Vinyl-aziridines and cyclopropanes in Pd-catalyzed (3+2)-cycloaddition reactions with cyclic N-sulfonyl imines

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Vinyl-aziridines and cyclopropanes in Pd-

catalyzed (3+2)-cycloaddition reactions with

cyclic N-sulfonyl imines

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K. Spielmann, E. Tosi, A. Lebrun, G. Niel, A. van der Lee, R. M. de Figueiredo and J.-M. Campagne

Institut Charles Gerhardt Montpellier (ICGM), UMR 5253, Univ Montpellier, CNRS, ENSCM

1

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Tetrahedron

journal homepage: www.elsevier.com

Vinyl-aziridines and cyclopropanes in Pd-catalyzed (3+2)-cycloaddition reactions

with cyclic N-sulfonyl imines

a

b

a

c

Kim Spielmann , Eleonora Tosi , Aurélien Lebrun , Gilles Niel , Arie van der Lee ,

a

Renata Marcia de Figueiredo ∗ and Jean-Marc Campagne ∗

a

Institut Charles Gerhardt Montpellier (ICGM), UMR 5253, Univ Montpellier, CNRS, ENSCM - Ecole Nationale Supérieure de Chimie, 8 Rue de l’Ecole

Normale, 34296 Montpellier Cedex 5, France

b

NMR Analysis: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Univ Montpellier, CNRS, ENSCM, Laboratoire de Mesures Physiques - Plateau

Technique, Bât 17, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France

c

X-Ray Structures Analysis: Institut Européen des Membranes (IEM), UMR 5632, Univ Montpellier, CNRS - Place Eugène Bataillon, 34095 Montpellier Cedex

5

, France

ARTICLE INFO

ABSTRACT

Article history:

Received

Received in revised form

Accepted

Efficient palladium-catalyzed (3+2)-cycloaddition reactions of cyclic N-sulfonyl imines and

vinyl-aziridines (or cyclopropanes) have been achieved. The reactions, with either vinylic

substrate, proceed with excellent yields affording highly functionalized imidazolidine and

pyrrolidine derivatives. The cycloadditions take place via the reaction of zwitterionic π-allyl

palladium intermediates with cyclic N-sulfonyl imines through i) the formation of two N−C

bonds in the presence of vinylaziridines (synthesis of imidazolidines) and ii) one C−C bond and

one N−C bond in the presence of vinylcyclopropanes (synthesis of pyrrolidines). Following on

preliminary works on the diastereoselective synthesis of imidazolidines, herein we wish to give a

broader view on the subject by describing derivatization reactions and attempts towards an

enantioselective version. Moreover, we describe and discuss the behavior of each vinylic

substrate (aziridine or cyclopropane) on the (3+2)-cycloaddition reactions. Mechanistic and

(intriguing) selectivity outcomes are also going to be discussed.

Available online

Keywords:

(3+2)-Cycloaddition Reactions

Palladium-Catalysis

Vinyl-Aziridines and Cyclopropanes

Tetrasubstituted Carbon

Cyclic N-Sulfonyl Imines

2

1

2

1

. Introduction

isomerization of the π-allyl palladium was early recognized,

paving the way for catalytic and asymmetric transformations.

Indeed, in 2003, Trost first described the dynamic kinetic

asymmetric cycloaddition of isocyanates to racemic

Following the seminal work of Alper in (3+2)-cycloaddition

1

reactions with heterocumulenes, the palladium-catalyzed ring-

opening of vinylaziridines has emerged as a powerful tool for the

construction of a plentiful family of N-heterocycle scaffolds

2b

vinylaziridines. It should be emphasized that relatively few

catalytic and asymmetric transformations have been described to

date (see red arrows in scheme 1). Moreover, the reactivity of 2-

2-11

(

Scheme 1).

In the presence of a Pd(0) source, the vinyl

aziridine is able to form a zwitterionic complex that can be

considered as a dipolar intermediate bearing an electrophilic π-

allyl palladium complex tethered to a nucleophilic nitrogen atom

4

substituted vinyl aziridines (R ≠ H) was also scarcely reported in

2b

the literature.

As we had established a simple and rapid organocatalytic

(

Scheme 2; complex A). The nucleophilic moiety is able to react

13

access

to

2-substituted

vinylaziridines

(and

with an external electrophile (e.g. CO₂, isocyanates,

isothiocycanates, carbodiimides or α,β-unsaturated carbonyl

derivatives) leading to a novel nucleophile (Scheme 2; complex

B), that can be in turn trapped by the π-allyl palladium leading to

the (3+2)-cycloaddition product. Moreover, the cis/trans

vinylcyclopropanes), we were keen to explore their potential in

3+2)-cycloadditions (Scheme 3). In this context, we have

(

recently described an efficient palladium catalyzed (3+2)-

cycloadditions of 2-substituted vinylaziridines 3 with cyclic N-

14,15

sulfonyl imines 4.

isomerization of the vinyl aziridine through

a

π−σ−π

—

——

∗

Corresponding author. Tel.: +3-346-714-7221; fax: +3-346-714-4322; e-mail: jean-marc.campagne@enscm.fr

Corresponding author. Tel.: +3-346-714-7224; fax: +3-346-714-4322; e-mail: renata.marcia_de_figueiredo@enscm.fr

2

Tetrahedron

ACCEPTED MANUSCRIPT

Scheme 1. Pd-catalyzed (3+2)-cycloadditions of vinylaziridines. Red arrows highlight catalytic asymmetric transformations.

Scheme 2. Simplified mechanism for the (3+2)-cycloadditions.

Scheme 3. Straightforward access to 2-substituted vinylaziridines 3

and reaction with cyclic N-sulfonyl imines 4.

In the presence of Pd(PPh ) in THF at room temperature, the

3

4

imidazolidines 5 have been obtained in high yields and

diastereoselectivities: a general overview of the scope of the

reaction is shown in scheme 4 (see examples with conditions A).

It was also noticed that in the presence of less bulky substituents

1

(

i.e. R = Me, H), low diastereoselectivities were generally

Scheme 4. Pd-catalyzed (3+2)-cycloaddition reactions between 2-

substituted vinylaziridines 3 and cyclic N-sulfonyl imines 4.

observed (Scheme 4, conditions A).

3

Anticipating that accelerating a π−σ−π is

A

om

C

er

C

iza

E

tio

P

n

T

c

E

ou

D

ld MA2.

N

R

U

esu

S

lt

C

s a

R

n

I

d discussion

P

T

have a beneficial impact on the diastereoselectivity outcome, the

reaction was carried out in the presence of two equivalents of

Asymmetric reactions

16

LiCl. Finally, by combining the use of LiCl and decreasing the

reaction temperature down to −30 °C, the imidazolidines 5ca-5cd

and 5da were obtained in excellent yields and

diastereoselectivities (Scheme 4, conditions B). The

diastereoselectivity of the imidazolidines 5 could be ascertained

With these aims in mind, we have thus started our studies first

seeking to devise an asymmetric version of the previous

developed Pd-catalyzed (3+2)-cycloaddion. In our previous

study, we have shown that enantioenriched vinylaziridine 3a

(80% ee) in the presence of 4a enabled the formation of 5aa in

14

by the determination of the X-ray structure of compound 5aa.

9

1% yield with a marked erosion of the enantiomeric purity (19%

The reaction could also be extended to Z and E substituted

double bonds substrates 3e and 3f obtained by either Wittig or

Horner-Wadsworth-Emmons from aldehyde 2a (see scheme 3).

In the case of imidazolidine 5fa, the isomerization of the Z

double bond was interpreted as a confirmation of the π−σ−π

isomerization of the π-allyl palladium intermediate.

ee) (Scheme 7).

Scheme 7. Prior trial on an asymmetric version from enantioenriched

2

-substituted vinylaziridine 3a (80% ee).

This observation suggesting a rapid π−σ−π interconversion of

the π-allyl palladium (correlated with the double bond

isomerization in 3f → 5fa) thus paved the way to the

development of a dynamic kinetic asymmetric transformation

17

(

DYKAT). The use of chiral ligands in the 3a + 4a → 5aa

model reaction was thus investigated. Extensive work (more than

2 different chiral ligands under various conditions) was thus

2

Scheme 5. Vinyl-substituted aziridines 3e and 3f as substrates in Pd-

catalyzed (3+2)-cycloaddition reaction.

undertaken to embrace a general overview of the nature of the

chiral ligand on the selectivity outcome (conversion, yield,

diastereo- and enantioselectivities). Results are summarized in

table 1.

Concerning a mono-catalytic system strategy, differently

substituted phosphoramidites were first tried (entries 1-10). With

these ligands, the reaction was, for some yet unclear reason, very

sensitive to the ligand structure (compare for example entries 1-

2) leading to either no reactivity or complete conversion. L2

proved to be the more efficient one leading to 5aa in 80% yield,

good ee (70%) but with a moderate diastereoselectivity (dr = 3:1)

With the objective to extend the scope of this methodology

and to better understand the mechanistic scenario, we decided

through this study, to focus our attention on i) asymmetric

versions, ii) the post-transformation of the aminals 5, and iii) the

use of alternative zwitterionic π-allyl palladium intermediates

starting from vinylcyclopropanes (Scheme 6).

(entry 2). Moving to biphosphines (entries 11-16), low

enantioselectivities have been generally observed (up to 40% ee

using BINAP but in a very low conversion, entry 11) and, as

observed with phosphoramidites, small modifications in their

structure have a dramatic impact on the reactivity: compare

Josiphos and Taniaphos (entries 13 and 15). Classical Trost

ligand L16, widely used in DYKAT Tsuji-Trost reactions, gave

the expected compound in very good yield and

diastereoselectivity albeit with a low ee (16%) (entry 16). A dual

catalysis combining a Pd source and the activation of the

electrophile (i.e. with a chiral Lewis acid or a Brønsted acid) was

attempted with albeit deceiving results in terms of conversion

and enantioselectivities (entries 17, 20 and 21). According to the

general mechanism proposed in scheme 6, the generation of the

−

first stereogenic center is mediated by the attack of the TsN

anion to the imine partner. Therefore, using a chiral counterion

could be interesting to promote this addition in an

enantioselective way. Thus, chiral ammoniums L18 and L19,

have

enantioselectivities.

Based on Oii’s work on (3+2)-cycloadditions with

been

tested,

albeit

unsuccessfully

regarding

7b,18

vinyloxazolidinones,

original ligand L22 bearing a

phosphine with a remote ammonium salt could be efficiently

obtained from the commercially available cinchona 7 in one step

and in 57% yield (Scheme 8). Even though good yield (80%) and

diastereoselectivity (>20:1) have been observed in the model

Scheme 6. New targeted objectives within the Pd-catalyzed (3+2)-

cycloaddition reactions with 2-substituted vinyl-aziridines and

cyclopropanes.

4

Tetrahedron

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Table 1. Screening of chiral ligands L1−L22 for Pd-catalyzed (3+2)-cycloaddition reactions with 2-substituted vinylaziridines and cyclic N-

a

sulfonyl imines.

b

c

d

e

Entry

Strategy

Ligand Class

Ligands L

Conversion (%) Yield (%)

dr

ee (%)

1

2

3

4

5

6

7

8

9

L1

L2

L3

L4

L5

L6

L7

L8

−

100

−

ND

80

ND

3:1

ND

6:1

8:1

6:1

ND

>20:1

ND

70

ND

55

33

9

ND

40

0

ND

21

16

ND

0

ND

82

Phosphoramidites

−

100

50

33

−

<10

100

<5

5

64

100

−

100

37

20

Mono-catalysis

L9

L10

1

0

1

2

3

4

5

6

ND

<10

80

ND

52

80

ND

86

BINAP (L11)

2-Furyl-MeOBIPHEP (L12)

JOSIPHOS (L13)

DTBM-SEGPHOS (L14)

TANIAPHOS (L15)

Trost ligand (L16)

tBu-bisoxazoline (L17)

L18

Biphosphines

ND

3:1

>20:1

ND

13:1

12:1

f

1

7

Bisoxazoline

g

1

2

8

9

0

1

g

Chiral ammoniums

L19

L20

L21

86

60

0

Dual-catalysis

Phosphoric acids

Phosphine/

ammonium salt

2

L22

100

80

>20:1

0

a

Reaction conditions: Unless otherwise noted, reactions were conducted with aziridine 3a (0.13 mmol) and imine 4a (0.16 mmol) under Pd

2

(dba)

3

ꢀCHCl

3

(2.5_c

b

1

mol%) catalyst, ligand L* (6 or 12 mol%) in THF (1.5 mL) at rt for 12 h. Conversion determined on the basis of H NMR analysis of crude reaction mixture.

