Reformatsky intermediate. A C-metallated species.

Tetrahedron Letters,Vol.23,No.38,pp PrInted ln Great Brltaln

0040-4039/82/383945-04$03.00/o 01982 Pergamon Press Ltd.

3945-3948.1982

REFORMATSKY INTERMEDIATE. A C-METALLATED SPECIES. F. Orslnl;F. Pellzzonl and G. Rlcca dl Studlo per le Sostanze OrganIche Natural1 de1 C.N.R. Istltuto dl Chlmlca OrganIca, via Venezian 21 20133 Milan0 Italy

Centro

1 13 H-NMR spectra of the Reformatsky reagent from t-butylbro C-NMR and Abstract species: wlthln the limits of detectabilitymoacetate, evidence a C-metallated species can be detected in solution. of the methods, no 0-metallated The reaction formulated

between

by Reformatsky

tlon 1s widely In spite

recognised

unsettled

may be formulated carbon

bond

and carbonyl

compounds

was

in 1887 and its utility

in carbon-carbon

bond

as a powerful

tool

chemists.

of it the mechanism

Even more

zinc metal

an <-haloester,

of this

1s the question as an analog

synthetic

fundamental

reactlon

of the nature

of the classical

(I) or as the bromozlnc

enolate

for organic still

remain

forma

unclear.

of the zinc Intermediate

Grlgnard

reagent, with

of an ester,

(II).

with

which

a zinc-

a zinc-oxygen

bond

1 I

I

CH2=C<'fNBR

BRAN-CH$OOC(CH3)3

II

!lCKH313 The huge

amount

structure

of papers

publlshed

on this sublect

of the reaction

and stereochemistry'

are mostly

products

dealing

and would

with

support

the

an

enolate anion. On the other hand only few Authors2 reported the infrared and 1 H-NMR data for some Reformatsky reagent as a direct proof of their structure: these

more

results,

supporting

a C-metallated

form,

are, however,

contradictory

and mlsleadlng. Up to now it 1s only known importance ning

in realizing

the real

To obtain

ry to isolate products. methyl-,

a good yield

structure

definitive

pure Reformatsky

experiments

t-butyl- x,-bromoproplonate,

amount,

in its bromoderlvative3.

ne at 40cC, product

re=60-80°C;

in very

after

acidic

[detected

inlector

CM+), 115,113,

chromatographlcally propionyl

rapid

propanoate

hydrolysis,

112, 88, 57, 561

143

that using

and in determi

uncontaminated ethyl

solvents

of "condensed

we obtained

analysis

temperature=l50‘C;

m/z

reagent

it is necessaby any side

bromoacetate

with

methyl

(10% Carbowax carrier

and,

CM+-Br), 3945

proplonyl

of methyl

sample)

142,115,114,88,57,56).

tempe-

in smaller in benze

propanoate

as

C 20 M; column

gas pressure=1

, a small amount an authentic

and ethyl-

and at different

ester"

In fact with methyl-d-bromopropionate

by GC-MS

identical

may be of grc2a.t

of the lntermedlate

in several

production

systhem

itself.

intermediate,

had shown

results

144

of the Reformatsky

on the structure

rature,

main

that the solvent

of the intermediate

evidence

a real,

Previous

for certain

temperatu5 Kg/cm2! m/z

propanoate

and traces

(gas

of pbromo _

Raising

'ihe tern -

3946

perature

of the reactlon

to benzene-ether

Also

with

ethyl

identified products

bromoacetate

which

in benzene

in THF we were

was contaminated

by comparison

indeed

or t-butyl--

from benzene

the results

as well

-bromopropionate

with

we have obtained

product

can be decanted,

which

Reformatsky

it affords

sample)

phenylproplonate 5.1

t-butyl

quantitatively

authentic

MS m/z

70.27,8

11; found

222

(in presence

(in 80 % yield) washed

in THF

by work

4.03

with

(bs,lH, disappears

C,H:

70.31,

goal we aimed

elucidation

state

in solution. DMSO,

I

at the elucldatlon

12

34

C-NMR

1s more

reaction

we have

(bs,

1.45

(d,2H,J=7Hz),

of the structure successfully

lnterestlng

is, as a matter

examlnated

in Table

(C13H,803)

C,H:

solvents

of the reagent achieved

in solution of fact,

of different

with

than in

carried

Out

basicity

34

BrZnCH2COOC(CH3)3

I and II and deserve

some comments.

