Synthesis and structural studies of novel fused seven-membered carbocycles derived from exo-2-oxazolidinone dienes through (4+3) cycloadditions

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Synthesis and structural studies of novel fused

seven-membered carbocycles derived from

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exo-2-oxazolidinone dienes through (4 + 3) cycloadditions

a

b

c

Patricia Alcázar , Indira Cruz , Carlos González-Romero , Erick Cuevas-Yañez , Eduardo Díaz , Joaquín

d

b

c

Tamariz , Hugo A. Jiménez-Vázquez , David Corona-Becerril , Rubén A. Toscano , and Aydeé Fuentes-

a,

Benítes *

a

Facultad de Química, Universidad Autónoma del Estado de México, Paseo Tollocan y Colón, 50000, Toluca, Estado de México,

México.

b

Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM. Carretera Toluca-Atlacomulco, Km. 14.5, Toluca, 50200,

Estado de México, México.

c

Instituto de Química, Universidad Nacional Autónoma de México, Circuito exterior, C.U. Coyoacán, 04510 México, D.F., México.

Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. Carpio y Plan de

d

Ayala S/N, 11340, México, D.F. México.

1

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Tetrahedron

journal homepage: www.elsevier.com

Synthesis and structural studies of novel fused seven-membered carbocycles derived

from exo-2-oxazolidinone dienes through (4 + 3) cycloadditions

a

b

c

Patricia Alcázar , Indira Cruz , Carlos González-Romero , Erick Cuevas-Yañez , Eduardo Díaz ,

d

b

Joaquín Tamariz , Hugo A. Jiménez-Vázquez , David Corona-Becerril ,

c

a,*

Rubén A. Toscano , and Aydeé Fuentes-Benítes

a

b

c

d

Facultad de Química, Universidad Autónoma del Estado de México, Paseo Tollocan y Colón, 50120, Toluca, Estado de México, México.

Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM. Carretera Toluca-Atlacomulco, Km. 14.5, Toluca, 50200, Estado de México, México.

Instituto de Química, Universidad Nacional Autónoma de México, Circuito exterior, C.U. Coyoacán, 04510 México, D.F., México.

Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. Carpio y Plan de Ayala S/N, 11340,

México, D.F. México.

ARTICLE INFO

ABSTRACT

Article history:

Received

Received in revised form

Accepted

A series of novel, fused seven-membered rings was obtained from (4 + 3) cycloadditions of

diverse exo-2-oxazolidinone dienes and an oxyallyl cation. 2D-NMR studies (COSY, NOESY,

HMBC and HSQC) showed that the fused carbocycles were obtained as endo/exo

diastereoisomeric mixtures. The structure of the predominant exo diastereoisomer was

unambiguously established for one of the analogues by X-ray crystallography. It is noteworthy

that for the N-benzyl diene, a highly exo stereoselective cycloaddition took place to afford a

single isomer.

Available online

Keywords:

Exo-2-oxazolidinone dienes

Oxyallyl cation

2

seven-membered carbocycles

1

. Introduction

Seven-membered carbocyclic rings represent an essential

moiety in the structure of many natural products and of several

compounds that display important medical and therapeutic

1-2

3-4

activities (e.g., some anticarcinogenics and antivirals). One

efficient and frequently used synthetic strategy for the formation

of seven-membered rings is the (4 + 3) cycloaddition approach

with a reaction that involves allyl or oxyallyl cations and 1,3-

dienes as starting materials. From the point of view of the

number of electrons involved in this process, a [4 + 2]

cycloaddition (4 electrons from the diene and 2 electrons from

the allyl ion) is electronically homologous to the Diels-Alder

reaction.

Scheme 1. Synthesis of exocyclic dienes of N-aryl-2-oxazolidinones.

exocyclic methylene carbons of the diene system increase the

regioselectivity in thermal and Lewis-acid catalyzed Diels-Alder

5-9

15

cycloadditions, under conditions of normal electron demand.

Despite the versatility of these exocyclic dienes in Diels-Alder

cycloadditions, few reactions have been studied that take

advantage of the reactivity potential of these systems.

1

6

Therefore, we have undertaken the evaluation of these dienes in

(4 + 3) cycloadditions, focusing on the preparation of novel

seven-membered rings fused to 2-oxazolidinones. A summary of

our recent success in this area is described herein.

The synthesis of exocyclic dienes derived from N-substituted

10-11

2

^-^o^x^a^z^o^lⁱ^dⁱⁿ^oⁿ^e^s^h^a^s^b^e^eⁿ^p^r^e^vⁱ^o^u^s^l^y^d^e^s^c^rⁱ^b^e^d^.1

They have

and used as

2-13

been extensively studied in Diels-Alder reactions

starting materials in a novel synthetic approach to the carbazole

core, which has allowed for the total synthesis of naturally

2

. Results and Discussion

14

occurring alkaloids. These exo-heterocyclic dienes have been

prepared through highly convergent and regioselective

a

The synthesis of the exo-2-oxazolidinone dienes 1–5 was

methodology, which involves the use of either symmetrical or

non symmetrical α-diketones and isocyanates to generate the

corresponding dienes linked to the 2-oxazolidinone ring (Scheme

carried out from the corresponding 1,2-diketones and aryl

isocyanates in the presence of triethylamine and lithium

carbonate, in accordance with the previously reported method

11

10-13

1

). It has also been established that alkyl groups attached to the

(Scheme 2).

*

2

Corresponding autor: Tel.: +52 722 2175 109x113; fax: +52 722

173 890. E-mail: mpagfuentesb@uaemex.mx

2

Tetrahedron

ACCEPTED MANUSCRIPT

case of diene 2 in which the exo adduct 8 was obtained as the

single product, these reactions were not stereoselective. This fact

can be tentatively explained by the steric hindrance, which would

be produced by the rotation of the N-benzyl group of the diene,

thus making the endo approach of the oxyallyl cation more

difficult. Table 1 displays the most relevant proton chemical

Scheme 2. Synthesis of exo-2-oxazolidinone dienes 1–5

Scheme 3. Formation of carbocycle

dibromoketone 6.

8 from diene 2 and

Scheme 5. Endo/exo transition states for the cycloaddition of dienes 1-5

and oxyallyl cations 7a-b leading to isomers 8, 9a/9b, 10a/10b, 11a/11b

and 12a/12b

shifts of compounds 8 and 10a.

Scheme 4. Synthesis of the exo/endo diastereoisomeric mixtures of

carbocycles 9a/9b–12a/12b from exo-2-oxazolidinone dienes 1 and 3–

1

We selected the pair of isomers 10a/10b for a detailed H

NMR structural analysis. Since the H spectrum of this mixture in

5

.

1

CDCl turned out to be very complex, with many overlapping

3

In a model reaction, the exo-2-oxazolidinone diene 2 reacted with

the oxyallyl cation 7a, which was generated in situ from 2,4-

dibromopentan-3-one (6), to yield the bicyclic-fused compound 8

as the single product (Scheme 3). The NMR analysis of this

structure revealed the anti relative configuration of the methyl

groups at the C-7 and C-8 centers of the cycloheptanone moiety.

This suggests that the cycloaddition between 2 and 7a essentially

took place through the exo transition state to stereoselectively

attain cycloadduct 8, which implies that the oxyallyl cation 7a

signals, we selected C D as solvent and used homonuclear

6 6

decoupling experiments to overcome the interpretation problems.

Under these conditions we were able to make a suitable

assignment of the signals of compound 10a and to identify it as

1

the major isomer in the 55:45 exo/endo mixture. The H NMR

13

and C NMR chemical shifts for 8, 9a, 9b, 10a, 10b, 11a, 11b,

12a, and 12b are summarized in Tables 2 and 3.

1

The H NMR signals of the 10a/10b mixture displayed

17

overlapping signals for the key protons (H-5, H-7 and H-8) of

both structures (Figure 1, (a)), which led to the collapse of the

multiplets of the AB pattern expected for methines H-7 and H-8

adopted the W conformation along the entire reaction pathway.

Considering this restriction and assuming a concerted process,

the reaction can occur through endo or exo transition states,

leading in each case to a distinct stereochemical relationship

between the methyl groups at the C-5, C-7, and C-8 positions of

the adducts. Accordingly, the endo approach leads to an all syn

configuration of the methyl groups, while the exo geometry

results in the anti configuration of the C-8 methyl group with

respect to the other two.

(δ = 2.55 and 2.51, respectively). However, through selective

irradiations on the Me-10 and Me-11 doublets (δ = 0.92 and 0.91,

respectively), we were able to discern the coupling constant (J =

5

.0 Hz) for methines H-7 and H-8 of 10b (Figure 1, (b)). This

18

simple experiment combined with the Karplus approach

enabled us to estimate a ca. 60° dihedral angle between protons

H-7 and H-8, which is consistent with the syn configuration of

the methyl groups Me-10 and Me-11.

The behavior of this successful diastereoselective reaction

encouraged us to explore the scope of the process. Thus, the exo-

2

-oxazolidinone dienes 1 and 3–5 were treated with dibromo

ketone 6, providing mixtures of the corresponding adducts

a/9b–12a/12b (Scheme 4). After purification of these mixtures

When the selected irradiations on the doublets for the methyl

groups Me-10 and Me-11 (δ = 1.06 and 0.96, respectively) of

isomer 10a were carried out, it was observed that the H-7 and H-

9

by column chromatography, the heterocyclic-fused seven-

membered carbocycles were isolated and identified as

diastereoisomeric pairs, which were characterized through a

detailed analysis of their H NMR spectra. In addition, the

structure of adduct 10a was established by X-ray crystallography

8

methines also displayed an AB pattern with a vicinal coupling

3

constant J = 9.0 Hz (Figure 1, (c) and (d)). This suggests that the

dihedral angle for these protons should be ca. 180°, with the

consequent anti configuration of Me-10 and Me-11.

1

We were able to assign the signals for H-5 in both isomers

through decouplin experiments (Figure 1 (e)). We also carried

out the conformational analysis of 10a and 10b, at the M06-

(vide infra).

These reactions took place with low exo/endo

19

stereoselectivity, giving an almost 1:1 ratio of the seven-

membered carbocyclic mixtures 9a/9b, 10a/10b, 11a/11b and

1

reaction proceeded through a concerted cycloaddition between

the locked s-cis conformation of the diene and the W

conformation of the oxyallyl cation 7a (Scheme 5). Unlike the

2

X/6-31+G(d,p)

level of Density Functional Theory

considering the effect of the dielectric constant of benzene,

20

2a/12b. According to the structure of these products, the

according to the PCM

formalism. The lowest-energy

conformers located for each isomer are shown in Figure 2, along

with the corresponding dihedral angles between H-7 and H-8.

5

3

Note that these angles correspond closely

expected from the NMR spectrum and the Karplus equation.

A

w

C

ithCEthePTva

E

lu

D

es MAth

N

ere

U

is

S

a

C

sy

R

n

I

relationship between protons H-5 and H-7 in both

P

T

isomers 10a and 10b. Moreover, protons H-7 and H-8 have an

anti relationship in 10a and a syn relationship in 10b.

