Umpolung of tropone: The synthesis of novel 2-substituted tropones via 2-halocycloheptadienone enolates

Tetrahedron Letters,Vol.29,No.37,pp Printed in Great Britain

UMPOLUNG

OF TROPONE:

TROPONES

THE SYNTHESIS

Miyano

and Makoto

School

of Chemistry,

Waseda

OF NOVEL

2-SUBSTITUTED

VIA 2-HALOCYCLOHEPTADIENONE

Hiroyuki Department

0040-4039/88 $3.00 + .oO Pergamon Press plc

4723-4726,1988

University,

ENOLATES

Nitta*

of Science

Shinjuku-ku,

and Engineering,

Tokyo

160, Japan

Summary: 2-Halocycloheptadienone enolates, which were generated by the reac7 reagents, tion of 2-halotropones with hydride, Grignard, and organolithium reacted with cationic electrophiles including tropylium ion to give 2-substituted tropone derivatives.

Tropone resonance

1 is easily

attacked Fairly

structure

-la. of 1 and its derivatives

the reactions have also

by nucleophiles extensive

studied

the nucleophilic

troponyl-1H-1,2-diazepine.3) tions

of 2-halotropones

ture of electrophilic

a formal variety

electrophilic

reaction

ion 2 involves

(1 mmol)

at ambient

of l-

forming

reac-

the resistant

na-

recog-

for realizing

for the synthesis

approach

of 2-halotropones

mmol)

of a

to an equivalent

enolates

4a_c

and S

3a-c and hydride,

which

tropylium

tetrafluoroborate

contains

ml) at 0 OC, and stirred

4a_c,

of 4a-c involves

or LiAlH(OBut)38)

in tetrahydrofuran

solution,

in the formation

isomers

organolithium,4'6)

strategy

2-halocycloheptadienone

for the preparation

LiA1H4(0.36

temperature

Our synthetic

and we tri-

is generally

(umpolung)

on

Grig-

reagents.

procedure with

three

Since

nucleus

to 1 must be fruitful

in situ by the reaction

A typical

polarity

with

for the C-C bond

Grignard,4f5)

the tropone

troponoids.

and organolithium

3a_c

onto

the study of a reverse

for 2-troponide

nard,

attack

of substituted

generated

carbanions,la)

the novel

reagents 7, have also been reported.

and organocopper nized, larb)

examples

been made

nucleophiles,"2)

of 2-halotropones

to provide

Several

with

have already

with various

reaction

carbonyl(4-7-n-IH-1,2_diazepine)iron

as can be seen from its

studies

(THF)

was then added

(1.3 mmol)

for another

of 2-tropyltropone

dropwise

(1.3

&

with

LiA1H4

respectively, enolates, 2

mixture in THF

of (5

The 'H NMR spectral could

reveal

generated

I- \ -

mmol)

The

10 min at ambient temperature to result 9,lO) 1 in good yields (Scheme 1; Table 1,

studies")

0

to a stirred

and triethylamine

of

at 0 'C or

(5 ml) for IO-20 min.

run l-4).

0_

a treatment

(1.3 mmol)

4723

and LiA1D4

in THF-d8,

are the mixtures

the counter

are presumably

that both -4a by the reaction of

cations

different

of two of which

from each

4724

LiAlH4 or

Ox

LiAlH(OButJ3 ) or LiAID4 THF

0

I- \ 3a_c

6a-c, 6a(D)

4a-c, 4a(D)

a: X=Cl b: X=Br c:X=I

(D)H

Scheme 1, other.

However,

hydride

the cationic

and deuteride

and -I 4a(D) reasonably probably

5ao

5&

attack

moieties

to g

are uncertain

were

and not onto

C2 to give a

reacted

tropylium

with

z, 70 proved

here.

Furthermore,

to take place

onto

C7 to give 5

and -5a(D) 'I) The enolate 4a(D) was cation to give a mixture of 1 and 7(D),',12)

Thus, the reaction pathways of 3a-c to 6a(D) -1, run I-5) elucidated as shown in Scheme 1. Although

via the intermediate

give 1 and 7(D)

(Table

the cycloheptadienone

enolate

has been

suggested

in the reaction

of j_ with

RMgX or RLi

3a

Et20 or THF

EtxN THF

Scheme 2, Table

b: R=Bu

8

1. The reactions borate

of tropylium

with 4a_c,

9a_c tetrafluoro-

and g. 4a(D) ------I

LiAlH4

tion to give dienone,13)

Hun

2-Halo-

Nucleophile

tropone

Product/ yield

studies

( % )

tural bond

LiAlH4 LiAIH(OBut '3 LiAIH(OBut 13 LiAIH(OBut '3 LiAlD4 MeMgI

a) A mixture

1

(74)

1

(87)

1

(83)

by protona-

3,5-cycloheptathe present

clarified

features forming

enolates

reaction

substituted

:::;a)

generated

2-chlorocycloenolate

(89)

J+ with

(88)

ether

BuLi

z?!?

