The stereochemistry of the reaction of 2-norbornylmagnesium bromide with formaldehyde

119 doumalofOrganomeidlicChemistry.l25~1977)11S-124 8 ElsevierSequoiaS.A..Lausanne --PrintedinTheNetheriands

THE STEREOCHEMISTRY

OF THE

REACTION

OF 2-ilORBOl7XYLMAGXESIUM

BROMIDE

WITH

EOR&'&LDEHYDE

DAVID

E. LIERGBREITER-

Department Texas

Chemistry,

M. REICiiERT

ASM

Texas

University,

September

17th.

Diastereomeric

Station,

19761

endo-f-norbornylmagnesium

and -exo-2-norbornylmagnesium

bromide

at the carbon-magnesium

expected

alcohol.

primary

to that observed organomagnesium is added.

This

previously reagents,

that single

of -set-alkylmagnesium

bond vith

in electrophilic is observed

electron

reagents

to simple

5 mole

both with

retention

is comparable

of stereolsomeric

I ferric

and without

is not important

aliphatic

of endo-

to form the

which

substitutions

transfer

with

formaldehyde

result.

even when

observed

and mixtures

stereospecifically

stereochemical

The stereospecificity

suggests

bromide

react

of configuration

salts

College

(U.S..%-)

77843

(Received

and OSCAR

chloride added metal

in 1.2 addition

aldehydes.

Introduction

The mechanism compounds

is a matter

the 1.2-addition thst single

of current

electron

transfer

realized,

especially

&&.23_

: Blectron

trsnsfe;

-_

__-. -_ ..

I:

interest.

of alkylmagnesium

previyly

,.

important

of synthetically

reagents

processes when

reactions

Recently,

has also been

mechanistic

to aryl ketones

are more

added

of organomagnesium

important

transition shown

studies

of

have revealed than had been

metal

salts

to he important

are prein overall

,

L. __

~..a_

______

c33

V_ . ..-A...+..

120 study

the importance

of such electron

of -set-alkylmagnesium addition

reactions

reagents,

We have

and ketones.

synthetic

yield

retention

of configuration free radical

Results --

and Discussion

intermediates

for which

stereochemistry

tinction

between

species_

Only

with both

diastereomers

to an aldehyde

bromide

reacts

for a 1.2 addition We have

&

MgBr

>95%

endo-

H

H

argues

-see-alkylmagnesium A comparison

or ketone

in sufficiently reagent

reaction found

of endo-

available high

of the and

permits

yield

determination

of a -see-alkylmagnesium

that endo-

react with

and mixtures

formaldehyde bond

dis-

to a tetrahedral

synthetic

to permit

at the carbon-magnesium

of these

+

alternatives

bromide

of configuration

The stereochemistry

an aldehyde

of this Grignard

or ketone_

The complete

reactions

and known mixtures

with

the stereochemical

and exo_Z-norbomylmagnesium retention

are available.

of endo-

formaldehyde

stereochemistry

is a representative

both diastereomers

-exo-2-norbornylmagnesium

in high

in such systems.

bromide

of reaction

reacts

reagent.

in these

of 1.2-

bromides CA' to

formaldehyde

of this Grignard observed

reactions

the stereochemistry

that only

at carbon

Z-Iiorbomylmagnesiu

in other

2-norbomylmagnesium

found

with both epimers

against

processes

we have examined

of diastereomeric

aldehydes

reagent

transfer

vith

(equation

of

reagent of andocomplete 1 and 2).

reactions

‘c=o.

H’

THF 480

. '

H 795%

H. ,c=o H. . -

THF - 7S”

q&&J-

(1)

-

121 parallels

that previously

reactions

like

carboxylation,

diastereomeric

transfer

free 2-norbornyl

and

leading

substitution

deuteration

of

these

and

other

reagents c4-83 and suggests

to a 2-norbornyl

of this Grignard

radicals

electrophilic

alkylmagnesium

processes

in the addition

in other

mercuration.

or enantiomeric

that electron involved

observed

reagent

radical

are not

to formaIdehyde.

had been intermediates,

predominantly

If

-exo- products

have been observed Cgl .

would

The stereochemistry used

in

these

subsequent

studies

glpc

of was

analysis

GB H

the

starting

determined of

the

product

1. I CuPBu3, 2.

by

norbornyl the

magnesium

reaction

bromide

reagents

in equation

shown

3 and

hOI_

2-tert-butylnorbornane

THF, -78O

C(CH3)3 Li, -78O (3)

3.

CgH5N02,

-78O

MgBr

The stereochemistry

of the product

1 and 2 was determined prepared

by borane

by

nmr

reduction

2-norbomyl

methanol

formed

and comparison

spectroscopy

of the corresponding

with

2-norbornane

in reactions

material carboxylic

acids. The addition

of transition

to have a pronounced magnesium

reagents

effect

No loss of stereochemistry

8~91 as

magn+m cm-_

in Table

of FeClg was a slight

Ye also briefly

acetaldehydc, .--_ brede.

aiaure _.l_

examined

the

addition

in yield

could be detected

of up to 5 mole I we have studied. effect

of other

and benzophemme

eavt.lw

of alkyl-

observed pro-

by nmr.

of our experiments

bromide

is known

of the 1.2-addition

of addition

acetone.

chloride

in the addition

of the reactions

decrease

the conditions

. ,--of 2-ho~_mylqgae+m

formed

1, the only measurable

the results

beazaldebydq

_ Under

such as ferric

Bowever.

on the stereochemistry

As can be seen from the data

duct.

salts

on the products

to aryl ketones.

