Tetrahedron Letters,Vol.29,No.48,pp 6369-6372,1988 oo40-4039/88 $3.00 + .OO Printed in Great Britain Pergamon Press plc

INTRAMOLECULAR DIELS-ALDER REACTIONS OF

SULPHONYL-SUBSTITUTED TRIENES

Donald Craig,* Doris A. Fischer,1 dznur Kemal, and Thomas Plessnerl

Department of Chemistry, Imperial College, London SW7 2AY, U.K.

Summary: The synthesis and intramolecular Die&Alder reactions of sulphonyl-substituted trienes 1 and 2 are described. The stereoselectivities of the cycloadditions are discussed, and some reactions of the bicyclic products are reported.

The continuing importance of the intramolecular Diels-Alder (IMDA) reaction in modem organic synthesis may be attributed in large part to its unique utility for the construction of polycyclic frameworks from relatively

simple precursors.2 IMDA reactions which yield as products bicyclo[4.3.0] and bicyclo[4.4.0] systems are invariably regiospecific, and by careful choice of substituents on the diene, dienophile and linking chain,

highly stereoselective cycloadditions may be observed. Although the use of vinylic sulphones3 in bimolecular

Diels-Alder reactions has ample precedent,4 examples of the corresponding intramolecular process are rare.5 We report herein the preliminary results of our investigations into the thermal IMDA reactions of E,E,E-l- benzenesulphonyl-1,6&decatriene 1, and E,E,E-l-benzenesulphonyl-1,7,9-undecattiene 2.

Trienes 1 and 2 were synthesised in a straightforward manner as outlined in Scheme 1. Julia reaction6 of O- protected sulphones 3 and 4 with crotonaldehyde gave an inseparable ca. 6:l mixture of E,E- and Z,E-

dienes upon reductive elimination of the intermediate benzoyloxysulphones. Coupling of the aldehydes 57

and 68 with (benzenesulphonyl)lithiomethane followed by mesylationlin situ elimination of methanesulphonic

acid from the product alcohols gave trienes 1 and 2 in high overall yield for the lo-step sequence.9 The E:Z

ratio of A12 isomers formed in the final step was shown by 1H nmr to be ca. 97:3!0

Scheme 1

n=l,2 3 (n=l): 63% 4 (n=2): 61%

(v) - (viii)

I

1 (n=l): 60% 2 (n=2): 84%

ca. 6:l EL? / 5 (n=l): 57% 6 (n=2): 58%

Reagents: (i) HBr, benzene, reflux; (ii) clihydropyran, lo-camphorsulphonic acid, CH2CI2; (iii) PhSNa, EtOH; (iv) CH@OOH, NaOAc, CH#z; (v) nBuLi, THF; CH&H=CHCHO; PhCOCI; (vi) Na(Hg), MeOH; (vii) 1Ocamphorsu~honic acid, MeOH; (viii) Swem; (ii) PhSO&H&i, THF; (x) Cal, Et& Cl+&.

6369

6370

Scheme 2

- S02Ph ,

MSOzPh 2

PhMe

I

175”C, 60h

93%

PhMe 172X, 96h

92%

The products of the IMDA reactions of 1 and 2 are shown in Scheme 2. Heating a toluene solution of 1 gave

a 1: 1 mixture of products 7 and 8; l2 diastereomerically pure cycloadducts could be obtained by repeated fractional crystallisation from benzene-petrol. The stereochemistry of 7 was indicated by a positive n.0.e.

between H-l and the methyl group: this effect was absent in isomer 8.13 The structure of 8 was confirmed by

X-ray crystallography (Figure 1).14 In contrast, thermolysis of the less reactive triene 2 gave a single bicyclic

product 9,12 whose structure was also unequivocally assigned by X-ray crystallography (Figure 2).14 We

rationalise these results both in terms of the asynchronous nature of the IMDA reaction,2(d)J5 and steric interactions in the competing diastereomeric transition states. 1,6,8_Nonatrienes with electron-withdrawing

groups at the terminal dienophile position generally exhibit modest selectivity for the rruns-fused bicyclic

product.16 In the absence of en&effects, t7 this is attributed to more advanced internal (as distinct from

peripheral) bond formation in the pseudo-five-membered cyclic transition state. The steric bulk18 of the

benzenesulphonyl group is such as to favour formation of a c&fused bicycle via a transition state in which the sulphone and diene moieties are exe-. The opposition of these two effects results in the formation of a mixture of products. Contrastingly, thermal IMDA reactions of the homologous 1,7,9-decatrienes show no

inherent selectivity.19 We attribute the stereospecificity of the IMDA reaction of 2 to repulsive steric interactions between the sulphone and diene units in the transition state leading to the unobserved nuns-fused

product (Scheme 3).

