Nucleophilic addition-elimination reactions of N-(p-tolylsulphonyl)vinylsulphoximines: preparation of α-methylene nitriles and phosphonates

Teuah.xIron Leuers.Vo1.32.No.26 pi 3119-3122.1991 Printedin GreatBritain

Nucleophilic

Addition-Elimination Prepamtion

oo40-4039/91 $3.00+ .oo PcrsamonPress pk

Reac&ms of N-@-Tolylsulphonyl)vinyJsuJphoximines:

of &vfethylcne

and F%osplmates

Nitrilt~

Peter L. Bailey and Richard F.W. Jackson* Department

of Chemistry,

Beckon Building,

The University,

Newcastle

upon Tyne,

NE1 7RU,

U.K. Key Words: Michael Addition; Abstract: Treatment of

Vinylsulphoximine;

Methylene

Nitrile;

Methylene

Phosphonate.

N-(p-tolyLsulphonyl)vinyLsulphoximines (1) with lithium cyanide in

DMF at room temperature leads to efficient formation of a,@-maturated

nitriles (3), via a

Michael addition-proton transfer-elimination process, in which the polarity of the double bond

is

reversed.

Analogous reaction sulphoximines (7),

p-dimethylphosphonyl

with lithium dimethylphosphonate leads to which are converted to a,p-unsaturated

phosphonates (6) by treatment with NaOMe. Electron-deficient strategies.

The

conditions

alkenes

ability

enhances

transformation by proton

are

to reverse

their

important

utility

even

is by Michael addition

transfer

and ~-elimination

the electron-withdrawing stabilise an adjacent

intermediates

the polarity further.

The

of a nucleophile

the

planning

simplest

approach

as a leaving

group. group,

of

alkenes to

to an electron-deficient

of the initial activating

group can function

in

of such electron-deficient

synthetic

under

mild

effecting

this

alkene,

This strategy

followed

requires

that

and that the nucleophile

can

anionic centre (Scheme 1).

E*G-L@q

-

NU

Nu

NIT

EWG

R

-

-

EWG

Nu R

-

’

R

Scheme 1 To

date,

the

activating

groups

phenylsulphonyll and nitro.2 During N - (p - tolylsulphonyl)vinylsulphoximines t-butylhydroperoxide

to

corresponding

to vinylsulphones,

addition

these

process.

vinylsulphoximines been briefly

Nucleophilic

have

been

our investigations (1),3

we

vinylsulphoximines

that N-(p-tolylsulphonyl)vinylsulphoximines reversal

which

employed into

together

with their reactivity

in Diels-Alder group on

sulphoximines

than

corresponding

epoxiclation

of

that addition of lithium significantly faster than the

has

of the electron-withdrawing

vinyl

are

addition to N-(p-tolylsulphonyl)-

nitrogen

the

purpose

4 and we therefore decided to explore the possibility (1) would be effective substrates for the polarity

reactions. 7 The presence renders

this

the nucleophilic

observed occurred

(1)s and N-(phthalimido)vinylsulphoximines~

explored,

for

N-alkylvinylsulphoximines

more

reactive

(2).5,8 3119

the

R’N.8 $s&R (1).

R’

= Ts

(2).

R’

=

alkyl

3120

Following

the precedent

to cY-methylene reflux,

we

nitriles

have

pleased

(l),

available

to discover

the

prepared LEN

that vinyl sulphones

between

cyanide

described

(OSM in dimethylformamide)

nitriles

could be converted

with KCN/dicyclohexyl-B-crown-6

reaction

by our previously

that the reaction

the desired cy-methylene

who established

(3) by treatment

investigated

vinylsulphoximines commercially

of Taber,

proceeded

within

(3) (Scheme 2).9

and

in t-butanol

method.3

without

We chose to employ additional solvent, and were

lh at r.t., to give satisfactory

Our results are described

yields of

in Table 1.

Table 1. Preparation of adfethylene

IWiks.