The COSY spectrum of the 10a/10b mixture was interpreted

in order to obtain all proton-proton correlations of the isomeric

mixture. The methines at δ = 2.55 and 2.51 (H-7 and H-8 of 10b)

correlate only with the overlapped doublets for methyls Me-10

Additional information obtained from the NOESY spectrum

established a relationship between the diagonal peaks and cross

peaks for H-7/H-8 (δ = 2.25 and 2.28, respectively) of 10a with

H-7/H-8 (δ = 2.55 and 2.51, respectively) of 10b. On the other

hand, the absence of EXSY cross peaks between both pairs of H-

/H-8 methines of 10b with H-7/H-8 methines of 10a enabled us

to rule out the possibility that 10a and 10b may be conformers.

To further explore this consideration, we recorded H NMR

Table 1. Proposal for the preferential conformations adopted by

1

compounds 8 and 10a, derived from the H NMR chemical shifts

7

3

(

δ) and JH-H coupling constants for 8.

1

spectra for 10a and 10b using perdeutero-acetone as solvent at

different temperatures (from 25° to -80°C). None of the

compounds displayed relevant changes in the chemical shift of

the proton signals of both molecules within this temperature

range.

8

10a

Having unambiguously assigned the Me-9, Me-10, and Me-11

protons, as well as the remaining H-5, H-7 and H-8 methine

protons, and the H-4 methylene protons of the seven-membered

Protons

∆δ ppm

δ ppm (CDCl

3

)

3

δ ppm (CDCl )

H

4b

2.84

2.14

2.77

2.79

2.46

2.80

2.12

2.85

2.88

2.54

- 0.04

- 0.02

+ 0.08

+ 0.09

H

4a

13

ring moiety of 10a and 10b, we aimed to assign the C NMR

H

5

H

7

H

8

signals using HSQC and HMBC spectra. For example, C-6

3

correlated ( J ) with the Me-9 and Me-10 methyl protons, as

C-H

3

well as with the H-4 methylene and the H-8 methine. The J

Coupling constants for 8 (in Hertz)

C-H

also showed that the quaternary C-8a carbon correlated with the

H-4 methylene as well as with the Me-11 and H-7 protons, while

Coupled protons

Coupling constants (Hz)

2

H4a - H4b

J = -16.0

2

3

H4a - H

H4b - H

5

8

5

8

J = 6.5

J = 1.0

J = 5.5

J = 2.0

the J demonstrated that this carbon correlated with H-8. The

C-H

5

J_C_-_Hshowed that the C-3a carbon correlated with the H-5 and H-8

3

2

methine protons, while the J demonstrated that this carbon

5

C-H

3

correlated with H-4. The remaining carbons of the phenyl ring,

attached to the nitrogen atom in the five-membered ring, were

assigned in a similar way for each compound (Table 4).

H

5

- H

9

J = 7.0

3

7

8

J = 10.0

3

H

10 - H

- H11

7

J = 7.0

3

H

8

After obtaining suitable crystals for 10a from the mixture of

1

0a/10b, the corresponding X-ray crystallographic analysis

and Me-11 at δ = 0.92 and 0.91, respectively (Figure 3).

Likewise, the overlapped signals (at δ = 2.25 and 2.28) for

methines H-7 and H-8, respectively, of derivative 10a correlate

with the cross peaks for methyls Me-10 (0.96 ppm) and Me-11

confirmed the proposed exo configuration of this isomer (Figures

5 and 6, Tables 5 and 6). Figure 5 shows the asymmetric unit

within the P−1 triclinic unit cell, which contains a pair of

enantiomeric structures (Z = 4) of 10a (5S, 7R, 8R and 25R, 27S,

28S), half a molecule of benzene (solvent), and one disordered

molecule of dichloromethane.

(1.06 ppm). The H-5 methine at δ = 2.15 ppm correlates with the

cross peaks for the Me-9 methyl of 10b at δ = 0.80 and the Me-9

methyl of 10a (δ = 0.80), and with the cross peaks of the H-4

methylene protons at δ = 2.09, 1.93 and 1.58 for both

compounds.

The enantiomeric structures correspond to slightly different

variations of the same seven-membered ring conformation,

particularly with respect to the orientation of the phenyl ring.

This was confirmed by the overlapping of both geometries.

Moreover, the solid state conformation is essentially the same as

that found in the theoretical conformational analysis mentioned

previously (see Figure 2). The heterocyclic five-membered ring

and the phenyl ring are essentially planar. The angle between

their normals is 66.15(5)° and 67.1(5)° for the molecules with the

Furthermore, the NOESY spectrum of the mixture of

molecules 10a and 10b (Figure 4) showed the vicinal correlation

of the H-7 and H-8 methines (at δ = 2.55 and 2.51, respectively)

with the Me-10 and Me-11 methyl groups (at δ = 0.92 and 0.91,

respectively). These signals correspond to isomer 10b.

The most important dipolar correlation was observed between

the diagonal peaks for methine H-7 (δ = 2.55) and two cross

peaks, those for the H-5 methine (δ = 2.15) and one of the

protons of the H-4 methylene. This suggests a long range spatial

correlation (NOE) between the H-7 and H-5 methines of 10b. A

dipolar correlation was also shown between H-7 (δ = 2.25) and

H-5 (δ = 2.11) of isomer 10a, detected from the cross peaks.

Regarding the H-7 methine of 10a, the expected vicinal

correlation with the Me-10 methyl protons (δ = 0.96) was also

observed, as was the dipolar correlation with the Me-11 methyl

group (δ = 1.06). The latter suggests the spatial proximity (syn

relationship) between the H-7 methine and Me-11, which was not

observed for isomer 10b. The H-8 methine (δ = 2.28) for isomer

5

S and 25R configuration, respectively. The Cremer & Pople

21

puckering parameters [Molecule 5S: q₂= 0.897(10), q =

0

Molecule 25R: q = 0.873(11), q = 0.333 (11), Q = 0.934(11) Å,

Φ = 197.5(7)°, Φ = 109.9(18)°] suggest a boat conformation

3

.349(10), Q = 0.963(10) Å, Φ = 18.8 (6)°, Φ = 287.5 (16)°.

2

3

2

3

22-24

2

3

(

Figure 5) for the seven-membered ring with a synclinal

relationship [Torsion angles: molecule 5S, 59.7° and 85.1°;

molecule 25R: -58.9° and -87.2°] between the methyl substituents

at C-5, C-7 and C-8 (C-25, C-27 and C-28 for the second

molecule). Relevant dihedral angles for structure 5S are: H(7)-

C(7)-C(8)-H(8), -180°; H(4B)-C(4)-C(5)-H(5), 74°; H(4A)-C(4)-

C(5)-H(5), -44°; H(5)-C(5)-C(7)-H(7), 57.6°. For molecule 25R:

H(27)-C(27)-C(28)-H(28), 179.0°; H(24A)-C(24)-C(25)-H(25), -

1

0

0a displayed a dipolar correlation with the Me-10 methyl (δ =

.96) and a vicinal correlation with the Me-11 methyl (δ = 1.06).

7

5

4°; H(24B)-C(24)-C(25)-H(25), 45°; H(25)-C(25)-C(27)-H(27),

7.6°.

The aforementioned observations allowed us to establish that

4

Tetrahedron

ACCEPTED MANUSCRIPT

Because an NMR pattern similar to that already described was

that acetonitrile has a dielectric constant high enough to allow for

+

observed for diastereoisomers 9a/9b, 11a/11b and 12a/12b, we

assume that the structural features of these epimeric pairs are

analogous to those determined for 10a/10b.

the dissociation of the Na ion and the oxyallyl zwitterion. Thus

we located the endo and exo transition states (TS) for the

cycloaddition of zwitterion 7b to diene 1, which led to the

formation of 9a and 9b at the M06-2X/6-31+G(d,p)/PCM level

of DFT theory in acetonitrile (stationary points are shown in

Figure 7).

Finally, we theoretically addressed the issue of the lack of

stereoselectivity in the cycloaddition of the oxyallyl species 7a-b

with the exocyclic diene. In a first approximation we assumed

1

Table 2. H NMR chemical shifts of compounds 8, 9a, 9b, 10a, 10b, 11a, 11b, 12a, and 12b.

8

9a

(ppm)

9b

(ppm)

10a

(ppm)

10b

(ppm)

11a

(ppm)

11b

(ppm)

12a

(ppm)

12b

(ppm)

Proton

H-4a

(

ppm)

2.84

2.25

2.95

2.09

1.93

2.82

2.62

2.75

2.44

H-4b

H-5

H-7

H-8

2.14

2.77

2.79

2.45

1.70

2.16

2.32

0.81

1.70

2.19

2.63

2.56

0.79

1.58

2.11

2.25

2.28

0.80

1.58

2.15

2.55

2.51

2.07

2.89

2.52

1.09

2.07

2.84

3.26

3.03

1.08

2.10

2.87

3.01

2.56

1.08

2.10

2.94

3.08

2.90

1.09

0

.92

H-9

0.80

0.92

H-10

1.14

1.34

0.97

1.08

0.93

0.96

1.06

1.12

1.38

1.15

1.10

1.18

1.17

1

.33,

.71

H-11

0.93

--

1.79, 1.97

CH

3

--

0.96

--

0.99

CH

2

4

.71(Ha); 4.76 (Hb)

--

(Bn)

CH

3

O

--

3.83

7.18

6.99

---

3.83

7.18

6.99

---

3.84

7.18

6.98

---

3.84

7.18

6.99

---

ortho

meta

para

C

1

Figure 1. H NMR (500 MHz, C

6 6

D ) of the 10a/10b mixture. (a) Normal spectrum of 10a and 10b. Expansion ranges δ 2.60–2.10 and δ 2.18–1.88. (b)

Irradiation at 0.92 ppm. (c) Irradiation at 1.06 ppm. (d) Irradiation at 0.96 ppm. (e) Irradiation at 0.80 ppm.

6

Tetrahedron

ACCEPTED MANUSCRIPT

Figure 2. H-7/H-8 dihedral angles for the M06-2X/6-31+G(d,p) lowest-energy conformers of 10a (179.7°) and 10b (−55.2°).

6 6

Figure 3. COSY (500 MHz, C D ) of the 10a/10b mixture.

7

ACCEPTED MANUSCRIPT

6 6

Figure 4. NOESY (500 MHz, C D ) of the 10a/10b mixture.

