylethyl)malonate (6):Cyclopropane
1g (0.05 g, 0.21 mmol) and 1-hydroperoxy-1-methylcyclohexane (0.054g, 0.42 mmol) were
dissolved in a mixture of dry DCM and cyclohexane (0.8 mL, 1:3, v/v) under argon and to this
solution was added Sc(OTf)3 (0.02g, 0.042 mmol) at room temperature. The reaction mixture was
29
ACS Paragon Plus Environment