Tcmhedron Lenen. Vol. 34. No. 18. PP. 29452948.1993

PIiIUdinGreatBritGl 00404039193 $6.00 + .OO PergamcmRessLad

Preparation of Laetones with Several Ring Sizes via the Same Intermediate

!&Me Robin

Laboretoire dcs Carbccycles, associt au CNRS, B&t. 420, Universitc de Paris Sud,

91405 ORSAY, France

Laboratoire de Synthbe Organique, ass& au CNRS, FbcuM des Sciences, BP 535,

Univenitc du Maine, 72017 Le Mans, France

AbstIact : several lactoma wac preped from (S)-I-@3-M 2 by cyclizalim of allylqianpakhcfadilssilyldaivuive3 wirhelcctlopfdlcrrsynfr~afimabnrlgoup

We-ntly showed that several hydmxy-sulfones couldbe obtained by micllobiological

teductions of kehsulfones (e.g. 2 from 1 by baker’s yeast teduction).l We anti~$&~~ that lactonc~3

BY p c1siMe#Bll

tBuM@iQ

-/ ,, z

SoLph 80% MSO#h >95% ee

S&Ph imiduo*,

1 2&f1) 90%

3

could be prepared via teduction product 2 by alkylation of the comspondingdianionwiththeappro-

priate electmphilic reagent followed by cyclization. However several attempts in such alkylations fai-

ledorledtobadnsults.Thenfarewetriedto&thesamevia monoanionofthecorre+nd&silyl

derivative 3.4 Alkylation with methyl cyanoformate5 led to the expected produet 4 ia mcdemte yield as

a mixtum of two dkkwxwm in a 6O/so ratio. Desilylation 4 and reduction 6-7 gave lactone 6. g

2945

3 nBuLi then CNC@Me

P

AI/Hg 0 Y i&z . l&lx 4.6 (60%)

[ah, -27.7 (c 1.89, CI-I$&) ee>95% (‘H NMR with Eu(hfc)j)

fiw, THP w

25’C

0

0 5 S@Ph

4. 5 (60/40) (65%)

Aftetwards we tried to pnpanz lactones 11 and 12 through the alkylation product of 3 with

tettiobutyl bromoacetate. Unfortunately the reactien* W to 24% only of isolated 7 along with several

unidentified products and a small amount of phenylsulfiic acid eliminatkn product ftom 7.

nBuLi, THP-HMFT 3 W

tBuMe$ig

then BICH&O@I Ax

co$Bu

z

SQPh 7 (24%)

Thetefote we used btomoacetaldehyde dimethyl acetal as an alkylating agent and obtained 8

in high yield as a 50/50 diaste~ric mixture. kcetalkation Jed to lactol10 as a mixture of

several isome& 0xid8tion9J” otdy gave one la&one+ p nsumably the cis product 11. This assignment

was deduced from lH NMR coupliag coustants @I4 : 11.7, 3.3 Hz ; Q : 11.5, 2.6 Hz). This unexpec-

ted stereochemical result leads to assumption that epimerixation occured either at the desa&aktion

step or at the oxidation step. Elimination of sulfinic acid with 1,8diazabiiclo [5.4.O)undec-7-ene

(DBU)ls3 led to lactone ltu3*l 1

nBuLii THF-BMPA 3

then BflzCH(OMe)2

8 (50/50) (89%)

nBo4NF,m gH

25T

9 (SO/So) (78%)

OH

10 (76%) 11 (74%) 12 (80%) [ah, +16 (c 1, CHCQ [ah +212 (c 0.3, CHQ) mp 109.2T ee>95% (‘H NMR with Eu(hfc)3)

2947

Alkylation of 3 with 3-bromoptopionaldehyde dimethyl acetal gave compound 13 as a 60/40

diastereomeric mixtum. Subsequent desilylation then hydrolysis yielded lactol15 which was unstable

in the presence of silica gel and was not purified. Oxidation gave lactone 16 in 26% yield from 14 as a

diasteleomeric luimue. Both isomem could be sepamted by column chromatography on silica gel

These seven membered ring lactones (SR,7S)-16 and (5S,7S)-16 wen thug obtained in moderate yield

but in rather simple experimental conditions. The configuration of both isomers could not be assigned.