CN

LiCN

TsN I: Ph$SdR

at

N-(p-tolylsulphonyl)-

Product

R

DMF rat.

-A

Yield, %

R .,

(3)

(1)

CH,CH,Ph

@a)

81

(CH,),Me

(3b)

63

w

64

Scheme 2

0 In

order

N-(p-tolylsulphonyl)sulphoximine vinyl sulphone (4a), prepared able to isolate some of the bk-nitrile (3a). It

for this suggestion

cyanide

appears

that

under

the

was formed

was provided

the same conditions

more

electron-withdrawing

greater

ability

of

group was responsible for the faster reaction, we treated the We were by the method of Oh, 10 under identical conditions. a-methylene nitrile @a), although the major product was the

(5a), which we presumed

Support

lithium

that

establish

to

rapid

(and

N-(p-tolylsulphonyl)vinylsulphoximine,

by subsequent

Michael addition

by the observation

perhaps

more

compared

complete)

with the

that treatment

@a) in good yield

gave the b&nitrile

vinyl

addition

of

sulphone,

of cyanide

to

of (3a) with (Scheme

cyanide

to

is responsible

3). the for

the difference. CN

LiCN

PhSO, w

R

CN R

+

(3a) 9%

(4a)

NC

R

(5a) 44%

R = (CH&Ph

f LiCN,

77%

Scheme 3 In an effort

to extend

the scope of the process, we have explored the reaction lithium and dimethylphosphonate. N - (p-tolylsulphonyl)vinylsulphoximines (1) phosphonates have been prepared by the nitroalkenes at 90 oC, followed by elimination N-(p-tolylsulphonyl)vinylsulphoximine

between Vinyl

addition of dimethyl hydrogen phosphite to of nitrous acid.2 Addition of a solution of the

(1) to lithium

dimethylphosphonate

in THF

at -78

oC,

3121

followed

by

a-methylene

warming to

r.t.

allowed

the

isolation

in

moderate

yields

of

the

desired

phosphor-rates’1 (6) (Scheme 4).

(MeO),

TSN
0.

&

-78%

‘P(OMa)2

Li THF -

-A

r.t.

(1)

R

(6) Scheme4

Subsequently, we established that it was more efficient to isolate the initial Michael adduct (7) (which was stable in the reaction mixture up to -20 OC), and then effect the @-elimination process in a separate step using sodium methoxide in refluxing methanol (Scheme 5, Table 2).’ 2

It is also possible to effect

the elimination at room temperature

using DBU

in

dichloromethane, although extended reaction times are necessary (typically 7 days). 0 (MeOJLi

TSNJ Ph”+R

TsNSl

THF -7a%--2oOc

Ph

0.

Zp(OMe)z YA

NaOMe/MeOH

R

reflux

-A

R (6)

(7)

(1)

‘P(OMe)z

scheme 5 Table 2.

Preparation of a-Methylene

R CH,CH,Ph @-I&Me

0 Ph iPr

Product

Phospl~~W~.

Overall Yield, % 64

(aa) (6b)

59

(&I

58

(6d)

60

(6e)

54

the use of observations significantly extend We believe that these N-(p-tolylsulphonyl)vinylsulphoximines in synthesis, 13 and we are currently exploring new applications of these systems. Acknowledgements: We thank the SERC for a postgraduate studentship (P.L.B.), Prof. 0. Meth-Cohn for helpful discussion, and Sterling Organics for support (CASE award to P.L.B).

3122

References 1.

D.F. Taber and S.A. Saleh, .I. Org. Chem., 1981, 46, 4817.

2.

M. Yamashita,

3.

P.L. Bailey, W. Clegg, R.F.W. Jackson, and 0. Meth-Cohn,

Yamashita,

M. Sugiura, T. Oshikawa,

Y. Tamada,

and S. Inokawa,

Syn&&,

A. Iida, and T. Oshikawa, Synrhe.&

1987, 62; M.

1990, 420. J. Chem. Sot., Perkin Trans. 1,

1990, 200. 4.

