Stereochemistry in the cyclization of o -azidophenylalkenes to indoles

Tetrahedron Letters,Vo1.24,No.47,pp Printed in Great Britain

STEREOCHEMISTRY

IN THE CYCLIZATION

of Chemistry,

OF o_-AZIDOPHENYLALKENES

C. D. Rowe, and D. W. Hansen,

P. A. S. Smith*, Department

0040-4039/83 $3.00 + .OO 01983 Pergamon Press Ltd.

5169-5172,1983

University

of Michigan,

TO INDOLES

Jr.

Ann Arbor, Michigan

48109

Abstract: Cis- and trans-o-azidostilbene, o-azido-B-methylstilbene, and (Z)-o-azido6-deuteriostyren=ive indoleson thermolysis by a mechanism involving attack by-a ;;itrene directly on the 6 carbon atom, and not by insertion. Aryl azides more generally

have been observed

intramolecularly

ortho substituent, however,

whether

that reaction

to produce

The parallel also been studied. group presents stituted,

involves

or whether

a diradical

on the 6 H or C-H bond. involves

formation

However,

a true nitrene,

implies

it may be abstraction

nitrene

(2) on the proximal

of the proximal

of a nitro group to generate

C-H

C-H by a trip-

succeeds

the nitrene

whether

and if both positions

on the B carbon are sub-

a carbon

indicate attack

on the B carbon

directly

there is some uncertainty

(which becomes

about whether

an E-hydroxyindole

can occur before deoxygenation

has

or not the alkenyl

from it to the erstwhile

for in one instance,

that ring closure

and

to an indole.

The reaction

to the nitrene,

These facts clearly

intermolecularly,

when thermolyzed.' With an alkenyl 2 It has not been clear,

attack of a singlet

reaction by deoxygenation 3 Indoles are obtained.

a cis-hydrogen

C-H groups

to form an indole.

(3) that collapses

one of the groups migrates

of the indole).

sarily

to an ortho substituent

the result is ring closure

bond or on the sp2 carbon, let nitrene

to insert in saturated

C-3

rather than

the reaction

neces-

was obtained.4

to a nitrene

Its

has taken

place. We have prepared ecompounds, trans The

and trans-o-azidostilbenes

using the reaction

isomer

(44% yield)

of the Grignard

had mp 95.5-96"C,

(l_, Z2 = N2) from the known bromo

reagents with toluenesulfonyl

and the cis isomer

azide. '

(48%) was obtained

The

as an oil.

IR spectra of the trans isomer (970 cm-') and the cis isomer (920 and 775 cm-'), and

the NMR spectra

[trans 6 6.75 (s), cis 6 6.49 (s)] were consistent

with the assigned

geometries. Thermolysis mixture

of the trans compound

mp 188-189"C,

phenylindole, and 6,8-8.0,

in 88% yield.

but in only 18% yield,

in boiling

decalin

The same treatment

gave E-phenylindole

of the cis isomer also gave 2-

along with intractable

tar

(IR 337 cm-'; NMR l-2.8

broad envelopes).

We originally

interpreted

these results

to imply stereospecificity

on the assumption

that the small amount of ring closure may have been due to some isomerization c&-stilbene

(4), mp and

during the reaction;

from c-nitrostilbenes,

this interpretation

if both reactions

is not consistent

involve nitrenes,

5169

and implies

of the azido-

with the results that the cyclization

5170

involves

attack on the a hydrogen

(nitreno)

or C-H bond, which therefore

must be cis to the azide

function.