Isolated yield after purification on column chromatography. Diastereomeric ratios (dr) were determined on the basis of H NMR analysis of crude reaction

mixture. Enantiomeric excesses were determined by HPLC on a chiral stationary phase. The reaction was carried with Cu(OTf)

and Pd(PPh

salts (L18/L19). ND = Not Determined.

d

1

e

f

2

(10 mol %), L17 (11 mol %)

g

3

) (10 mol%) in THF at rt for 12 h. Pd(PPh ) (10 mol%) was used as catalyst with 10 mol% of chiral phosphoric acid (L20/L21) or ammonium

4

3

4

Figure 1. Structures of chiral ligands L1-22 screened on this study.

5

reaction of 3a with cyclic N-sulfonyl imine 4a,

in a racemic form (entry 22).

A

5a

C

a

C

wa

E

s

P

ob

T

ta

E

in

D

ed MATr

N

os

U

t ra

S

is

C

in

R

g uIP

p the enantioselectivity from 42 to 82% ee in the

T

2b

cycloaddition of vinylaziridine with isocyanates. When the

reaction was performed in toluene at −30 °C in the presence of 10

mol% of acetic acid, the ee raised up to 90% with no

modification of the diastereoselectivity (entry 8). Playing on the

pka of the carboxylic acid (acetic acid; pKa = 4.8) by using either

benzoic acid (pKa = 4.2) or pivalic acid (pKa = 5.0) proved

detrimental: 67 and 83% ee were respectively obtained (entries 9

and 10). Similar behavior was observed when the reaction was

carried out in THF at −30 °C in presence of 10 mol% of acetic

acid: 80% ee (entry 11). In order to obtain a synergistic effect, we

have tried the combination of TBACl (that increased our dr

ratios) and AcOH (that provided higher ees). Unfortunately, even

though excellent diastereoselectivity and yield could be

maintained (dr = 20:1 and 84% yield) the compound was isolated

in a racemic form (entry 12).

Scheme 8. Synthesis of phosphine tethering an ammonium salt

ligand L22.

After this chiral ligands’ overview, the reaction was re-

optimized in order to improve not only the enantioselectivity

(70%) but also, ideally, the 3:1 diastereoselectivity. Changing the

solvent to DMF or toluene has no impact on the

diastereoselectivity outcome (Table 2, entries 2-3) but a small

enantioselectivity improvement was observed with toluene (75%

vs 70% ee). Decreasing the reaction temperature to −30 °C led to

a marked improvement of the enantioselectivity to 82% (entry 4)

but no further improvement could be observed at −78 °C (entry

Interestingly, compound 5aa obtained in 90% ee and 3:1 dr

entry 8) could be recrystallized in a CH Cl /pentane system to

give the diastereomeric pure compound in >99% ee. An X-ray

analysis could be thus realized establishing the absolute

configuration of the two stereocenters as R and S for the C5 and

(

2 2

5

). We previously observed in our original communication, that

the diastereoselectivity could be improved by using additives to

promote rapid π−σ−π interconversion of the π-allyl

intermediate. Indeed when the reaction was carried out in toluene

19

C7 stereocenters respectively (Figure 2).

a

2g

at −30 °C, in the presence of two equivalents of TBACl, the

diastereoselectivity raised up to >20:1 but unexpectedly the

compound was obtained in a racemic form (entry 6). In a control

experiment, the same reaction in the presence of only 20 mol% of

TBACl led to the originally observed 3:1 diastereoselectivity and

5

6% ee (entry 7).

Figure 2. X-ray analysis of 5aa in >99% ee and dr.

Table 2. Re-optimization of the reaction conditions in the presence

of chiral ligand (S)-L2.

a

These optimized conditions have been next tested on

differently substituted vinylaziridines 3a-3d and N-sulfonyl

imines 4a-4c, with however moderate success (Table 3). The

reaction is highly dependent on the substituent bulkiness: When

1

relatively small substituents (R = H or Me) are used low

diastereo- and enantioselectivities are observed whereas moving

to bulkier iPr group good diastereo (dr

= 9:1) and

enantioselectivity (82% ee) are obtained. When substituted N-

sulfonyl imines 4b and 4c (entries 5 and 6) were used, low

diastereoselectivities and moderate ees have been reached.

b

d

Additive

Yield

(%)

85

c

ee

Entry

Solvent

T °C

dr

(mol%)

(%)

70

a

Table 3. Reaction scope.

1

2

THF

rt

−

3:1

DMF

84

40

O

_R1

S

Pd2(dba)3•CHCl3

S)-L2

O

3

4

5

6

7

toluene

rt

−

86

88

83

88

3:1

>20:1

3:1

75

82

79

0

O

N

S

(

O

N

NTs

−30

−78

−30

3

AcOH (10 mol%)

toluene, 30 °C

R2 ₄

N

_R2

3

a-3d

H

Ts

1

2 h

TBACl (200)

TBACl (20)

4

a-4c

5

56

R¹= Bn (3a), iPr (3b), Me (3c), H (3d)

_R2 = H (4a), 4-Br (4b), 3-Cl (4c)

8

toluene

−30

AcOH (10)

85

3:1

90

9

toluene

THF

−30

PhCO

Pivalic acid (10)

AcOH (10)

TBACl (200)

AcOH (10)

2

H (10)

80

87

86

84

2:1

67

83

80

0

1

0

1

2

1

2

b

c

d

Entry

1

2

R

Product

5aa

Yield (%)

dr

ee (%)

e

Bn

Me

H

85

84

3:1

2:1

90 (99)

40

toluene

20:1

5

ca

a

3

4

5

6

H

Η

4-Br

3-Cl

5da

5ba

5ab

5ac

86

83

90

88

1:1

9:1

2:1

13

82

65

64

Reaction conditions: Unless otherwise noted, reactions were conducted with

aziridine 3a (0.13 mmol) and imine 4a (0.16 mmol) under Pd (dba) ꢀCHCl

2.5 mol%) catalyst, ligand (S)-L2 (12 mol%) and additive (X mol%) in

iPr

Bn

2

3

(

b

solvent (1.5 mL) at T °C for 12 h. Isolated yield after purification on column

a

c

Reaction conditions: Unless otherwise noted, reactions were conducted with

aziridines 3 (0.13 mmol) and imines 4 (0.16 mmol) under Pd (dba) ꢀCHCl

3

2.5 mol%) catalyst, ligand (S)-L2 (12 mol%) and AcOH (10 mol%) in

toluene (1.5 mL) at −30 °C for 12 h. Isolated yield after purification on

column chromatography. Diastereomeric ratios (dr) were determined on the

basis of H NMR analysis of crude reaction mixture. Enantiomeric excesses

were determined by HPLC on

recrystallization in a CH Cl /pentane system.

chromatography. Diastereomeric ratios (dr) were determined on the basis of

1

d

H NMR analysis of crude reaction mixture. Enantiomeric excesses were

2

3

(

determined by HPLC on a chiral stationary phase.

b

c

These very disappointing results (for mechanistic discussion

vide infra) prompted us to investigate the use of other additives.

The use of acetic acid as additive has been first described by

1

d

e

a

chiral stationary phase.

After

2

6

Tetrahedron

ACCEPTED MANUSCRIPT

Post-transformations of aminals 5

Vinylcyclopropane 14a was next engaged in a model reaction

with N-sulfonyl imine 4a in the presence of Pd(PPh ) (Table 4).

3

4

Aminals 5 can also be considered as potential synthetic

In the absence of any additive, the reaction led to the expected

3+2)-cycloaddition in good yields, however in the complete

platforms as illustrated in scheme 9. In the presence of KHMDS

(

(1.2 equiv.), the corresponding compound 8 was cleanly obtained

absence of diastereoselectivity, whatever the solvent used (THF,

DMF or toluene). No impact on the yield or the

diastereoselectivity could be observed when decreasing the

temperature to −30 °C (entries 4-5). The use of LiCl (200 mol%)

as an additive was also unproductive either at room temperature

or at −30 °C (entries 6-7, 9). Diastereoselectivity could be finally

only slightly improved to 1:3 by using TBACl (200 mol%) at

in 90% yield through the elimination of the tosylate group. This

compound could further be transformed by addition of MeMgBr:

interestingly the acyclic aminal product 9 was obtained in 64%

yield through an S 2’ reaction. When compound 8 was subjected

N

to hydrogenation conditions, two products could be isolated. In

both products, the vinylic double bond is reduced and this

expected reduction is accompanied by both the reduction of

C(IV)−N bond (47% yield, compound 10) and the reduction of

the aromatic C−O bond (45% yield, compound 11). Moreover,

under reductive ozonolysis conditions, aldehyde 12 was isolated

in 34% yield and its structure was unambiguously confirmed by

−30 °C in toluene (entry 10). These results are in sharp contrast

to those observed with vinylaziridines where high

diastereoselectivities have been generally observed (Scheme 4).

1

2

Moreover, the diastereomers (±)-15aa and (±)-15aa could be

separated by column chromatographic and their relative

configuration could be thus successfully assigned by NOESY

20

X-ray analysis.

25

experiments (Scheme 11).

Table 4. Pd-catalyzed (3+2)-cycloaddition reactions with 2-

a

substituted vinylcyclopropane 14a and cyclic N-sulfonyl imine 4a

b

c

Entry

1

Solvent

THF

T °C

rt

Additive

Yield (%)

dr

−

90

1:1

2

DMF

rt

87

1:1

3

4

5

6

7

toluene

THF

toluene

THF

rt

−30

rt

−

LiCl

85

84

82

83

1:1

toluene

rt

8

toluene

rt

TBACl

83

1:1

9

toluene

−30

LiCl

TBACl

85

88

1:1

1:3

Scheme 9. Post-transformation of aminal 5aa.

1

0

a

Reaction conditions: Unless otherwise noted, reactions were conducted with

vinylcyclopropane 14a (0.13 mmol) and imine 4a (0.16 mmol) under

Pd(PPh (10 mol%) catalyst and additive (200 mol%) in solvent (1.5 mL) at

T °C for 12 h. Isolated yield after purification on column chromatography.

Diastereomeric ratios (dr) were determined on the basis of H NMR analysis

of crude reaction mixture.

Vinylcyclopropanes as zwitterionic precursors

3 4

)

b

c

2

-Substituted vinylcyclopropanes 14 can also be easily

1

obtained from the corresponding α-substituted enals 1 under

21

organocatalytic reactions, and we were thus keen to use them

22,23

in Pd-catalyzed (3+2)-cycloadditions (Scheme 10).

It is worth

mentioning that to the best of our knowledge 2-substituted

vinylcyclopropanes (R ≠ H) have not been used in Pd-catalyzed

2

4

(

4

3+2)-cycloadditions yet. Aldehydes 13 have been obtained in

21

3-81% yields. Further Wittig or HWE reactions lead to the 2-

substituted vinylcyclopropanes 14 in good yields (42-76%).

1

2

Scheme 11. Relative configuration of (±)-15aa and (±)-15aa via

NOESY experiments.

25

The scope of the reaction was next investigated using several

substituted vinylcyclopropanes 14a-14f and N-sulfonyl imines

4

a-4d and the reactions have been tested either in the absence

(conditions A: THF, rt) or in the presence of TBACl (conditions

B: toluene, −30 °C); Results are summarized in table 5.

In general, the reaction outcomes are very good delivering the

expected compounds with very high conversions and yields

(entries 1-9, 13). As previously observed, no diastereoselectivity

Scheme 10. Synthesis of 2-substituted vinylcyclopropanes 14a-f.

is obtained: conditions B exhibiting a marginal effect. The

reaction was also very sensitive towards the bulkiness of the

7

−

tetrasubstituted vinylcyclopropanes as illustrat

A

ed

C

w

C

he

E

n

P

R

T

=

E

i

D

Pr MAca

N

se

U

of

S

v

C

in

R

yl

I

a

P

ziridines 3 or X = (EtO C) C in the case of

2 2

T

(entries 11 and 12). Curiously, cyclic N-sulfonyl imine 4d

vinylcyclopropanes 14). It should also be emphasized that in the

presence of chiral ligand L* the ionization could occur in either a

substituted at the position 5 with a tBu group did react very well

to give pyrrolidine 15ad when conditions A were employed

1

2

matched or mismatched fashion to give either A and/or A .

1

2

(entry 13); however switching to conditions B, no conversion

Moreover, A and A could be in equilibrium through a π−σ−π

isomerization of the π-allyl palladium depending on the reaction

could be observed (entry 14). When the terminal vinylic position

1

−

on the cyclopropane partner was substituted (R = Me or CO Et),

conditions (X nature, palladium source, ligand, additives…).

2

the (3+2)-cycloaddition process was somehow reluctant (entries

1

5-18, pyrrolidines 15ba and 15fa). Indeed, in these particular

Table 6. Trials from chiral vinylcyclopropane 14a.

1

cases, only vinylcyclopropane 14f (R = Bn, R = CO Et)

2

sluggishly reacts with unsubstituted cyclic N-sulfonyl imine 4a to

give the product in moderate conversion and low yield (60% and

3

7% respectively) (entry 17).