2

3

Table 4. JC-H and JC-H relationships derived from HMBC for compounds 10a and 10b

1

0a

10b

Carbon

0a

Carbon

10b

δC

Interaction with proton

δC

Interaction with proton

1

C-2

C-4

153.2

26.8

C-2

C-4

153.3

27.2

0.82 (Me-9), 2.11 (H-5)

0.82 (Me-9), 2.08 (H-4a)

0.81 (Me-9), 2.15 (H-5)

1.92 (H-4a)

C-5

45.4

C-5

C-6

44.8

0

(

.82 (Me-9), 0.96 (Me-10), 1.56

H-4b), 2.08 (H-4a), 2.11 (H-5),

0

.81 (Me-9), 0.91 (Me-10), 1.56

C-6

211.8

211.4

(H-4B), 1.92 (H-4a), 2.15 (H-5),

.51 (H-8), 2.55 (H-7)

2

.25 (H-7), 2.28 (H-8)

2

0

.96 (Me-10), 1.06, (Me-11),

.28 (H-8)

C-7

C-8

48.3

36.5

C-7

C-8

46.7

33.9

0.92 (Me-11), 2.51 (H-8)

0.92 (Me-11), 2.55 (H-7)

2

0.96 (Me-10), 1.06, (Me-11),

.25 (H-7)

2

0

(

.92 (Me-11), 1.56 (H-4b), 1.92

H-4a), 2.51 (H-8), 2.55 (H-7)

C-8a

C-3a

137.9

120.4

1.06, (Me-11), 1.56 (H-4b), 2.08

H-4a), 2.25 (H-7), 2.28 (H-8)

C-8a

C-3a

139.3

119.2

(

1

.56 (H-4b), 1.92 (H-4a), 2.51

H-8)

1.56 (H-4b), 2.08 (H-4a), 2.28

H-8)

(

C-9

16.08

13.3

1.56 (H-4b), 1.92 (H-4a)

2.51 (H-8), 2.55 (H-7)

C-9

C-10

15.8

14.7

1.56 (H-4b), 2.11 (H-5)

2.25 (H-7)

C-10

8

Tetrahedron

ACCEPTED MANUSCRIPT

C-11

C-12

C-13,17

C-14,16

C-15

10.6

134.2

128.9

129.6

132.5

2.28 (H-8)

6.59 (H-16), 6.94 (H-17)

6.59 (H-16)

C-11

C-12

C-13,17

C-14,16

C-15

13.3

134.0

128.6

129.6

132.7

2.51 (H-8), 2.55 (H-7)

6.68 (H-16), 6.98 (H-17)

6.98 (H-16)

6.94 (H-17)

6.59 (H-16)

6.68 (H-17)

6.98 (H-16)

a

Table 5. Crystal data for compound 10a

Crystal data

Empirical Formula

Formula Weight

Crystal color

Crystal system

Space group

a, Å

C

18.75 20 3

H C1.25NO

351.67

Colorless needle

Triclinic

P -1

7.822(2) α = 100.384(4)°

b, Å

13.453(3) β = 90.104(4)°

c, Å

Volume, Å

Z

Density (calcd.),g/cm

Absorption coefficient, (mm )

19.602(5) γ = 101.064(4)°

1989.9(8)

4

1.174

0.240

3

-

1

F(000)

739

Crystal Size (mm)

0.356 x 0.302 x 0.072

Data collection

Temperature, K

298(2)

Radiation, λ (Å)

0.71073

θ

min, max,°

1.72, 25.42

Index ranges

-9 ≤ h ≤ 9, -16 ≤ k ≤ 15, 0 ≤ l ≤ 23

7288

7293 (Rint = 0.1189)

R1 = 0.1609, wR2 = 0.2948

Reflections Collected

Independent reflections

Observed reflects

[

I>2.0σ(1)]

Refinement

Data-to-parameter ratio

R, wR2

G.O.F.

7293 / 407 / 449

R1 = 0.2323, wR2 = 0.3282

1.230

-

3

Largest diff. peak,hole ,e Å

0.370, -0.253

a

Deposition number of Cambridge Crystallographic Data Centre: CCDC 984027

9

ACCEPTED MANUSCRIPT

Table 6. Selected bond distances (Å) and angles (°) for 10a.

Bond

Distance (Å)

Cl(1)-C(14)

O(2)-C(2)

O(3)-C(6)

O(1)-C(2)

O(1)-C(9)

1.744(10)

1.202(10)

1.198(11)

1.375(11)

1.401(10)

1.357(11)

1.401(10)

1.437(11)

1.509(11)

1.539(12)

1.517(13)

1.519(14)

1.558(14)

1.510(13)

1.571(13)

1.494(12)

1.514(14)

1.312(11)

1.375(12)

1.388(12)

1.385(13)

1.361(14)

1.384(13)

1.370(12)

1.760(10)

1.207(10)

1.203(13)

1.339(10)

C(2)-N(3)

N(3)-C(10)

N(3)-C(11)

C(4)-C(10)

C(4)-C(5)

C(5)-C(17)

C(5)-C(6)

C(6)-C(7)

C(7)-C(18)

C(7)-C(8)

C(8)-C(9)

C(8)-C(19)

C(9)-C(10)

C(11)-C(16)

C(11)-C(12)

C(12)-C(13)

C(13)-C(14)

C(14)-C(15)

C(15)-C(16)

Cl(2)-C(34)

O(22)-C(22)

O(23)-C(26)

O(21)-C(22)

Bond

Angle (°)

C(2)-O(1)-C(9)

O(2)-C(2)-N(3)

O(2)-C(2)-O(1)

N(3)-C(2)-O(1)

C(2)-N(3)-C(10)

C(2)-N(3)-C(11)

C(10)-N(3)-C(11)

C(10)-C(4)-C(5)

C(17)-C(5)-C(6)

C(17)-C(5)-C(4)

107.7(7)

130.3(10)

123.5(9)

106.3(7)

109.7(7)

122.5(7)

127.8(7)

111.5(7)

109.8(8)

111.3(8)

Figure 5. ORTEP representation of the structure of compound 10a.

Figure 6. Crystal-lattice of the X-ray structure of compound 10a

10

Tetrahedron

ACCEPTED MANUSCRIPT

Figure 7. Transition states for the cycloadditions of oxyallyl zwitterion 7a

and cation 7b to 1, obtained at the M06-2X/6-31+G(d,p)/PCM (acetonitrile)

level of theory. The smaller bold numbers correspond to internuclear distances

(

ꢀ

Å). The first set of numbers in the lower section of the figures correspond to

ꢀH in kcal/mol and the numbers in parentheses to ꢀꢀG (25 °C, 1 atm). See

‡

text.

We also located the TS for the cycloaddition between the

oxyallyl cation 7b and (Figure 7), considering that

1

The most interesting feature of these TS is the fact that they

+

complexation with an ion such as Na stabilizes the open oxyallyl

occur rather early in the reaction coordinate. Whereas the shortest

internuclear distances for the interacting atoms are found for the

endo TS, for the exo TS both distances are slightly longer than

25,26

species with respect to the corresponding cyclopropanone.

Furthermore, complexation is expected to yield

a

more

26,27

electrophilic cationic species,

favoring the cycloaddition to an

3

.0 Å. In both cases the shortest C–C distance is found for the

electron-rich diene such as 1. The corresponding transition states

located under the same conditions as before are also shown in

Figure 7.

interaction of the exocyclic methylene with the zwitterion, as

expected from the combined polarization effects of the nitrogen

atom and methyl group in the diene. It is also of interest to note

that the endo TS seems to have an additional C-H⋅⋅⋅O interaction

It can be seen that the complexed TS are very similar to those

+

(

2.650 Å) between the oxygen of the zwitterion and one of the

obtained for the neutral system. In the endo TS the Na ion is

ortho hydrogen atoms of the phenyl ring. This interaction should

contribute to the stability of the structure by making it tighter.

The analysis of the energetics of the process reveals that in terms

of energy contents (electronic energies, ZPE-corrected energies,

or enthalpy-corrected energies) the endo TS is indeed more stable

than the exo by ~2 kcal/mol (Figure 7). We would have expected

a relatively high endo stereoselectivity, something that was not

observed experimentally.

interacting with all three oxygen atoms of the complex, giving a

more compact TS. In this case the ortho hydrogen is farther away

from the oxyallyl oxygen (2.892 Å), as expected when

considering that the interaction with the sodium cation was

stronger. The complexed exo TS is slightly more compact than in

the neutral reaction but it is less stable relative to the endo

geometry by some 3.5 kcal/mol, when taking only enthalpy-

corrected energies are taken into account. As aforementioned, the

higher entropy of the exo TS decreases the energy difference as

temperature rises. At 328 K the free energy-corrected difference

amounts to 0.79 kcal/mol, still favoring the endo approach. Our

theoretical results agree quite well with the experimental

observations.

However, from the consideration of entropy effects, which can

be calculated from the difference in free energies between both

‡

TS (ꢀꢀG ), a very slight predominance of the exo TS can be

appreciated. This becomes more important as the temperature

‡

raises (ꢀꢀG = 0.1 kcal/mol at 298 K, with a 53:47 exo/endo

‡

ratio; ꢀꢀG = 0.33 kcal/mol at 328 K, the temperature at which

3

. Conclusions

the experimental reaction was carried out, with a 63:37 exo/endo

ratio). The effect of the solvent polarity is not really important in

terms of the energetics of the reaction, evidenced by the fact that

the results obtained in the gas phase were rather similar to those

already described. So, it is the higher entropy of the exo TS (a

looser interaction) that leads to the loss of stereoselectivity.

According to our calculations, at r.t. the exo TS is 8.1 e.u. higher

in entropy than the tighter endo stationary point at the level of

theory employed.

In conclusion, the heterocyclic-fused seven-membered rings

9–12 were obtained when exo-2-oxazolidinone dienes 1 and 3–5

reacted with the oxyallyl species 7, to afford diastereoisomeric

mixtures whose structures were established by NMR and X-ray

techniques. This work indicates that either the oxyallyl ion 7a or

the sodium complex 7b was added to the dienes in a W

conformation through concerted endo/exo transition states.

Despite the fact that the endo TS has more stabilizing interactions

‡

and is more stable when only ꢀH is considered, the higher

1

entropy of the exo geometry leads to a greater c

A

on

C

tr

C

ibu

E

ti

P

on

T

o

E

f t

D

he MA(2

N

.02

U

g

S

,

C

20

R

mmol) were added. The mixture was protected

IP

T

‡

latter TS (in terms of ꢀG ) and to a 1:1 stereoisomeric kinetic

mixture of adducts. In this mixture, the endo product is only

slightly predominant and this predominance is expected to

decrease as the temperature rises. In contrast to the behavior of

dienes 1 and 3–5, diene 2 reacted with 7 through a highly

stereoselective (4 + 3) cycloaddition to provide the exo isomer 8

from light and stirred for 30 min. The appropriate aryl isocyanate

(30 mmol) dissolved in anhydrous toluene (5 mL) was added

drop by drop (for 20 min) into the reaction mixture and stirred at

room temperature for 18 h. The mixture was filtered through

Celite and extracted with CH Cl (3 × 15 mL). The organic

2

extracts were combined, dried over Na SO , and the solvent was

2

4

-

as the single product. It is likely that in this case the C-H⋅⋅⋅O or

removed under vacuum. The final product was purified by

column chromatography (SiO₂with 10% triethylamine,

hexane/AcOEt, 95:5) to afford the corresponding exo-2-

oxazolidinone diene.

+

O⋅⋅⋅Na interactions mentioned previously are nonexistent and

that the steric interactions of the rotating benzyl group make the

endo approach more energetic, leading to the selective formation

of the exo adduct.

5

-Ethylidene-4-methylene-3-phenyloxazolidin-2-one

(1).

11a,11b

1

The synthetic versatility of the oxazolin-2-one moiety, which

Yellow solid, 1.2 g (30%), m.p. 82-84 °C (lit.

83-84 °C). H

28

can be readily functionalized or broken to be transformed to

NMR (300 MHz, CDCl ) δ: 1.86 (d, J = 7.3 Hz, 3H, H-8), 4.18

(d, J = 2.9 Hz, 1H, H-6a), 4.58 (d, J = 2.9 Hz, 1H, H-6b), 5.42 (q,

J = 7.3 Hz, 1H, H-7), 7.31-7.52 (m, 5H, PhH). C NMR (75

MHz, CDCl ) δ: 10.4 (C-8), 81.6 (C-6), 99.0 (C-7), 127.1 (C-10),

128.5 (C-12), 129.5 (C-11), 133.0 (C-9), 139.0 (C-4), 143.0 (C-

5), 152.6 (C-2).

