Synthesis of indolizines from n-(2,2,2-trifluoroethyl)pyridinium triflate; evidence for the generation of pyridinium (trifluoromethyl)methylide

JournalofFluorine

Chemistry,38(1988)289-293

289

Received: October17,1987;accepted: October30,1987

PRELIMINARY

Synthesis

NOTE

of

pyridinium

from

N-(2,2,2-Trifluoroethyl)-

Evidence

Triflate;

Pyridinium

RONALD

Indolizines

for

Generation

the

of

(Trifluoromethyl)methylide

ERIC BANKS*

Chemistry

and SUAD NAJMALDIN

Department,

Institute

of

Science

University

The and

MOHIALDIN

of

Technology,

Manchester

Manchester

M60

1QD

(U.K.)

SUMMARY

3-(trifluoromethyl)indolizine-1,2-

Dimethyl dicarboxylate (5),

and

(4), 1,2,3-tris(trifluoromethyl)indolizine ethyl

trans-2,3-bis(trifluoromethyl)-2,3-

dihydroindolizine-lvia

treatment

triflate

(2)

carboxylate of with

base

a [e

perfluorobut-2-yne

(B =

enquiries

0022-1139/88/%3.50

obtained

-N-(2,2,2-trifluoroethyl)pyridinium

acetylenedicarboxylate

* To Whom

have been

(7)

L-5

should

be

4

and

(B) (B

K2C03);

+7

=

dimethyl Et3N)]

or

(B = Et3N)].

addressed.

OElsevier Sequoia/Printedin The Netherlands

290

Published

knowledge

indolizines

carrying

3-position

via and

work

pyridinium

with

Noting

that

a

methylide

fluorinated

reactions

methylides

the

concerning

substituents

between

dipolarophiles

fluorinated

seems

yellow

formation

develops

N

0I’+/

1

I

I’+/ c) TfO-

the a

with

of

dipolarophilic

yield

[I].

trap

in

classical carbonate

suspended

in

procedure

chloroform

was

for

the (3).

tangible pyridinium

fashion can

(see

isolation

also

albeit

triflate

be

in

evidence

Scheme used

of -N-(2,2,2-trifluoroethyl)pyridinium

as

pyridinium

Subsequent 4,

in

(DMAD)

presumptive

indolizine

is

repeated

acetylenedicarboxylate

the

dissolved

(3)

or

provided of

when

I -CHCF3

the

dimethyl

of

N

(DMF)

(ll%),

Potassium involvment

(1)

I’+/ cl

trifluoromethylated

a-deprotonation occurred

to

(2)

CH2CF3

(trifluoromethyl)methylide new

restricted

immediately triflate

triethylamine,

presence

the

pyridinium

(2)

dimethylformamide

the

indicative

N

(1)

treated

be

coloration

-N-(2,2,2-trifluoroethyl)pyridinium

in

to

of

at

(trifluoroacetyljmethylide

bright

-CHCOCF3

synthesis

of low that

(2)

had

trigger

the

1): to

triflate

* Exocyclic a-deprotonation of quaternary pyridinium provides the commonest method for the production pyridinium methylides [2].

salts of

291

in

(2)

1,3-dipolar

isolation yield)

from

complex

perfluorobut-2-yne

adding

the

carbonate

material

to

a

and

mechanism the

no

the

of

shaking

produced

the

by

anhydrous

isolate (3)

light

[a

has

concerted

1,3-dipolar

yet

-vs

reactions

described

iS

available

yet

have

dihydroindolizinic

on

(see involved

of

the

Scheme

Similarly,

mode

unsuccessful

thrown

step

the

proved

been

above.

on

pyridinium

stepwise

cycloaddition

the

presumptive

by

mixture

slurry

to

(trifluoromethyl)methylide far,

by

DMF.

Attempts

so

revealed

obtained

yellow

the

triflate

in

as

1,2,3-tris(trifluoromethyl)indolizine

of

(5)(12X with

cycloadditions,

in no

l)]

of

each

of

information

oxidation

(6)

precursors

last

area

actual

of of

the

4 and

5

** (Scheme

1).

possible

through

treatment (2)

Progress plans

to

pursue

hopefully

the

chloroform

perfluorobut-2-yne gave

with (20

'C

a complex

7 days

mixture

from

be

that triflate

followed

triethylamine for

may

discovery

of -N-(2,2,2-trifluoroethyl)pyridinium

in

hours)

the

in

then

~a.

which

65*C only

by for

3

ethyl

trans-2,3-bis(trifluoromethyl)-2,3-dihydroindolizine-lcarboxylate plausible Scheme

(7) mechanism

2;

stabilizer

** See ref. formation of the type

the in

the

could for ethanol chloroform

be the

isolated

(16%

formation

of

required used

was as

the

3 for relevant discussion of of indolizines via 1,3-dipolar described here.

yield).

7 is present

reaction

shown

A in

as

a

medium.

the mechanism of cycloadditions

292

(2ja

0I’+/ N

_(3) B

1

_

CF3CH -cx=cx X

=

C02Me,

B = K2C03

X = CF3,

(4) (5)

B = Et3N

X = C02Me, X = CF3,

m.p. m.p.

126-128 65-67

'C

'C

+ Pyridine (90% yield); a From CF3S03CH2CF3 1 Stepwise. -d "Spontaneous" -c Concerted. Scheme

1

Et3N

(6) X =

m.p. 50-52°Cc. aromatization.

* CF3

3 3

CF$Et CF

3

(7) a $

Dry-column flash chromatographic shown were groups The CF X-ray c?ystallography.

Scheme

2

to

work up. be trane

disposed

by

293

Correct

elemental

analyses

[C,H,F and N

case of the triflate

(Z), where

spectroscopic

(i.r., n.m.r.,

structures

data

assigned

were

except

in the

F was not determined] mass)

obtained

consistent

for compounds

and with

2, 4, 5

and 7. The structure

absolutely

established analysis

being

(UMIST),

t0

indebted Science

1

Iraqi

for the award

and S.

R.

ZugraVvescu

out

by

Ministry

Dr.

R.

G.

grateful. of Higher

N.

Mohialdin,

M

Petrovanu,

was the

crystallography,

of a Scholarship

Sot.,

and

New York,

E. Banks,

Chem.

X-ray

(7)

Pritchard We are also

Education

and

(to S. N. M.).

J. Fluorine

Chem.,

275.

McGraw-Hill: 3

dihydroindolizine

whom we are extremely

R. E. Banks

I.

by

carried

to the

-34 (1986) 2

the

of

1976, p 156.

R. G. Pritchard,

Perkin

‘N-Ylid Chemistry:

and

Trans. 2,(1986)

J. 1769.

Thomson,

-J.