2 singlet

I

+ tar,

etc.

triplet

4-

We have prepared g-azidostyrene (20% yield

(99% s-d), obtained then hydrogenation

over 5% Pd/CaC03, polymerized

prepared

doublets,

the splitting

without

only traces of absorption plet) were present. preparative

TLC.

by the nitrene

corresponds

fore conclude

of 2l+indole

molysis

The large difference azidostilbenes

insertion

of the c-nitrenophenyl

group, making

It appears, derivatives

isolated

is not consistent

We there-

to be the case for ther7

-via the nitrenes.

of 2-phenylindole

from the geometrically

differences

it difficult

step is

is not a direct one, but in-

step, as is believed

crossing

with

step, but

at the B carbon.

in these reactions

by

at C-2 (the N-D was

This distribution

groups are cis, there is steric

sult, there is time for intersystem of the observed

content

and

(ABMX multi-

bond in the product-determining

may be due to the conformational

the phenyl and g-azidophenyl

formation

67% deuterium

which form carbazoles

in yields

analogues,

value6 only if the product-determining

in the initial

of o_-azidobiphenyls,

to that of (Z)as simple

(L)-B-H resonance

formed by attack of the nitrene

that the apparent

volves N-C bond formation

and (1)-o-

cumene gave indole in 50% yield,

during work-up).

at H(D) or the C-H(D)

appeared

in the nondeuterated

of the normal

indicated

identical

NMR signals

observed

in boiling

to kH/kD = 2, a reasonable

tautomerization

the &)-6-H

at the position

with water

The (L)-g-bromo-

by DCl, and

and had to be used at once, but they could

which were essentially

by @)-6-H

The NMR spectrum

exchanged

with BuLi followed

in 50% overall yield).

analogously;

Thermolysis

atom in place of the z-6 hydrogen

from o-bromo-s-deuteriophenylacetylene by treatment

rapidly,

by IR and NMR spectra,

be characterized @-deuteriostyrene

completely

prepared

from g-bromophenylacetylene

azido-6-deuteriostyrenes

attack

having a deuterium

from g-bromostyrene-@)-B-d,

between

interference

for it to engage

to the triplet

nitrene

isomeric c-

the isomers.

When

with rotation

the 8 carbon.

As a re-

to take place, and

tars results.

therefore,

that the mechanism

is the same for both the c-nitro

for cyclization

and g-azido

of g-substituted

systems.

To confirm

styrene this, we

prepared

(E)-g-bromo-s-methylstilbene

with acetophenone

in 28% yield,

with toluenesulfonyl

(m, 9H)]in

duct with triphenylphosphine; for 2 h gave a complex chromatography

in VPC.

and distillation

Thermolysis

ponding

Thermolysis

in a yield

of 77% reported

nitro compound

identified

ad-

at 195°C

(6_) was isolated

by

by IR and retention

time

port of a gas chromatograph

of 59% of the volatile components. .3 and Yamazaki for deoxygenation

This compares

by Sundberg

with triethyl

reagent

iminophosphorane

of the azide in decalin

2-methyl-3-phenylindole

in low yield,

synthesis

(5), an oil [NMR 6 2.15 (d, 3H),

of a sample of the azide in the injection

gave 2-methyl-3-phenylindole with the yield

from which

by the Wittig

of its Grignard

It formed a crystalline

72% yield.

mp 192-193°C.

mixture

bromide

it by the reaction

azide to c-azido-B-methylstilbene

6.37 (m, lH), 6.5-7.2

column

from g-bromobenzyl

and converted

of the corres-

phosphite.

Ph

H 22 6

5 In addition

to the indole and the expected c-aminostyrene,

from attack on the solvent are worthy cumene

of note.

isopropyl

resonances

in the thennolysis

In one (12% yield)

group appeared

(6 6.2-6.8,

bond.8

In the second

m, 6H; 6.8-7.1, in equilibrium attributable

protons

m, 4H), implying with

ported

are formally

insertion

in rare instances.'

formed azanorcaradiene.lO'll has been reported heretofore

structure

valence

on another

products

benzene

of arylnitrenes

They are presumably The alternative

for the reaction

of sulfonyl

has only been encountered

with the structure

insertion intact

(NMR 6 1.2, d, 6H; 2.8-

Compound

(6 6.2-6.6,

isomer

(probably

8 had no absorption

at 6 3.4.

ring is exceptional.