3

14

natural alkaloids,

grants carbocyclic seven-membered

13

compounds 8–12 structural characteristics that make them useful

6,29

intermediates for the synthesis of natural products

and

3

30

pharmacologically active agents. We are currently exploring

methods for the synthesis of the five-membered heterocyclic

framework in analogues of naturally occurring sesquiterpenes

31

3-Benzyl-5-ethylidene-4-methyleneoxazolidin-2-one

(2).

1

80 °C). H

that possess the bicyclo[5.3.0]decane system.

In such

11b,11c

Yellow solid, 1.3 g (40%), m.p. 78-80 °C (lit.

analogues, the seven-membered ring would be maintained and

endowed with similar substituents (Figure 8). Among these

NMR (300 MHz, CDCl ) δ: 1.79 (d, J = 7.2 Hz, 3H, H-8), 4.08

(d, J = 2.7 Hz, 1H, H-6a), 4.48 (d, J = 2.7 Hz, 1H, H-6b), 4.70 (s,

H, H-9), 5.31 (q, J = 7.2 Hz, 1H, H-7), 7.12-7.47 (m, 5H, Ar).

C NMR (75 MHz, CDCl ) δ: 10.4 (C-8), 45.1 (C-9), 81.2 (C-6),

3

32

33

sesquiterpenes, the skeletons of guaiane, nor-guaiane, daucane

2

and lactarane may serve as carbocyclic targets in the reference

parent compounds used to prepare or synthetically approach their

^fⁱ^v^e^-^m^e^m^b^e^r^e^d3 heterocyclic ring analogues through (4+3)

13

3

9

9.3 (C-7), 128.0 (C-11), 128.7 (C-13), 129.6 (C-12), 134.9 (C-

1

10), 137.8 (C-4), 143.2 (C-5), 154.0 (C-2).

cycloadditions.

3

-(4-Chlorophenyl)-5-ethylidene-4-methyleneoxazolidin-2-

11a,11b

one (3). White solid, 1.8 g (40%), m.p. 79-80 °C (lit.

C). H NMR (300 MHz, CDCl ) δ: 1.86 (d, J = 7.5 Hz, 3H, H-

78-79

1

°

3

8

5

), 4.18 (d, J = 3.0 Hz, 1H, H-6a), 4.60 (d, J = 3.0 Hz, 1H, H-6b),

.43 (q, J = 7.5 Hz, 1H, H-7), 7.27-7.34 (m, 2H, H-10), 7.44-7.50

13

(

m, 2H, H-11). C NMR (75 MHz, CDCl ) δ: 10.4 (C-8), 81.7

C-6), 99.5 (C-7), 128.3 (C-10), 129.9 (C-11), 131.6 (C-9), 134.4

C-12), 138.7 (C-4), 142.9 (C-5), 152.4 (C-2).

3

5

-Ethylidene-3-(4-methoxyphenyl)-4-methyleneoxazolidin-

11b,11c

2

7

3

4

7

-one (4). Yellow solid, 2.06 g (64%), m.p. 76-78 °C (lit.

8-79 °C). H NMR (300 MHz, CDCl ) δ: 1.86 (d, J = 7.5 Hz,

1

3

H, H-8), 3.83 (s, 3H, CH O), 4.11 (d, J = 3.0 Hz, 1H, H-6a),

3

.54 (d, J = 3.0 Hz, 1H, H-6b), 5.40 (q, J = 7.5 Hz, 1H, H-7), 6.9-

Figure 8. Natural skeletons of sesquiterpene to be used as the reference

compounds for the preparation of their five-membered heterocyclic ring

analogues such as adducts 8-12, through (4+3) cycloadditions.

13

.0 (m, 2H, H-10), 7.23-7.25 (m, 2H, H-11). C NMR (75 MHz,

CDCl ) δ: 10.5 (C-8), 55.7 (C-13), 81.6 (C-6), 99.2 (C-7), 115.1

3

(C-11), 125.8 (C-10), 128.6 (C-9), 139.8 (C-4), 143.4 (C-5),

4

. Experimental Section

153.2 (C-2), 159.8 (C-12).

3

-(4-Methoxyphenyl)-4-methylene-5-propylideneoxazo-

35

Melting points were determined with an Electrothermal capillary

1

13

melting point apparatus and they are uncorrected. H and

C

lidin-2-one (5). Use of the general procedure with 2.0 g of 2,3-

hexanedione and 3.9 g of p-methoxyphenyl isocyanate gave 1.67

g (39%) of 5 as a white solid. M.p. 76-78 ºC (lit. 76-78 °C). H

NMR (300 MHz, CDCl ) δ: 1.09 (t, J = 7.5 Hz, 3H, H-9), 2.32

(q, J = 7.5 Hz, 2H, H-8), 3.84 (s, 3H, OCH ), 4.12 (d, J = 2.7 Hz,

H, H-6a), 4.56 (d, J = 2.7 Hz, 1H, H-6b), 5.37 (t, J = 7.5 Hz,

1H, H-7), 6.96-7.04 (m, 2H, H-12), 7.21-7.29 (m, 2H, H-11).

NMR (75 MHz, CDCl ) δ: 13.7 (C-9), 18.5 (C-8), 55.9 (OCH

1.6 (C-6), 106.0 (C-7), 114.9 (C-12), 125.6 (C-10), 128.4 (C-

11), 139.7 (C-4), 142.1 (C-5), 153.0 (C-2), 159.5 (C-13).

NMR spectra were recorded using a Varian 500 and Bruker

Advance Ultrashield 300, and the chemical shifts (δ) are given in

ppm relative to TMS as internal standard (0.00). The mass

spectra were recorded on a JEOL JMS-SX102A spectrometer in

the EI mode, at 70 eV and 200 ºC via direct inlet probe. Only the

molecular and parent ions (m/z) are reported. IR spectra were

recorded on a Nicolet Avatar 360 FT-IR-ESP instrument. For the

X-ray diffraction studies, crystals of compound 10a were

obtained by slow evaporation of a diluted CH Cl /benzene

11c

1

3

1

3

C

),

3

8

2

solution, and the reflections were acquired with a Bruker

Synthesis of 3-Benzyl- and 3-Aryl-5,7,8-trimethyl-4,5,7,8-

tetrahydro-3H-cyclohepta[d]oxazole-2,6-diones 8-12. General

Procedure. The corresponding exo-2-oxazolidinone diene (2.12

diffractometer. 2,4-Dibromopentan-3-one (6) was prepared

34

according to the procedure described by Hoffmann.

3

6

Synthesis of exo-2-oxazolidinone dienes. General

Procedure. Lithium carbonate (9.00 g, 176.5 mmol) was placed

in a flask and dried at 300 °C for 24 h. Toluene (10 mL), 2,3-

pentanedione (2.00 g, 20 mmol), and anhydrous triethylamine

mmol) was added to a suspension of freshly activated copper

0.872 g, 13.72 mmol) and dry NaI (3.74 g, 24.9 mmol) in dry

(

acetonitrile (8.7 mL, 6.86 g, 167.07 mmol). The resulting mixture

was stirred under a nitrogen atmosphere and 2,4-dibromopentan-

3

-one 6 (0.58 mL, 4.2 mmol) was added. The reaction mixture

1

2

Tetrahedron

ACCEPTED MANUSCRIPT

was stirred at 55 °C under a nitrogen atmosphere for 20 h. The

solvent was removed under vacuum and the solid was poured

into cold water (10 mL) and cold CH Cl (10 mL). The insoluble

of acetonitrile and 1.0 g of 6, gave 0.648 g (76%) of 10a/10b as a

white powder. R 0.38 (hexane/EtOAc, 7:3); m.p. 76-78 °C

f

2

(CH Cl -hexane); IR (KBr) 2981 (CH ), 2869 (-CH -), 1739 (-

2

3

2

-

1

copper salts were filtered and the organic phase was separated at

°C. The aqueous phase was extracted with cold CH Cl (6 × 5

NCO -), 1702 (C=O) cm . Signals assigned to adduct 10a: H

2

0

NMR (500 MHz, C D ) δ: 0.80 (d, J = 7.0 Hz, 3H, H-9), 0.96 (d,

2

6

mL). The organic extracts were combined, washed with a 25%

J = 6.0 Hz, 3H, H-10), 1.06 (d, J = 6.5 Hz, 3H, H-11), 1.58 (m,

1H, H-4b), 2.09 (ddd, J = -16.0, 5.0, 1.5 Hz, 1H, H-4a), 2.11 (m,

1H, H-5), 2.25 (m, 1H, H-7), 2.28 (m, 1H, H-8), 6.59 (dd, J =

aqueous solution of NH Cl (10 mL), then with cold distilled

4

water (3 x 10 mL), and dried over Na SO . The solvent was

2

4

1

3

removed under vacuum. The final product was purified by

9.0, 1.0 Hz, 2H, H_o_r_t_h_o), 6.95 (dd, J = 9.0, 1.0 Hz, 2H, H_m_e_t_a).

C

column chromatography (SiO , hexane/AcOEt, 8:2) to afford the

corresponding cycloheptaoxazole-2,6-dione.

NMR (125 MHz, C D ) δ: 14.8 (C-10), 15.8 (C-9), 18.2 (C-11),

26.8 (C-4), 36.5 (C-8), 45.4 (C-5), 48.3 (C-7), 120.4 (C-3a),

2

6

1

8

28.9 (C_o_r_t_h_o), 129.7 (C_m_e_t_a), 132.6 (C_p_a_r_a), 134.2 (C_i_p_s_o), 137.9 (C-

a), 153.2 (C-2), 211.9 (C-6). Signals assigned to adduct 10b: H

(

3

7R*,8R*,5S*)-3-Benzyl-5,7,8-trimethyl-4,5,7,8-tetrahydro-

H-cyclohepta[d]oxazole-2,6-dione (8). Use of the general

1

NMR (500 MHz, C D ) δ: 0.80 (d, J = 7.0 Hz, 3H, H-9), 0.92 (d,

6

procedure, with 0.50 g of 2, 0.88 g of copper, 3.8 g of sodium

iodide and 1.12 g of 6 in 10.2 mL of acetonitrile, gave 0.505 g

J = 6.0 Hz, 3H, H-10), 0.93 (d, J = 6.5 Hz, 3H, H-11), 1.58 (m,

H, H-4b), 1.93 (ddd, J = -16.0, 5.0, 1.5 Hz, 1H, H-4a), 2.15 (m,

1H, H-5), 2.51 (m, 1H, H-8), 2.55 (m, 1H, H-7), 6.68 (dd, J =

1

(73%) of 8 as a reddish oil. R 0.45 (hexane/EtOAc, 7:3). IR

f

1

(

KBr) 2979 (-CH ), 2860 (-CH -), 1750 (C=O). H NMR (500

3

2

13

9

.0, 1.0 Hz, 2H, H_o_r_t_h_o), 6.98 (dd, J = 9.0, 1.0 Hz, 2H, H_m_e_t_a).