DATA cl

CH3COOC(CH3)3

2

2.66

(CDC13)i7 .39

Anal.:calcd.

this has been

of the reagent

data are collected 13

-

acid

an

8.19

as the Reformatsky

To this purpose 4

with

t-butyl,3_hydroxy,3-

'H-NMR

D20),

for the

hydrochloric

Py and THF.

Spectroscopic

TABLE

gives

with

as expected

diluted

C at 0.05 mm:

of

amount

mlcrocrystalllne

in all respects

(M+),166,165,149,147,107,106,105.

side

from a 2 M solution

It behaves

benzaldeyde

( bp=98-100°

of these

of an equlmolecolar

up with

(identical

(I or II) as a function of the solvent: 13 1 C-NMR and H-NMR spectroscoples. Structural

the Reformatsky

(gaschromatographycally

a colorless

and dried.

t-butylacetate

and on treatment

(t,lH,J=7Hz),

(s,9H):

the solid

acetoacetate

t-butylbromoacetate:

reagent:

exclusively

As the first

by ethyl

in tetrahydrofurane

of zinc wool)

so called

not able to isolate

with

successful

t-butylbromoacetate

11

the solvent

slgnlflcantly

an authentic samole). The presence the assignments in the 13 C- and 'H-NMR spectra.

infirms

We were

HMPT,

or changing

temperature.

lntermedlate

5H),

benzene)

did not improve

ethyl- i -bromopropionate

as using at room

(refluxlng

I:1 or ether

c2

JC-H

c3

DMSO

22.2

169.5

79.4

27.1

128.8

PY

22.2

169.5

79.5

28.1

128.8

HMPT

23.1

170.2

80.4

28.9

THF

21.3

168.8

79.6

27.4

128.8

DMSO

20 8

177.4

75.5

28.6

128.6

PY

20.4

179.5

76.7

29.1

130.0

HMPT

22 1

179.0

75.2

29.8

THF

22.7

186.2

80.4 27.6 132.0 -The values of the chemical shifts are given in ppm (r) with TMS as internal standard. The 13C-NMR spectra were determined on a XL 100 Varian spectrometer (25.18 MHz):spectral width 6000 Hz, acqulsltlon 0.6 sec., pulse delay 0.5 sec.: 45 o pulse width.

as

3947

From

the little

upfleld

Py, HMPT

In DMSO, chemical

shift

shift

observed

and the little

of the same carbon

no slgnlflcant

change

shift

for the C-l carbon

In THF compared it emerges

In t-butylacetate,

In the electron

bond by a zinc-carbon

(I-=- 1 to -1.8 ppm)

downfield

dlstrlbutlon

replaclng

with that

the there

is

a carbon-hydrogen

in a sp3 hybridlzation5.

bond

Concerning a possible zinc enolate, the C-l carbon, In passing from a sp3 to 2 should resonate in the range observed for the scarcely sP hybridization, 6 electropositive-metal enolates as, for Instance, magnesium enolates , that 1s in the range

80-110

ppm. The signals

can not be therefore unequivocally In all

spectra

to the quaternary

we also observed

respect to t-butylacetate. 1 H-NMR spectra in DMSO, The vlnyllc

TABLE

protons

II

I1 2 34 BrTnCH2COOC(CH3)3

In DMSO, by single

solvents

frequency

In a similar

and the resonances

by the invariance 7 zed carbon .

PY THF

1.43(s,9H)

1.85(~,3H)

1.40(s,9H)

DMSO

l.O4(s,2H)

1 30(s,9H)

PY THF

2.00(s,2H)

1.46(s,9H)

shift

decoupling

are given

singlet

coordlnatlon

results.

downfield

In no cases

GH

with

13

1s observed. were

at 1.04

confirmed

and

1

spectrum

in DMSO,

the methy

to a singlet. at

1.88 and at

flpH2.00 and at sc 20.4

correlated

/qc 22 7 in THF.

constant

H-NMR

in Py were

data

species

JC_H,

(I) 1s once more

characteristic

confirmed

of a sp3 hybrid&

let us do some preliminary

observations

sites.

the carbonyl

results

TMS as internal

- in THF. The assignments

a real organometalllc

C-NMR

with

due to -ZnCH2-

at 1.04 in the proton

of the coupling

the

(r)

in ppm

experiments.

the resonances

In the comparison These

carbon,

1.40(s,9H)

1.88(~,2H)

a two-proton

on the zinc coordlnatlnq

acetate.