Scheme 3

PhSO,

PhSO,

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Crystal structure of 9 Crystal structure of 9 Flgure 1 Flgure 2

We have carried out a number of simple synthetic transformations of the IMDA reaction products, as depicted in Scheme 4. Treatment of 7,s and 9 with sodium amalgam in methanol effected smooth desulphonylation

to the bicyclic alkenes. Exposure of 7 or 8 to one equivalent of r&S&i in THF followed by quenching with

methyl iodide gave a cu. 1: 1 mixture of epimeric methylated products. *O Interestingly, identical processing of 9 gave a 3: 1 mixture of products in which the methyl group had been introduced with retention and inversion of configuration, respectively. Some methylation on the orrho- position of the phenyl ring of 9 was also

observed.20

Scheme 4

H , f

m

0) _

H

Lb (0 ~ H

-&p+& (ii)) & +&

S S

-@+J$ S S

(1:l)

(1:1)

(3:l)

S = S02Ph

Reagents: (i) 5.5 % Na(Hg), anhyd. MeOH, 25°C; (ii) nBuLi, THF, -78OC; Mel, -78°C to 25°C

The findings described herein demonstrate that the benzenesulphonyl group exerts a profound influence upon the stereochemical course of the cyclisation process by virtue of its steric bulk. As such, it may be regarded as a removable stereocontrolling element which may also serve as a focal point for further synthetic manipulations. We are currently exploring the IMDA chemistry of more highly substituted analogues of 1 and 2, including trienes bearing carbon and heteroatomic functionality on the dienophilic group, and substituents

in the linking chain. The results of these investigations, together with applications to natural products synthesis will be reported in due course.

6372

Acknowledgements

We thank Pfizer Central Research and the Nuffield Foundation for financial support. 0. K. gratefully acknowledges the James Black Foundation for a grant.

References and notes

1. 2.

3.

4.

5.

6.

7. 8. 9.

10.

11.

12.

13. 14.

15.

16.

17.

18.

19.

20.

Students of the Deutscher Akuiemischer Austauschdienst, 1987-88. (a) D. F. Taber, ‘Intramolecular Diels-Alder Reactions and Alder Ene Reactions’, Springer Verlag, New York, 1984; (b) E. Ciganek, Org. React., 1984, 32, 1; (c) A. G. Fallis, Can J. Chem., 1984,62, 183; (d) D. Craig, Chem. Sot. Rev., 1987.16, 187. Major reviews: (a) B. M. Trost. Bull. Chem. Sot. Jpn., 1988, 61, 107; (b) P. D. Magnus, Tetrahedron, 1977,33,2019. See, for example: (a) R. V. C. Carr, R. V. Williams, and L. A. Paquette, J. Org. Chem., 1983,48, 4976; (b) J. C. Philips and M. Oku, J. Am. Chem. Soc.,1972, 94, 1012; (c) 0. de Lucchi, V. Lucchini, L. Pasquato, and G. Modena, J. Org. Chem.,l984,49,596. For recent examples in which the dienophilic group contained additional electron-withdrawing functionality, see: (a) L. Strekowski, S. Kong, and M. A. Battiste, J. Org. Chem., 1988,53,901; (b) E. J. Corey, P. Da Silva Jardine, and J. C. Rohloff, J. Am. Chem. Sot., 1988, 110, 3672. (a) M. Julia and J.-M. Paris, Tetrahedron Lett., 1973,4833; (b) P. J. Kocienski, B. Lythgoe, and S. Ruston, J. Chem. Sot., Perkin Trans. 1, 1978, 829; (c) P. J. Kocienski, B. Lythgoe, and I. Waterhouse, ibid., 1980, 1045. M. J. Kurth, M. J. O’Brien, H. Hope, and M. Yanuck. J. Org. Chem., 1985,50,2626. S. D. Larsen and P. A. Grieco, J. Am. Chem. Sot., 1985,107, 1768. The yields cited are of isolated, pure materials. All compounds exhibited spectral (IH nmr, ir, ms) characteristics consistent with the assigned structures. Acceptable elemental analyses (& 0.3%) were obtained for all new compounds. Peterson olefinationll using the lithio-anion of (benzenesulphonyl)trimethylsilylmethane gave a ca. 1:2 mixture of E- and Z- vinylic sulphones. D. Craig, S. V. Ley, N. S. Simpkins, G. H. Whitham, and M. I. Prior, J. Chem. Sot., Perkin Trans. 1, 1985, 1949. Signals due to bicyclic products formed via cyclisation of the minor triene isomers were also observed in the tH nmr spectrum of the crude product. Comprehensive details will be published in the full account of this work. We thank Mr. Richard N. Sheppard of this department for this experiment. We thank Dr. David J. Williams, Alexandra M. Z. Slawin, and Craig A. Marby of this department for this determination. For a discussion of the concept of “twist asynchronicity”. see: F. K. Brown and K. N. Houk, Tetrahedron L&t., 1985,2297. (a) W. R. Roush, A. I. Ko, and H. R. Gillis, J. Org. Chem., 1980, 45, 4264; (b) W. R. Roush, H. R. Gillis, and A. I. Ko, J. Am. Chem. Sot., 1982, 104, 2269. Endo-selectivity in bimolecular Diels-Alder reactions decreases sharply with increasing temperature: (a) J. Sauer, Angew. Chem., Int. Edn. EngL1967, 6, 16; (b) J. G. Martin and R. K. Hill, Chem. Rev., 1961, 61, 537. The endo-selectivity of intermolecular Diels-Alder reactions of benzenesulphonylethene with cyclopentadiene and 1,3-cyclohexadiene‘t(a) results from the greater steric demand associated with the sp3-hybridised methylene and ethylene chains linking the diene termini, as compared to the planar, spz-hybridised diene unit. (a) Y.-T. Lin and K. N. Houk, Tetrahedron L&t., 1985, 2269; (b) W. R. Roush and S. E. Hall, J. Am. Chem. Sot., 1981, 103, 5200; (c) W. R. Roush and H. R. Gillis, J. Org. Chem., 1982,47, 4825. Products of the alkylation reactions of 7,s and 9 were unambiguously identified by high-field nmr studies, and by chemical correlation with the IMDA reaction products of 1-methylated 1 (for 7 and 8). Full details will be published at a later date.

(Received in UK 29 September 1988)