C

MHz, CDCl ) δ: 0.92 (d, J = 7.0 Hz, 3H, H-9), 1.14 (d, J = 7.0

Hz, 3H, H-10), 1.34 (d, J = 7.0 Hz, 3H, H-11), 2.14 (ddd, J = -

3

NMR (125 MHz, C D ) δ: 13.3 (C-11), 13.3 (C-10), 16.0 (C-9),

6

2

(

1

7.2 (C-4), 33.9 (C-8), 44.8 (C-5), 46.7(C-7), 119.2 (C-3a), 128.3

C_o_r_t_h_o), 128.6 (C_m_e_t_a), 132.7 (C_p_a_r_a), 134.0 (C_i_p_s_o)₊, 139.3 (C-8a),

53.3 (C-2), 211.4 (C-6). MS C H ClNO [EI ] m/z (%): 319

1

5

4

1

5.5, 6.5, 1.0 Hz , 1H, H-4b), 2.45 (m, 1H, H-8), 2.77 (m, 1H, H-

), 2.79 (m, 1H, H-7), 2.84 (ddd, J = -15.5, 5.5, 2.0 Hz, 1H, H-

17

18

3

a), 4.71 (d, J = -16.0 Hz, 1H, Ar-CH ), 4.76 (d, J = -16.0 Hz,

a

+

(M ), 304 (12), 286 (17), 260 (15), 204 (12), 168 (100), 167 (85),

H, Ar-CH ), 7.22 (d, J = 8.0 Hz, 2H, H ), 7.30 (t, J = 1Hz,

b

ortho

+

1

3

151 (22), 137 (20). HRMS (EI) m/z [M ] calcd for C H ClNO :

3

17 18 3

H, H_p_a_r_a), 7.35 (t, J = 8.0, 1.0, 2H, H_m_e_t_a). C NMR (125 MHz,

19.0975. Found: 319.0972.

CDCl ) δ: 14.6 (C-10), 15.6 (C-9), 19.7 (C-11), 26.7 (C-4), 36.3

3

(

1

C-8), 45.4 (C-5), 45.8 (C-ArCH ), 50.0 (C-7), 120.1 (C-3a),

27.4 (C_o_r_t_h_o), 129.3 (C_m_e_t_a), 129.4 (C_p_a_r_a), 136.0 (C-8a), 136.3

+

2

Mixture of adducts 11a/11b. Use of the general procedure, with

0.50 g of 4, 0.825 g of copper, 3.6 g of sodium iodide in 8.5 mL

of acetonitrile and 1.05 g of 6, gave 0.513 g (75%) of 11a/11b as

(C_i_p_s_o), 155.7 (C-2), 213.6 (C-6). MS C H NO [EI ] m/z (%):

18

21

3

+

2

4

99 (M ), 284 (7), 266 (9), 208 (11), 125 (22), 65 (59), 43 (58),

1 (76). HRMS (EI) m/z [M ] calcd for C H NO : 299.1521.

+

a yellow oil. R

0.42 (hexane-EtOAc, 6:4). IR (KBr) 2950 (-CH ),

f 3

18

21

3

2

890 (-CH -), 1780 (-NCO -), 1710 (C=O), 1399 (C=C), 1280

2

Found: 299.1524.

-

1

(Ar-O), 2296 (CH O) cm . Signals assigned to adduct 11a: H

3

NMR (500 MHz, CDCl ) δ: 1.09 (d, J = 6.5 Hz, 3H, H-9), 1.12

3

Mixture of adducts 9a/9b. Use of the general procedure, with

.50 g of 1, 1.02 g of copper, 4.3 g of sodium iodide in 10.2 mL

of acetonitrile and 1.21 g of 6, gave 0.498 g (72%) of 9a/9b as a

(d, J = 6.5 Hz, 3H, H-10), 1.38 (d, J = 6.5 Hz, 3H, H-11), 2.07

(ddd, J = -16.0, 5.0, 1.5 Hz, 1H, H-4b), 2.52 (m, 1H, H-8), 2.82

(m, 1H, H-4a), 2.89 (m, 1H, H-5), 2.89 (m, 1H, H-7), 3.83 (s, 3H,

0

reddish solid. R 0.43 (hexane/EtOAc, 6:4); m.p. 78-80 ºC

OCH ), 6.99 (dd, J = 9.0, 1.0 Hz, 2H, H_m_e_t_a), 7.18 (dd, J = 9.0,

f

3

13

(

CH Cl -hexane). IR (KBr) 2970 (-CH ), 2934 (-CH -), 1741 (-

1.0 Hz, 2H, H_o_r_t_h_o). C NMR (125 MHz, CDCl ) δ: 15.7 (C-9),

2

3

2

3

-

1

NCO -), 1699 (C=O), 1396 (C=C) cm . Signals assigned to

2

16.0 (C-10), 18.2 (C-11), 26.5 (C-4), 36.5 (C-8), 45.7 (C-5), 48.1

1

adduct 9a: H NMR (500 MHz, C D ) δ: 0.81 (d, J = 7.0 Hz, H-

(C-7), 55.4 (CH O), 114.8 (C_m_e_t_a), 121.2 (C-3a), 125.7 (C_i_p_s_o),

6

3

9

1

), 0.97 (d, J = 6.0 Hz, 3H, H-10), 1.08 (d, J = 6.5 Hz, 3H, H-11),

.70 (dd, J = -16.0, 6.5 Hz, 1H, H-4b), 2.16 (m, 2H), 2.25 (dd, J

128.8 (C_o_r_t_h_o), 137.5 (C-8a), 154.3 (C-2), 159.7 (C_p_a_r_a), 213.2 (C-

1

6). Signals assigned to adduct 11b: H-NMR (500 MHz, CDCl )

3

=

-16.0, 4.0, 3.5 Hz, 1H, H-4a), 2.32 (m, 1H, H-7), 2.32 (m, 1H,

δ: 1.08 (d, J = 6.5 Hz, 3H, H-9), 1.10 (d, J = 6.5 Hz, 3H, H-11),

1.15 (d, J = 6.5 Hz, 3H, H-10), 2.07 (m, 1H, H-4b), 2.62 (ddd, J

= -16.0, 5.0, 1.5 Hz, 1H, H-4a), 2.84 (m, 1H, H-5), 3.03 (m, 1H,

H-8), 6.99 (t, J = 7.0 Hz, 1H, H⁾^,⁷^.⁰⁴⁽^t^,^J⁼⁷^.⁰^,²^H^,^Hmeta),

para

13

7

1

.05 (d, J = 7.0 Hz, 2H, H_o_r_t_h_o). C NMR (125 MHz, C D ) δ:

6 6

4.8 (C-10), 15.8 (C-9), 18.2 (C-11), 26.8 (C-4), 36.6 (C-8), 45.6

H-8), 3.26 (dq, J = 6.5, 4.5 Hz, 1H, H-7), 3.83 (s, 3H, CH O),

3

(

C-5), 48.3 (C-7), 120.9 (C-3a), 127.5 (2C_o_r_t_h_o), 129.5 (2C C_m_e_t_a),

6.99 (dd, J = 9.0, 1.0 Hz, 2H, H_m_e_t_a), 7.18 (dd, J = 9.0, 1.0 Hz,

13

1

6

0

4

2

1

28.3 (C_p_a_r_a), 134.3 (C_i_p_s_o), 137.7 (C-8a), 153.6 (C-2), 212.2 (C-

2H, H_o_r_t_h_o). C NMR (125 MHz, CDCl ) δ: 13.3 (C-9), 13.4 (C-

3

1

). Signals assigned to adduct 9b: H NMR (500 MHz, C D ) δ:

10), 14.5 (C-11), 27.2 (C-4), 33.8 (C-8), 45.0 (C-5), 46.8 (C-7),

6

.79 (d, J = 7.0 Hz, 3H, H-9), 0.93 (d, J = 6.5 Hz, 3H, H-10 ),

.93 (d, J = 6 Hz, 3H, H-11), 1.70 (dd, J = -16.0, 6.5 Hz, 1H, H-

b), 2.19 (m, 1H, H-5), 2.95 (dd, J = -16.0, 4.0, 3.0 Hz, 1H, H-

a), 2.56 (m, 1H, H-8), 2.63 (m, 1H, H-7), 6.92 (d, J = 8.0 Hz,

H, H_o_r_t_h_o), 6.97 (t, J = 8.0, 1.0 Hz, 1H, H_p_a_r_a), 7.04 (t, J = 8.0 Hz,

55.4 (CH O), 114.8 (C_m_e_t_a), 120.2 (C-3a), 125.7 (C_i_p_s_o), 128.7

3

(C_o_r_t_h_o), 139.0 (C-8a), 154.4 (C-2), 159.8 (C_p_a_r_a), 213.8 (C-6). MS;

+

C H NO [EI ] m/z (%): 315 (M ), 300 (14), 282 (12), 258

18

21

4

(35), 244 (27), 228 (24), 123 (31), 77 (30), 69 (26), 55 (31), 41

+

(38). HRMS (EI) m/z [M ] calcd for C H NO : 315.1471.

18

21

4

13

H, H_m_e_t_a). C-NMR (C D , 125 MHz) δ: 13.3 (C-10), 13.4 (C-

Found: 315.1478.

6

1), 16.0 (C-9), 27.3 (C-4), 34.0 (C-8), 45.0 (C-5), 46.7 (C-7),

19.6 (C-3a), 127.8 (2C_o_r_t_h_o), 128.3 (C_p_a_r_a), 129.5 (2C_m_e_t_a), 134.2

Mixture of adducts 12a/12b. Use of the general procedure, with

0.50 g of 5, 0.882 g of copper, 3.78 g of sodium iodide in 8.8 mL

of acetonitrile and 1.05 g of 6, gave 0.524 g (74%) of 12a/12b as

(C_i_p_s_o), 139.2 (C-8a), 153.7 (C-2), 211.8 (C-6) ppm. MS

+

C H NO [EI ] m/z (%): 285 (M ), 270 (20), 252 (17), 240 (9),

2

17

19

3

+

28 (60), 214 (49), 198 (30), 77 (50). HRMS (EI) m/z [M ] calcd

a brown powder. R 0.42 (hexane/EtOAc, 6:4); m.p. 105-107 °C

f

for C H NO : 285.1365. Found: 285.1359.

(CH Cl -hexane); IR (KBr) 2972 (-CH ), 2932 (-CH -), 1746 (-

17

19

3

2

3

2

NCO -), 1707 (C=O), 1399 (C=C), 1301, 1251 (Ar-O), 3096

2

-

1

Mixture of adducts 10a/10b. Use of the general procedure, with

.50 g of 3, 0.872 g of copper, 3.74 g of sodium iodide in 8.7 mL

(CH O) cm . Signals assigned to adduct 12a: H NMR (500

3

0

MHz, CDCl ) δ: 0.96 (t, J = 7.5 Hz, 3H, CH ), 1.08 (d, J = 6.5

3

1

3

Hz, 3H, H-9), 1.18 (d, J = 6.5 Hz, 3H, H-10), 1.79 (m, 1H, H-

References and notes

ACCEPTED MANUSCRIPT

1

2

5

1), 1.97 (m, 1H, H-11), 2.10 (m, 2H, H-4b), 2.56 (m, 1H, H-8),

.75 (ddd, 1H, J = -14.5, 5.0, 1.5 Hz, 1H, H-4a), 2.87 (m, 1H, H-

1.

Hayakawa, Y.; Shimizu, F.; Noyori, R. Tetrahedron Lett. 1978,

1, 993.