Table 5. Reaction scope with vinylcyclopropanes 14a-f.

a

b

c

Entry Conditions dr

ee dia 1 % ee dia 2 % Yield %

1

2

A

B

1:1

1:3

81

86

78

30

90

92

a

1

Diastereomeric ratios (dr) were determined on the basis of H NMR analysis

of crude reaction mixture. Enantiomeric excesses (ee) were determined by

HPLC on a chiral stationary phase. Isolated yield after purification on

b

1

2

Conditions/

Conversion (%) (Yield %)

Product

c

Entry

R

a

b

dr

c

1

2

Bn

H

A / 100%

B / 100%

15aa (90)

1:1

1:3

column chromatography.

15aa (88)

3

4

5

6

7

8

9

Me

H

Me

H

A / 100%

B / 100%

A / 100%

B / 100%

A / 100%

B / 80%

A / 70%

B / 40%

A / 20%

B / 0%

A / 100%

B / 0%

A / 0%

B / 0%

A / 60%

15ca (92)

15ca (90)

15ea (91)

15ea (89)

15ac (89)

15ac (68)

15ab (66)

15ab (<10)

15da (14)

15da (−)

15ad (95)

15ad (−)

15ba (−)

15fa (37)

15fa (−)

1:1

9:1

>20:1

−

1:1

−

Scheme 12. Mechanism proposal.

H

Bn

iPr

Bn

3-Cl

4-Br

Η

1

0

1

2

3

4

5

6

7

8

Η

5-tBu

H

Bn CO

2

Et

3:1

−

2

H

B / 0%

a

1

Conversion determined on the basis of H NMR analysis of crude reaction

mixture. Isolated yield after purification on column chromatography.

Diastereomeric ratios (dr) were determined on the basis of H NMR analysis

b

c

1

of crude reaction mixture.

The low observed diastereoselectivities prompted us to study

the (3+2)-cycloaddition of enantioenriched vinylcyclopropane

1

4a (86% ee). In the absence of any additive (Table 6, conditions

A), a 1:1 mixture of the two diastereomers of 15aa was obtained

in 90% yield and, as one could expected, each diastereomer was

recovered with a slight erosion on the initial enantiomeric excess

(

Table 6, entry 1). Under ‘equilibrating’ conditions B (i.e.

−

TBACl, toluene, −30 °C), a 1:3 mixture of the two diastereomers

The attack of the nucleophile X to the N-sulfonyl imine 4

was obtained and as a consequence, the major diastereomer was

obtained in reduced ee (30%).

next enables the formation of the zwitterionic intermediates B

(Scheme 12, step b). This A → B reaction also results in the

creation of the first stereogenic center. The chiral ligand could

indeed directly control the facial selectivity of the addition but

the reaction could also be unselective leading to a mixture of four

26

Mechanistic discussion

The obtention of imidazolidines 5 and pyrrolidines 15, as

illustrated in scheme 12, results from three consecutive reactions.

The π-allyl palladium A is first formed (Scheme 12, step a),

1-1

1-2

2-1

potential epimeric π-allyl palladium complexes B , B , B

2-2

and B . These four intermediates are anyway potentially in

equilibrium through π−σ−π interconversions and/or through a

reversible addition.

−

resulting in the liberation of the nucleophile X (X = TsN in the

8

Tetrahedron

The third step is the cyclization, i.e. the int

A

ram

C

o

C

lec

E

ul

P

ar

T

a

E

tta

D

ck MAad

N

di

U

tiv

S

e t

C

o

R

pro

I

mote the π−σ−π isomerization of π-allyl palladium

P

T

2

b

of the sulfonyl-amidate to the π-allyl palladium, thus generating

the second, tetrasubstituted, stereogenic center (Scheme 12, step

c). According to the Curtin-Hammett principle, this cyclization

could be ideally stereocontrolled to give the diastereo- and

enantio-enriched imidazolidines 5 or pyrolidines 15.

In our mechanistic scenario, two π−σ−π isomerizations are

potentially occurring: are they both effective? What is the

influence of the coordination of the X to the palladium in the

complexes, the diastereoselectivity remains moderate (Table 3,

entry 1). Interestingly, additives known to promote π−σ−π

isomerizations could have divergent issues: the use of TBACl

(200 mol%) ensures a good diastereoselectivity (dr = 20:1) but

no enantioselectivity (Table 2, entry 6), whereas acetic acid has

no effect on the dr outcome (dr = 3:1) but allows a 90% ee

(Table 2, entry 8). It thus appears that in our current reaction

conditions, we are not able to efficiently manage the two π−σ−π

isomerization events in order to control both diastereo- and

enantioselectivity outcomes at once.

−

π−σ−π isomerizations?

As observed in control experiments (Scheme 13), the nature of

−

the leaving group X [TsN vs (EtO C) C ] has a dramatic

2

influence on the stereochemical outcome of the reaction. When

Scheme 14.

vinylaziridines 3a and 3c.

R

groups steric effect on the 2-substituted

−

starting from enantiomeric enriched vinylcyclopropane 14a (X =

−

(

EtO C) C , 86% ee), pyrrolidine 15aa is obtained as a 1:1

2

mixture of the two diastereomers and a slight erosion of the

chirality (78 and 81% ee), whereas starting with vinylaziridine 3a

−

(

X = TsN , 80% ee), the corresponding imidazolidine 5aa is

isolated in excellent diastereoselectivity (dr = 14:1) and a

dramatic drop of the enantioselectivity (19% ee).

Scheme 13. Control experiments: Influence of the leaving group in

the diastereoselectivity outcome.

3

. Conclusion

In conclusion, we have developed a synthetically practical and

useful protocol to allow the synthesis of several imidazolidines 5

and pyrrolidines 15 bearing a tetrasubstituted carbon. The

method goes through

a Pd-catalyzed (3+2)-cycloaddition

reaction, via zwitterionic π-allyl palladium intermediates, in the

presence of cyclic N-sulfonyl imines with either vinylaziridines

or vinylcyclopropanes. Divergent and interesting behaviors were

observed depending on the leaving group bore by the vinylic

substrate (NTs vs malonate). In the former case, excellent

It thus appears that limited π−σ−π isomerizations occur with

26

cyclopropanes 14 in these reaction conditions. This result is

rather surprising since DYKAT (3+2)-cycloadditions of

vinylcyclopropanes have been described elsewhere in high

reaction

outcomes

were

accompanied

by

high

23,27

diastereo- and enantioselectivities.

Nonetheless, it should be

diastereoselectivities thanks to a rapid π−σ−π isomerization of π-

allyl palladium complexes. In the case of recalcitrant substrates

emphasized that, to the best of our knowledge, all reported

examples describe the use of non-substituted vinylcyclopropanes

R = H). The use of various additives (LiCl, TBACl) was found,

(i.e. less encumbered ones, for which moderate-to-low dr were

(

first obtained) the addition of additives such as TBACl or LiCl

was favorable to promote such ‘equilibria’ and considerably

improve the diastereoselectivities. Seeking to develop a DYKAT

process, chiral ligands were tried; unfortunately, good

enantioselectivity was followed by a substantial drop on the

diastereoselectivity even if additives were used. On the other

hand, moving to vinylcyclopropane substrates, the π−σ−π

isomerization of π-allyl palladium complexes seems somehow

trickier and very limited and the chirality of the substrates was

almost completely transferred to the products at the expense of

the diastereoselectivity. The method proposed within this study

in our hands, to be unsuccessful to dramatically change the

diastereoselectivity outcome.

The situation appears more complex with vinylaziridines 3.

When using bulky R-substituents, such as benzyl, the

imidazolidine 5aa was obtained in 92% yield with a 14:1

diastereoselectivity whereas in the presence of smaller groups (R

=

Me, H) very low diastereoselectivity is observed (dr = 2:1

when R = Me, Scheme 14). In the latter case, the use of LiCl or

TBACl (200 mol%) was necessary to obtain good

a

diastereoselectivity control (dr > 20:1). With bulky substituents

the cyclization (Scheme 12, step c) could be slow, enabling the

π−σ−π isomerization and a good diastereoselectiviy. With

smaller substituents (R = Me, H), the cyclization could be faster,

and in this case, an additive (such as LiCl or TBACl) is required

to promote a rapid π−σ−π isomerization of the π-allyl palladium

and ensure a good diastereoselective outcome.

affords

a

quite simple procedure to prepare several

imidazolidines (and analogues through derivatization) as well as

pyrrolidines richly functionalized and bearing a tetrasubstituted

carbon. Currently, work is ongoing on the combination of other

vinylic substrates with palladium-catalysis in order to propose

novel versatile compounds through cycloaddition reactions.

Based on the observation of the erosion of the

enantioselectivity in the reaction with enantiomerically enriched

vinylaziridine 3a (80% ee) (Scheme 13), the reaction in the

presence of chiral catalysts was thus investigated. With various

chiral ligands, catalytic and asymmetric reactions have been

attempted leading to the expected imidazolidines in high yields,

high enantioselectivities albeit in poor diastereoselectivities.

Even in the presence of 10 mol% of AcOH, an efficient known

4

. Experimental section

4

.1. General information

Unless otherwise specified, all commercial products and reagents

were used as purchased. Reactions were carried out in round-

9

-

1

bottom flasks and schlenks equipped with a ma

under argon atmosphere. Analytical thin-layer chromatography

TLC) of all reactions was performed on silica gel 60 F254 TLC

A

gn

C

et

C

ic

E

sti

P

rr

T

ing

E

b

D

ar MACH

N

C

U

l )

S

;

C

FT

R

IRIPne

T

at (cm ): 2928, 2864, 1418, 1270, 1224, 1207,

3

976, 955, 873, 843, 805, 780, 750, 687; HRMS-TOF (+)

calculated for C H NO P (m/z): [M+H] : calculated: 480.3031,

+

(

30

43

2

+

plates. Visualization of the developed chromatogram was

found: 480.3031; MS (ESI+): m/z 480.30 (100, [M+H] )

performed by UV absorbance (254nm), using p-anisaldehyde

(

1S,2S,4S)-1-(2-(diphenylphosphanyl)benzyl)-2-((R)-

and/or KMNO . Flash chromatography was carried out on silica

4

TM

hydroxy(quinolin-4-yl)methyl)-5-vinylquinuclidin-1-ium (L22)

To a suspension of cinchonidine (0.189 g, 0.64 mmol) in dry and

degassed

(chloromethyl)phenyl)diphenylphosphane

mmol). This mixture was stirred at reflux for 2 h under argon

atmosphere. The solution was cooled to rt, poured into 50 mL of

diethyl ether and filtered. A white solid was obtained (220 mg,

5

gel 60 Å (35-70 nm) and Biotage Isolera Flash Purification

System. FT-IR spectra were recorded with a Perkin-Elmer

-

1

toluene

(4

mL)

was

added

the

(2-

Spectrum 1000; absorptions are given in wave numbers (cm ).

28

1

13

(0.300 g, 0.97

H (400 MHz), C (100 MHz), NMR spectra were recorded with

1

a Bruker Ultra Shield 400 Plus. H chemical shifts are reported in

delta (δ) units in parts per million (ppm) relative to the singlet at

13

7

.26 ppm for d-chloroform (residual CHCl₃). C chemical shifts

are reported in ppm relative to the central line of the triplet at

7.0 ppm for d-chloroform. Splitting patterns are designated as s,

1

7% yield). M.p.: 109.5-115.7 °C; H NMR (400 MHz, CDCl ):

3

δ 8.98 (d, J = 4.4 Hz, 1H), 8.34 (ddd, J = 7.9, 4.5 and 1.6 Hz,

7

1

2

1

H), 8.29 (d, J = 7.0 Hz, 1H), 8.16 (ddd, J = 10.7, 8.5 and 1.4 Hz,

H), 7.91 (d, J = 4.5 Hz, 1H), 7.82 (ddd, J = 8.5, 6.9 and 1.2 Hz,

H), 7.67-7.62 (m, 2H), 7.59 (ddd, J = 7.6, 7.6 and 1.2 Hz, 1H),

singlet; d, doublet; t, triplet; q, quartet; quint, quintet; m,

multiplet; and br, broad and combinations thereof. All coupling

constants (J values) are reported in Hertz (Hz). Enantiomeric

®

7.52-7.17 (m, 12H), 6.85 (d, J = 6.9 Hz, 1H), 6.63 (dd, J = 12.3

and 2.1 Hz, 1H), 5.71-5.58 (m, 2H), 5.38 (ddt, J = 12.3, 11.1 and

3.1 Hz, 1H), 4.87-4.82 (m, 2H), 4.09-4.05 (m, 1H), 3.66-3.42 (m,

3H), 2.76-2.70 (m, 1H), 2.43-2.35 (m, 3H), 1.99-1.93 (m, 1H),

1

excesses were measured on a Shimadzu LC 20A HPLC with a

UV/visible detector at 254nm and 210nm. Optical rotations were

®

measured with a Bellingham + Stanley ADP 440 Polarimeter or

®

a Perkin Elmer Polarimeter with a sodium lamp at 589nm. Low

31

.75-1.68 (m, 1H) ppm; P NMR (400 MHz, CDCl ): δ −16.7

3

resolutions mass spectra were recorded on a Waters QTof-I

spectrometer using electrospray ionization. High resolution mass

spectra were obtained using the mass spectrometers operated by

the “Laboratoire de Mesures Physiques of the University of

Montpellier”. THF was dried by distillation over sodium metal

and benzophenone under argon.