0. Meth-Cohn,

C. Moore, and H.C. Taljaard,

and R.F.W. Jackson, J. Chem. Sot., Perkin Trans. 1, 1989, 835.

M. Ashwell 5.

C.R. Johnson,

J.P. Lockard,

6.

R. Anntmziata

and M. Cinquini,

7.

R.S. Glass, K. Reinecke,

8.

S.G. Pyne,

M. Cinquini,

9.

J. C&m. Sot., Perkin Trans. 1, 1988, 2663;

and E.R. Kennedy,

J. Org. Chem., 1980, 45, 264.

J. Chem. Sot., Perkin Trans. 1, 1979, 1684; R. Amnmziata,

J. Chem. Sot., Pet-kin Trans. I, 1980, 2422.

and S. Colonna,

and M. Shanklin,

J. Org. Gem.,

1984, 49, l527.

J. Org. Chem., 1986, 51, 81; S.G. Pyne, Tetrahedron Lett., 1986, 27, 1691. procedure: lithium cyanide (OSM in N,N-dimethylformamide, ex Aldrich, 1.3 cm3)

General

(l),

was added to the N-(p-tolylsulphonyl)vinylsulphozimine mixture

was stirred at r.t. for between

was added, and the mizture

extracted

extracts were dried (MgSO,), chromatography colourless

(eluent

30 and 60 min. with CH,Cl,

concentrated

(0.5 mxnol) under

Phosphate

(3 x 10 cm3).

buffer

The combined

and the residue was purified

10% ethyl acetate in petrol)

N,.

The

(pH 7, 1 cm3) organic

by flash

to yield the cr-methylene

nitriles

(3) as

oils.

10. J.W. Lee and D.Y. Oh, Syruh. Commw~., 1989, 19, 2209. 11. For previous

routes to cr-methylenephosphonates,

Tetrahedron, 1970, 26, 5529; J.-N. 3725.

See also reference

12. General

procedure:

see: P. Tavs and H. Weitkamp,

Collard and C. Benezra,

a solution

of dimethyl hydrogen

0C.

min, a solution

of the N-(p-tolylsulphonyl)vinylsulphoximine

warmed to -20 then extracted (MgSO,)

n-Butyllithium

phosphite

cooled to -78

cm3) was added.

The mixture 0C over 2h.

(1.1 mmol, solution

buffer

(1.1 mmol) in dry THF was

in hezanes)

was stirred for a further Phosphate

with ethyl acetate (3 x 20 cm3).

and concentrated

flash chromatography

Tetrahedron Lat., 1982, 23,

2. was added and, after 5

(1) (1 mmol) in dry THF (5

10 min at -78

OC, and then

(pH 7, 10 cm3) was added, and the mixture The combined

organic extracts were dried

to yield the Michael adducts (7), which could be purified

(eluent

ethyl acetate),

although

recovery

by

from the column was rather

inefficient. A solution of the crude Michael adduct (7) was treated with sodium methozide (2 mmol) in dry MeOH (10 cm3) under reflux for 4 h and, after being cooled, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography

(eluent

70% ethyl acetate in petrol)

colourless oils. 13. For other methods to prepare

to yield the vinyl phosphonates

N-(p-tolylsulphonyl)vinylsulphozimines,

(6) as

see: I. Erdelmeier

and H.-J. Gais, Tetrahedron L&t., 1985, 26, 4359; H.-J. Veith, H.-J. Gais, and I. Erdelmeier, Helw. Chim. Acta, 1987, 70, 1041. Recently, methods for the preparation unprotected vinylsulphoximines, which could likely be applied to the synthesis of N-(p-tolylsulphonyl)vinylsulphozimines, Logusch,

have been described: K.-J.

on

Hwang and E.W.

Tetrahedron Lett., 1987, 28, 4149; R.S. Paley and S.R. Snow, Tetrahedron Lett.,

1990, 31, 5853. (Received in UK 27 March 1991)