Paquette, L. A.; Okazaki, M. E.; Caille, J. J. Org. Chem. 1988, 53,

77.

Wender, P. A.; Keenan, R. M.; Lee, H. Y. J. Am. Chem. Soc. 1987,

109, 4390.

1

), 3.01 (qd, J = 8.0, 7.0 Hz, 1H, H-7), 3.84 (s, 3H, CH O), 6.98

3

13

2.

(d, J = 8.0 Hz, 2H, H_m_e_t_a), 7.18 (d, J = 8.0 Hz, 2H, H_o_r_t_h_o).

C

4

NMR (125 MHz, CDCl ) δ: 9.3 (CH ), 14.9 (C-10), 15.8 (C-9),

3

.

2

4.2 (C-11), 26.7 (C-4), 41.9 (C-8), 45.1 (C-5), 45.1 (C-7), 55.5

(

1

CH O), 114.8 (C_m_e_t_a), 122.5 (C-3a), 125.7 (C_i_p_s_o), 128.8 (C_o_r_t_h_o),

4.

5.

Barbosa, L. C. A.; Demuner, A. J.; Borges, E. E. L.; Mann, J. J.

Braz. Chem. Soc. 1997, 8, 19.

Harmata, M. Chem. Commun. 2010, 46, 8886.

Harmata, M. Acc. Chem. Res. 2001,

3

36.4 (C-8a), 154.4 (C-2), 159.7 (C_p_a_r_a), 213.6 (C-6). Signals

1

assigned to adduct 12b: H NMR (500 MHz, CDCl ) δ: 0.99 (t, J

=

3

6

.

7.5 Hz, 3H, CH ), 1.09 (d, J = 6.5 Hz, 3H, H-9), 1.17 (d, J =

3

7.

8.

9.

34, 595.

6

.5 Hz, 3H, H-10), 1.33 (m, 1H, H-11), 1.71 (m, 1H, H-11), 2.10

m, 1H, H-4b), 2.44 (dd, J = -14.5, 4.5 Hz, 1H, H-4a), 2.90 (td, J

8.0, 4.5 Hz, 1H, H-8), 2.94 (m, 1H, H-5), 3.08 (dq, J = 7.0, 4.0

Hz, 1H, H-7), 3.84 (s, 3H, CH O), 6.99 (d, J = 8.0 Hz, 2H, H_m_e_t_a),

Harmata, M. Tetrahedron 1997, 53, 6235.

Rawson, D. I.; Carpenter, B. K.; Hoffmann, H. M. R. J. Am.

Chem. Soc. 1979, 101, 1786.

(

=

1

0. Montaña, A. M.; Ribes, S.; Grima, P. M.; García, F.; Solans, X.

3

Tetrahedron 1997, 53, 11669.

13

7

1

^.¹⁸⁽^d^,^J⁼⁸^.⁰^H^z^,²^H^,^Hortho). C NMR (125 MHz, CDCl ) δ:

3

11. Hernández, R.; Sánchez, J. M.; Gómez, A.; Trujillo, G.; Aboytes,

R.; Zepeda, G.; Bates, R. W.; Tamariz, J. Heterocycles 1993, 36,

1951.

2.4 (CH ), 13.3 (C-10), 16.3 (C-9), 21.6 (C-11), 28.1 (C-4), 40.2

3

(C-8), 44.1 (C-5), 48.7 (C-7), 55.5 (CH O), 114.8 (C_m_e_t_a), 120.4

3

1

2. a) Mandal, A. B.; Gómez, A.; Trujillo, G.; Méndez, F.; Jiménez,

H. A.; Rosales, M. J.; Martínez, R.; Delgado, F.; Tamariz, J. J.

Org. Chem. 1997, 62, 4105. b) Martínez-Palou, R. Síntesis de

dienos exo-heterocíclicos alquil-sustituidos de 2-oxazolidinonas y

su estudio en cicloadiciones de Diels-Alder. M.Sc. Thesis, IPN,

México, 1997. c) Fuentes-Benítes, M.P.A.G. Estudio de la

reactividad de dienos funcionalizados de 2-oxazolidinonas y

aplicación en la síntesis de benzoxazolonas. PhD Thesis, IPN,

México, 2006.

(C-3a), 125.7 (C_i_p_s_o), 128.6 (C_o_r_t_h_o), 139.2 (C-8a), 154.3 (C-2),

+

1

59.7 (C ), 213.4 (C-6). MS C H NO [EI ] m/z (%): 329

para

19 23

4

+

(M ), 300 (67), 272 (22), 244 (100), 200 (32), 174 (16), 69 (29),

+

4

1 (13). HRMS (EI) m/z [M ] calcd for C H NO : 329.1627.

19 23 4

Found: 329.1633.

Theoretical Methodology. All calculations were carried out

37

1

3. Martínez, R.; Jiménez-Vázquez, H. A.; Reyes, A.; Tamariz, J.

Helv. Chim. Acta 2002, 85, 464.

4. Martínez, R.; Jiménez-Vázquez, H. A.; Delgado, F.; Tamariz, J.

Tetrahedron 2003, 59, 481.

with the Gaussian 09 program package at the M06-X/6-

3

19

1+G(d,p) level of density functional theory using the

INT(GRID=ULTRAFINE) option. All optimizations to minima

and transition states were carried out using the OPT=TIGHT

option. The transition states were located with the OPT=QST3

options and stationary points were characterized by the

determination of vibrational frequencies. The corresponding

thermochemical analyses were carried out at 298.15 K and 1 atm

of pressure. No scaling factors were used for the vibrational

frequencies or zero-point energies. The electronic energies

corrected by the inclusion of thermal free energies were used to

obtain the relative free energies discussed in the text. The saddle

points were confirmed by the presence of a single imaginary

frequency, and the normal mode associated with this frequency

was analyzed visually in order to confirm that the molecular

motion corresponded to the cycloaddition. The minima showed

only real vibrational frequencies. The presence of solvent was

accounted for with the default method in Gaussian 09

15. Bautista, R.; Bernal, P.; Montiel, L. E.; Delgado, F.; Tamariz J.

Synthesis 2011. 929, and references cited therein.

1

6. Fuentes, A.; Martínez-Palou, R.; Jiménez-Vázquez, H. A.;

Delgado, F.; Reyes, A.; Tamariz, J. Monatsh. Chem. 2005, 136,

1

77.

7. a) Benavides, A.; Martínez, R.; Jiménez-Vázquez, H. A.; Delgado,

F.; Tamariz, J. Heterocycles 2001, 55, 469. b) Benavides, A.;

Peralta, J.; Delgado, F.; Tamariz, J. Synthesis 2004, 2499.

8. a) Ashcroft, M. R.; Hoffmann, H. M. R. Org. Synth. 1978, 58, 17,

b) Hoffmann, H. M. R. Angew. Chem. Int. Ed. Engl. 1984, 23, 1.

c) Hoffmann, H. M. R.; Eggert, U.; Gribbles U.; Giesel, K.; Koch,

O. Tetrahedron 1988, 44, 3899.

1

9. Williams, N. S.; Bhacca, D. H. Applications of NMR

Spectroscopy in Organic Chemistry. Steroid Field. Holden Day:

S.F. (1964).

0. Zhao, Y.; Truhlar, D. G. Theor. Chim. Acta 2008, 120, 215.

1. Tomasi, J.; Menucci, B.; Cammi, R. Chem. Rev. 2005, 105, 2999.

2. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97, 1354.

3. Favini, G.; Nava, A. Theor. Chim. Acta 1973, 31, 261.

2

20

(

IEFPCM). The minima and TS obtained in the gas phase were

reoptimized under these conditions and vibrational frequency

analyses were carried out again, also within the PCM formalism.

24. Glazer, E. S.; Knorr, R.; Ganter, C.; Roberts, J. D. J. Am. Chem.

Soc. 1972, 94, 6026.

2

5. St-Jacqueas, M.; Vaziri, C. Can. J. Chem. 1973, 51, 1192.

26. Liebman, J. F.; Greenberg. A.; J. Org. Chem. 1974, 39, 123.

7. Cramer, C. J.; Barrows, S. E. J. Phys. Org. Chem. 2000, 13, 176.

Acknowledgements

2

Financial support from SIEA-UAEMEX (project No.

28. Rawson, D. I.; Carpenter, B. K.; Hoffmann, H. M. R. J. Am.

Chem. Soc. 1979, 101, 1786.

2

692/2008U) is gratefully acknowledged. The authors would

2

9. a) Santoyo, B.; Gonzalez-Romero, C.; Merino, O.; Martinez-

Palou, R.; Fuentes-Benites, A.; Jimenez-Vazquez, H. A.;

Delgado, F.; Tamariz, J. Eur. J. Org. Chem. 2009, 15, 2505. b)

Merino, O.; Santoyo, B.; Montiel, L.; Jiménez-Vázquez, H. A.;

Zepeda, L. G.; Tamariz, J. Tetrahedron Lett. 2010, 51, 3738.

like to thank Nieves Zavala, Alejandra Núñez, and Lizbeth

Triana for technical assistance, and Bruce Allan Larsen for

proofreading the manuscript. J.T. is grateful to Conacyt (México)

(grant 178319) and SIP-IPN (grant 20130686) for financial

support. Financial support from Instituto de Química (UNAM) is

gratefully acknowledged. We thank Héctor Ríos Olivares and Dr.

Beatriz Quiroz for the NMR spectra, Luis Velasco and Javier

Pérez for the mass spectra. H.A.J.-V. and J.T. are fellows of the

EDI-IPN and COFAA-IPN programs.

30. a) Ramesh, N. G.; Hassner, A. Eur. J. Org. Chem. 2005, 1892. b)

Battiste, M. A.; Pelphrey, P. M.; Wright, D. L. Chem. Eur. J.

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006, 12, 3438. c) Ovaska, T. V. Arkivoc 2011, (v), 33. d) Rigby,

J. H.; Pigge, F. C. Org. React. 1997, 51, 351. e) Liu, N.; Song,

W.M.; Schienebeck, C. M.; Zhang, M.; Tang, W. Tetrahedron

2

014, 70, 9281.

3

1. a) Weinstock, J.; Gaitanopoulos, D. E.; Stringer, O. D.; Franz, R.

G.; Hieble, J. P.; Kinter, L. B.; Mann, W. A.; Flaim, K. E.;

Gessner, G. J. Med. Chem. 1987, 30, 1166. b) Caccarelli, S. M.;

Jaeschke, G.; Buettelmann, B.; Huwyler, J.; Kolczewski, S.;

Peters, J.-U.; Prinssen, E.; Porter, R.; Spooren, W.; Vieira, E.

Bioorg. Med. Chem. Lett. 2007, 17, 1302. c) Ononye, S. N.;

VanHeyst, M. D.; Oblak, E. Z.; Zhou, W.; Ammar, M.;

Supplementary data

Supplementary data related to this article can be found at http://

dx.doi.org/XXXX-XX.

14

Tetrahedron

ACCEPTED MANUSCRIPT

Anderson, A. C.; Wright, D. L. ACS Med. Chem. Lett. 2013, 4,

7

57. d) Day, J. A.; Cohen, S. M. J. Med. Chem. 2013, 56, 7997.

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2. Foley, D. A.; Maguire, A. R. Tetrahedron 2010, 66, 1131.