13

ppm; C NMR (100 MHz, CDCl ): δ 150.2, 148.4, 145.8, 140.2

3

(d, J = 15.0 Hz), 137.4, 136.7 (d, J = 9.0 Hz), 136.0 (d, J = 2.0

Hz), 135.7 (d, J = 5.0 Hz), 134.7 (d, J = 9.0 Hz), 133.8 (d, J =

2

1

7.0 Hz), 133.9, 133.7, 133.4, 133.2, 130.6, 130.5, 129.9, 129.4,

29.2, 129.0, 129.0 (d, J = 1.0 Hz), 128.9, 128.2, 127.0, 125.2,

24.9, 122.8, 120.4, 115.9, 71.9, 62.9, 61.6 (d, J = 13.0 Hz), 61.2

4

.2. General procedures

(d, J = 21.0 Hz), 50.9, 38.1, 26.6, 24.8, 21.2 ppm; [α] = +21.7 (c

D

-

1

.29, CHCl ); FTIR neat (cm ): 3051, 1591, 1508, 1457, 1434,

3

.2.1 Racemic synthesis of compounds 5

325, 1091, 1065, 1028, 923, 882, 858, 801, 744, 696; HRMS-

+

TOF (+) calculated for C H N OP (m/z): [M+H] : calculated :

38

2

Compounds 3, 4 and 5 were synthesized according to a described

methodology. Analytical data were identical in all respects to

those previously reported.

14

569.2722, found: 569.2724; MS (ESI+): m/z 569.27 (100,

+

14

[M+H] )

4

.2.3 Asymmetric synthesis of compounds 5

4

.2.2 Synthesis of chiral ligands L9 and L22

(

3S,10bR)-3-benzyl-1-tosyl-3-vinyl-1,2,3,10b tetrahydrobenzo[e]

2

,6-di-tert-butyl-N,N-dimethyl-8,9,10,11,12,13,14,15-

imidazo[1,2-c][1,2,3]oxathiazine 5,5-dioxide (5aa)

octahydrodinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin-4-

amine (L9)

Representative procedure 1

(R)-(+)-5,5’,6,6’,7,7’,8,8’-octahydro-3,3’-di-tert-butyl-1,1’-bi-2-

In a flame-dried 10 mL flask equipped with a stir bar was

charged with the Pd (dba) .CHCl (3.4 mg, 0.0033 mmol.) and

naphthol, dipotassium salt (150 mg, 0.31 mmol) was partitioned

between chloroform and saturated aqueous NH Cl, the aqueous

2

3

4

the ligand ((S)-L2) (5.9 mg, 0.0156 mmol.). Then 1.4 mL of

dried toluene was added, this mixture was stirred at room

temperature 10 min. A stock solution of acid acetic in dried

toluene was added [100 µL of THF containing acetic acid (0.76

µL, 0.0132 mmol)] to the mixture. After 10 min of stirring the

catalyst solution was poured dropwise to a flame dried flask

containing the vinylaziridine 3a (41 mg, 0.13 mmol) and the

cyclic N-sulfonyl imine 4a (29 mg, 0.16 mmol) at –30 °C. This

solution was stirred at this temperature for 12 h. The reaction was

quenched with 1M HCl (2 mL). The aqueous layer was extracted

with CH Cl (3 x 5 mL), the combined organic layers were

phase was extracted 3 times with CHCl . The combined organic

3

layers was dried over anhydrous MgSO₄, filtered, and

concentrated. The residue was mixed with P(NMe ) (73 µL, 0.4

2

3

mmol) in dry toluene (2 mL) at room temperature under argon

atmosphere. The reaction mixture was warmed to 100 °C, and

stirred overnight. After reaction completion (TLC monitoring),

the solvent was removed in vacuum and the residue was directly

purified by silica-gel column chromatography using pentane

(100%) to pentane/AcOEt (9:1). The expected fractions were

combined and the solvent was removed under reduced pressure to

afford pale yellow oil (30 mg, 20% yield). Rf = 0.70 (eluent:

2

1

washed with brine (5 mL), dried over MgSO , filtered, and

4

pentane/Et O 8:2, UV and KMNO staining); H NMR (400

2

4

concentrated under vacuum. The expected compound was

isolated by silica gel chromatography using pentane (100 %) to

pentane/AcOEt (7:3) as eluent. The solvent was removed under

reduced pressure and afford a white solid (59 mg, 90% yield).

Analytical data were identical in all respects to those previously

MHz, CDCl ): δ 7.03 (s, 1H), 6.98 (s, 1H), 2.83-2.68 (m, 5H),

3

2

1

.48-2.32 (m, 6H), 2.20-1.96 (m, 3H), 1.78-1.65 (m, 6H), 1.59-

.52 (m, 2H), 1.44 (s, 9H), 1.38 (s, 9H) ppm; C NMR (100

13

MHz, CDCl ): δ 147.1 (d, J = 1.0 Hz), 145.8 (d, J = 1.0 Hz),

3

1

6

2

3

38.2 (d, J = 3.0 Hz), 137.2, 134.7 (d, J = 1.0 Hz), 134.1 (d, J =

.0 Hz), 132.2 (d, J = 1.0 Hz), 131.2 (d, J = 1.0 Hz), 130.7 (d, J =

.0 Hz), 129.8 (d, J = 3.0 Hz), 126.9 (d, J = 3.0 Hz), 126.9 (d, J =

.0 Hz), 34.6 (d, J = 1.0 Hz), 34.6 (d, J = 1.0 Hz), 31.2, 31.1,

12

reported in the literature. Chiral HPLC: analytical column

®

CHIRALCEL IC column (250 x 4.6 mm); nhexane/iPrOH 97:3,

1

.0 mL/min, 25 °C): t = 20.94 min and t_R₂= 26.84 min; dr: 3:1

R1

1

32

(determined by H NMR of the crude product; up to > 20:1 by

0.6 (6C), 29.6, 29.5, 27.4, 27.0, 23.3, 23.2, 23.1, 22.9 ppm;

P

recrystallization); ee: 90% (up to > 99% by recrystallization);

NMR (400 MHz, CDCl ): δ 140.7 ppm; [α] = −222.2 (c 1.35,

3

D

[

α] = −34.1 (c 0.82, CHCl )

D 3

10

Tetrahedron

ACCEPTED MANUSCRIPT

(

3R,10bS)-3-benzyl-8-bromo-1-tosyl-3-vinyl-1,2,3,10b-

tetrahydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazine 5,5-dioxide

5ab)

4.2.4 Post-transformation of compound 5aa

3

-benzyl-3-vinyl-2,3-dihydrobenzo[e]imidazo[1,2-c][1,2,3]

(

oxathiazine 5,5-dioxide (8)

The title compound was prepared according to the representative

procedure 1 from the corresponding vinylaziridine 3a (41 mg,

In a flame-dried 10 mL flask equipped with a stir bar was

charged with the imidazolidine 5aa (105 mg, 0.21 mmol) and 2.0

mL of dried THF. Then a solution of KHMDS 0.5M in toluene

was added dropwise (500 µL, 0.25 mmol) at 0 °C. The mixture

was warmed up to room temperature and stirred for 2 h. The

0

.13 mmol) and cyclic N-sulfonyl imine 4b (42 mg, 0.16 mmol)

using (R)-L2 as ligand to give a white solid (68.0 mg, 90%

yield). Analytical data were identical in all respects to those

14

previously reported in the literature. Chiral HPLC: analytical

reaction was quenched with saturated aqueous NH Cl solution (5

4

®

column CHIRALCEL

IC column (250

x

4.6 mm);

mL), and the resulting mixture was extracted with AcOEt (3 × 20

mL). The combined organic layers were washed with brine (15

nhexane/iPrOH 97:3, 1.0 mL/min, 25 °C): t = 15.87 min and t_R₂

R1

1

=

21.31 min; dr: 2:1 (determined by H NMR of the crude

mL) and dried over anhydrous MgSO . Filtration and evaporation

4

product); ee: 65%

under vacuum furnished the crude product, which was purified

by column chromatography using pentane/AcOEt (9:1 to 6:4) as

eluent. The expected fractions were combined and the solvent

was removed under vacuum to afford colorless oil (64 mg, 89%

(

3S,10bR)-3-benzyl-7-chloro-1-tosyl-3-vinyl-1,2,3,10b-

tetrahydrobenzo[e]imidazo[1,2-c][1,2,3]oxathiazine 5,5-dioxide

5ac)

(

yield). Rf = 0.5 (eluent: pentane/AcOEt 8:2, UV and KMNO4

The title compound was prepared according to the representative

procedure 1 from the corresponding vinylaziridine 3a (41 mg,

1

staining); H NMR (400 MHz, CDCl ): δ 7.93 (dd, J = 7.8 and

3

1

.6 Hz, 1H), 7.56 (ddd, J = 8.3, 7.4 and 1.7 Hz, 1H), 7.34-7.17

0

.13 mmol) and cyclic N-sulfonyl imine 4c (34 mg, 0.16 mmol)

(m, 7H), 6.40 (dd, J = 17.4 and 10.8 Hz, 1H), 5.49 (d, J = 17.5

using (R)-L2 as ligand to give a white solid (61.4 mg, 88%

yield). Analytical data were identical in all respects to those

previously reported in the literature. Chiral HPLC: analytical

column CHIRALCEL AD column (250

nhexane/iPrOH 98:2, 1.0 mL/min, 25 °C): dia 1: t_R₁= 23.09 min

and t_R₂= 32.10 min; dia 2: t = 20.59 min and t_R₂= 26.69 min;

dr: 2:1 (determined by H NMR of the crude product); ee: 64%

Hz, 1H), 5.46 (d, J = 10.8 Hz, 1H), 4.20 (d, J = 15.9 Hz, 1H),

14

3.99 (d, J = 15.8 Hz, 1H), 3.64 (d, J = 13.9 Hz, 1H), 3.14 (d, J =

13

®

13.8 Hz, 1H) ppm; C NMR (100 MHz, CDCl

3

): δ 151.2, 151.1,

x

4.6 mm);

1

37.6, 134.7, 134.0, 130.8 (2C), 128.4 (2C), 128.0, 127.1, 126.6,

18.6, 117.6, 115.1, 72.4, 64.0, 41.1 ppm; FTIR neat (cm ):

-1

R1

1

2929, 1651, 1460, 1388, 1344, 1202, 1176, 854, 788, 760, 655;

+

HRMS-ASAP (+) calculated for C H N O S (m/z): [M+H] :

18

17

2

3

(

[

3R,10bS)-3-isopropyl-1-tosyl-3-vinyl-1,2,3,10b-tetrahydrobenzo

e]imidazo[1,2-c][1,2,3]oxathiazine 5,5-dioxide (5ba)

calculated : 341.0960, found: 341.0963; MS (ESI+): m/z 341.09

(100, [M+H] )

+

The title compound was prepared according to the representative

procedure 1 from the corresponding vinylaziridine 3b (35 mg,

(

2

Z)-4-((2-benzylpent-2-en-1-yl)amino)benzo[e][1,2,3]oxathiazine

,2-dioxide (9)

0

.13 mmol) and cyclic N-sulfonyl imine 4a (29 mg, 0.16 mmol)

In a flame-dried 2 mL flask equipped with a stir bar was charged

with the sulfamate 8 (12 mg, 0.035 mmol) and 0.2 mL of dried

THF. Then a solution of MeMgBr 3M in Et O was added

dropwise (35 µL, 0.11 mmol) at 0 °C. The mixture was warmed

up to room temperature and stirred overnight. The reaction was

quenched with saturated aqueous NH Cl (5 mL), and the

resulting mixture was extracted with AcOEt (3 × 20 mL). The

combined organic layers were washed with brine (15 mL), and

using (R)-L2 as ligand to give a white solid (51.7 mg, 88%

yield). Analytical data were identical in all respects to those

14

2

previously reported in the literature. Chiral HPLC: analytical

®

column CHIRALCEL

IC column (250

x

4.6 mm);

nhexane/iPrOH 97:3, 1.0 mL/min, 25 °C): t = 14.34 min and t_R₂

R1

1

4

=

17.90 min; dr: 9:1 (determined by H NMR of the crude

product); ee: 82%; [α] = −53.1 (c 0.98, CHCl )

