Stereochemistry of nucleophilic displacement reaction at thiophosphoryl centre. An example of a walden cycle involving phosphorus

Tetrahedron Letters No.23, pp, Printed in Great Britain.

1779-1784, 1965. Pergamon Preaa Ltd

STEREOCHEMISTRY OF NUCLECPHILIC I)ISPLACEk!EXl! REACTION AT

'T~Ia~~i(?S~HORYL CENTR~. id EX&VLE CYCU

IZVOJ,VINF

@F h ~~~~~EN

PHOSPHi!TcTlS

J.n1.ohalski,M.nikoZajcsyk. J.@melaSceuk Institute of Crganic Chemistry, Polish n08aeay of Sciences, Lads, Poland 1%&k (Received 8 April

40, i?wirki36) 1965)

Attempts to devise stereochemicalWalden aycles in order to establish inversion of configuration at the asymmetric phosphoryl and thlophosphoryl centres were so far only partly successful (1,2). It

was desirable, for the puqose of

carrying out stereochemical studies of displacement reaction at the thio~~hosphor,yl centre by Kenyon-Phillips method (3), to have ootioal1.yactive compounds of special grogerties. With this end in mind the optically active (+)triethyl ethylpyrophosphonodithionate(II), Et(EtO)?(S)CP(s)(QEt)2,was prepared by condensation of (-)sodiun C-ethyl ethylphosphonothioate with diethyl ~hospborooh~or~dot~~onate.

1779

No.23

1780

Study of the ;jyroThosohorodithionate sptem>~(S;)O~'(t)( reveals a considerable change of susccptlbilit;r of tFe ohosohorus atom to nucleooh%lio attack when an ester bond is reolaoed by the direct C-P bond. Yor instance, the nuoleophilic fission of the (+)oyrophosohonodithionate

(II) hg

methoxide anion affords the (+)meth,vl ethyl ethyl:~hosplionothionate (IJI) and diethpl !phosphorotF:ioicacid.

&-

mt

!

mt

o-;-out i..le

(lj;t

i;t,-F-c)! e II S

II

s

(II),io(jL+3C.650

+

(TJ~U)~PSO-

(iJI),j~ji,+3.i;Qo

The attaok of the reagent j.s directed on the more eleotrophilio ghoaphorus atom containing the C-? bond.

','liiSi::

consistent with the hic:her reactivity of uhos~~lonothionates than that of L>hosnhorothionates towards nucleophilio reagents (4). The lack of ootical activitv of the acid fraction is indicative of a unidirectional

course of this delradation.

it was reasonable to expect that the attack of the hydroxide anion will I'ollow the same sattern. iience, alkaline hydrolysis of (+)p.vroohosphonoc!it?_ionate (II) was chosen to prove the inversion at the thiophos;horyl centre. Vhf2

sanole of (+)(I;),L~lL~;:~..~~O,was h.ydrol.ysedin an

excess of aqueous hvaroxidc to {yive, after acidification, (+)+ethyl

ethylllhosallocot;~ioic. acid (I) and diethvl

acid ahosohorothioic acid. !+I(‘!- .th.vlet‘r!.l?hoslJhonott~ioic (T),;*Jh+lS.!~iflq isolated from the mixture b:/ distillc.tions ;has a rotation sipn on;)osite to the startin;: one.

1781

No.23

~4t

U

I

,,t-.

-_Ljy

1. L.

i

Qi< t 05x Et-+ - 0 -+t

s

.:

(z),Lo(JL-14..350

_

ON

JQP Edou + cEto)qso-

S

(II),LajD+29.85'

ii

(I),Loc] D +12.90°

This shows definitely that reaction of (+)pyrophosphonodlthlonate (II) with hydroxide anion Involves Inversion at the asymmetric thio?hosphorpl centre since In the formation of (+)anh,vdrldc(II) LO-phosphorylationof the (-Jacid (I)] no bond is exchanged at the asymmetrio phosphorus atom. This reaction sequence comprises the example of a Walden cycle InvolvlnE;phosphorus. The stereospecificityof the hydrolysis is 9%. The decrease of optical activity (10%) of the (+)acid (I) in comoarison with the startinp:(-1aci.d(I) is most likely to be due to other factors than retention mecPSanisms. In view of the reasonable assumption that the nucleoohillc attack of the hydroxide and of the methoxide anions -on (+)pyrophosphonodi.thionate (II) follows the same sterlc course (li),(+)ester (III) is ex;jectedto have a configuration like that of (+)aoid (I). Yoreover, alkaline hydrolysis of (i-jester(III)

affords (-Iacid (I).

No.23

1782

Therefore, alkaline hydrolysis of (+)ester (III) should oocur with inversion of configuration. Resides the reactions outlined above, (-)ester (111) and (+)pyrophosphonodithionate ting from the (-)ðyl CEt Et-+-Cl

(II) were synthesized star-

ethylshosphonochloridothionate CEt

pst Meo-*

wo- _

~Gt0)2P(Shma

(Iv),[DQ-70.0C"

8

c

(

q?a fit-i-

into

0s

qlst -cat F,

(11),[oq1;+26.0'j0

The fact that (-)ahosohonochloridothlonate phosphoncdithionate

St-L!,

(lli),[d]D-Z.','50

(Iv),eqJ-7*/.z5°

j‘Et Et-+ !:.

Bt-;-@Me s

9

(IV)(6).

(17) and (+)p.yro-

(II) can be converted by methoxide anion

methyl eth,yl ethylphosphonothionate

(III) of oa;)osite

configurations, strongly sup:jorts the assumption that (-)(IV) and (+)(]I) have also opdosite configurations. !Ience, the reaotiou of (-)acid (I) with ohosphorus pentachloride and conversion of C-)(IV) into (+)(Ti) should qocceti with inversiorL. The interrelations and pro:>osed relative configuratiocs are represented by the scherre given below.

No.23

1783

Et0 \

No.23

1784

REFERENCES

(1). El.Green, R.F. Hudson, [J.Chem.Soo.,3883 (1963)] have been showed that alkaline hydrolysis of an Optloally active diethyl methylpyrophosphonodithionategives optically inactive O?ethyl methylphosphonothioicaold. This result is strongly in favour of the inversion accompanying the hydrolysis. (2). A. Ratajczak, Bull.Acad.Polon.Soi.,I&

145 (1964).

(3). E.L. Ellel, Stereochemlstrvof Carbon ComDounds, MoGrawHill ComD., Inc., New York, 1962, p. 117. (4). J.R. Cox, O.B. Ramsay, Chem.Revs., 2,

317 (1964).

(5). M. G
Neat compounds were used for all specific rotation determinationsmentioned in the paper.