Michael additions of benzoins versus Michael-Stetter additions of aldehydes

~efrahedron Let%rs Vol. 21, rp L2"1 - 2294 OPergamon Press Ltd. 1980. Prm.*wi IA Great Br;talr,

MICHAEL Josep

ADDITIONS *

Castells,

Sanahuia

and

Departament

Summary:

Elisabet Laura

!&Each,

de Quimrca

thlarolium

and

describe

our

Thiazolium of

aldehydes

new

and

when

2

on

results ion

in

4,5

synthetically

this

in

ADDITIONS’

L&pez-falahorra,

OF

ALDEHYDES

Margarita

Prats,

Olga

anions

and

related

fields.

catalysts

bonds’

-prepared

to

chalcone

benzoins

in

de

Barcelona.

to chalcone

conjugate

as addends

for

the

bases

Barcelona.

con prevarl

-prepared

from

to give

Michael

in

situ

Spain.

over from

the the

condensations,

condensationJ

the the

expected pertinent

conlugate

base of

corresponding

promptsus

as well

In a typical

additions).

as catalyst situ

In

benzoin

(Michael-Stetter using

ion

Universitat

as catalysts.

acyloin

are

of ion

of

reaction,

adds

additrons

used

as for

example

of

to

the

this

addition

relatively

3-benzyl-4-methyl-5

thiazolium

chlorrde

I-(2-furyl)-2,4-diphenyl-l,4-butanedione

(la) (II),

and in

85%

.

isolated

we

find

from

now

the

that

reaction

when

the

reaction

Formotion

of

mixtures

can

hydroxy-diketone

the

mixture

di(P-furyl)-3,5-diphenyl-I,5_pentunsdIone, (II)

Francisco

thlazolium

are

bases

double

useful

furfural

However, directly

use

conjugate

(2-hydroxyethyl)thiclzolium

yield

ne-

the

to activated

triethylamine-

MICHAEL-STETTER

de Q&mica,

Michael certain

triethylami

report

own

Geilo,

Facultat

catalyzed

additions

recent

VERSUS

Fernando

Organica,

Triethylamine

salts

BENZOINS

ViJ Janova

Michael-Stetter

A

OF

thiazolium (1520% m-p.

be established (Illa)

could

salt

employed

IS no longer

yields) l43-5O

(lllo)7.

by spectral

The

(Id)’

dlketone

presence

of

or (II)

small

(Ie)6, but

the

after

we

had

found

that,

compound

2-hydroxy-l,2-

amounts

of

under

the

means.

be understood

2291

IS either

diketone

action

catalytic (18%

yield).

of

We

characteristics

triethylamlne,

can

and

furoin

hypothesize

that

the

that

conlugate

ions are good benzain

condensation

with

we

this

hypothesis,

supercetded

by the

can

adds not

all

triethylamine

chaicone

thiazolium

(in ion

ethanol

that

but particularly the

catalyzed

expected

addition

solution)

conjugate

bases of 3-( I-phenylethyl)-

catalysts

explain

to

bases

to

gtve

have

that

compound

identical

catalytic

and 3-(I-benzylethyl)-4-methylthiazolrum

poor Michael-Stetter addition

of

furfural

to chalcone

of

the

condensation to

furoin

chalcone which

catalysts,

be

is

being

formed

simultaneously. As

can

behaviour

between

condensation of

be seen

from

those

catalytic

a 5-(2-hydroxyethyl)

the

results

described

actlvtty,

collected

above.

There

branching

substituent

in

in

Table,

appears

the

is a positive

the

that

other with

N-subsrituent

thiazolium regard

salts

to good

is a negative

show an intermediate Michael-Stetter

feature

while

the

one.

TABLE

Thlazolium

solt

(I)

R1 a)

PhSH2

b)

Ph-CH2

c)8

Ph-CH-CH3

d)

Ph-CH-CH3

e)

Ph-CH2-CH-CH3

R2

Yield

of

(II)/%

Yield

of

X Cl

84

___

Cl

56

3

8r

26

lo

H

I

___

20

H

Cl

_--

15

HOCH2-CH2 H HOCH2-CH2

Fu-CO-CH(

Ph)-CH2-CO-Ph

(I I) Fu

Ar-CO-C(OH)(Ar)-CH(Ph)-CH2-C0-Fh

(III)

a)

Ar

= Fu

b)

Ar

= Ph

=

(Illa)/??

presence

There After

are few reports

our initial

solution; (lllb)7

finding,

triethylamine in 1%

yield

on the use of acyloins

we have confirmed

or KOH (KCH).