D

3

(3S,10bR)-3-methyl-1-tosyl-3-vinyl-1,2,3,10b-tetrahydrobenzo[e]

dried over anhydrous MgSO . Filtration and evaporation under

4

imidazo[1,2-c][1,2,3]oxathiazine 5,5-dioxide (5ca)

The title compound was prepared according to the

representative procedure 1 from the corresponding vinylaziridine

vacuum furnished the crude product, which was purified by

column chromatography using pentane/AcOEt (9:1 to 6:4) as

eluent. The expected fractions were combined and the solvent

was removed under vacuum to afford 8 mg of white solid (yield:

3

0

8

c (31 mg, 0.13 mmol) and cyclic N-sulfonyl imine 4a (29 mg,

.16 mmol) using (S)-L2 as ligand to give a white solid (48.7 mg,

8% yield). Analytical data were identical in all respects to those

64%). m.p.: 138.7-143.9 °C; Rf = 0.3 (eluent: pentane/AcOEt

1

8:2, UV and KMNO

staining); H NMR (400 MHz, CDCl

): δ

4

3

14

previously reported in the literature. Chiral HPLC: analytical

column CHIRALCEL

7.56 (ddd, J = 8.4, 7.4 and 1.5 Hz, 1H), 7.35-7.19 (m, 6H), 7.09

(dd, J = 7.6 and 0.8 Hz, 1H), 6.49 (dd, J = 7.9 and 1.5 Hz, 1H),

®

IC column (250

x

4.6 mm);

nhexane/iPrOH 97:3, 1.0 mL/min, 25 °C): t = 33.31 min and t_R₂

5.71 (t, J = 7.3 Hz, 1H), 5.47 (brs, 1H), 4.17 (d, J = 5.0 Hz, 2H),

R1

1

13

=

38.28 min; dr: 2:1 (determined by H NMR of the crude

3.47 (s, 2H), 2.24-2.17 (m, 2H), 1.06 (t, J = 7.5 Hz, 3H) ppm;

NMR (100 MHz, CDCl

C

product); ee: 40%

3

): δ 158.8, 153.5, 140.0, 136.4, 135.3,

1

4

1

6

31.0, 129.2 (2C), 128.6 (2C), 126.8, 124.7, 123.5, 119.6, 112.0,

4.1, 42.1, 21.5, 14.3 ppm; FTIR neat (cm ): 3340, 2962, 1598,

(

[

3R,10bR)-1-tosyl-3-vinyl-1,2,3,10b-tetrahydrobenzo[e]imidazo

1,2-c][1,2,3]oxathiazine 5,5-dioxide (5da)

The title compound was prepared according to the

-1

576, 1529, 1334, 1185, 1152, 1111, 1047, 918, 857, 768, 737,

+

82; HRMS-TOF (+) calculated for C H N O S (m/z): [M+H] :

19

21

2

3

representative procedure 1 from the corresponding vinylaziridine

3

0

calculated : 357.1273, found: 357.1276; MS (ESI+): m/z 357.13

d (29 mg, 0.13 mmol) and cyclic N-sulfonyl imine 4a (29 mg,

.16 mmol) using (R)-L2 as ligand to give a white solid (51.0

+

(100, [M+H] )

mg, 90% yield). Analytical data were identical in all respects to

4

-((2-benzylbutyl)amino)benzo[e][1,2,3]oxathiazine 2,2-dioxide

14

those previously reported in the literature. Chiral HPLC:

(10) + 4-benzyl-4-ethyl-2-phenyl-4,5-dihydro-1H-imidazole (11)

®

analytical column CHIRALCEL IC column (250 x 4.6 mm);

In a round bottom flask was put the sulfamate 8 (34 mg, 0.1

mmol) and the MeOH at room temperature. Several

vacuum/argon cycles were performed in the flask prior to the

nhexane/iPrOH 97:3, 1.0 mL/min, 25 °C): t = 42.98 min and t_R₂

R1

1

=

48.93 min; dr: 1/1 (determined by H NMR of the crude

product); ee: 13%

1

addition of the Pd/C (10 wt%). The argon

A

a

C

tm

C

os

E

ph

P

er

T

e

E

w

D

as MA4.

N

2.6

U

S

yn

C

th

R

esi

I

s of compounds 14a-f

P

T

replaced by H and the suspension was stirred for 12 h at room

2

Diethyl 2-benzyl-2-vinylcyclopropane-1,1-dicarboxylate (14a)

temperature. After reaction completion (TLC control), the

catalyst was filtered off with a syringe filter, and the filter was

rinsed several times with the solvent. Then, the solvent was

removed under vacuum. The crude product (1:1 mixture of 10

and 11) was purified by column chromatography using

pentane/AcOEt (9:1 to 0:10) as eluent. The expected fractions for

each compound were combined and the solvent was removed

under vacuum to afford 10 as colorless oil (16 mg, 47% yield)

and 11 as colorless oil (12 mg, 45% yield). Combined yield: 92%

Product 10: Rf = 0.4 (eluent: pentane/AcOEt 8:2, UV and

Representative procedure 2

KHMDS in toluene (0.5 M, 11.8 mL, 5.92 mmol) was added to

an ice-cooled (0 ˚C) solution of methyltriphenylphosphonium

bromide (2.35 g, 6.60 mmol) in THF (18 mL). After 15 min of

stirring, a solution of the corresponding aldehyde (1.0 g, 3.30

mmol) in THF (10 mL plus 2 × 1 mL rinse) was added, and the

mixture was stirred for 30 min at 0 °C. The reaction was

quenched with saturated aqueous NH Cl (10 mL), and the

resulting mixture was extracted with AcOEt (3 × 20 mL). The

combined organic layers were washed with brine (15 mL), and

dried over anhydrous MgSO . Filtration and evaporation under

vacuum furnished the crude product, which was purified by

column chromatography using pentane/AcOEt (9.8:0.2 to

.5:2.5) as eluent. The expected fractions were combined and the

solvent was removed under vacuum to afford 450 mg of colorless

oil (yield: 45 %). Rf = 0.70 (eluent: pentane/Et O 8:2, UV and

KMNO staining); H NMR (400 MHz, CDCl ): δ 7.28-7.16 (m,

5H), 5.76 (dd, J = 17.1 and 10.5 Hz, 1H), 5.06 (dd, J = 10.6 and

.8 Hz, 1H), 4.97 (dd, J = 17.2 and 0.8 Hz, 1H), 4.21-4.12 (m,

4H), 3.22 (d, J = 15.5 Hz, 1H), 3.02 (d, J = 15.5 Hz, 1H), 1.91 (d,

J = 5.4 Hz, 1H), 1.79 (d, J = 5.4 Hz, 1H), 1.25 (td, J = 7.2 and

6.1 Hz, 6H) ppm; C NMR (100 MHz, CDCl ): δ 168.4, 167.4,

38.6, 136.3, 128.9 (2C), 128.1 (2C), 126.1, 117.3, 61.6, 61.4,

0.9, 38.3, 36.9, 23.3, 14.1, 14.1 ppm; FTIR neat (cm ): 2981,

719, 1369, 1297, 1248, 1215, 1097, 1023, 921, 861, 721, 697;

4

1

KMNO staining); H NMR (400 MHz, CDCl ): δ 7.56 (ddd, J =

4

3

8

1

8

4

.4, 7.4 and 1.5 Hz, 1H), 7.35-7.22 (m, 5H), 7.19 (dd, J = 8.4 and

.2 Hz, 1H), 7.11 (ddd, J = 8.1, 7.3 and 1.6 Hz, 1H), 6.59 (dd, J =

.0 and 1.5 Hz, 1H), 5.76 (brs, 1H), 3.76 (ddd, J = 13.9, 6.6 and

.3 Hz, 1H), 3.28 (ddd, J = 13.9, 8.7 and 4.4 Hz, 1H), 2.97 (dd, J

4

7

=

13.9 and 4.7 Hz, 1H), 2.50 (dd, J = 13.9 and 8.6 Hz, 1H), 2.11-

2

.09 (m, 1H), 1.52-1.45 (m, 2H), 1.04 (t, J = 7.4 Hz, 3H) ppm;

1

3

2

C NMR (100 MHz, CDCl ): δ 159.0, 153.4, 140.6, 135.3, 129.2

3

1

4

3

(

4

1

2C), 129.0 (2C), 126.5, 124.7, 123.7, 119.6, 112.0, 46.5, 41.2,

0.1, 26.1, 11.3 ppm; FTIR neat (cm ): 3363, 2927, 1598, 1568,

-

1

0

533, 1348, 1186, 1165, 1110, 856, 746, 680; HRMS-TOF (+)

+

calculated for C H N O S (m/z): [M+H] : calculated: 345.1273,

found: 345.1275; MS (ESI ): m/z 345.13 (100, [M+H] ). Product

18

21

2

3

+

13

1

3

1

1: R = 0.4 (eluent: AcOEt 100%, UV and KMNO staining); H

f

4

1

4

1

NMR (400 MHz, CDCl ): δ 7.39-7.18 (m, 10H), 3.71 (d, J = 12.0

3

-1

Hz, 1H), 3.62 (d, J = 14.2 Hz, 1H), 3.47 (d, J = 12.0 Hz, 1H),

2

1

.73 (d, J = 14.2 Hz, 1H), 2.42 (dq, J = 14.4 and 7.4 Hz, 1H),

.67 (dq, J = 14.4 and 7.3 Hz, 1H), 1.00 (t, J = 7.4 Hz, 3H) ppm;

+

HRMS-TOF (+) calculated for C H O (m/z): [M+H] :

calculated: 303.1596, found: 303.1599; MS (ESI+): m/z 303.16

100, [M+H] ) ; [α] = +17.4 (c 1.15, CHCl , (S)-isomer, 86%

18

23

4

1

3

C NMR (100 MHz, CDCl ): δ 158.8, 153.5, 140.0, 136.4,

3

+

(

ee)

D

3

1

35.3, 131.0, 129.2 (2C), 128.6 (2C), 126.8, 124.7, 123.5, 119.6,

12.0, 44.1, 42.1, 21.5, 14.3 ppm; FTIR neat (cm ): 3215, 2926,

610, 1516, 1485, 1282, 1252, 1052, 1035, 915, 731, 704;

-

1

Diethyl

(Z)-2-benzyl-2-(prop-1-en-1-yl)cyclopropane-1,1-

+

HRMS-TOF (+) calculated for C H N (m/z): [M+H] :

18

21

2

dicarboxylate (14b)

calculated: 265.1705, found: 265.1711; MS (ESI+): m/z 265.17

KHMDS in toluene (0.5 M, 5.9 mL, 2.95 mmol) was added to an

ice-cooled (0 ˚C) solution of ethyltriphenylphosphonium bromide

+

(

100, [M+H] )

(

1.22 g, 3.26 mmol) in THF (9 mL). After 15 min of stirring, a

3

-benzyl-1-tosyl-1,2,3,10b-tetrahydrobenzo[e]imidazo[1,2-c]

solution of the corresponding aldehyde (500 mg, 1.63 mmol) in

THF (6 mL plus 2 × 1 mL rinse) was added, and the mixture was

stirred for 30 min at 0 °C. The reaction was quenched with

saturated aqueous NH Cl (10 mL), and the resulting mixture was

extracted with AcOEt (3 × 20 mL). The combined organic layers

were washed with brine (15 mL), and dried over anhydrous

[

1,2,3]oxathiazine-3-carbaldehyde 5,5-dioxide (12)

Imidazolidine 5aa (50 mg, 0.1 mmol) was dissolved in

CH Cl /MeOH (5:1, 5 mL), and the solution was cooled to –78

2

4

°

C. Ozone was bubbled through the cooled solution until a blue

color was obtained (~5 min). Argon was then bubbled through

for 10 min., and then methyl sulfide (37µL, 0.5 mmol) was

added. The reaction was allowed to warm to room temperature

and stir overnight. The solvent was removed under reduced

pressure and the crude was recrystallized using a AcOEt/pentane

MgSO . Filtration and evaporation under vacuum furnished the

4

crude product, which was purified by column chromatography

using Pentane/AcOEt (9.8:0.2 to 8:2) as eluent. The expected

fractions were combined and the solvent was removed under

system to afford white crystal (17 mg, 34% yield). m.p.: 159.5-

1

vacuum to afford 240 mg of colorless oil (yield: 48 %). Rf = 0.70

62.7 °C; H NMR (400 MHz, CDCl ): δ 9.89( s, 1H), 7.86-7.84

3

1

(eluent: pentane/Et O 8:2, UV and KMNO staining); H NMR

2

4

(m, 2H), 7.56 (dt, J = 7.9 and 1.3 Hz, 1H), 7.43-7.37 (m, 3H),

(400 MHz, CDCl ): δ 7.28-7.18 (m, 5H), 5.54 (dq, J = 10.8 and

3

7

1

.29-7.23 (m, 4H), 6.99-6.96 (m, 3H), 6.64 (s, 1H), 3.86 (d, J =

2.8 Hz, 1H), 3.76 (d, J = 12.9 Hz, 1H), 3.35 (d, J = 14.3 Hz,

7

.1 Hz, 1H), 5.35 (dq, J = 10.8 and 1.8 Hz, 1H), 4.26 (q, J = 7.1

Hz, 2H), 4.19-4.12 (m, 2H), 3.13 (d, J = 14.1 Hz, 1H), 2.64 (d, J

14.0 Hz, 1H), 1.86 (d, J = 5.0 Hz, 1H), 1.76 (d, J = 5.0 Hz,

H), 1.45 (dd, J = 7.1 and 1.8 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H),

