Temhedmn Lcws, Vol. 33. No. 48, pp. 7445-7446.1992 Priitcd in Great Britain

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1-Benzyloxy-3-(p-tolylsulfonyl)propene as an Acrolein PAnion Equivalent.

Synthesis of 46ubstituted 2-Butenolides

Donald Craig,* Christopher J. E&ridge, and Alison M. Smith

Akfmcf: Lithiion of 1-benzyloxy-3-(p-tolylsulfonyl)propene 6 and readon with aldehydcp gives akdols 7. Sequential hydmlysip-eycliion, oxidation and DELI-mediated eliminalion of Ihe elements of p-TolSO$ gives 4- sllbailuled 2-butenoli~ 10 in goud ovcdl yield.

During recent studies directed towards tetrahydrofuran synthesis via 5-et&-trig cyclization reactions of sulfonyl-substituted homoallylic alcoho1s.t we obsen& dte rapid, quantitative isomerization of the allylic ether 1 to the enol ether 2 on exposure to r-BuOK-r-BuOH in THF. It occurred to us that the analogous transformation of vinylic sulfones 3 would yield the enol ether-containing allylic sulfones 4. Deprotonation of

4, and reaction of the resulting anions with electmphiles followed by hydrolysis and elimination of AI-S&H would give the products of formal reaction with electmphiles of the acrolein Banion equivalent 5. In this Letter we report the successful application of this strategy to the synthesis of Csubstituted Zbutenolides, starting

from l-benzyloxy-3-@-tolylsulfonyl)propene 6 and aldehydes.

PhSO*

v

PhSOp

OH

OSn OBn OR OR

1 2 3 4

-\ = 6 5

l-Benzyloxy-3-(p-tolylsulfonyl)propene 6 was prepared as a cu. 3:1 Z:E mixture by reaction of (diethylphosphonyl)lithio(p-tolylsulfonyl)methane~ with 2benzyloxyethanals in THF (90%), followed by isomerization using potassium r-butoxide (0.1 eq.) in the presence of r-BuOH (20 eq.) in THF (0.16M) at r.t. (99%). Stepwise treatment of cold THF solutions of 6 with n-B&i and an aldehyde gave the alcohols 7 as diastereomeric mixtures upon low-temperature proton quench and chromatographic purification. Interestingly, compounds 7 wem generally obtained almost exclusively as the Z-isomers. Acidic hydrolysis of 7 in aqueous acetonitrile effected ring-closure to give lactols 8. PDC-Mediated oxidation to lactones 9 followed by eliination using DBU in CH&!l,ll gave Csubstituted 2-butenolides 10 in good uvcrall yields for the four-step sequence from 6 (Scheme, Table). Although aryl- and (1-alkenyl)-substituted &tone precursors 9 were all successfully prepared according to the Scheme, attempted DBU-mediated elimination under a variety of

conditions gave unacceptably low yields of butenolides 10. Reaction with DBU of the 4-ptopenyl-substituted analogue of 9 gave a mixture of the corresponding cr$- and g,y-unsaturated y-lactones.4

7445

7446

(i) x-BuLi (1.1 q.). THF (0.12-0.15M). -78’C. 5 min; add RCHG-THF (1 q.). -7g”c, 5 min: add A&H-THF (1.1 q.), .78v to r-t.; (ii) cont. H2SG4 (100 @/ml). 15% q. MeCN (O.OSM), 65oC. 2-7 h; (iii) PDC (1.5 q.). 4A sieves (1 mglinmd), C~2Ct2 (0.05-O.lM). r.t., 1.54 h; (iv) DBU (0.6 q.). CH2CI2 (O.lM). -78oc, 0.54 h; add A~GH-THF (0.6 q.), -78~ to r.t.

Scheme

EW R Yield of 75 Yioldof6 Yield of 9 Yieldof

a ncllk3 99 85 83 91 b CPr 90 95 87 87 C &cd+1 85 95 86 95 d 1.BU 95 59s 85 93 e (E,E)-M&H:CHCH:Cli(CHg)4 98 89 82 91 f BnOCHg 98 99 81 93

6 Bno(4=2)2 96 87 477 90 h ~DMSO(CH2)s 78a SO9 88 94

Table

In summary, the present method enables the synthesis of a variety of 4-substituted Zbutenolides in good overall yield from readily available 1-benzyloxy-3.@-tolylsulfonyl)propene and aldehydes.10 We are currently looking at the synthesis of fwans using related methodology involving the elimination of the elements of H20 and p-TolS&H fmm 8. The results of these and related studies will be reported in due course.

Acknowledgements

We thank the SERC (Quota studentships to C. J. E. and A. M. S.), ICI plc and Pfizer Central Research for financial support of this research.

References and notes

1. 2.

3. 4. 5.

6. I. 8. 9. 10.

Craig, D.; Smith, A. M. Tetrahedron Lett. 1992.33,695.

@iethylphosphonylXp-tolylsulfonyl)methane was pnpand in 91% recrystaliii yield by sequential addition to LDA-THF (2.2 q.) at -78“C of @-tolylsulfonyl)methane (1 q.) and (EtO)zP(O)Cl (1.1 q.), followed by warming to r.t. and quenching with A&H-THF. Pmpared in 87% yield by omnolysis (MeOH. -78’C; 0.5 q. thiiurea wok-up) of 3.benxylo~ypmpe. CarreXem, J. C.; De Lomlwrt. S.; Ghosez. L. Tetrahedron Lat. 1987.28.2135. All 46 yields cited herein am for pun mate&Is isolated by tlash chromatography on silica gel. All new compunds gave nmrandirdata,andelanentalcombustionenalysesinaccordwithIhepoposedstructures. Q4Hydroxy-5,5-dimethyl-2.Mxenal wm formed as a by-pmduct (26%) in this reaction. Buteuolii 19g (35%) was formed 811 a by-product in this reaction. R = AcGQ-H)s. R = HG(CHz)s. This hydroxylactol was converted into gh in 85% yield using TBDMSCI-EBN-DMAP in CHzCl2. For another acmlein g-anion quivalent, see: Meyers, A. 1.; Spohn, R. F. J. Org. Chem. 1985.50.4872. For acryhue g-anion quivalents, see in&r &a: (i) ref.4, and references therein; (ii) Tanaka, K.; Wakita. H.; Ioda. H.: Kuji. A. Chem. L&t. 1984, 1359; (iii) Dxiadulewicz. E.; Hodgson, D.; Gallagher, T. J. Chem. Sot.. Perkin Trans. I 1988. 3367.

(Received in UK 27 August 1992)