Asymmetric tandem additions to chiral 2-naphthyloxazolines. The synthesis of enantiomerically pure 1,2,2-trisubstituted- 1,2-dihydronaphthalenes

Tetrahedron Letters,Vo1.25,No.34,pp Printed in Great Britain

ASYMMETRIC THE SYNTHESIS

Department

Summary:

3667-3670,1984

TANDEM ADDITIONS

OF ENANTIOMERICALLY

TO CHIRAL

0040-4039/84 $3.00 + .OO 01984 Pergamon Press Ltd.

2-NAPHTHYLOXAZOLINES.

PURE 1,2,2-TRISUBSTITUTED-1,2-DIHYDRONAPHTHALENES

A. I. Meyers and Denton Hoyer Colorado State University, Fort Collins,

of Chemistry,

Colorado

80523

Addition of organolithium reagents to optically active 2-naphthyloxazolines followed by trapping with methyl iodide gives, after oxazoline removal, the titled compounds whose absolute configuration was determined by x-ray diffraction.

We recently containing

described

the efficient

the chiral oxazoline,

merit ratios of E (8.5-9.5:1) which were easily

purified

addition

(+)-A followed

were

of organolithium

by electrophilic

found to contain

by chromatography.

reagents trapping'.

A three step, efficient

E

‘Q,,,,

a5 remove

the chiral auxiliary

chiral

elements

became apparent

-03

RLi E@

00

0

furnishing

were introduced

stereoselectivity

arose that regiochemical

selectivity

o--L R -a?

‘*%;

,

pure aldehydes

(+)-C.

Thus, two

ring in a single step (A-+B). --

product

in the 2-naphthyl (to either

cl-lo

1+1 -c

into the naphthalene natural

products,

process was used to

E

OX.

the enantiomerically

that for some projected

had to show similar

,

The diastereo-

only trans tandem addition

Phw\OMe 0 9

to naphthalene

adjacent

It soon

syntheses,

this tandem alkylation

system 1.

The possibility

l- or 3-positions)

also

may also pose

n

problems

for this route to substituted

dihydronaphthalenesL.

with the 2-naphthyloxazoline,

(+)-1, which demonstrate

both a high degree of stereo-

and regioselectivity

Addition followed

of organolithium

by trapping

reagents

of the intermediate

We now describe

that the tandem additions

proceed with

(Table).

to (+)-1, under conditions lithioazaenolate

3667

our results

depicted

with methyl

in the Table,

iodide3 gave the

3668

dialkylated

dihydronaphthalene

The process

is also devoid of any -cis-addition

that derived bottom

from diastereofacial

(re-face) -

results

2. in good yields

of the naphthalene

of the major product

mp 133-134").

ring generates

lene occurs

interesting

products

(Table) whether

the major

in the presence

isomer, while

Confirmation

observed

of the absolute

from addition

study on 2 (R=Ph,

addition

for the

to the naphthaFurthermore

to 1 in the J-position. to the temperature

Similarly,

Another

of the

in 2 were only slightly

out at -78" or 25".

changed

the ratios were

of HMPA as a cosolvent.

to 1 and Cleavage

to Enantiomerically

Pure Aldehydes

4 Aldehydes,

Diast. Ratiob RLi

Equiv.

n-Bu

1.1

n-Bu

1.1

n-Bu

isomer

stereo-

for the 1-naphthalenes'.

is the lack of sensitivity

was carried

the minor

shows the lS, 2s configuration

Thus the ratio of diastereomers

the addition

Addition

TABLE

system,aswas

being

Thus, entry of RLi from the

by a single crystal x-ray

(Fig. 1) clearly

were found resulting

addition.

2a, with the only impurity

Thus, the same sense of asymmetric

aspect of the process

organolithium

unaffected

respectively4.

in the 2-naphthalene

-no detectable

(si-face).