13

H), 2.70 (d, J = 14.3 Hz, 1H), 2.50 (s, 3H) ppm; C NMR (100

=

1

MHz, CDCl ): δ 195.7, 149.7, 145.5, 134.0, 133.0, 131.5, 130.5

3

(2C), 130.2 (2C), 128.9 (2C), 128.0 (2C), 127.8, 127.7, 126.5,

13

-1

1.25 (t, J = 7.1 Hz, 3H) ppm; C NMR (100 MHz, CDCl ): δ

1

6

neat (cm ): 2981, 1722, 1445, 1368, 1302, 1212, 1202, 1098,

1020, 862, 723, 698; HRMS-TOF (+) calculated for C H O

4

3

1

3

9

18.3, 118.0, 77.5, 73.0, 49.4, 39.9, 21.7 ppm; FTIR neat (cm ):

070, 1735, 1596, 1454, 1407, 1353, 1204, 1166, 1089, 1024,

68.7, 167.9, 138.6, 130.2, 129.4 (2C), 128.0 (2C), 127.7, 126.2,

1.5, 61.3, 39.8, 39.8, 36.0, 25.8, 14.1, 14.1, 13.76 ppm; FTIR

83, 890, 829, 756, 729, 667; HRMS-TOF (+) calculated for

-

1

+

C H N O S (m/z): [M+H] : calculated: 499.0998, found:

4

24

23

2

6 2

+

1

9

25

99.1006; MS (ESI+): m/z 499.10 (100, [M+H] )

+

(m/z): [M+Na] : calculated: 317.1753, found: 317.1754; MS

+

4

.2.5 Synthesis of compounds 13

(ESI+): m/z 317.18 (100, [M+Na] )

Compounds 13a-d were synthesized according to a described

Diethyl 2-methyl-2-vinylcyclopropane-1,1-dicarboxylate (14c)

The title compound was prepared according to the representative

procedure 2 from the corresponding aldehyde (1.1 g, 4.82 mmol)

21

methodology. Analytical data were identical in all respects to

21

those previously reported.

12

Tetrahedron

ACCEPTED MANUSCRIPT

to give colorless oil (456 mg, yield: 42 %). Rf = 0.80 (eluent:

4.2.7 Synthesis of compounds 15

1

pentane/Et O 8:2, UV and KMNO staining); H NMR (400

2

4

Diethyl

3-benzyl-3-vinyl-2,3-dihydrobenzo[e]pyrrolo[1,2-

1

MHz, CDCl ): δ 5.84 (dd, J = 17.6 and 10.8 Hz, 1H), 5.18 (dd, J

3

c][1,2,3]oxathiazine-1,1(10bH)-dicarboxylate 5,5-dioxide (15aa

and 15aa )

=

17.6 and 1.2 Hz, 1H), 5.13 (dd, J = 10.8 and 1.2 Hz, 1H), 4.26-

2

4

1

.13 (m, 4H), 1.76 (d, J = 5.2 Hz, 1H), 1.60 (d, J = 5.3 Hz, 1H),

.35 (s, 3H), 1.27 (dt, J = 13.4 and 7.2 Hz, 6H) ppm; C NMR

13

Representative procedure A

(

4

1

100 MHz, CDCl ): δ 168.2, 168.1, 138.5, 115.4, 61.5, 61.4,

3

-1

A flame-dried 10 mL flask equipped with a stir bar was charged

with vinylcyclopropane 14a (32 mg, 0.13 mmol), the Pd(PPh₃)₄

(15 mg, 0.013 mmol.) and the cyclic N-sulfonyl imine 4a (29 mg,

0.9, 33.6, 26.0, 17.8, 14.1, 14.1 ppm; FTIR neat (cm ): 2982,

721, 1447, 1368, 1298, 1227, 1174, 1104, 1002, 914, 862, 781;

+

HRMS-TOF (+) calculated for C H O (m/z): [M+Na] :

12

19

4

0

.16 mmol). Then 1.5 mL of dried THF was added, the yellow

calculated: 227.1283, found: 227.1284; MS (ESI+): m/z 227.13

+

mixture was stirred at room temperature for 12 h. The reaction

was quenched with 1M HCl (2 mL). The aqueous layer was

extracted with CH Cl (3 x 5 mL), the combined organic layers

(

100, [M+Na] )

Diethyl 2-isopropyl-2-vinylcyclopropane-1,1-dicarboxylate (14d)

The title compound was prepared according to the representative

procedure 2 from the corresponding aldehyde (0.330 mg, 1.30

2

were washed with brine (5 mL), dried over MgSO , filtered, and

4

concentrated under vacuum. Expected compounds were isolated

by silica gel chromatography using pentane (100%) to

pentane/AcOEt (7:3) as eluent. The solvent was removed under

mmol) to give colorless oil (200 mg, yield: 60 %). Rf = 0.80

1

(

eluent: pentane/Et O 8:2, UV and KMNO staining); H NMR

2

4

1

400 MHz, CDCl ): δ 5.96 (dd, J = 17.1 and 10.4 Hz, 1H), 5.19

dd, J = 10.4 and 1.5 Hz, 1H), 5.05 (dd, J = 17.1 and 1.5 Hz, 1H),

reduced pressure and afford two colorless oils (15aa : 29 mg,

3

2

1

15aa : 28 mg, combined yield: 90%); dr: 1:1 (determined by H

4

.24-4.07 (m, 4H), 1.87-1.80 (m, 2H), 1.47 (dd, J = 5.1 and 1.2

NMR of the crude product)

Hz, 1H), 1.28 (t, J = 7.2 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H), 0.99

13

(

d, J = 6.9 Hz, 3H), 0.90 (d, J = 6.9 Hz, 3H) ppm; C NMR (100

Representative procedure B

A flame-dried 10 mL flask equipped with a stir bar was charged

with vinylcyclopropane 14a (32 mg, 0.13 mmol), the Pd(PPh₃)₄

MHz, CDCl ): δ 168.7, 167.5, 132.5, 118.7, 61.4, 61.1, 44.5,

3

-

4

1.0, 30.9, 30.1, 22.9, 19.9, 19.1, 14.1, 14.1 ppm; FTIR neat (cm

1

): 2965, 1721, 1446, 1369, 1291, 1232, 1213, 1164, 1124, 1098,

(15 mg, 0.013 mmol.) the cyclic N-sulfonylimine 4a (29 mg, 0.16

1

051, 1030, 994, 920, 860, 802; HRMS-TOF (+) calculated for

mmol). and TBACl (72 mg, 0.26 mmol). Then 1.5 mL of dried

Toluene was added at –30 °C and the yellow mixture was stirred

at this temperature for 12 h. The reaction was quenched with 1M

HCl (2 mL). The aqueous layer was extracted with CH Cl (3 x 5

+

C H O (m/z): [M+Na] : calculated

2

: 255.1596, found:

14

23

4

+

55.1598; MS (ESI+): m/z 255.16 (100, [M+Na] )

2

Diethyl 2-vinylcyclopropane-1,1-dicarboxylate (14e)

mL), the combined organic layers were washed with brine (5

The title compound was prepared according to the representative

procedure 2 from the corresponding aldehyde (0.500 mg, 1.30

mmol) to give colorless oil (300 mg, yield: 60 %). Analytical

data were identical in all respects to those previously reported in

mL), dried over MgSO , filtered, and concentrated under

4

vacuum. Expected compounds were isolated by silica gel

chromatography using pentane (100%) to pentane/AcOEt (7:3) as

eluent. The solvent was removed under reduced pressure and

29

the literature. R = 0.70 (eluent: pentane/Et O 8:2, UV and

f

2

1

2

afford two colorless oils (15aa : 14 mg, 15aa : 42 mg, combined

KMNO staining).

4

1

yield: 88%); dr: 1:3 (determined by H NMR of the crude

1

Diethyl (E)-2-benzyl-2-(3-ethoxy-3-oxoprop-1-en-1-yl)

cyclopropane-1,1-dicarboxylate (14f)

In a flame dried round bottom flask was charged the phosphonate

product). Rf 15aa = 0.32 (eluent: pentane/Et O 8:2, UV and

2

KMNO staining); Rf 15aa = 0.28 (eluent: pentane/Et O 8:2,

4

2

1

UV and KMNO staining); H NMR (400 MHz, CDCl ) 15aa : δ

4

3

(236 µL, 1.18 mmol) with 3 mL of dried THF. To this solution

7.43 (d, J = 8.3 Hz, 1H), 7.32-7.20 (m, 6H), 7.13 (td, J = 7.6 and

1.4 Hz, 1H), 7.03 (dd, J = 8.4 and 1.5 Hz, 1H), 6.18 (dd, J = 17.3

and 10.9 Hz, 1H), 5.50 (s, 1H), 5.36 (d, J = 10.8, 1H), 5.07 (d, J

= 17.3, 1H), 4.38-4.21 (m, 2H), 3.90-3.70 (m, 2H), 3.58 (d, J =

13.6 Hz, 1H), 3.42 (d, J = 13.6 Hz, 1H), 2.89 (d, J = 14.2 Hz,

1H), 2.49 (d, J = 14.2 Hz, 1H), 1.30 (t, J = 7.2, 3H), 0.82 (t, J =

was poured the NaH (28 mg, 1.18 mmol). The mixture was

cooled at –78 °C and a solution of the corresponding aldehyde

(300 mg, 0.99 mmol) in THF (2 mL plus 2 × 0.5 mL rinse) was

added. The mixture was stirred for 1h min at –78 °C, then

allowed to warm up to rt and stirred overnight. The reaction was

2

quenched with saturated aqueous NH Cl (10 mL), and the

7.2, 3H) ppm. 15aa : δ 7.27-7.35 (m, 6H), 7.21 (d, J = 8.3 Hz,

4

resulting mixture was extracted with AcOEt (3 × 20 mL). The

combined organic layers were washed with brine (15 mL), and

dried over anhydrous Na SO . Filtration and evaporation under

vacuum furnished the crude product, which was purified by

column chromatography using pentane/AcOEt (9.8:0.2 to 8:2) as

eluent. The expected fractions were combined and the solvent

was removed under vacuum to afford a colorless oil (280 mg,

1H), 7.10 (td, J = 7.6 and 1.4 Hz, 1H), 7.01 (dd, J = 8.4 and 1.5

Hz, 1H), 6.50 (dd, J = 17.5 and 11.1 Hz, 1H), 5.45 (s, 1H), 5.22

(d, J = 11.1, 1H), 5.17 (d, J = 17.5, 1H), 4.25 (q, J = 7.1 Hz, 2H),

3.81 (q, J = 7.1 Hz, 2H), 3.40 (d, J = 13.6 Hz, 1H), 3.22 (d, J =

13.6 Hz, 1H), 2.88 (d, J = 14.2 Hz, 1H), 2.73 (d, J = 14.2 Hz,

2

4

1

3

1H), 1.28 (t, J = 7.2, 3H), 0.94 (t, J = 7.2, 3H) ppm; C NMR

1

(100 MHz, CDCl ) 15aa : δ 169.9, 168.7, 150.3, 137.4, 136.1,

3

yield: 76%). Rf = 0.45 (eluent: pentane/Et O 8:2, UV and

131.0 (2C), 129.4, 128.0 (2C), 127.4, 126.8, 125.0, 120.4, 118.3,

117.6, 71.0, 65.8, 62.6, 62.0, 61.7, 44.3, 40.0, 14.0, 13.3 ppm.