3. a) Marshall, J. A.; Greene, A. E. J. Org. Chem. 1971, 36, 2035.

b) Lange, G. L.; Gottardo, C. Tetrahedron Lett. 1994, 35, 8513.

4. a) Yamasaki, M. J. Chem. Soc., Chem. Commun. 1972, 606. b)

Audenaert, F.; Dekeukeleire, D.; Vandewalle, M. Tetrahedron

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1

987, 43, 5593.

3

5. Hoffmann, H. M. R. Angew. Chem. Int. Ed. Engl. 1973, 12, 819.

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Kociok-Köhn, G. Tetrahedron 2000, 56, 425.

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J. Gaussian, Inc., Wallingford CT, 2013.

ACCEPTED MANUSCRIPT

SUPPLEMENTARY DATA

Synthesis and structural studies of novel fused seven-membered

carbocycles derived from exo-2-oxazolidinone dienes

through (4 + 3) cycloadditions

a

b

c

Patricia Alcázar , Indira Cruz , Carlos González-Romero , Erick Cuevas-Yañez , Eduardo Díaz ,

d

b

c

Joaquín Tamariz , Hugo A. Jiménez-Vázquez , David Corona-Becerril , Rubén A. Toscano ,

a,

and Aydeé Fuentes-Benítes

a

Facultad de Química, Universidad Autónoma del Estado de México, Paseo Tollocan y Colón, 50000, Toluca, Estado de México,

México.

b

Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM. Carretera Toluca-Atlacomulco, Km. 14.5, Toluca, 50200,

Estado de México, México.

c

Instituto de Química, Universidad Nacional Autónoma de México, Circuito exterior, C.U. Coyoacán, 04510 México, D.F., México.

Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. Carpio y Plan de

d

Ayala S/N, 11340, México, D.F. México.

*Corresponding author: Tel.: +52 722 2175 109x113; fax: +52 722 2173 890. E-mail: mpagfuentesb@uaemex.mx

CONTENTS

General procedure for the synthesis of 2,4-dibromopentan-3-one (6)

Previous treatments for the [4 + 3] cycloaddition reaction

of diverse exo-2-oxazolidinone dienes and the oxyallyl cation

General computational methods

S2-S2

S2-S3

S3-S8

1

13

H, C and 2D NMR spectra of compounds 8, 9a-b, 10a-b, 11a-b, and

1

2a-b

S9-S36

1

ACCEPTED MANUSCRIPT

General procedure for the synthesis of 2,4-dibromopentan-3-one (6).

3

-Pentanone (5 mL, 47.14 mmol) and phosphorus tribromide (0.09 mL, 0.94 mmol) was

placed in a flask protected from moisture with an anhydrous calcium chloride trap, magnetic

stirring and a glass tube immersed in a trap with a saturated solution of sodium bicarbonate

(10%). The mixture was stirred for 30 min. Then, bromine (4.8 mL, 94.3 mmol) was added

dropwise; stirring and cooling (-10 to 0 °C) was continued for 1 hr. The reaction was stopped

by addition of distilled water (20 mL), the organic phase was separated and the aqueous phase

washed with ether (3 x 10 mL). The combined organic phase was washed with 10% aqueous

solutions of sodium carbonate (3 x 15 mL) and 10% sodium bisulphite (3 x 10 mL), and later,

dried over dry sodium sulphate and filtered. The solvent was removed under vacuum and the

residue was purified by fractionated distillation at 65-70 °C and 10 mm Hg, obtaining 8.36 g

1

(

73%) of 7 as a light dark oil R 0.82; (hexane-EtOAc, 9:1). H-NMR (300 MHz, CDCl ) δ:

f

3

13

1

5

.81 (d, J = 6.6, 3H), 4.99 (q, J = 6.6, Hz, 1H). C NMR (75 MHz, CDCl ) δ: 19.45 (C-1, C-

3

), 43.79 (C-2, C-4), 195.92 (C-3).

Previous treatments for the [4 + 3] cycloaddition reaction of diverse exo-2-

oxazolidinone dienes and the oxyallyl cation. Synthesis of 3-Benzyl- and 3-Aryl-5,7,8-

trimethyl-4,5,7,8-tetrahydro-3H-cyclohepta[d]oxazole-2,6-diones 8-12.

1

. Activation of copper powder: In a 250 mL round-bottomed flask, containing copper

powder (10 g) a solution of iodine in acetone (2% w/v) (100 mL) was added. The suspension

was stirred for 30 min and filtered through a Büchner funnel. The solid was washed with 60

mL of a 1:1mixture of 35% (w/w) aqueous HCl and acetone, and afterwards with distilled

water (100 mL) followed by acetone (50 mL). Copper powder with a metallic luster was

obtained, which was dried under high vacuum for 30 min and stored in an inert atmosphere

2

(N ), in the dark, in a desiccator.

2

ACCEPTED MANUSCRIPT

2

. Activation of NaI. Sodium iodide used in cycloaddition reactions should be activated

(dehydrated) before use. For this purpose, NaI was ground and then dehydrated in an oven at

1

00 °C for 5 h. It is necessary to cool it to room temperature in a desiccator prior to use.

COMPUTATIONAL DATA

Cartesian coordinates and energies of the stationary points mentioned in the text.

M06-2X/6-31+G(d,p)/PCM(benzene) cartesian coordinates and energies of the lowest-energy

conformer of 10a.

SCF Done: E(RM062X) = -1398.92604795

Sum of electronic and zero-point Energies=

Sum of electronic and thermal Energies=

Sum of electronic and thermal Enthalpies=

Sum of electronic and thermal Free Energies=

A.U. after

1 cycles

-1398.601676

-1398.581638

-1398.580694

-1398.651678

C

N

C

O

C

O

C

O

C

H

Cl

3.2859667446

2.3892528404

2.7622613616

4.0276404519

4.9142526168

4.5592848617

1.0950720077

-0.1460640229

-1.0756667611

-0.4597405073

0.884305309

-0.3190627839

-1.2937129286

-0.6235686416

1.6879292462

-2.5627323324

-2.984033557

-3.1003984287

-2.5965735409

-3.2286342842

-4.6269050822

-2.9812473304

-0.6414011417

0.6478040457

-1.6004735582

-2.68887659

0.2277175993

-4.9884799771

-4.9898728959

-5.0555876146

-0.2597734547

-1.3277597025

-4.0650946732

-2.5048117356

-2.6867882761

2.0675477201

4.3284475368

6.5047006212

0.0810842868

0.1492068436

-0.2967758693

-0.8394009586

-0.9049698759

-0.4420015479

0.6930883295

0.1359447442

1.0540008165

2.1617899705

-0.950739036

0.1146947585

1.3829840202

1.5845528156

0.5138112322

-0.7500324594

-0.091985367

0.2917022448

-0.0211081672

-0.578019929

1.94479826

-0.6306574314

-1.2565866567

-2.0817540254

-2.5592448543

2.7338301135

1.1004363285

2.266161796

0.8217771167

-0.0418327182

-1.3296243314

-1.0691144479

0.109981804

1.0144888531

0.6085033494

-0.3528181101

-1.356386589

0.6762884392

-0.8935555868

1.86745311

0.8161654569

0.5489050076

1.6087228312

-1.0970641799

1.4498046765

0.9112610961

-0.2851842339

-1.9066973074

-1.9539090024

0.9811853788

0.6861221852

2.0506469949

2.2130293561

2.5642853617

0.762581105

-0.265080078

-1.340812292

-1.6003239439

-0.2809541808

1.2660582943

-1.2245277694

-1.7666840398

-2.9584676995

-0.4502175047

-3.2043259919

0.3996496427

-1.2847015915

0.0132440765

-1.7014766329

-3.1098356565

2.4159111878

3.1914352579

2.0719819452

-0.2095230107

-1.1930687786

-1.575600868

3

ACCEPTED MANUSCRIPT

H

5.2682611042

2.9887887535

-0.4963346886

0.4466506214

-1.5683609195

-1.9274503772

M06-2X/6-31+G(d,p)/PCM(benzene) cartesian coordinates and energies of the lowest-energy

conformer of 10b.

SCF Done: E(RM062X) = -1398.92638417

Sum of electronic and zero-point Energies=

Sum of electronic and thermal Energies=

Sum of electronic and thermal Enthalpies=

Sum of electronic and thermal Free Energies=

A.U. after

2 cycles

-1398.601592

-1398.581566

-1398.580621

-1398.650835

C

N

C

O

C

O

C

O

H

Cl

H

2.7235882012

2.4848114921

3.4748448673

4.704451386

4.9234698506

3.9444193467

1.2345592793

-0.0586336455

-0.9226696452

-0.2100332812

1.123052953

0.8443186912

-0.0800791296

-0.3674504628

0.2790265386

1.2185411627

1.5091075881

-0.7491709483

-0.1724572933

-1.2025480182

-2.3920774677

-2.1201565241

1.3085009878

1.800910044

3.3213450783

-2.9589146918

-1.3619016648

-0.2185458208

-0.4096929808

-1.5638576392

1.1303289484

1.6412606306

-2.2785181969

1.7988293608

1.6557514278

1.4917055594

-0.2446983886

1.0602937415

0.0432873509

-0.8960338404

-0.8255265848

0.1779616954

1.1230876594

-0.0298969086

-0.0104318165

-0.0561034364

-0.0974570746

-0.0938759031

0.0354366833

-0.7026825588

-0.6068956755

-0.1419644961

0.0383833509

-0.6679829322

-0.5546508216

1.5052285511

-0.1001036317

0.8293232136

-0.5149667999

-0.4172211795

1.0761612835

-1.7505002076

-1.7227219862

-0.2669512001

-1.5273912498

-1.6289434196

1.9926451411

-2.4068149445

-3.1834925643

-4.694563137

-2.8196253379

-2.75872676

-3.3520023217

-2.6457755075

0.6012924557

-0.3198730972

-1.4434300912

-2.8874444005

-0.7401781572

-4.9748270097

-5.2169874048

-5.0334534281

-1.7192078685

-2.5075198033

-3.8635285123

-2.6941355555

-2.2001345264

3.2841856364

5.4841382371

6.4572711518

4.1396542913

1.9617295793

3.7880549

-1.0402140951

-1.4225805656

0.2998325257

-0.2387113467

3.6323429638

3.6883088901

-1.8769984689

-0.6389056166

-2.3410254784

-1.1033056037

0.0610214338

2.0441680183

2.2333287438

1.0365958137

-0.8586884154

-1.2013506589

0.4685772372

0.4366536369

-1.1431629131

1.5794349506

2.0764407966

1.9600445241

-1.6692361806

-1.546600067

0.2566319949

1.9057888549

1.8088486588

M06-2X/6-31+G(d,p)/PCM(acetonitrile) cartesian coordinates and energies of the endo transition

state of the cycloaddition between 7a and 1.

