(+)-(S)-α-diethoxyphosphorylvinyl p-tolyl sulfoxide: A new chiral Michael acceptor and dienophile

Tmhedrw Prirmd

Asymmetry

in Grcti

Vol. 3. No. 12, pp.

1515-1518, 1992

09574166,92$500+.0(:

Brmin

PergamonPress Lid

(+)-(S)-a-D’ le th oxyphosphorylvinyl

p-Tolyl Sulfoxide:

a New Chiral Michael Acceptor and Dienophile Marian Hikolajcsyk+ and Wanda B. Midura

Centre of I4olecular and Macromolecular of Organic

Sulfur

Studies , Polish

Compounds,

of Sciences,

90-363 tddi, Sienkiewicza

(Received in UK6

Abstract:

Academy

Department

t12, Poland

October 1992)

The title reagent, (+)-(S)-1, was prepared from (+)-(S).-a-diethoxysulfoxide 7. by p-to1y1 phenylselenylation-deselenylation

phosphorylethyl

procedure. Its reactivity was demonstrated by diastereoselective Michael addition of ethanethiol

giving rise to 3, tandem Michael addition/intramolecular

-Wittig reaction with 2-formyl pyrrole leading to the corresponding

Horner-

pyrrolizine

sulfoxide 5 and cycloaddition with cyclopentadiene affording the diastereomeric adducts 6. The steric course of the Diels-Alder reaction is briefly discussed. Chiral oulfoxides have found a wide application as powerful ehiral auxiliaries

in

asymmetric synthesis and as chiral synthons.L Recently, chiral vinyl sulfoxides have been used as dienophiles in asymmetric Diels-Alder reactions.' However, because of a very Low reactivity of simple vinyl sulfoxides in Diels-Alder reactions, it was necessary to activate the carbon-carbon

double bond by introduction of an additional ele-

ctron-withdrawing group. Usually, the alkoxycarbonyl group is used for such a purpose.' In

this

phosphorylvinyl

paper

we

p-tolyl

would

like

sulfoxide

to

report

the

synthesis

(+)-(S)-a-diethoxy-

of

(1) and exemplify its reactivity

as a new type of

chiral Michael acceptor and dienophile.4 In contrast to other n- or p-substituted vinyl sulfoxides reported in the literature, the phosphoryl moiety in 1 functions not only as a double bond activating substituent but also allows the Homer-Wittig carried out following

the Michael addition. Moreover, the phosphoryl

reaction to be group,

like the

sulfinyl one, may be chiral thus allowing double asymmetric induction in the Michael and Diels-Alder reactions to be studied.

PhSe 1

X

n-BuLi

2 PhSeBr -(EtO!$

I

_

;/.+p

0

HZO*/CHZC1 K 63% &(Eto,,i

r"'-P

0 I

(+)-(S)-2, 6,,-22.7 and 21.1

1

3, sp-20.7

J (+)-(S)-1, 6p-9.9;

[aID -+157 (acetone) Scheme 1

1515

M. MIKOLAJCZYK and W. H. MIDLJKA

1516

A two-step involves mixture

synthesis

selenylation of

two

sulfoxide

affords

sulfoxide

1 is shown

in Scheme

(+)-(S,)-a-diethylphosphorylethyl with

diastereomers)'

PhSe-substituted elimination,

of the chiral of

3

phenylselenenyl

which,

the desired

after

bromide

subsequent

sulfoxide

1 which

1. The first step

p-tolyl

sulfoxide

to give

oxidativs

is obtained

the

2

(a

corresponding

benzeneselenenic

rn a pure

acid

form by column

chromatography. Preliminary nucleophilic presence

experiments

addition

revealed

easily.

of triethylamine

For

gave

that

example,

the

chiral

the

1 with

4 ae a 2:1 mixture

the adduct

sulfoxide

vinyl

renctiOI1of

1

undergoes

ethanethiol

in

the

of diaszereomers.

C-01,

P

A

rp

II 0

0

0

[aI,

5,

--SO.8

4, zP=20.1,

(acetone) Scheme

The

synthetic

condensed illustrated tandem

Michael

The

Table

Of

1

as

a

the

are

Diels-Alder

Reaction

collected

phosphoryl

1.

in

Table

2

H20/Ms2C0

3.

ZnCl2

4.