BrCH&H(OMe)2

13 @O/40) (65%) 14 (50/50) (78%)

16 (70/30) (26% fmm 14)

Our results show that several lactones ate obtained in high enantiomeric excess from com-

pound 1 which is easily available. They also suggest alternatives to circumvent difficulties in several

alhylation reactions.

References and Notes

1) Robin, S. ; Huet, F. ; Fauve, A. ; Veschambre, H. Tetrahedron Asymmetry, in press.

2) Sato, T. ; Olmmura, Y. ; Itai, J. ; Fujisawa, T. Chem. Len., 1988, 1537-1540 ; Tanikaga, R ; Ho-

soya, K. ; Kaji, A. Synthesis, EM, 389-390 ; Koxikowski, A.P. ; Mugrave, B.B. ; Li, C.S. ; Felder, L.

Tetrahedron Lett. ,l!JS6,27,4817-4820.

3) Gopalan,A.S. ; Jacobs, H.K. Tetrahedron Left., l!J90,31,5575-5578.

4)Corey, E.J. ; Venkateswarlu, A.J. Amer. Chem. Sot., 1972,94,6190-6191.

5) nBuLi in hexane (3.6 mmol) was added at -78’C under argon to a stirred solution of 3 (3.3 mmol) in

THF (6 mL). The reaction mixture was allowed to warm up to O’C, stirred 1 h at 0“C and cooled again

to -78OC. HMPA (3 mmol) and CNCC$Me (3.3 mmol) wem added at -78°C and the reaction mixtum

was allowed to warm up slowly to room temperatum and stand at this temperature overnight. Hydtoly-

sis, extraction and columu chromatography on silica gel led to 4. Componds 8 and 13 were obtained si-

milarly.

2948

6) Corey, E.J. ; Chayhovshy, M. J. Amer. Chem. Sot., 1964.86, 1639-1640.

7) Ah&nium amakgant (L.F. Fieser, M. Fieser, Reagents for Grganic Synksis, VQ~. 1, J. Wiley aud

Sons, Inc. New-York L.ondcn Sydney, 1967.20) was added to a solution of5 in tk mixture THF&O

90/10 and teaction minture washeated to reflux for 1 h. Cooling, filtration, drying, evaporation and

cohUnt~ Chromatography on sika ~1 kd to 6.

8) Batbier, P. ; Benesra, C. J. Mea! Chem. ,1%2,25,943-946 ; Uemaw T. ; Matmo, N. ; Sancmit-

su, Y. A&c. Mol. Chem. ,198#, 48,2477-2481 ; Scrai, K. ; Yohoyama, S. ; Hayasalra, T. ; Ebihara,

K. Chem. L&f., 1988,843-846 ; Ohta, T. ; Miyake, T. ; Seido, N. ; Kumobayashi, H. ; Ahutagawa, S. ;

Tahaya, H. Tetrahedron Lett., 199233, 635638.

9) Corey, E.J. ; Suggs, J.W. Tetrahedron Lef?., 1975, 2647-2650 ; Kuttb, MI. ; 0’ Brien, M.J. ;

Hope, H. ; Yam& M. J. Org. Chem. , l%S, 50.2626-2632 ; Wadsworth, D.H. ; Geer, S.M. ; Betty,

M.R. J, Org. Chem. ,1987,52 ,3662-3&X

10) Pyridinium chlorochnxnate (4 mmol), anhydrws scdium acetate (2 mmol), c&e (1.5 g) and

CH2Cl2 (8 mL) were strongly stirred then a solution of lactol 10 (1 mmol) in CH2C12 (2 mL) was

added. Reaction mixtute was stitred at room temperature (” 2 h) then at 4ooC (- 24 h depending on

TLC monitoring). Filtration through a pad of florisil, evaporation and column chmmatography on sili-

ca gel led to 11. Compound 16 was obtained similarly.

11) Kuhn, R. ; Kum, K. Chem. Ber. , 1%2, 95, 2009-2011 ; Procter, G. ; Russell, AT. ; Murphy,

P.J. ; Tan, T.S. ; h&her, A.N. Tetrahedron, 1988,44,3953-3973.

(Received in France 9 February 1993; accepted 11 Match 1993)