(1) was obtained

The ORTEP structure

phenyl and methyl

products,

high diastereoselectivity.

entry of the organolithium.

from RLi entry from the topside

chemistry

with generally

T",timea

% yieldb

4

[alDCHC13(c)d

85

98:2

81

25', 5 min

70

92:8

__

1.1

-78O(HMPA),2h

92

98:2

_-

Me

2.0

-3O", 15h

67

91:9

65

-85.8' (0.5)

Ph

2.0

-30°, 5h

89

9O:lO

89

-333.6"(0.5)

&Bu

2.0

-loo',

74

76~27

70

+244.4"(0.7)

a) Conditions

-78=', 2h

2

% yieldC (from 2)

for addition

1.5h

of organolithiums,

b) Yields are for isolated mixture mined

by HPLC (Sorbax,

removed removal.

of diastereomers

20% THF-Hexane,

by radial chromatography

1 ml/min).

for pure homogeneous

iodide added in all cases at -78". of 2 and diastereomeric

c) The minor

(20% ethyl acetate-hexane,

HPLC and 270 MHz NMR confirmed

d) Rotations

methyl

homogeneity

product.

+190.8'(1.0)

of 2.

diastereomer

ratios deterin 2 was

silica gel) prior to oxazoline Yields of homogeneous

product.

3669

The minor

diastereomer

stereomerically 4 was performed nitrogen

pure (HPLC, CMR) materials. by two related methods.

was accomplished

25", 15 h) followed iminium water,

linkage

in 2 was readily

using methyl

by direct addition

to 2 in 5 min (mixture

stirred

after radial chromatography.

CONH,

aY

al

in THF-water

by chromatography

Cleavage

Originally, fluorosulfonate

the quaternization

with water,

with excess oxalic

After this cleavage

The mixture

the

pure aldehydes

3.5 equiv,

0") which

was diluted

acid (3h, 25') affording

Et,OBF,

00

1+1-1

a1

RLI

bl

Mel

CH2C12,

reduced

and concentrated.

was accomplished,

dia-

of the oxazoline

("magic methyl,"

of diastereomers). washed

furnishing

to the enantiomerically

of NaBH4 (4 equiv in MeOH-THF,

CH2C12 added, and the layer separated,

due of crude zwas

removed

the

with The resipure 4

the future unavailability

t

2. FS&Me al

or Me,OBF,

bl

FIGURE 1

1+1 or I-I

-4

NaBH,,

3670

of "magic methyl 'I5 caused

us to develop

It was found that Me30BF4

(2.0 equiv,

sodium borohydride

and hydrolysis

This facile and efficient number of naturally

occurring

an alternative

CH2C12,

(as above)

method

8h) completely

using Me30BF46 quaternizes

gave comparable

yields

route to chiral dihydronaphthalenes and biologically

important

in its place.

2 and reduction

of the aldehyde,

with

4.

now opens the way to a

substances

whose

synthesis

is in

progress.

REFERENCES

AND NOTES

1.

B. A. Barner

2.

Prepared

and A. I. Meyers,

by treating

24h) then addition

3.

of 1.2 equiv S,S-methoxyamino (cf. ref. 1).

CHC13).

Additions

to the 3-position

truction

of the aromaticity

In addition

to methyl

products

The absolute

Health

according

unlikely

(25',

to previously

due to the des-

in both rings of the naphthalene

and phenyl group respectively; R. J. Raker, Tetrahedron

2,

placed on "magic methyl"

nucleus.

such as PhSSPh,

C1C02Me,

diastereofacial

Ht

also

efficiency.

1 has been shown to be 4S, 5s at

see:

A. I. Meyers,

M. A. Hanagan,

1991 (1983), and earlier have caused

suppliers

references

therein.

to cease sales of

1983.

Alfa; Org. Syn. Coll. Vol. 5, 1096. quaternary

would appear

of the chiral oxazoline

as of October

in 1,2-dichloroethane

(+)-1 was obtained in 68% yield, [aID 124.3" (c 2.8,

with high trans ratios and comparable

restrictions

this reagent

alcohol

iodide, other electrophiles

configuration

L. M. Trefonas,

6.

with 1.2 equiv Et30BF4

procedure

the methoxymethyl

5.

2-naphthamide

described

provide 4.

J. Am. Chem. Sot. 106, 1865 (1984)

Attempts

to use Et30BF4

failed

to give the N-ethyl

salt of 2.

ACKNOWLEDGMENT The authors

are grateful

to the National

support.

(Received

in

USA

1 May

1984)

Institutes

of Health

for generous

financial