BF3'0Et2

cycloadducts and

25.4

column

CH2C12 CH2C12

6 was determined

ppm)'/ obtained

chromatography

in

(hexane:

or is the

of 1 with

into the carbonyl

1.

of

the

moiety

was found

ratio

of

salt

group.

in 1 considerably

The

sodium

in 5 may be enhanced

to occur

the

its

easily.

diastereomeric

of 1 with cyclopentadiene

Sulfoxide

Sulfide

(%)

a

b

c

d

(%)

ex0-?

endo-P

r.t

10d.

9.8

54.4

30.1

5.7

84.5

15.5

r.t.

2d.

13.2

53.6

27.5

5.7

85.3

14 7

-

74.5

25.5

18.4

31.5

68.5

-200

24h

25.5

74.5

-20"

Ih

46.4

10 7

by 31P NMH spectroscopy the

mono-

sulfoxide moiety 5' resulting from

sulfoxide

with cyclopentadiene

Temp. Time

CH2C12

construction

vinyl

vinyl

group

conditions

Solvent

the

reaction

Entry Catalyst

for

chiral

the chiral

or converted

of the

reaction

the

Homer-Wittig

is that

and cycloaddition

obtained

reagent

3H-pyrrolizine-2-sulfoxide

reactions

presence

key

containing

of tolyl

interest

asymmetric

reactivity

results

1

addition/intramolecular

expected,

dienophilic

of

carbocycles

synthesis

pyrrofe.

for further As

or

by the

of 2-formyl used

utility

hetero-

18.5 (2:lj

2

ZnC12-catalyzed

acetone,

24.5

and the two diastereomers

reaction

15:l). The endo/exo

(entry

3)

were

configuration

(sP=25.6

separated

by

(with respect

(+)-(S)-a-Diethaxyphosphorylvinyl

to P) of 6 absence

was assigned

(exe)

Additionally, cycloadducts

of

the

utilizing

coupling

the endofexo

the Quin's criterion'

constant

1517

p-tolyl sulfoxide

between

P

i.e. the presence

and

C(7)

in

ratio in all experiments was confirmed

6 to the corresponding

I%

(endo) or

NMR

spectra.

by reduction

of the

sulfides 7. Thermal elimination of p-toluenesulfenic

acid from 6 was also carried out and gave the chiral phosphonate 8.

~ (c%y P(OEt),

I\ (+)-(S)-1 -0

NaI,

STol-p 7,

STol-p

II

endo/exa

sP=28.3/29.3

0

6, a/b/c/d EP=25.6/25.4/25.3/24

7 A

8, ?$,=17.9 Scheme 3

An inspection

of the results

(entry 1) performed exe-selectivity moderate.

in methylene

[aID-+14 (acetone)

in Table chloride

1 reveals that the non-catalyzed

is very slow. Although

for the phosphoryl group is observed, the n-facial selectivity

An increase of the solvent polarity

may suggest a non-synchronous

(entry 2) accelerates

reaction

reactivity

occurs

Lewis

acid

of 1 and also improves n-facial

also with the predominant

two diaetereomers such

cycloaddition

which

selectivity.

exo-selectivity

increases the

In this

case the

for the P(O)-group

and only

are formed (31P NMR assay). On the contrary, the presence of a strong as

BFs'OEt>

(entry

favoures the endo phosphonate The above preliminary investigated

of

is rather

transition state with the advanced o-bond formation at the

b-carbon atom in 1. The addition of zinc chloride (entry 3) substantially dienophilic

reaction

the preponderance

4)

considerably

decreases

stereoselectivity

observations on the steric course of the Diels-Alder

may reasonably

and

moiety approach. be explained

reaction

in terms of steric factors and conformational

changes induced by Lewis acids. Thus, zinc chloride as a chelating agent links together both

polar

conformation

phosphoryl of the

boron trifluoride more

favoured

presence

of

BFg

sulfinyl

steric

reaction the

ratio

Therefore,

observed, of

in

1 what

On the other

results hand,

only one polar group, the

reasons. is

groups

dienophile.'

can coordinate

for

ZnC!l~-catalyzed

and

complexed

the

whereas

a

high

uncatalyzed 6

a

rigid

s-cis conformation

in

diastereomeric

in

s-trans

since one molecule

diastereoselectivity reflects

reaction

and

population

of

of 1 is in in of

the the both

conformers.

Acknowledgement. Research

Financial

support of this work by the State Committee

(Grant number 226709203) is gratefully acknowledged.

for Scientific

1518

References 1.

and

Notes

MikoXajczyk,M.;

Drabowicz,J.

’ an

Posner,G.,

"The

Stirling,C.J.M.; 2.

Kolzumi,T., therein;

3.

vinyl

reactions

by

and

5.

Mikotajczyk

6.