C-NMR

1.36(s,9H)

at

That we are dealing

In all solvents

13

1.93(s,3H)

at frc 20.8 collapses

manner

In addition

the

1.84(s,3H)

of the signal

lene resonance

field

Py and THF complete

at 2.00 ' ln Py and at 1.88

By irradiation

of the carbonyl

DMSO

of the chemical

In all three

the presence

form and are

of the ester moiety.

DATA

$H,:OO:(:H,,,


of an enolate

carbon

they

can be detected.

1 H-NMR

-

at 75-81 ppm are singlets:

for the sp2 carbon

mistaken

attributed

observed

with

carbon

resonates

the corresponding

indicate

to the zinc atom,

that

in the range carbon

the carboxyllc

decreasing

atom

group

the electron

-10 to -20 ppm dowE in the related 1s involved

density

t-butyl-

in the

on the carbonyl

3948

carbon.

When

carboxylrc

the solvent

group

downfield

with

effect

Infrared

1s the less coordlnatrng

the zinc atom is quite

A more NM;!

spectra

are also in agreement

detalled

with

with

a strong

investigation

particular

From Tables group

the Interactron and causes

of the

the highest

(-20 ppm).

In THF the lntermedlate shows -1 it shifts to 1660 cm . "0

THF,

important

with

the above mentioned results. -1 , while in DMSO at 1580 cm

absorption

on zinc coordination

is in progress,

using

tecniques.

I and II it is also

the zinc atom

clear

influence

that

as well

the coordination

the C-l chemical

of the carboxyllc

shift

and coupllnq

constant. Concerning unchanged

the stability

in the solvents

bromoacetate

which

from the chemical the same carbon t-butylacetate

intermediate

resonates

itself 13

In conclusion, acetate, absence

of the -CH2Br

supported

It 1s still present days,

gives

a pyrldlnlum

which

resonates

elimination

verified

C-NMR

4 - 6

unlike salt

by addition

spectra

by infrared

of any 0-metallated

and

as

t-butyl

indicated

slow nydroiysls

of zinc t-butoxybromide of t-butyl

mostly

starting

at 61 7 <((In THF and DMSO

at 26.7 and 28.3$respectlvely).A

and a gradual

the latter

observed*

even after

immediately

in Py shift

of the intermediate,

used

alcohol

was,

to

however,

to the Reformatsky

of the Reformatsky reagent from t-butylbromo 1 H-NMR data, do indicate unambigously the

species

in solution,

within

the llmr'cs of detectabi_

llty of the methods. References (1)

(2) (3) (4)

(5)

(6) (7) (8)

and Notes.

a) Zimmerrrann,H.E.; Traxler,M.D. J.Am.Chem.Soc. 1957, 2, 1290, b) Mous Neyrolles,J., Beziat,Y. Bull.Soc.Chlm.(France), seron,M.; Mousseron,M., 1963, 1483; c) Bezlat,Y.;Mousseron Canet,M. rbldem 1968, 1187; d) Canceil, J : Gabard,J.; Jacques,J. Bull.Soc.Chim. 1968, 231, e) Matsumoto,T.; Tanaka, Gaudemar, I - Fukul,K. Bull.Chem.Soc Japan 1971, 44, 3378: f) Pausard,J., M.'Bull.Soc. Chum. (France) 1973, 3472. Gaudemar,M., Martin,M. C.R. Acad.Scl, serie C, Paris 1968, 267, 1053. Vaughan,W.R ; Knoess,H.P. J.Org Chem., 1970, 35, 2394. Relatively high concentrations (0 8-1.4 M) of the reagent rn DMSO, Py, HMPT were used in order to obtain satisfactory natural abundance13C-NMR spectra in a reasonable oerlod of time.Due to the less solublllty of the reagent In THF (about 0.4 M at room temperature) spectra in THF were run at 54" C. The Reformatsky intermediate was always prepared in THF solution, isolated and drssolved in the selected solvent to avoid possible side reactlons due to the interaction of the starting t-butylbromoacetate with the solvent. a) Weigert,F.G., Winokur,M.; Roberts,J.D. J.Am.Chem.Soc. 1968, =,1566; b) Frei]ee,F.G.M.;Seetz,J.W.F.L.;Akkerman, O.S.; Bickelhaupt,F. J.Organometal. Chem. 1982, 217. Letters 1977, 247. Fellman,P .;Dubols,J E. Tetrahedron "Carbon-13 NMR Spectroscopy" 1st ed.; Academic Press, Inc. Stothers,J.B. New York, 1972; Chapter III. To this purpose, 13C-NMR spectra were recorded every 24 hours. (Received

in UK 20 July

1982)