Diarylamines,

into an Ar-H bond, have been re-

derived

from rearrangement

isomerization

represented

azides with aromatic

with arylnitrenes

of o-

into the tertiary-C-H

(8) or a position

tautomer).

to N-H, but 1 showed a broad lump centered

Such attack of an arylnitrene which

of nitrene

group remained

the azepine

in cumene

groups of the erstwhile

and only four aryl protons were evident

its azanorcaradiene

arising

(6 1.45, 6H), and the other

m, 8H) were consistent

(I), a product

(lo%), the isopropyl

3.0, m, lH), but new vinylic

products

of L_ cis-o-azido-B-deuteriostyrene

(MS m/e 252), the methyl

in the NMR as a singlet

m, 2H; 6.8-7.1,

(cumylamino)+-deuteriostyrene

two minor

of an initially

by formation

of S

hydrocarbons, l2 but

in the case of deoxygenation of 10 perfluoronitrosobenzene in the presence of benzene or anisole, and deoxygenation of 11 nitrosobenzene in the presence of benzene in trifluoroethanol. Neither phenyl nor per10,ll fluorophenyl azides give rise to azepines by thermolysis or photolysis, however. 13 The analogous reaction of aryl carbenes to form tropilidenes is well known.

5172

u

ArNH-i’ ’ \

HMe2

Me

I

Me

-

7

[Ar = o_-deuteriovinylphenyl] The foregoing volved

products

in thermolysis

Acknowledgment. tional Science

provide

confirmation

of o_-alkenylphenyl Financial

Foundation,

support

GP 15830,

of the presumption

that nitrenes

are in-

azides. for a part of this work by a grant from the Na-

is gratefully

acknowledged.

References 1.

P. A. S. Smith, Chapter

in "Nitrenes,"

4; R, A. Abramovitch

W. Lwowski,

ed., John Wiley and Sons, New York, 1970,

and E. P. Kyba, in "The Chemistry

of the Azido Group,'

S. Patai, ed., John Wiley and Sons, New York, 1971, pp. 256-278. 2.

R. J. Sundberg,

L.-S. Lin, and D. E. Blackburn,

3.

R. J. Sundberg

and T. Yamazaki,

4.

R. J. Sundberg,

J. Org. Chem.,

5.

P. A. S. Smith,

L. B. Bruner,

6.

This is a minimum substrate,

value;

correction

conclusions,

which

7.

R. J. Sundberg,

8.

Preferential

J. Heterocyc'l. Chem.,

J. Org. Chem., 2,

3&

290 (1967).

3604 (1965).

and C. D. Rowe, J. Org. Chem.,

if some non-deuterated

for it would

azidostyrene

lead to a correspondingly

insertion

and B. A. DeGraff,

For example, Commun.,366

10.

551 (1969).

were present

into the tertiary

see J. Ashby,

C-H of saturated

E. F. V. Striven,

(1972); R. A. Abramovitch,

J. Org. Chem., 37,

2705 (1972).

R. A. Abramovitch,

S. R. Challand,

higher value,

R. J. Sundberg

12.

R. A. Abramovitch

and R. H. Smith,

hydrocarbons Lett.,

and H. Suschitzky,

S. R. Challand,

13.

P. A. S. Smith and E. M. Bruckmann,

has been ob2211 (1965).

J. Chem. Sot., Chem.

J. Am. Chem. Sot.,

Lett., 267 (1971).

and V. Uma, J. Chem. Sot., Chem. Commun., J. Org. Chem -3 _I 39

(Received in USA 16 August 1983)

(1975).

and E. F. V. Striven,

and E. F. V. Striven,

Jr., Tetrahedron

but the

not be affected.

(1972). 11.

in the

J. Am. Chem. Sot., 97, 6193

served by J. H. Hall, J. W. Hill, and H.-C. Tsai, Tetrahedron 9.

-3,

do not depend on the exact value of kH/kD, would

D. W. Gillespie,

2, 441 (1969).

797 (1972).

1047 (1974).

94, 1374