(79)

reagents

PhMgBr

SC

(90)

sequently

reacted

tropylium

cation

: 73.

8 was

by the reaction

%! -9a

of 27

of the

and -* 4a(D) In a similar way, 7-

MeLi

of 1. and 7(D) in a ratio

the struc-

and the C-C

4a_c

heptadienone 7+;(D) --

c: R=Ph

followed

Grignard

reagents

of in

or organolithium in THF, and sub-

substituted

with to give

7-

2-tropyltropones

4125

Ph

E

E:

c:

a:

Ph

4a

(75%)

b:

lOa-c Scheme 3, 9a-c in good tack to &

yields

(Scheme

and its related

2; Table compound

Since

1, run 6-9). has been

reported

the nucleophilic

to take place

C7 I 6t14) the intermediacy of 8 is reasonably accepted. The enolate 4a reacted with other cationic electrophiles,

substituted

tropones

able

interest

IOa-c

here

isomers

which

under

reflux

have become

useful

and 2-

3).

to I, have attracted

use for the synthesis

can also be very

consider-

of novel

available

in further

r-elec-

through

synthesis.

to 1 ,4-diazabicyclo[2.2.2loctane

z was reactive

in 1,2-dimethylbenzene

such as

the corresponding

(Scheme

similar

The 2-tropyltropones

described

to give

yields

of its potential

the compound

example,

in moderate

have a skeleton

because

tron systems.15) methodology

tetrafluoroborates

which

Bitropones,

onto

tricarbonyl(cyclopentadienylium)iron,

tricarbonyl(cyclohexadienylium)iron, diphenylcyclopropenylium

at-

for 30 min to give a mixture 12, 9,16) in 85% yield,

of dihydrodicyclohepta[b,d]furan,

the For

(DABCO)

of three probably

via

Although the mixture -12 was not separable by column chromato11 _* the subsequent hydride abstraction of -12 with trityl tetrafluoroborate in dichloromethane gave the cation 13,'~'~) in 96% yield as a single product

the enolate graphy,

(Scheme

4).

11

Scheme 4, We believe the synthesis

that the foregoing

of a variety

cycloheptadienone tions

1)

13

has considerable

troponoids.

electrophiles

potential

The reaction

for

of 2-halo-

and the synthetic

applica-

are now underway.

and Notes "Non-Benzenoid

Interscience,

New York,

293-364

Tropone

other

2h

rt

methodology

of substituted with

(a) T. Nozoe,

73, 2)

enolates

of the products

References

12

(1973);

j_ has been

J. H. Rigby

used

Act.

conveniently

and C. Senanayake,

and M. Nitta,

Compounds,"

N. Y., 1959, pp 339-464;

(c) F. Pietra,

Funk and G. L. Bolton, 3) H. Miyano

Aromatic

J. Org. Chem.

Chem.

Lett.,

(b) F. Pietra,

Res.,

l2,

for the synthesis

J. Am. Chem. Chem.,

D. Ginsburg,

52, 1987,

Sot., 109,

3173 401.

(1987).

132

Ed., C h em. Rev.,

(1979 1 .

of natural 3147

products:

(1987 ) ; R. L.

4726

4)

W. von E. Doering

5)

A. P. ter Borg,

and C. F. Hiskey,

R. van Helden,

J. Am. Chem.

Sot., 74,

and A. F. Bickel,

Rec.

5688

Trav.

(1952).

Chim.,

8I,

591

(1962). 6)

M. Cavazza,

7)

M.

G. Morganti,

I, 1984,

Trans.

Cavazza

Elemental

analyses

(2H, dddd, 6.60

0.9 Hz), 7.42

A max

Hz), 5.59 62.58, 12)

broad

dd, J=8.8, t, J=3.0

6=186.2

0. L. Chapman,

31, 15)

M.

16)

'H NMR

Iyoda,

Bull.