5:

Data

its

exo-6

Hz,

(less

(a3CH20,

d J=7

(d, CHzr

Jpc=11.5

been

Rappoport,Z.;

pp.823-849.

111

58,

efficiently

1991,

and

references

1991,

activated

ethoxy

cited

2, 93. for

sulfonium

Diels-Alder

salt;

Ronan,B.

2, 75.

sulfoxide

analog

1988,

Asymmetry,

corresponding

was

obtained

and by

Tetrahedron

W.,

Miller

3H);

4.45

IH);

in

Korbacz,K.

Durst

Lett.

21.4

Hz

and

1981,

Wiecrorek

(s, lH),

31P 25.6

(s, CHx);

C7);

126.6,

A.,

(m, 2H);

7.29

polar):

Hz);

CH3%20);

Hz,

(9,

6.1

1991,

13, 333. Patai.S.;

a

racemic

form

Tetrshedron coworkers 191)

22,

in

Lett.,

our

1981,

(Venugopnlan,B.,

by

oxidation

of

the

sulfide.

Midura

8: 2.39

has

Grzejszczak,S

@-phenyl

vinylic

Hz,

for

methyl

Chichester,

Tetrahedron

the

1982,

Sulfoxides",

Silicon,

Asymmetry,

Durst,T.,

M.,

lH NMR

Sons.

and

into

Tetrahedron

and

and

sulfoxide

conversion

and

corresponding

(dt J-2.1

Wiley

(Mikokajczyk,M.,

3097),

22,

and

Sulfones

Sulfur

u-Diethoxyphosphorylvinyl

Ham1et.A.B.

in Stereochemistry,

of

Carretero,J.C.,

p-tolyl

its

Kagan,H.B.;

laboratory

7.

John

Phosphorus,

Lopez,R.

Topics

Chemistry

Eds.,

Recently,

and 4.

md W. H. MKXJKA

M. MIKOLAICZYK

49.6

129.1,

7.29

ppm,

31.3

(d,

Tetrahedron,

(s, lH]; and

6.25

7.56

62.3

5=3.8

43, 2967.

c=O.8),

(d, J=5.2 Hz,

Hz,

IH);

6.49

4U aromatic).

(acetone 42.5

(d, J=6

Hz),

1987,

(dt 5=2.0

(AA'BE'

[0]~=+35.5

(s, CH2,C3)

(s, CH,Cl);

135.3

M.

5.93

Hz,

CH$H20);

13C NMR

16.3

CH,CQ);

45.9

62.5

137.5,

141.5,

142.2

2.32

(s, 3H);

2.68

(d, J=7

(aromatic

+

vinyl). IH NMR,

1.23

4.08

7.72

(AA'BB'

Data

for

15.7

(C3,

128.7,

(more

=3,C3);

CHsCH20);

1.5-2.2

5.93

polar):

42.0

63.1

6: 1.21

(d,

(dt, 6.28

31P

(9, CHC4); 5x6.7

(d, Jc11.2

(m, 4H);

Quin,L.D.,

6H,

411, CHsm20);

(m, 3H);

(m, lH,

vinyl);

6.28

(m,

lH,

(m,

Vinyl);

1H);

2.9

7.35

and

4H aromatic).

endo-

129.3

'H NMR 4.05

(dt,

(m,

CH3=20);

HZ,

8.

6:

1H)i

(m,

HZ);

6H);

HZ,

ppm,

(s, CH2,C7);

CH3a20);

139.0

(m,

1.45-2.4

4H)i

7.15

and

Cunkle,G.T.

[a]~=+lSl.S

70.1

(aromatic

(m, 2H vinyl),

Gallagher,N.J.,

25.4 48.6

(aCetOne

49.9

(de

Cc2.6);

(s, CHCl);

5~137.6

61.6

13C NMR (d, J=7.2

HZ,C2);

126.4,

(m, 1H);

3.45

128.3,

+ vinyl). 2.29 7.5

and

(s, 3H), (AA'BB'

2.97

(m, 1H);

4H aromatic).

Chesnut,D.B.,

J.Am.Chem.Soc.,

1980,

102,

not

only

A

high

3136. 9.

Zinc in

salts the

were

used

as chelating

Diels-Alder

stereoselectivity

observed

coworkers;

G.H.

New

York,

Posner, 1983;

~01.2,

agents

reaction in

but the

"Asymmetric Part

A, Ch.8,

for

a-substituted

also latter

in case

Synthesis"; p.225.

vinyl

conjugate was

sulfoxides additions.

rationalized

Morrison,J.D.,

Ed.;

by

Posner

Academic

and

Press: