Addition of Grignard and lithium reagents to Eschenmoser's salt. A convenient synthesis of terminal olefins.

Tetrahedron Letters No. 15, pp 1299 - 1302, 1977. Pergamon Press. Printed in Great Britain.

ADDITION

OF GRIGNARD AND LITHIUM

SALT. John

L.

A CONVENIENT

Roberts,

Peter

Department

of

Salt

(Received in USA

Terminal useful for

double

construction

simple

or

ducing

this

of

proceed

it

bond

is

to

oxide

functionality

it

is

not

In

this

moiety.

an

in

occurring methylene

yield.

to

Pyrolysis the add

C.

0LEFINS.l

Dale of

Poulter*2*3

Utah

84112

the

with

we describe oxidation

that

from

a major

of

for

afford

the

are

for

intro-

In most

construct

the

the

with

operationally

portion

the

methods

method

methylene

as

introducing

synthetically

several

procedure

such

olefins

many

limitation.

the to

approaches

method

elimination

procedures an excellent

become

time)

in are

is

required

and

found there

the

oxides

will

one-pot

a direct

and

of

4 few

amine

(yield

yield

are

group,

manipulations

efficiency

moderate

which

Although

suffers

carbon

The

groups compounds.

of

approach

the

fragment.

reduce

communication

and

University

Utah

common functional

However,

competitive

City,

are

desirable

Subsequent

Lake

unsaturated

a simpler

Borromeo,

Chemistry,

naturally

high

moiety.4a

sequences, double

and

S.

OF TERMINAL

January 1977; received in UK for publication 2 March 1977)

12

bonds

intermediates

REAGENTS TO ESCHENMOSER’S

SYNTHESIS

to

synthetic

of

the

desired the

Wittig

amine

point

where 4b

reaction.

dimethylaminomethyl

terminal

methylenes

in

high

yield. Our

approach

R’

to

1)

H-:-X 2)

R

addition typical

of

(ca. -

appropriate sion

at

construction

Mg or

10% excess)

mixture

was

addition

of

vigorously water

until

(Grignard

or

ether

(I-2H

a gentle

stirred

for

one

the

suspended

lithium

in

was (ca -*

ether)

hour salts

at just

150”

reagent)

to

5 ml/rmmol added

of -via

1299

C=CH2

Eschenmoser’s

salt.5

In

a

dimethyl(methylene)atmnonium salt).

A solution

syringe was

temperature.

dissolved,

involves

R’

with

When addition room

R’ \

H7.02

charged

was

reflux.’

group

) 2)

flask

anhydrous

reagent

maintained

1)

functional

2

R

nitrogen-filled and

dimethylaminomethyl

7’ H-y-CHzN(CHs)

+

nucleophile a dry,

which

the

Li

organometallic a rate

of

+ CH2=N(CH3)21

a carbon

experiment,

iodide5’6

the

followed

to

the

complete,

Work-up

the

stirred the

involved

by vigorous

of

suspen-

resulting careful

stirring

for

wo

No. 15

30 min. times

The with

anhydrous a 500’

by

test)

For

in

The

usual

layers

tubular

column

(Carbowax

oxidation,

the

amount residue was

platinum

was

heated

complete,

layer,

washed

removed

ZOM) was

one

was

oxide,

the

to -ca.

160”

water

was

to

(I the

equivalent

solution with

other

of

quenched

added

brine

methanol

progress

additional

latter

pressure.B

no products in

The

the

saturated

reduced

dissolved

peroxide

and

with

at

showed

added.

and

Excess of

were

was

test,4a

aqueous

was

amine

peroxide

periodically.

reaction

and

over

than

filtered,

dried

on

desired

of

amine),

ml/mnol

and

analysis

the

reaction

was of

a negative

30% hydrogen

solvent

stirring,

and

olefin

and

the

and

monitored

potassium

the

trap,

three

Glpc

portions

(to

extracted

was

iodide

removed

at

trapped

at

product

was

worked-

way.4a

results

isolated

ether

the

solvent

The

the

fran

before

a catalytic

oxides,

amine

combined

phenolphthalein

pressure.

the

separated

30% hydrogen

added

After

was

sulfate

the

of

were

reduced

an

open

alcoholic

with

-780.

when

The

(>95%).

peroxide

up

ether.

equivalent the

layer

magnesium

x 0.03”

amine one

ether

for and

yield

workingon

a

four

representative

olefins

gave

of

material,

I-15

pure IWlOl

alkyl

satisfactory and

Scale.

The

halides IR and

some overall

TABLE Organometallic

Reagent

Yield Amine

of (%)

Yield, methyl

losses

I.

listed

in

are

Table

Each

inevitably

yields

occurred

higher

than

I.

All

reported during shown

of

yield

in

the

amines,

represents

purification the

Table

when

YIELDS

Isolated iodide (%)

n-Octylmagnesium

are

NMR spectra.

as salt

Yield Amine

of Dlefin via Oxide (%)

Overal Yield Halide

I from

91CVd

90-95h,i

a7

78-83

_-

92-9Sh’j

(88) p

al-84

asCpf

______ I

a3

70

-_

84”

__

__

bromidea Cyclohexylmagnesium bromidea Benzylmagnesium chloride n-Butyll

ithium

a b

a) Stock solutions of Grignard reagent were prepared in diethyl ether. R. Lespieau and M. Bourguel, O&g. Syn., Coll. Vol. 1, (Second Ed.), 186 (1941) and F.S. Prout, R.J. Hartman, E.P.Y. Huang, C.J. Korpics and G.R. Tichelaar, o&g. Sgn.,Coll. Vol. IV, 93 (1963). Excess magnesium was used to insure complete reaction, and the ether solutions of the Grignard reagents G.1.c. analysis of hydrolyzed aliquots were f i 1tered through a Schlenk f i I ter before storage. showed no starting halide and only traces (<5%) of other impurities, presumably from coupling during Grignard formation. Molarity of the Grignard solutions were determined by the procedure of Watson and Eastham; S.C. Watson and J.F. Eastham, 1. O~g~norn~. C&m., 2, 165 (1967). b) c) From experiments carried out on a Commercial product from Alfa Ventron, 2.4H in hexane. e) H. King and T. Work, J. Chem. SOC., IO-15 mnol scale. 20 mm (lit.e 209”, 741 mn). d) bp 97”. g) R.N. Icke, B.B. Wisegarver and G.A. Alles, 403 (1942). f) bp 850, 12 mm (lit.g 980, 22 mm). scale. o&g. Sgn., Coil. Vol. III, 723 (1955). h) From experiments carried out on a l-5 mmol i) mp 180-181.5° (1it.e 170”) j) mp 227-227.5O (lit. k 226.5-227.5’), k) 0. Wallach, Ann., 353, 284 (1907). I) mp 228-229” (lit.“’ 229”). m) T. Kato, T. Morikawa, and Y. Suzuki, J. Phaiim’Y1.SOC. Japan, 2, 1177 (1952); Chtic& AbHxuCt6, 42, 7433f (1953). n) mp 222-224” (lit.0 222-223”). p) Ref. 4. o) R. Willstatter and E. Waser, BQA., 9, 1176 (1910).

1301

No. 15

the

amines

the

intermediates.

large the

are

batches

should

the

the

ful

a variety

enolates ing

until

only

limiting

synthesis

of

Wittig

in

the

amine

oxides

be emphasized

needed;

that

thereby,

factor

in

pyrolyzed

eliminating

using

without

Eschenmoser’s

the

the

iminium

attempting

salt

need

salt

can

to

freshly

approach

to

purify

be prepared

in

prepare

appears

to

one

of

be pre-

reagent.g

methylene-containing

reaction of

in

carbon

olefins

convenience

and

nucleophiles12

preparation

a-methylene

resulting

also

organometallic

plements with

the

stored

The

of

The

and

It and

reagents.

paration

oxidized,

of

-via

such

Mannich

the

amine

Also,

yield. as

ketone,“’

intermediates

that

oxide

the

route

ester,14 can

now nicely

procedure

is

and

com-

apparently

use-

lactone14y15

be converted

into

the

correspond-

derivatives.

REFERENCES

I.

We wish and

to

acknowledge

2.

Alfred

P.

3.

Career

Development

4.

a)

A.C.

Sloan

Cope

Schoelkopf,

support

from

the

National

Institutes

of

Health,

GM 19557

J.

E.

Am.

the

Vol.

5,

Sot.,

72,

N.

Institutes Coil.

751

7_9, 4729

Sot.,

Maag,

National

O/Lg. Syn.,

Coil.

C&m.

C&m.

H.

from

Ciganek,

Syn.,

Am.

Schreiber,

1975-1977.

Award

and

J.

Okamoto, J.

Fellow,

&cg.

Schweizer,

5.

financial

CA 16824.

3145

(1973); d)

and

e)

A.

Health

A.C.

H.E.

C.L.

(HL

000841,

612 (1963); b)

4, c)

(1957); (1957);

Hashimoto,

of

Vol.

Cope,

C.L.

Eschenmoser,

F.A.

Chem.

and

and

lnd.,

Tti.

U.

and

Bower,

Chem.

Angm.

and

Bumgardner,

Baumgarten, Bumgardner,

1975-1980.

G. Wittig

E.E. T.T.

1555

Ed.,

I$,

(1958).

330

(1971). 6.

Other M.

dimethyl(methylene)arrmonium

Gaudry,

Tietze,

7.

8.

9.

and

A.

Angu.

1917

(1970).

Salt

can

C&m.

obta i ned.

For

isolation

of

an ether

solution

the

was

salt

New high R.D.

Rieke

II.

P.K.

Freeman

the of

the with

S.E.

and

L.F.

L.L.

N.Y.,

lminium

salts

have

served

Dean,

H.C.

Padgett,

and

as

F.P.

its

239

c)

iodide 5-10

Am.

H.

as

Chem.

SOC.,

Jtihedrron

J.

Volz

the

Y.

(1974); and

reagent

and

excess resulting

Jasor, b)

H.H.

G.

H.J.

and

L.F.

Tetrraheo%on

comparable

yields

iodide

suspension

luche,

Kinast

Kiltz,

methyl

570,

H. Am.

and

organolithium”

9_6,

1775 (1974).

Lett.,

“Reagents

was

was

La.,

of

added

amine

to

filtered

and

for

1849 Organic

compounds

(19761,

and

Synthesis”,

are

references Vol.

1,

available.

cited Wiley

and

618.

synthetically and

a)

263

dried.

Fieser, pp.

H.

salt,

hr

organomagnesiuml” J.

prepared.

Comm.,

organometallic

methyl

and

been

Chern.

(1976);

After

ether

Hauck,

have

SOC.

the

amine.

1967,

a)

Leonard

into

Hutchinson, and

12.

N.J.

12,

of

13.

R.T.

Ed.,

Bales,

Fieser

New York,

Chum.

amine

syntheses

and

salts

J.

ladled

washed

yield

IO.

Sons,

7ti.

be carefully

are

therein;

Marquet,

useful

J.

Rapoport, Chem.

Sot.,

electrophiles

Am. Chm. 72,

5279

Sot., (1957).

for

a number

9_8, 7448

c)

G.H.

of

(1976). Alt

and

years.13 b) A.J.

No. 15

1302

Speziale,

sot., 14.

J.L.

15.

S.

J. O&g. Chem., 3,‘, 8_2, 5148 (I!+%),

Roberts, Oanishefsky,

P.S. T.

e)

1340 (1966)) d) N.J.

L.A.

Te,?hzhhon

Paquette,

Borromeo,

C.D.

Kitahara,

R.

Poulter, McKee,

Leonard

P. F.

unpublished Schuda,

and

Lett.,

W. K.

Musker,

J. hi.

Chem.

1291 (1965).

results.

J. ht.

Chem. Sot.,

9_8, 6715 (1976).