The use of phosphonodithioformates for the synthesis of ketene dithioacetals

Tetrahedron Letters,Vo1.30,No.26,pp Printed in Great Britain

3415-3418,1989

0040-4039/89

Maxwell

Perqamon

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THE USE OF PHOSPHONODITHIOFORMATES FOR THE SYNTHESIS OF KETENE DITHIOACETALS

Andrew Bulpin, Serge Masson* and Aboubacary Sene Laboratoire des Compost% Thioorganiques (associd au CNRS ), ISMRA, Universite' , F 14032 CAEN (FRANCE). Summary : Phosphonodithiofotmates 1 undergo thiophilic addition with both organolithium and Grignard reagents to give metalladed dithioacetals offormyl-phosphonates 2, available for protonation, alkylation or use in Wittig-Horner reactions. Oxidation of 1 by meta-chloroperbenzoic acid leads to the corresponding sulphine 4 equally suitable for thiophilic addition. Dithioesters

are known to undergo either thiophilic

Moreover,

in the case of organolithium

additions.

Phosphonodithioformates

diallcylphosphites

allowing 70,c.

dithioacetal,

1 are non-enethiolisable,

of organometallic reagents

the analogous a-phosphonic effect,

1 or carbophilic

functionalised

to a thiocarbonyl

can compete

dithioesters

group is enhanced

reagents. with these

easily accessible

from

the generation

of metallated

Such a carbanion

dithioacetals

has previously

of formyt-phosphonates

been obtained

7g or chloro(arylthio)methanephosphonates 1 with organolithium

compounds

alkylation

to produce the same

2, suitable for Wittig-Homer

by the basic deprotonation

prepared by an Arbusov Reaction between trialkylphosphites

substituent ;

by an ~-carbonyl

1 was expected

ester group found in phosphonodithioformates

of dialkyl sulphides to the methanephosphonate

protonation,

2 addition with organometallic

3, when possible,

a-deprotonation

and carbon disulphide 4. Previous work by our research group 5 and a recent review 6 have shown

that thiophilic addition

reactions

compounds,

of the corresponding

and chlorodithioacetals

7d, by the addition

carbanion 7e,f, and by the reactions of diethoxymethane

phosphonates

8 with thiols. We describe here, the reaction of phosphonodithioformates

and Grignard reagents which readily led to these carbanions

and also their use in Wiaig-Homer

reactions

to synthesise

and their subsequent

ketene dithioacetals,

important

intermediate reagents in organic synthesis 7a, When

the phosphonodithioformate

hydrolysis,

the corresponding

1 was treated

dithioacetai

with one equivalent

of organolithium

3 was obtained in high yield. This result confirmed

reagent

followed

a thiophilic

by

addition

with the formation of a lithiated carbanion 2. (scheme and table I> : ii *

/cb?

p?.Ni-f;q

:;;

5-

“.“6-$:’

~‘olzli 0 Y=S

1

Y=SO

4

2 5

3 6

SCHEME 1 It can be seen that the yields for an isopropyl group at Rl are 7-8 % higher than the corresponding an ethyl group and a slight increase in the yield was observed

when phenyllithium

reagent. When a crotyl chain is introduced at RI, no [2,3] sigmatropic

3415

rearrangement

values for

was used as the organometallic was observed 9.14

3416

Compound

Rl

:zI

Et iPr Et iPr Et iPr Et iPr iPr

6f

iPr

3c :I 3:

R3

R2

7d 16 7f

nBu Ph Ph Ph & nBu Ph

:z 16 ::: :z

TABLE 1

The corresponding

stable sulphine

of meta-chloroperbenzoic

4 was prepared

acid in methylene

kinetically formed which progressively temperature

Reference

E nBu

*seefootnote I1

equivalent

Yield %

by treatment

chloride

1 (R1 = Et) with one

of the dithioester

at O’C. The E sulphine

changed to the thermodynamically

was the initial isomer

stable Z isomer over a 24 h period at room

12.The sulphine 4, as obtained, underwent the expected thiophilic addition 13 when treated with a lithium

reagent . After hydrolysis&e

lithiated dithioacetal5

led to the formation of two diastereomers

1:

6 in an approximate

1 ratio. 1 was treated with one equivalent

By contrast, when the dithioformate major product , obtained Chemical verification followed

after hydrolysis,

was compound

8, identified

of the result was obtained by treating the dithioester

by diethyl disulphide

to obtain the symmetrical

of Grignard reagent,

H,O+

)S

-78%

1

EtMgBr

1 with one equivalent of Grignard reagent to the starting dithioester

7 R’=Et:RZ=Me

sh

6Soh7e ’ 7f

R’=iFr:R’=Me

I

74%

EtS

MeS

ld

$Me

EtS

Me.5

79%

)

MeS I

(R’of, P-i-S-C--P !

SCHEME

The high yields of the coupled products,

obtained when using one equivalent

lp2. To obtain the dithioacetal a large excess (five equivalents)

AMe

2

once more that for a simple thiophilic addition two equivalents

compounds,

(OR’h

0

EtS

dithioester

II

’ H 8

‘ITIF/-78°C

0

I

(R’C&-S-C-P

2

L-_7s’,

spectroscopy.

product 9. These products may have been obtained via a

competing secondary reaction between the metallated carbanion 2, itself adding thiophilically 1, to give the coupled intermediate

(scheme 2) the

by NMR, mass and infra-red

3 in a comparable

of organomagnesium

0 II

(OR’),

SEt ’

9

9%

a

68%

+

reagent, show

of Grignard reagent are required for one equivalent of yield range to those obtained

of Grignard reagent was required.

obtained from these reagents, unsuitable for use in siru in Wittig-Homer

reactions.

with organolithium

This excess makes the carbanion,

3417

The lithiated carbanion treated with 1.2 equivalents

2, prepared

from the phosphonodithioformate

1 and an organolithium

of alkyl or ally1 halide , after work-up and purification

reagent,

was

by silica gel chromatography,

phosphonodithioacetals 10a-c' were obtained (scheme 3 and table 2). ____________________________________________________________-______________________________________________ Compound

10a lob 1oc 1Oc'

Rt

R2

Et

Me

iPr

E Me

E

R3

R4

E

Z Crotyl CHz=CH-C(Me)H

E

Yield %

Reference

:; 60 12

Z ;;

TABLE 2 The isolated Compounds

yields were very similar for 10a and 10b :compounds

lOc,containing

differing

the crotyl chain and its isomer lOc', with an inverted

.

only in the Rt substituent

crotyl chain, are the two major

products obtained after alkylation with crotyl bromide. Partial or complete alkylation with inversion of the allylic chain is commonly observed with stabilized carbanions such as a-alkylthio an intermediate formation

ylid which undergoes

a [2,3] sigmatropic

or a-alkylseleno

rearrangement

enolates 9, lo. The formation of

or an S$’

reaction14

could explain the

of 10~'. SF?

R3Li 1

b THF/-78°C

11 mixture of E + Zisomers SCHEME 3 When one equivalent of aldehyde or ketone was added directly to the lithiated carbanion 2, the expected ketene dithioacetals

11 wereobtained after hydrolysis and purification with the yields indicated below (scheme and table 3) : Compound

Rt

R*

iFJr

lla lib llc lid lie llf

iPr iPr

iPr iPr iPr

R3

R5

R6

E

E Me

H H H

g h4e

Me iPr Ph ~~“o-c”H4

Ph

Me

E

Yield %

References 3,7a

::. 82 73

a67a 16 3,7a 16

Ee 2:

- (CH2)5 -

TABLE 3 The following dithioester

is a standard experimental procedure for all of these reactions. Under an inert atmosphere,

1 (lmmole)

(5mL). The metallated THF (SmL).For

is added, dropwise carbanion

the reactions

at -78’C, to a solution of organolithium

2 is treated at -78°C with a solution of methanol,

with enolisable

carbonyl

temperature from -7S’C to room temperature immediately

compounds,

higher

over anhydrous

sodium

and by sulphur anaIysisl6.

sulphate.

in dry THF

RX, or RR’CO (1.3mmole)

yields were obtained

by raising

in the

after the addition l5,The solvent is evaporated and the crude

product extracted between diethyl ether and a saturated solution of ammonium distillation.Identification

reagent (1.2mmole)

the

The solvent is evaporated

chloride , washed with brine and dried

and the product

of the new products was obtained by investigation

purified

by gel chromatography

or

of their 1H, 31P, 13C and mass spectra

3418

The

regioselectivity

of the addition of other nucleophilic reagents with phosphonodithioformateates is currently under

investigation References

(1)

Lcger, L.; Saquet, M. Bull. Sot. Chim. Fr. 1975, 657-666.

(2)

Masson, S.; Saquet, M.; Thuillier, A. Tetrahedron

(3)

Berrada, S.; Metzner,

(4)

Grisley,

(5)

Metzner, P.; Vialle, J.; Vibet, A. Tetrahedron Left. 1976,4295-4296.

(6)

Viola, H.; Hartenhauer,

(7)

(a) Mikolajczyk,

P.; Rakotonirina,

. 1977, 33,2949-2954.

R. Bull. Sot. Chim. Fr. 1985, 881-890.

D.W. J. Org. Chem. 1961, 26, 2544-2546.

H.; Mayer, R. Z. Chem. 1988, 28, 269-277.

M.; Grzejszczak,

S.; Zatorski, A.; Mlotkowska,

B.; Gross, H.; Costisella,

B. Tewuhedron,

1978, 34, 3081-3088. (b) Mikolajczyk,

M.; Midura, W.; Grzejszczak,

(c) Mikolajczyk,

M.; Balczewski,

(d)Mlotkowska,

Lat. 1984, 25,2489-2492.

S. Tetrahedron

P.; Graczyk, P. Phosphorus

B.; Gross, H.; Costisella,

B.; Mikolajczyk,

& Sulphur. 1987, 30, 225-228.

M.; Grzejszczak,

S.; Zatorski, A. J. F. P&t.

Chem. 1977, 319, 17-22. (e) Mikolajczyk,

M.; Grzejszczak,

(f) Mikolajczyk,

M.; Balczewski,

S.; Chefczynska, P.; Grzejszczak,

(g) Gross, H.; Keitel, I.; Costisella,

A.; Zatorski, A. J. Org. Chem. 1979,44,2967-2972. S. Synthesis.

B.; Mikolajczyk,

1980, 127-129.

M.; Midura, W. Phosphorus

& Sulphur. 1983, 16,

257-262. (8)

Kim, T.H.; Oh, D.Y. Synth. Commun..

1988, 18,,1611-1614.

(9)

Reich, H.J.; Cohen, M.L. J. Am. Chem. SCJC.1979, 101, 1307-1308.

(10)

Ogura, K.; Furukawa,

(11)

Purification

S.; Tsuchihashi,

G.I. J. Am. Chem. Sot. 1980, 102, 21252127.

of product 3 was attempted

by chromatography

on silica and fluorosil

gel and by classical.and

bulb to bulb distillation (at reduced pressure). The same technique did not prove to be suitable for all cases and for a significant

comparison,

the yields were determined

by IH NMR of the crude product, using benzene or

methylene chloride as an internal standard. (12)

The E sulphine was previously with sulphur dioxide

prepared by the reaction between diethyl trimethylsilylmethane

13. ‘H NMR (CC4)

; Z sulphine

: &SC&=

2.73 ppm, E sulphine

phosphonate : S-SC&=

2.53

wm. (13)

Porskamp,

(14)

Solomon,

M.; Hoekstra,

Although

no thorough

(15)

P.A.T.W.;

Lammerlink,

B.H.M.; Zwanenburg,

was carried out , it was noticed that at -78”C, no attack of the

yield optimisation

carbonyl group by the carbanion

was observed.

position of the aldehydeketone

was thought, when possible,

small amount of the enolate ketone condensation investigations (16)

B. J. Org. Chem. 1984, 49, 263-268.

W.; Zima, G.; Liotta, D. J. Org. Chem. 1988, 53, 5058-5062. Furthermore,

of the new products:tH

3.80 ; 3g 3.87 ; 3i 3.57 .(doublets

NMR (CC4),

; 2J HP = 18 Hz ; P-C-II)

; 2J HP = 17 & 21 Hz ; P-C-H ; 2 diastereoisomers 19 Hz ; P-C-H ; 2 diastereoisomers ). (CDC13),

at the aand a Further

these results.

(doublets

31P NMR

by the carbanion

to be taking place as the dithioacetal3

product were both isolated under these conditions.

using deuterated acetone have confirmed

NMR characteristics

basic deprotonation

6 (ppm) : 3b 3.43 ; 3d 3.48 ; Se 3.98 ; 3f ; 6b 3.92 & 4.37 ; 6d 3.85 & 4.31 . ) ; 6f 3.57 & 4.03 .(doublets

6 (ppm) : 8 15.87 & 18.82 ; 9 19.05 ; 10a

22.08

; lob

;2J HP = 18 &

20.20 ; 1Oc 21.36 ;

10~’ 21.86 *(singlets). 13C NMR (63X13),

6 (ppm) : llb

(singlets ; =cR2 & =QSR)2 respectively) (Received

in

France

8 March

130.66 & 156.03 ; lld

. 1989)

129.38 & 133.06 ; llf

119.89 & 155.72