6.2 Hz),

(IH, broad

t, J=6.0 J=8.9,

0.7 Hz),

6.89-7.21

C

tory

1577,

5.9 Hz),

1514,

7.25-

1466,

837,

124.7

686 cm-';

5.25

became

(2H, broad (3.27H,

dt, J=9.7,

respec-

dd, J=7.9,

7.7

(3H, m), on irradiation

doublets,

dt, J=8.8,

Hz),

3.0 Hz), (IH, m);

134.8

(4C, d), 43.9

and A. A. Griswold,

at

respectively.

t, J=6.0

(d, weak),

125.0

doublets,

(0.7H, broad

m), 7.18-7.42

(s), 140.6

broad

(3H, m), on irradia-

became

(IH, broad

(2C, d),

I

(d), I34 . 8

(2C, d),

(0.56H,

5.80-6.72

5.80-6.72

6=3.45

124.8

Hz

3.9, 2.7,

(4H, m),

(s), 140.3

(2C, d),

and 65.59

J. M. Palmer,

Chem.

5.36

(2H,

6.59

(2H,

13C NMR

(d), 134.2

(d),

(d).

J. Am. Chem.

and S. C. Dickerman,

Sot. Jpn., 40,

(m), 3.05

6=2.28-2.57

(m), 5.80-6.73

'C (decomp);

(IH,

dt,

Jz9.9,

7.14

Hz),

13C NMR

(CD~CN),

355

Sot., 84,

J. Org.

I213

Chem.,

(1967).

Sot.,

Chem.

(d, J=5.9

(m); IR (CHC13),

(IH, d, J=9.9 (s),

(d), 140.3

(d), 28.1

(EtOH)

'H NMR

6.6 Hz),

6zI66.9

(d), 142.1

(d), 117.9 x max

are satisfa

2992,

Commun.,

Hz),

3.28

2863,

1985,

1547.

(d, J=6.2

1640,

1563,

Hz),

1409,

909 cm-'.

J=IO.2

445

data

501.

(3.86).

Sato, and M. Oda, J. Chem.

K.

Mp 127-129

144.0

Perkin

(1958).

(2H, dddd,

(2H, m), 5.24

and 65.59

(s), 154.0 (d), 130.2

D. J. Pasto,

(CDC13),

5.05-5.56

5.92

Sot.,

(1966).

K. Kikuchi,

1147,

1627,

(IH, m),

6.23

6.25

(s), 153.7

307

at 65.24

6.84-7.15

D. I. Schuster,

14)

17)

6.0 Hz),

Hz),

(d), 132.9

4281

2990,

(4.29),

(CDC13),

1974, 5372

spectral

(d), 130.0

6=2.50-2.78

at 65.25

'H NMR

broad

(1962);

6=185.9

(d), 132.8

(0.3H, dd, J=9.7,

Commun.,

Sot., a,

6=3.47

2.7, 0.9,

6=2.48-2.76

the signals

(CDC13), I31

(CDC13),

the signals

For 1 + 7(D):

133.3

J=3.9,

for a:

for 4a(D):

mass

(CDC13),

(0.44H, dt, J=10.8,

tion at 62.62, tively;

'H NMR

(log E), 229

5.59

6.7 Hz),

J. Chem.

in this paper.

(d); IR (CHC13),

(THF-d8),

Chem.

6.0, 0.9, 0.7 Hz),

13C NMR

(EtOH)

'H NMR

oil;

J=8.9,

(d), 133.1

(2C, d), 43.7 Ill

described

(2H, dddd,

(IH, m);

(d), 134.1

Sot.,

J. Am. Chem.

and high resolution

For z: pale yellow 5.37

J. Chem.

and R. F. McFarlin,

for all new compounds IO)

and F. Pietra,

199.

and F. Pietra,

8) H. C. Brown 9)

A. Guerriero,

(logs),

(CD3CN), 6.47

Hz), 8.68-9.06 165.0

(4.45),

in Japan

20 June

1988)

288

(d), 148.5

1478,

(4.06),

t, J=6.7

6.8 Hz),

7.12

(3H, m), 9.10-9.43

(d), 127.0

(t); IR (KBr), 2926, 235

(2H, broad

(s), 148.9

(d), 135.7

(sh, 3.91).

(Received

6=2.88

(lH, dt, J=I0.2,

322

(2H, m);

(s), 144.6

(d), 124.8

1445,

Hz), (IH, d,

1083,

(d),

(s), '19.2 1037 cm-';

(sh, 3.89),

430

(3.94),