Tetrahedron Letters No. 6, pp 551 - 554, 1977. Pergamon Press. Printed in Great Britain.

INTRAMOLECULAR 1,3-DIPOLAR CYCLOADDITIONS OF VINYL AZIDES

* Albert Padwa, Audrey Ku, Hao Ku, and Arthur Mazzu

Department of Chemistry State University of New York at Buffalo

Buffalo, New York 14214

(Received in USA 17 November 1976; received in UK for publication 12 January 1977)

Intramolecular 1,3-dipolar cycloaddition is an extremely versatile and im-

portant reaction. The range of synthetic possibilities which it opens for the

construction of fused heterocycles is extremely large. 1 With azides, intra-

molecular cycloadditions have been occasionally reported 2-5

but systematic data

are available only for a series of azidoalkenes. 4

Although bimolecular 1,3-

dipolar cycloadditions of vinyl azides have appeared in the literature, 6-8

intramolecular cycloadditions of this 1,3-dipole have not been described. The

present communication reports the first example of such a process.

Reaction of iodine azide with 2,2'-divinylbiphenyl' followed by treatment

of the initially formed iodine azide adduct with potassium g-butoxide gave

mono-vinyl azide A. When i was allowed to stand at O" for 3 days, it quanti-

tatively cyclized to give A2-1,2,3_triazoline 2, mp 140-142', nmr (CDC13, 100

MHz) T 6.00 (g, lH, J = 17.0 and 10.0 HZ), 5.62 (2, lH), 5.31 (g, lH, J =

10.0 and 3.0 Hz), 4.90 (G, lH, J = 17.0 and 3.0 HZ), 4.73 (g, lH), and 2.32-

2.92 @,8H). Further heating of this material resulted in the loss of nitrogen

and formation of 3,llb-dihydro-3-methylene-l~-azirino[l,2-a]di~nz[c,elazepine

(31, nmr (CDC13, 100 MHz) T 8.01 (d, lH, J = 3.0 Hz), 7.49 (a, lH, J = 6.0 Hz),

6.67 (g, lH, J = 6.0 and 3.0 Hz), 5.57 (g, lH), 5.43 (s, lH), and 2.37-2.88

@, 8H). Treatment of 2 with hydrochloric acid afforded chloride 4 in high

yield.

551

552 Ho. 6

1 =

4 = 3 =

Although the isolation of 2 from & is not surprising, it is noteworthy as

the first example of intramolecular cycloaddition of a vinyl azide. Thermoly-

sis of vinyl azides generally produce 2g-azirines by a process involving ring

closure simultaneous with loss of nitrogen. 10

The facile formation of 2 is

also unusual in light of the earlier work of Logothetis 4

who found that azido-

alkenes require heating at 50' for 18 hr before intramolecular cycloaddition

will occur. The high reactivity of vinyl azide 1 toward dipolar cycloaddition

can be nicely rationalized by the frontier molecular orbital method. 1,3-Di-

polar cycloadditions of azides with olefins may be classified as a set which

involves dipole LUMO-dipolarophile HOMO control. 11,12 Attachment of a phenyl

group to the v-system will raise the HOMO and lower the LUMO energy levels Of

the olefin and thus bring about an acceleration of the rate of 1,3-dipolar cyc-

loaddition with azides. Another factor which undoubtedly plays an important

role in the intramolecular cycloaddition reaction of vinyl azide & is the high

degree of order present in the transition state. Bimolecular cycloadditions

exhibit large negative entropies of activation 13 since the reactants must be

NO. 6 553

precisely aligned with respect to each other. The interplay of favorable en-

tropy and enthalpy factors in the above system undoubtedly facilitates the rate

of cycloaddition.

We also attempted to study the intramolecular 1,3-dipolar cycloaddition re-

action of the closely related vinyl azide g in order to assess the generality of

this cycloaddition. Treatment of c-allylstyrene(2) with iodine aside followed

by reaction with potassium t-butoxide afforded vinyl aziridine 2 as the major

product: nmr (CDC13, 100 MHz) 'I 7.24-7.40 (m_, 2H), 6.1-6.4 @, lH), 5.90 (d&

lH, J = 17.0 and 8.0 Hz), 5.58 (g, lH, J = 17.0 and 11.0 Hz), 2.4-3.0 @, 4H).

Thick layer chromatography of 2 resulted in the opening of the three-membered

5 =

CH3

ti ‘

/ H+

\/ CH3

6 H2 =

1 -N2 CH2

@iY

/

\

7 =

ring and gave 1,3-dimethylisoquinoline (g) 14

in quantitative yield. The forma-

tion of 2 from 2 can reasonably be interpreted in terms of a rapid intramolecu-

lar 1,3-dipolar cycloaddition of an initially formed vinyl aside (5) followed

by loss of nitrogen.

Acknowledgement: We wish to thank the National Institutes of Health (Grant No.

CA-12195) for generous support of this work.

554 No. 6

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