that benzoin

as the base) to give

We

have found,

3,4,5-triphenyld-hydroxy-2-cyclohexenone place can be visualized

and benzoins

too, (IV),

as addends In Michael

behaves as furoin

2-hydroxy-I,

in 50%

and adds to chaicone

2,3,5-tetraphenyl-I,

that benzoin

reacts with

yield.

condensations

2,9

(ethanol

5-pentanedione

benzalacetone

to give

The sequence of events which

take

as follows

Ph-CH-CH-CO-C%

+

(OH -) -

Ph-CHOH-CO-Ph

Ph -FH- C%-CO-CH3 HO-C-Ph do-Ph I

1

(V

0 (OH-)

l

‘h

-(j:

benroin

(IV)

and acetone.

them catalyzed postulated:

benzaldehyde

to give

The interplay ion,

reversion

basic catalyst.

products

11

The resulting

possibility

by cyanide

(retro)benzoin

nicely

Smith

results,

to benzaldehyde, Michael

addition

catalized

reaction

and aldol

Aldol

of benzoin

between

condensations,

for which

ii)

of using a chiral

, we have studied hydroxy-diketone

resolved

by column chrotnotography

specific

rotation,[a]

F

iii)

10

the following

condensation

the three of rationale

can be

between acetone and

to benzalacetone,

followed

by the

above.

In vrew of the established addition

of Michael,

of benzoin

Ph HO- -Ph

long ago

explains

benzalacetone,

sequence of events depicted

Michael

Ph

Ph

was obtained

by cyanide

i) Partial

l

ot 4

HO

Cyclohexenone

-t-w

Ph

- 3.4’,

the addition (Illa)

(4%

in samples of different

and another,

a positive

basic catalyst of furoin

to chaloone,

yield),

which

optical

activity

one, [a]

to prepare optically

p

with

brucine

has two choral centers,

4.7’.

.

active as the was

one of them had a negative

Substituent

effects

benzorns

and

acylorns

benzorns

are

berng

on the

cutalytrc

as addends

actively

rn

activrtres

Mrchael

of

condensations,

In

view

of

to activated

ion,

Hermann Tapro

3.-

R.

4.-

In

J. ---

our

of

were

refluxed in

for the

the

synthetic scope

of

extensions Michael

of

the

use

oddrtrons

of

of

!&.,

thiazolium

20

by Stetter action

w.,

and

of

condensations Ed.

NOTES

coworkers

cyanide thus type

1976,

IS&‘

Ion of

on

or

of

the

addrtron

a conjugate

reactions.

For

of base

aldehydes of

a review,

a

see

639.

36

Chem.

orrginal

and

AND

done

catalytic

Int.

1980, =

ethanol

about

the

Chem. ---

Am.

Dry

work

Michael-Stetter

experiments,

I 6~20.20

93??

nome

Synthesis,

Breslow,

ratio

under

Angew.

Hase,

all

considerable

bonds,

we

Stetter,

2.-

very

double

thiazolium

5.-

the

ions,

explored.

REFERENCES

1 .-

thiazolium

wos

1958,

80,

salt,

triethylamine,

used

3719

as solvent

furfural

(8.5

cm3

und

Manfred

for

and mmol

chalcone of

were

thiazolrum

used

in

salt).

a molar

The

solutrons

hours. Hermann

reference:

Stetter

Schreckenberg,

Chem.

&,

1974,

107,

2453.

6.-

J.C.

present 7.-

Sheehan,

Hara,

--J.

Org.

-Chem.,

1974,

39 =,

1196.

Racemic

amines

were

used

in

the

work.

N.m.r.,

i.r.,

Stereochemistry 8.-

Takeshi

This

salt

as well

m.s.,

remains was

OS elemental

undefined

prepared

(two

patrs

by reaction

analysis of

between

were

drastereomers

in

agreement

are

possrble).

with

the

4-methyl-5-(2-hydroxyethyl)thiazole

proposed

and

constitution

I-bromo-l-

phenylethane. 9 .Pierre 1962,

a) Jacob

Szmuskovicz

Brison,

Bull. ---

Sot.

and

Harry

Born,

chim.

k.,

1962,

-_J.

Am.

96,

-Chem.

c) Jean

k.,

Colonge

1953, et

75,

Pierre

98.

IO.-

A.

II.-

Cf. -

(Recewed

Smith, K.

&.,

Hermann

1893,

26, =

and

Hans

1x1UK 2 Anrll

1960)

65. Wynberg,

1.

Org.

a.,

1979,

2,

2238.

3350, Brrson,

b) Jean Bull. --

Sot.

Colonge -chim.

et L,