2

1

KMNO staining); H NMR (400 MHz, CDCl ): δ 7.28-7.16 (m,

4

3

2

5

4

1

H), 6.78 (d, J = 15.7 Hz, 1H), 5.71 (d, J = 15.7 Hz, 1H), 4.23-

.09 (m, 6H), 3.28 (d, J = 16.1 Hz, 1H), 3.05 (d, J = 16.1 Hz,

H), 1.95-1.92 (m, 2H), 1.19-1.28 (m, 9H) ppm; C NMR (100

15aa : δ 169.3, 168.1, 150.8, 140.1, 135.4, 131.3 (2C), 129.3,

128.3 (2C), 127.1, 126.9, 124.9, 120.7, 118.6, 114.8, 71.8, 67.0,

13

-1

62.7, 62.6, 61.9, 44.4, 42.5, 13.9, 13.4 ppm; FTIR neat (cm ):

1

MHz, CDCl ): δ 167.6, 167.0, 165.8, 146.8, 137.6, 128.5 (2C),

15aa : 2982, 1729, 1489, 1454, 1382, 1263, 1194, 1173, 1102,

3

2

1

28.4 (2C), 126.3, 123.0, 62.0, 61.8, 60.5, 41.8, 36.3, 36.2, 25.0,

4.1, 14.0, 14.0 ppm; FTIR neat (cm ): 2982, 1716, 1647, 1369,

1056, 1031, 935, 840, 783, 757, 702. 15aa : 2984, 1730, 1488,

-

1

1454, 1388, 1263, 1195, 1176, 1102, 925, 892, 850, 825, 783,

755, 705; HRMS-TOF (+) calculated for C H NO S (m/z):

253, 1174, 1097, 1030, 984, 860, 729, 698; HRMS-TOF (+)

2

5

28

7

+

calculated for C H O (m/z): [M+Na] : calculated : 375.1808,

found: 375.1807; MS (ESI+): m/z 375.18 (100, [M+Na] )

[M+H] : calculated : 486.1586, found: 486.1590; MS (ESI+):

21

27

6

+

1

m/z 486.15 (100, [M+H] ); Chiral HPLC 15aa : analytical

1

3

®

column CHIRALCEL

IC column (250AC

x

CE4.6PT

m

E

m

D

); MA52

N

0.

U

11

S

97

C

,

R

fou

I

n

P

d

T

: 520.1199; MS (ESI+): m/z 520.12 (100,

+

nhexane/iPrOH 97:3, 1.0 mL/min, 25 °C): t_R₁= 19.07 min and t

[M+H] )

R2

=

26.06 min (ee: 81% with procedure A and 86% with procedure

2

®

Diethyl

3-benzyl-9-(tert-butyl)-3-vinyl-2,3-dihydrobenzo[e]

B); Chiral HPLC 15aa : analytical column CHIRALCEL IC

column (250 x 4.6 mm); nhexane/iPrOH 97:3, 1.0 mL/min, 25

pyrrolo[1,2-c][1,2,3]oxathiazine-1,1(10bH)-dicarboxylate 5,5-

dioxide (15ad)

°

C): t_R₁= 24.49 min and t_R₂= 30.82 min (ee: 78% with

1

The title compound was prepared according to the representative

procedure A from the corresponding vinylcyclopropane 14a (32

mg, 0.13 mmol) and cyclic N-sulfonyl imine 4d (38 mg, 0.16

mmol) to give colorless oil (66.9 mg, 95%). dr: 1:1 (determined

procedure A and 30% with procedure B); [α] 15aa = +38.7 (c

D

2

0

.62, CHCl , 81% ee); [α] 15aa = +15.5 (c 1.55, CHCl , 78%

3

D

3

ee)

1

Diethyl

3-benzyl-8-bromo-3-vinyl-2,3-dihydrobenzo[e]pyrrolo

by H NMR of the crude product); Rf = 0.50 (eluent:

1

[

1,2-c][1,2,3]oxathiazine-1,1(10bH)-dicarboxylate 5,5-dioxide

Pentane/Et O 8:2, UV and KMNO staining); H NMR (400

2

4

(15ab)

MHz, CDCl ): δ 7.46 (m, 1H), 7.36-7.22 (m, 13H), 6.95 (d, J =

3

The title compound was prepared according to the representative

Procedure A from the corresponding vinylcyclopropane 14a (32

mg, 0.13 mmol) and cyclic N-sulfonyl imine 4b (42 mg, 0.16

mmol) to give colorless oil (48.4 mg, 66%). dr: 1:1 (determined

8.8 Hz, 1H), 6.93 (d, J = 8.8 Hz, 1H), 6.50 (dd, J = 17.5 and 11.1

Hz, 1H), 6.18 (dd, J = 17.4 and 10.8 Hz, 1H), 5.48 (s, 1H), 5.43

(s, 1H), 5.36 (d, J = 10.9 Hz, 1H), 5.21 (d, J = 11.1 Hz, 1H), 5.16

(d, J = 17.5 Hz, 1H), 5.09 (d, J = 17.3 Hz, 1H), 4.38-4.17 (m,

4H), 3.89-3.65 (m, 4H), 3.54 (d, J = 13.5 Hz, 1H), 3.44 (d, J =

13.6 Hz, 1H), 3.39 (d, J = 13.8 Hz, 1H), 3.21 (d, J = 13.8 Hz,

1H), 2.92 (d, J = 14.2 Hz, 1H), 2.86 (d, J = 14.1 Hz, 1H), 2.71 (d,

J = 14.1 Hz, 1H), 2.55 (d, J = 14.1 Hz, 1H), 1.31 (dt, J = 13.4

and 7.2 Hz, 6H), 1.26 (s, 9H), 1.23(s, 9H), 0.90 (t, J = 7.2 Hz,

1

by H NMR of the crude product); Rf = 0.40 (eluent:

1

pentane/Et O 8:2, UV and KMNO staining); H NMR (400

2

4

MHz, CDCl ): δ 7.35-7.19 (m, 15H), 7.11-7.09 (m, 1H), 6.47

3

(

1

dd, J = 17.5 and 11.1 Hz, 1H), 6.17 (dd, J = 17.2 and 10.9 Hz,

H), 5.42 (s, 1H), 5.37 (d, J = 11.0 Hz, 1H), 5.33 (s, 1H), 5.23 (d,

J = 11.1 Hz, 1H), 5.16 (d, J = 17.5 Hz, 1H), 5.07 (d, J = 17.3 Hz,

13

3H), 0.75 (t, J = 7.2 Hz, 3H) ppm; C NMR (100 MHz, CDCl ):

3

1

H), 4.38-4.22 (m, 4H), 3.95-3.75 (m, 4H), 3.57 (d, J = 13.5 Hz,

H), 3.41 (d, J = 13.6 Hz, 1H), 3.38 (d, J = 14.0 Hz, 1H), 3.20 (d,

δ 169.9, 169.5, 168.9, 168.3, 148.4, 148.0, 148.0, 147.9, 140.4,

137.4, 136.1, 135.4, 131.3 (2C), 131.0 (2C), 128.3 (2C), 128.0

(2C), 127.1, 126.8, 126.3, 126.2, 124.3, 123.8, 119.9, 119.6,

117.9, 117.6, 117.6, 117.6, 114.7, 114.7, 71.8, 71.0, 67.2, 66.0,

62.9, 62.7, 61.9, 61.8, 44.4, 44.2, 42.6, 40.0, 34.6, 34.5, 31.2

J = 13.8 Hz, 1H), 2.91-2.86 (m, 2H), 2.72 (d, J = 14.0 Hz, 1H),

.48 (d, J = 14.1 Hz, 1H), 1.29 (dt, J = 9.1 and 7.2 Hz, 6H), 0.99

2

13

(

t, J = 7.2 Hz, 3H), 0.89 (t, J = 7.2 Hz, 3H) ppm; C NMR (100

MHz, CDCl ): δ 169.8, 169.1, 168.5, 167.9, 151.1, 150.6, 139.9,

-

1

(3C), 31.2 (3C), 14.0, 14.0, 13.4, 13.3 ppm; FTIR neat (cm ):

2965, 1731, 1496, 1384, 1368, 1261, 1179, 1121, 1099, 1060,

860, 730, 705; HRMS-TOF (+) calculated for C H NO S (m/z):

3

1

6

1

37.3, 136.0, 135.2, 131.3 (2C), 131.0 (2C), 130.2, 130.0, 128.8,

28.4 (2C), 128.2, 128.2, 128.1, 128.1 (2C), 122.3, 122.1, 121.9,

21.5, 119.9, 119.5, 117.8, 115.0, 72.1, 71.2, 66.8, 65.6, 62.8,

2.8, 62.6, 62.2, 62.1, 61.7, 44.5, 44.2, 42.4, 39.8, 14.0, 13.9,

2

9

36

7

+

[M+H] : calculated: 542.2212, found: 542.2213; MS (ESI+): m/z

+

542.22 (100, [M+H] )

-

1

3.5, 13.5 ppm; FTIR neat (cm ): 2983, 1730, 1604, 1482, 1388,

Diethyl

[1,2-c][1,2,3]oxathiazine-1,1(10bH)-dicarboxylate 5,5-dioxide

15ca)

3-benzyl-8-bromo-3-vinyl-2,3-dihydrobenzo[e]pyrrolo

261, 1195, 1177, 1096, 909, 861, 786, 755, 732, 703; HRMS-

+

TOF (+) calculated for C H NO SBr (m/z): [M+H] : calculated:

5

25

27

7

(

64.0692, found: 564.0690; MS (ESI+): m/z 564.07 (100,

+

The title compound was prepared according to the representative

procedure A or B from the corresponding vinylcyclopropane 14c

(29 mg, 0.13 mmol) and cyclic N-sulfonyl imine 4a (29 mg, 0.16

mmol) to give white solid (A: 49 mg, 92%; B: 48 mg, 90%). m.p.:

[

M+H] )

Diethyl

3-benzyl-7-chloro-3-vinyl-2,3-dihydrobenzo[e]pyrrolo

[

1,2-c][1,2,3]oxathiazine-1,1(10bH)-dicarboxylate 5,5-dioxide

1

(15ac)

76.5-85.7 °C; dr: 1:1 (determined by H NMR of the crude

The title compound was prepared according to the representative

procedure A or B from the corresponding vinylcyclopropane 14a

product); Rf = 0.30 (eluent: pentane/Et O 8:2, UV and KMNO

2

4

1

staining); H NMR (400 MHz, CDCl ): δ 7.40 (dt, J = 7.9 and 1.2

3

(

32 mg, 0.13 mmol) and cyclic N-sulfonyl imine 4c (34 mg, 0.16

Hz, 1H), 7.36 (dt, J = 7.9 and 1.2 Hz, 1H), 7.32-7.27 (m, 2H),

7.17-7.11 (m, 2H), 7.01 (d, J = 1.2 Hz, 1H), 6.99 (d, J = 1.2 Hz,

1H), 6.30 (dd, J = 17.5 and 10.8 Hz, 1H), 6.05 (dd, J = 17.2 and

10.7 Hz, 1H), 5.74 (s, 1H), 5.69 (s, 1H), 5.34-5.18 (m, 4H), 4.41-

4.28 (m, 4H), 4.00-3.86 (m, 4H), 2.83 (d, J = 13.8 Hz, 1H), 2.74

(d, J = 13.6 Hz, 1H), 2.68 (d, J = 13.6 Hz, 1H), 2.43 (d, J = 13.6

Hz, 1H), 1.76 (s, 3H), 1.68 (s, 3H), 1.34 (td, J = 7.2 and 4.8 Hz,

mmol) to give colorless oil (A: 60 mg, 89%; B: 46 mg, 68%). dr:

1

:1 (determined by H NMR of the crude product); Rf = 0.28

1

(eluent: pentane/Et O 8:2, UV and KMNO staining); H NMR

2

4

(400 MHz, CDCl ): δ 7.39-7.22 (m, 13H), 7.14-7.11 (m, 1H),

3

7

.36 (dt, J = 18.1 and 8.0 Hz, 2H), 6.49 (dd, J = 17.5 and 11.1

Hz, 1H), 6.18 (dd, J = 17.2 and 10.8 Hz, 1H), 5.51 (s, 1H), 5.40

1

3

(

s, 1H), 5.38 (d, J = 10.8 Hz, 1H), 5.24 (d, J = 11.0 Hz, 1H), 5.18

d, J = 17.5 Hz, 1H), 5.08 (d, J = 17.3 Hz, 1H), 4.39-4.22 (m,

6H), 0.97 (t, J = 7.2 Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H) ppm; C

NMR (100 MHz, CDCl ): δ 169.8, 169.6, 168.2, 167.9, 150.7,

3

4

1

H), 3.92-3.73 (m, 4H), 3.59 (d, J = 13.6 Hz, 1H), 3.42 (d, J =

3.6 Hz, 1H), 3.40 (d, J = 14.0 Hz, 1H), 3.21 (d, J = 13.8 Hz,

H), 2.93-2.88 (m, 2H), 2.73 (d, J = 14.1 Hz, 1H), 2.50 (d, J =

4.1 Hz, 1H), 1.29 (dt, J = 10.5 and 7.1 Hz, 6H), 0.96 (t, J = 7.2

150.4, 141.7, 140.0, 129.5, 129.5, 127.6, 127.4, 124.8, 124.8,

120.1, 120.0, 118.6, 118.5, 67.4, 66.3 (2C), 65.8, 62.7, 62.6, 62.3,

62.3, 62.2, 62.0, 47.7, 45.7, 24.9, 24.1, 14.0, 14.0, 13.5, 13.4

-

1

ppm; FTIR neat (cm ): 2989, 1723, 1455, 1390, 1374, 1267,

1186, 1164, 1039, 929, 892, 850, 818, 797, 766, 756, 721, 705;