SCF Done: E(RM062X) = -939.243787122

Sum of electronic and zero-point Energies=

Sum of electronic and thermal Energies=

A.U. after

2 cycles

-938.919074

-938.898389

4

ACCEPTED MANUSCRIPT

Sum of electronic and thermal Enthalpies=

Sum of electronic and thermal Free Energies=

-938.897444

-938.969283

C

N

C

O

C

O

C

O

C

H

C

H

-0.1267240816

0.9947401126

0.6924536315

-0.5657969988

-1.1289911906

1.3878090171

2.1573439565

-2.405672516

-3.3319705563

-0.2660130787

-1.5457952748

-1.8537508301

-1.0121715308

-3.1997734981

-3.8217802667

-0.3727068002

-2.7419201585

-1.1572277908

0.5610548722

-2.3003278747

-3.818324948

-0.059494104

-4.7372100659

-4.0853376039

-3.1035890528

0.45540063

-0.6605841685

-4.345050232

-2.9965044875

-3.3855765582

3.0551967844

4.1743012451

4.3921129719

3.4875235721

2.3577983027

2.8741723294

4.8780239518

5.266563941

-0.2650672648

-0.7496038029

-1.9272352809

-2.299932685

-1.3031774769

-2.5835500987

0.0185125088

-1.3500027286

-2.4934970603

0.9383019869

2.1429764897

0.9247685122

0.2775668472

0.5470406263

-0.5070991761

2.9674376349

-0.5455075848

1.1547905356

1.6371247227

2.5788524257

1.1207954898

3.6337926302

-0.903054176

-0.083311644

-1.3109647073

-1.1754679546

-0.4907036689

0.1477966233

-0.2156374395

-0.9977099245

0.8849512188

-0.1866549749

-1.4046065805

-1.1364831573

-1.7698675199

0.1686776951

0.8369424282

1.5419000793

0.6499402429

1.4865042701

0.54776008

-2.0518491308

-2.3446507138

-1.8137852369

-0.4818603547

-0.0347634774

-0.2582336442

1.0438560892

2.4668672842

1.6754950015

2.3326677432

3.5990971379

-2.1336768107

-3.089709638

0.8700592998

1.4018556119

-0.9422449239

-0.2853523791

-3.1492563306

0.3331598272

1.1096036588

1.5488262654

1.220384428

0.4586934868

-0.0284770368

1.3639935319

2.1489401684

1.5676704306

0.2154274143

-2.0130771878

-1.2037955214

-0.9057396144

0.4004882193

1.4118498385

1.1207868381

-2.2115489799

-1.6914268081

0.6307957313

2.4261386429

1.8759659984

3.6555061047

1.6163562444

M06-2X/6-31+G(d,p)/PCM(acetonitrile) cartesian coordinates and energies of the exo transition state

of the cycloaddition between 7a and 1.

SCF Done: E(RM062X) = -939.239941226

Sum of electronic and zero-point Energies=

Sum of electronic and thermal Energies=

Sum of electronic and thermal Enthalpies=

A.U. after

2 cycles

-938.916071

-938.894651

-938.893706

-938.969412

Sum of electronic and thermal Free Energies=

C

N

C

-3.2228068772

-2.5093212742

-3.0022580864

-4.2351902377

-4.9547233341

-4.4473284664

-1.2520992263

-0.0960664127

0.1125262502

-0.1687260549

0.1915277493

0.8363130658

1.1289751667

0.7701846956

-0.8352581102

-0.3165538054

-1.2160812811

-0.0519531036

1.2002497278

1.2861811567

0.1276424574

-1.1219801193

-0.1492039811

-0.7656956415

5

ACCEPTED MANUSCRIPT

C

O

C

O

C

O

C

H

0.8896307905

0.2555324943

-1.0312082643

0.0394464272

1.8295854914

1.6349381596

-1.8002725876

2.1674687993

3.0375697442

3.2028682755

2.7615552646

3.3105868857

4.5750736566

2.5793014246

-0.789444217

0.986482426

1.2533372982

2.5289147469

0.6436730683

4.5667942366

5.1970817819

5.0297842822

2.3878008562

1.6389351937

3.9932162182

3.268184533

-1.3973651575

-0.6162377921

0.053586146

-2.4438244145

-2.0993631551

0.8936459356

2.2994058771

3.7099571175

-2.8316974202

-1.4744921804

-2.6753028084

0.5694160814

1.4516325925

1.6526764154

0.0122823688

-0.6057635446

1.5918334372

1.1820021066

1.9144818571

0.3257326215

3.8095409247

-1.0168530914

0.5886035461

0.0604907013

4.0144557171

4.3759863424

-2.388028635

-3.1395527617

-3.420615865

-0.0389825366

1.1150295662

1.6367843583

0.9952293573

-0.183650311

0.3325752553

-1.3204747389

0.7732681967

0.3687185571

0.9075397152

-0.992008092

-0.7907709805

1.1415499242

0.1269876773

-0.995271081

1.1649313801

-1.5022808991

-1.3468139227

-1.7636471046

1.6088800726

1.9567308996

-0.0959896371

1.5368253884

1.8631582208

0.1735438696

-0.3597313614

1.2364281631

-0.3423650757

-1.7557700766

-0.1540335958

2.0908743096

2.2579758947

0.1982477844

-2.0237864962

-2.1790628165

2.5582448375

-2.4259457122

-4.6291444283

-5.9112175923

-5.0071696359

-2.8178035398

M06-2X/6-31+G(d,p)/PCM(acetonitrile) cartesian coordinates and energies of the endo transition

state of the cycloaddition between 7b and 1.

SCF Done: E(RM062X) = -1101.46027899

Sum of electronic and zero-point Energies=

Sum of electronic and thermal Energies=

Sum of electronic and thermal Enthalpies=

Sum of electronic and thermal Free Energies=

A.U. after

1 cycles

-1101.133308

-1101.111118

-1101.110174

-1101.184489

C

N

C

O

C

O

C

2.5308043984

2.1513563149

3.0682645585

4.3864639472

4.7810828227

3.8550001434

0.7987164813

-0.0920114322

-1.3530924332

-1.1587662005

0.1080760159

0.134573075

0.4932017542

-2.5542952088

-3.7859012702

-0.7729190153

0.5621863373

-1.5219254754

-2.89218745

-0.0219754312

-0.4984559631

-0.5935302402

-0.1956364086

0.27588106

0.9824931037

-0.2708368547

-1.3159948692

-1.1026676823

0.1497923611

0.3586317237

-0.8872471038

-0.2387438044

-0.9305877714

-1.8728771214

-1.7551722335

0.8875817869

-2.3409774311

-0.7114424891

-1.4977716995

2.4818471253

2.9577464784

1.542558342

1.1902302969

-0.5069165048

-1.3687709645

-1.1729963842

-0.1734160038

0.300565337

-2.0835194468

1.2864693362

-1.7248475075

-1.4136490923

-0.354362991

0.0838187296

0.410668619

1.5644014623

0.1274587096

6

ACCEPTED MANUSCRIPT

C

O

H

Na

-3.8674277143

-0.970346742

-2.5999049691

-0.6233368864

1.1259135701

-1.3039567172

-3.2503084179

0.4001008425

-4.8687033196

-3.9236300527

-3.5303247004

1.132811445

1.1272243814

-4.6411395407

-3.6577922658

-4.0288128393

2.7472603798

5.1053512642

5.8097829222

4.1597737735

1.7902710833

-1.06417786

0.8318505919

0.9740939483

1.2716752638

-2.5105347045

-2.7691211236

-2.1403367774

-1.1097126637

-0.6692663989

0.8389788192

0.5424631246

1.9646790991

1.1429753411

-0.7322660565

0.5590058106

-1.2697634451

-0.521617235

-2.2555031631

-2.2800126961

-1.9122227792

0.3148467073

2.1633443291

1.7710780226

2.9164833852

0.7605204612

0.0370083149

1.244873043

1.3209100955

3.0554305241

2.2098166185

3.7416367665

0.8264515682

1.3045057085

-0.1972958844

3.4030401611

2.1546903893

-0.8321960252

-2.113153238

-2.1552456495

-0.9762863215

-0.2638059106

0.5789397625

0.7291588056

0.059173659

-0.711291722

M06-2X/6-31+G(d,p)/PCM(acetonitrile) cartesian coordinates and energies of the exo transition state

of the cycloaddition between 7b and 1.

SCF Done: E(RM062X) = -1101.45657611

Sum of electronic and zero-point Energies=

Sum of electronic and thermal Energies=

Sum of electronic and thermal Enthalpies=

Sum of electronic and thermal Free Energies=

A.U. after

2 cycles

-1101.128450

-1101.105588

-1101.104644

-1101.182841

N

C

O

C

O

C

O

C

H

-1.1688528922

-0.0128689078

0.9689235112

0.3289587333

-2.4037876184

-3.187938842

-4.3830537117

-4.7883568211

-3.9971059976

-2.7936854821

0.1323921244

2.2574557742

3.1163082238

-1.7265972723

1.5661803303

2.712381501

3.3692844047

1.1515271943

3.1092830297

4.4524775296

2.6705523624

-0.6933198709

1.0804402486

1.0266275778

2.4344371396

0.0715118545

4.4476650164

5.1249397591

-0.809422488

-0.3082702345

-1.3817562011

-2.426306149

-0.1053461262

0.1097515714

0.8150431031

1.2872164874

1.0610850175

0.367889228

-0.1937752932

-0.8136839532

-0.6421461492

0.0170044389

-0.0641411458

-1.1960128767

-1.0701717311

0.1790031322

1.3056874645

1.1867848135

-1.3885441965

-0.9902630535

-0.7985786045

0.8867965019

0.7714124518

0.298039705

0.8939855562

-1.4487424082

-2.6586669861

-2.7909317785

2.1619888663

1.4859660804

1.8275416132

3.4800339935

0.4770345305

-0.1352832529

-0.5794383134

1.5947743579

1.1658916032

1.7395620936

0.205064047

-0.7495132884

0.2484173447

1.1967611771

1.1537585117

-1.4992597006

-1.4357104063

-1.8400825401

1.6145992636

2.0032276425

0.323514639

3.6220645126

-1.1520889025

0.4548142317

1.5520737376

1.7945840352

7

ACCEPTED MANUSCRIPT

H

Na

4.8607650511

1.4972598061

1.6214893316

4.108703675

3.2606862809

2.6660014229

-2.1602907823

-4.3127008932

-5.7222502795

-4.999646971

-2.8593256102

4.7495070746

-0.107580542

0.1406132152

-0.7779525732

0.866432592

3.6172540863

4.2599262812

-2.3809111556

-3.1683136281

-3.3650643497

0.1891198908

1.4278845378

1.8314338244

0.9888535278

-0.2729115785

2.4782941691

-0.4351581013

-1.7577685134

-0.0993467219

2.0501823222

2.2766822799

0.2743567846

-1.9457072752

-2.1574936701

-2.267461977

8

ACCEPTED MANUSCRIPT

1

H NMR spectrum of compound 8.

9

ACCEPTED MANUSCRIPT

1

3

C NMR spectrum of compound 8.

1

0

ACCEPTED MANUSCRIPT

DEPT spectra of compound 8.

1

ACCEPTED MANUSCRIPT

HSQC spectrum of compound 8.

1

2

ACCEPTED MANUSCRIPT

COSY spectrum for compound 8.

1

3

ACCEPTED MANUSCRIPT

NOESY spectrum of compound 8.

1

4

Article Doi

Synthesis and structural studies of novel fused seven-membered carbocycles derived from exo-2-oxazolidinone dienes through (4+3) cycloadditions

DOI: 10.1016/j.tet.2014.12.065

Source and publish data:

Authors:

Article abstract of DOI:10.1016/j.tet.2014.12.065

Full text of DOI:10.1016/j.tet.2014.12.065

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