FeC13 has no effect

on addition

metal

yields

carbonyl

compounds

to 2-norbornyla 57143 endo_/ of 1.2 addition

122 TABLE I REACTION OF FORMALDEHYDE HALIDES

2-Norboruylmagnesium Bromide <% endo-_)a

WITH

WITH

ADDED

Alcohol Yield <%lb

L-NORBORNYIMAGNESIDM

FERRIC

CHLORIDE

Alcohol Stereochemistry <% endo-)=

Mole X FeC13 addedd

>95

70

>95

o.oe

57

75

60

o.oe

>95

50

>95

5-O

57

45

59

5.0

>95

60

a95

o-of

aDetenained by formation of a 2-norbornyl(tert-butyl)copper(E)ate complex. oxidative coupling with nitrobenzege, and subsequent glpc analysis of the rodtlct2-s-butyl norbornane. Isolated yield. %etermined by nmr, ?5%. 8Added as the hydrate. eGrignard reagent prepared using Grignard grade turnings. fGrignard reagent prepared using 99.99% purity magnesium.

detailed examination showed that the predominant product was due to reduction by the Grignard reagent as previously described by Morrison and Lambertml_

We believe similar reactions occur vith the other listed compounds although low yields of alcohol (ea. 30%) were obtained in some cases. These results have been confirmed in independent uork by San Filippo who also shoved that the isolated alcohola are formed preferentially from the eudo- Grigoard

Experimental

section

All reactions of organometallic ccmpounds were carried out in flame dried glassware under pre-purified nitrogen or argon using standard techniquesw

Tetrahydrofuran and other ethereal solvents uere distilled

from a purple solution of bensopheoone dianioiiprior to -ke.

=2-

123 2-norbornane

carboxylic

and reagents

were

Reaction according

purchased

epimerization

this reaction

pouring ether

into excess (4 x 100 ml),

bp 11%150° exo-Cg20H.

procedure

of Drake

drying

Experiments

and Cooke

ammonium

cl61

After

with

directly

added

-

was accomplished

stirring

to avoid

for 4 h at

and quenched Extraction

by

with

gave a crude mixture,

by nmr

ferric

solvents

quality.

at -78O

chloride.

and distillation

at 50 mm which was analyzed 6 3.58).

in reagent

to room temperature,

aqueous

(Na2S04)

Other

and formaldehyde

reagent.

was warmed

saturated

sources

bromide

of the Grignard

mixture

reductionC133.

from commercial

of 2-norbomylmagnesium

to the general

possible -78OC

acids Cl51 by borane

(endo-CX20H.

chloride

were

6 3.87;

performed

similarly. Reactions were

carried

reagents. alcohol

of 2-norbornylmagnesium out in an analogous

Work-up

products_

of benzophenone shoved

as described

beuahydrol

A detailed

bromide

fashion above

vith

yielded

examination

and an epimeric and norboraeue

mixture

and other

aldehydes

an epimeric

mixture

at best

low yields

of the products

of Grignard ( ~30%)

of

from the reaction

of 2-norbornylmagnesium

to be major

or ketones

bromide

products.

Acknowledgements

Acknowledgement administered

is made

by the American

and to David P. Rainville

to

the Donors

Chemical

of the Petroleum

Society,

for assistance

for support

in obtaining

Research

Fund.

of this research,

100 MHz mu

spectra.

Reference5

1.

E. C. Ashby, (1975) 521.

2.

I. G. Lopp, J. D, Buhler, and E. C. A&by. J. Amer. Chem. 4966; E_ C. A&by, Y. G. Lopp, and J. D. Buhler, J. Amer. (1975) 1964.

3.

-J. Ki Kochi. J. Grganc+U+

Accounts

Chem. Res.,

7 (1974) 272; E. C. Ashby,

Chem.

Rev.,

Sot.. 97 (1975) Chem. SOL. 97

Accbunts Chem. Res.. 7 (1974) 351; B. A. Budnick and J- Rochi, Ghem., 116 (1976) C3. _~

.

124 5.

G_ R_ Buske

6.

B. Hecbin

7.

8. R. Walborsky

8.

U. N. Smith.

9.

G_ H. Uhitesides and J. San Filippo. 6611 and references therein.

and W_ T_ Ford, J_ Org_ Chem.

and N. Laulet,

J. Organmetal.

and R. S. Aronoff.

J. Org. Chen.,

41

(1976) 1995_

Chem.,

39 (1972)

J. Organometal.

229.

Chem.,

51 (1973)

31.

38 (1973) 4463. Jr.. J. Amer.

and G. M. Whitesides,

Chem.

Sot.,

Sm.,

92 (1970)

10.

D. E. Bergbreiter 4937.

11.

J. D. RonSson and G. Lambert. J. Org. Chem.. 37 (1972) 1034 and references therein have described the stereochemical aspects of this reaction.

12.

Ptivate comauoication Professor San Filippo publication.

13.

?I. C. Brown, York. 1975.

14_

J. D. Roberts, E. R. Trumbell. Chem. sot., 72 (1950) 3116.

15.

G. H_ Whitesides

16_

H. L_ Drake and G. B_ Cooke. Organic New York, New York, 1943, p. 401.

"Organic

J. Amer.

Chem.

96 (1974)

with Professor San Filippo. Ue are grateful for informing us of these results prior to

Syntheses

via Boranes,"

Wiley-Interscience.

Jr., W. Bennett.

and P. E. Kendall,

and R. Armstrong,

.J. Org. Chem., Syntheses.

37 (1972)

Coil. Vol.

to

Rev

J. Amer.

3718.

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