13

Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H) ppm; C NMR (100 MHz,

CDCl ): δ 169.8, 169.1, 168.5, 167.9, 146.9, 146.4, 139.9, 137.3,

+

HRMS-TOF (+) calculated for C H NO S (m/z): [M+H] :

3

19 24

7

1

6

1

36.0, 135.2, 131.3 (2C), 131.0 (2C), 130.2, 130.0, 128.4 (2C),

28.1 (2C), 127.2, 126.9, 125.7, 125.2, 125.1, 125.0, 123.7,

23.4, 122.8, 122.3, 117.8, 115.0, 72.2, 71.3, 67.1, 65.9, 62.8,

2.8, 62.8, 62.2, 62.0, 61.9, 44.5, 44.2, 42.7, 40.1, 14.0, 13.9,

calculated : 410.1273, found: 410.1275; MS (ESI+): m/z 410.13

(100, [M+H] )

+

Diethyl

3-isopropyl-3-vinyl-2,3-dihydrobenzo[e]pyrrolo[1,2-

-

1

3.4, 13.4 ppm; FTIR neat (cm ): 2983, 1730, 1447, 1390, 1264,

c][1,2,3]oxathiazine-1,1(10bH)-dicarboxylate 5,5-dioxide (15da)

The title compound was prepared according to the representative

procedure A from the corresponding vinylcyclopropane 14d (33

mg, 0.13 mmol) and cyclic N-sulfonyl imine 4a (29 mg, 0.16

196, 1178, 1147, 1072, 926, 854, 756, 731, 704; HRMS-TOF

+

(+) calculated for C H NO SCl (m/z): [M+H] : calculated:

25

27

7

14

Tetrahedron

ACCEPTED MANUSCRIPT

Dedication

mmol) to give white solid (8 mg, 14%). m.p.: 77.2-81.7 °C; dr >

1

2

0:1 (determined by H NMR of the crude product); Rf = 0.30

1

In honor of Prof. Leon Ghosez, a fantastic mentor, for his

commitment with Tetrahedron.

(eluent: pentane/Et O 8:2, UV and KMNO staining); H NMR

2

4

(

400 MHz, CDCl ): δ 7.30-7.28 (m, 1H), 7.20-7.18 (m, 1H),

3

7

=

5

(

.13-7.09 (m, 1H), 7.00 (dd, J = 8.2 and 1.2 Hz, 1H), 6.33 (dd, J

17.5 and 11.1 Hz, 1H), 5.59 (s, 1H), 5.20 (d, J = 11.2, 1H),

.18 (d, J = 17.6 Hz, 1H), 4.39 (dq, J = 7.1 and 1.8 Hz, 2H), 3.85

q, J = 7.1 Hz, 2H), 2.82 (d, J = 14.1 Hz, 1H), 2.69 (d, J = 14.1

Hz, 1H), 2.52-2.45 (m, 1H), 1.37 (t, J = 7.2, 3H), 1.14 (d, J = 6.7,

Acknowledgments

The authors are grateful to ENSCM (Ecole Nationale Supérieure

de Chimie de Montpellier) for a grant (K. S.) and to CNRS

13

(Centre National de la Recherche Scientifique).

3

1

H), 0.97-0.92 (m, 6H) ppm; C NMR (100 MHz, CDCl ): δ

3

69.7, 167.1, 150.8, 137.5, 129.1, 126.5, 124.8, 121.1, 118.7,

15.2, 76.2, 67.5, 62.9, 62.5, 61.8, 37.4, 35.1, 18.2, 17.1, 14.0,

Supplementary data

-

1

3.4 ppm; FTIR neat (cm ): 2981, 1731, 1455, 1386, 1253, 1196,

176, 1102, 1002, 850, 824, 783, 756; HRMS-TOF (+)

+

Supplementary material related to this article can be found at

[insert DOI url for website].

calculated for C H NO S (m/z): [M+H] : calculated: 438.1586,

found: 438.1587; MS (ESI+): m/z 438.16 (100, [M+H] )

21

28

7

+

Diethyl 3-vinyl-2,3-dihydrobenzo[e]pyrrolo[1,2-c][1,2,3]

oxathiazine-1,1(10bH)-dicarboxylate 5,5-dioxide (15ea)

References and notes

The title compound was prepared according to the representative

procedure A or B from the corresponding vinylcyclopropane 14e

1

5

2

. Butler DCD, Inman GA, Alper H. J. Org. Chem. 2000; 65:

887−5890.

(28 mg, 0.13 mmol) and cyclic N-sulfonyl imine 4a (29 mg, 0.16

.

Selected examples on Pd-catalyzed ring-opening of

mmol) to give white solid (A: 46.8 mg, 91%; B: 45.7 mg, 89%).

1

vinylaziridines: (a) Blackham EE, Knowles JP, Burgess J, Booker-

Milburn KI. Chem. Sci. 2016; 7: 2302−2307.

(b) Trost BM, Fandrick DR. J. Am. Chem. Soc. 2003; 125:

1

m.p.: 67.2-70.6 °C; dr: 1:1 (determined by H NMR of the crude

product); Rf = 0.28 (eluent: pentane/Et O 8:2, UV and KMNO

2

4

1

staining); H NMR (400 MHz, CDCl ): δ 7.54-7.51 (m, 1H),

3

1836−11837.

7

1

.46-7.44 (m, 1H), 7.33-7.27 (m, 2H), 7.18-7.13 (m, 2H), 7.03-

.00 (m, 2H), 6.14 (ddd, J = 17.1, 10.1 and 8.7 Hz, 1H), 5.92 (s,

H), 5.87 (ddd, J = 17.2, 10.0 and 6.8 Hz, 1H), 5.45 (s, 1H), 5.40

(c) Trost BM, Fandrick DR. Org. Lett. 2005; 7: 823−826.

(d) Aoyagi K, Nakamura H, Yamamoto Y. J. Org. Chem. 2002; 67:

5

(

1

977−5980.

e) Dong C, Alper H. Tetrahedron: Asymmetry 2004; 15:

537−1540.

(d, J = 17.3 Hz, 1H), 5.32 (d, J = 17.0 Hz, 1H), 5.27-5.23 (m,

2

3

H), 4.92 (ddd, J = 9.7, 7.2 and 6.7 Hz, 1H), 4.41-4.25 (m, 5H),

.99-3.66 (m, 4H), 2.80-2.65 (m, 3H), 2.18 (dd, J = 13.5 and 9.7

(f) Yuan Z, Wei W, Lin A, Yao H. Org. Lett. 2016; 18: 3370−3373.

Hz, 1H), 1.33 (dt, J = 16.9 and 7.1 Hz, 6H), 0.94 (td, J = 7.4 and

(g) Lowe MA, Ostovar M, Ferrini, S, Chen CC, Lawrence PG,

1

3

1

6

1

.7 Hz, 6H) ppm; C NMR (100 MHz, CDCl ): δ 169.7, 169.1,

3

Fontana F, Calabrese AA, Aggarwal VK. Angew. Chem. Int. Ed.

011; 50: 6370−6374.

h) Xu C-F, Zheng B-H, Suo J-J, Ding C-H, Hou X-L. Angew. Chem.

Int. Ed. 2015; 54: 1604−1607.

i) For X = H (dual, synergistic Pd- and organo-catalysis): Næsborg

68.3, 168.1, 151.0, 150.4, 137.0, 136.2, 129.7, 129.6, 128.3,

27.8, 125.4, 124.8, 120.4, 119.7, 119.0, 117.8, 67.1, 66.7, 65.2,

4.8, 62.7, 62.5, 62.4, 62.1, 61.8, 40.0, 39.6, 14.0, 14.0, 13.5,

3.4 ppm; FTIR neat (cm ): 2986, 1714, 1491, 1458, 1392, 1277,

196, 1180, 1108, 1056, 928, 857, 793, 776, 757, 715; HRMS-

2

(

-

1

(

L, Tur F, Meazza M, Blom J, Halskov KS, Jørgensen KA. Chem.

Eur. J. 2017; 23: 268−272.

+

TOF (+) calculated for C H NO S (m/z): [M+H] : calculated:

18

22

7

3

96.1117, found: 396.1119; MS (ESI+): m/z 396.11 (100,

(j) Rivinoja DJ, Gee YS, Gardiner MG, Ryan JH, Hyland CJT. ACS

Catal. 2017; 7: 1053−1056.

+

[

M+H] )

(

k) Li T-R, Cheng B-Y, Fan S-Q, Wang Y-N, Lu L-Q, Xiao W-J.

Chem. Eur. J. 2016; 22: 6243−6247.

l) Fontana F, Chen CC, Aggarwal VK. Org. Lett. 2011; 13:

Diethyl

(E)-3-benzyl-3-(3-ethoxy-3-oxoprop-1-en-1-yl)-2,3-

dihydrobenzo[e]pyrrolo[1,2-c][1,2,3]oxathiazine-1,1(10bH)-

dicarboxylate 5,5-dioxide (15fa)

The title compound was prepared according to the representative

procedure A from the corresponding vinylcyclopropane 14f (49

mg, 0.13 mmol) and cyclic N-sulfonyl imine 4a (29 mg, 0.16

mmol) to give white solid (26.8 mg, 37%). m.p.: 93.6-98.7 °C;

(

3

454−3457.

. For a review, see: Allen BDW, Lakeland CP, Harrity JPA. Chem.

Eur. J. 2017; 23: 13830−13857.

. For Rh(I) catalyzed reactions, see : (a) Zhu C-Z, Feng J-J, Zhang

J. Angew. Chem. Int. Ed. 2017; 56: 1351−1355.

b) Lin T-Y, Wu H-H, Feng J-J, Zhang J. Org. Lett. 2017; 19:

897−2900.

c) Lin T-Y, Zhu C-Z, Zhang P, Wang Y, Wu H-H, Feng J-J, Zhang

J. Angew. Chem. Int. Ed. 2016; 55: 10844−10848.

d) Feng J-J, Lin T-Y, Wu H-H, Zhang J. J. Am. Chem. Soc. 2015;

37: 3787−3790.

e) Lin T-Y, Wu H-H, Feng J-J, Zhang J. Org. Lett. 2018; 20:

587−3590.

4

1

dr: 3:1 (determined by H NMR of the crude product); Rf = 0.30

(

2

(

eluent: pentane/Et O 8:2, UV and KMNO staining); Major dia:

2

4

1

H NMR (400 MHz, CDCl ): δ 7.49 (d, J = 16.0 Hz, 1H), 7.36-

3

7

.27 (m, 7H), 7.12 (t, J = 7.5 Hz, 1H), 7.04 (dd, J = 8.1 and 0.8

Hz, 1H), 5.96 (d, J = 16.0 Hz, 1H), 5.39 (s, 1H), 4.27-4.18 (m,

(

1

(

3

4

1

H), 3.83-3.67 (m, 2H), 3.48 (d, J = 13.7 Hz, 1H), 3.22 (d, J =

3.7 Hz, 1H), 2.93 (d, J = 14.3 Hz, 1H), 2.69 (d, J = 14.2 Hz,

H), 1.31-1.25 (m, 6H), 0.92 (t, J = 7.2 Hz, 3H) ppm; C NMR

13

(100 MHz, CDCl ): δ 169.0, 167.8, 166.0, 150.6, 149.4, 134.4,

3

5. For an example on Ir catalyzed reaction, see: Lin T-Y, Wu H-H,

Feng J-J, Zhang J. Org. Lett. 2017; 19: 6526−6529.

6

Liffey RM, Regentová D, Ward J-P, Dutton J, Lewis W, Churcher I,

Walton L, Souto JA, Stockmann RA. Angew. Chem. Int. Ed. 2016;

55: 10047−10051.

1

31.3 (2C), 129.4, 128.6 (2C), 127.5, 127.2, 125.2, 121.0, 120.5,

18.7, 70.8, 67.1, 62.7, 62.1, 60.6, 44.4, 43.1, 14.2, 13.9, 14.0,

3.4 ppm; FTIR neat (cm ): 2982, 1721, 1454, 1390, 1264, 1178,

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-

1

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28

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Article Doi

Vinyl-aziridines and cyclopropanes in Pd-catalyzed (3+2)-cycloaddition reactions with cyclic N-sulfonyl imines

DOI: 10.1016/j.tet.2018.09.040

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Article abstract of DOI:10.1016/j.tet.2018.09.040

Full text of DOI:10.1016/j.tet.2018.09.040

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