A convenient in situ procedure for effecting inter- and intramolecular Diels-Alder reactions of N-sulfonyl imines

Tetrahedron Letters,Vo1.30,No.23,pp Printed in Great Britain

0040-4039/89

3037-3040,1989

Maxwell

$3.00

Pergamon

+ .oo

Macmillan

Plc

ACONVEN~INSITDPROCEDURg FOREFFRCTINGIKPEB-AND

IINImmLRm

DIRE+AIDER REACTICMUS OF I-SULFONYL II¶INRS Joseph Department

Sisko

and Steven

of Chemistry,

University.

University

M. WeinrebX

The Pennsylvania Park.

State

Pennsylvania

16802

Treatment of an aldehyde and a 1,3-diene with N-sulfinyl-p-toluenesulfonamide/boron S-q: trifluoride etherate leads to products of an imino Diels-Alder reaction via an N-sulfonyl imine produced in situ. Since powerful

its inception

nearly

tool for construction

of the methodology

have been widely

in this area is the procedure of inmnonium salts under for effecting A number converted

five decades

utilized

cycloadditions

to the corresponding

3

in alkaloid

inter-

synthesis.

reaction

has become

a

and intramolecular

versions

A recent

advance

important

reaction et al., for in situ generation and Diels-Alder 2 We now describe a new one-pot method Mannich-like conditions.

of years ago Kresze

presence of a Lewis acid.

Both

of Grieco,

aqueous

Diels-Alder

ago, the imino Diels-Alder

of tetrahydropyridines.l

of N-sulfonyl

and co-workers

N-tosyl

We recently

imines

reported

imine using

derived

from a variety

that non-enolizable

N-sulfinyl-p-toluenesulfonamide

used the Kresze

reaction

of aldehydes.

aldehydes

to generate

could

be

in the

N-tosyl

imines

from

several

enolizable aldehydes which underwent subsequent intramolecular electrophilic cyclizations 4 We have now found that these in situ produced N-sulfonyl imines can be with olefins. efficiently Thus, followed

trapped treatment

by 1,3-dienes

by 2.3-dimethyl

butadiene

TsNSO BFJ-Et20/hAgS0.,

with N-sulfinyl-p-toluenesulfonamide

gives Diels-Alder

adduct

3 in good yield

and BP3 etherate (IQ 1).

It was also

O-so

EtCHO PhMe/CH&I,

in a [4+2]-cycloaddition.

of propionaldehyde

Et

A

I&

=/!:I

&ID&

Kq

-30% 1

2

3037

3

1)

3038

discovered anhydrous

that yields magnesium

are effective an initial intermediate complexed

is suspended

are slightly

of Die&-Alder

below.

Cycloadditions

stereoselectivity is that

be noted

compounds

derived

Moreover,

these

temperatures

than

cis-fused

structure

cases

shown

if

(4 A> also

presumably

involves

acid

aldehydes

which

aldehydes

the general

and

procedure

to be fully regioselective.

A useful

feature

sensitive

of the

enolieable

of N-sulfonyl

such as chloral

imines,

these

cycloadditions was obtained

these reactions

in the Scheme.

In this case,

Thus,

of adduct

such as 5 are potentially

aldehydes.

involve and glyoxylate. 3,5

generally

imines

require

higher

useful

intramolecularly

as shown

here which was tentatively

by the example assigned

the

experiments.

with other N-sulfinyl sulfonamide

4 with

EtCHO

SESNSO

6-10).

of relatively

product

based upon NOESY

Scheme

were found

of [4+2]-cycloadditions

the neutral

using

in our procedure.

to effect

treatment

(cf entries

non-enolizable

stereoisomeric

One can also perform

Me+

sieves

formation

of different

conducted

dienes

with a variety

all utilize

is necessary

A single

shown

was observed

from simple

in Eq 2.

Compounds

improved

Molecular

Imine

a number

were

with unsymmetrical

that existing

reactions

using

The reactions

it is successful

It is also possible

conditions.

mixture.

lower than with HgSO4,

cycloadditions

in the Table.

are shown

methodology

series

in the reaction

are substantially

salt 2.

Only modest

It should

in the reaction

!2+21-cycloaddition of the N-sulfinyl compound with the aldehyde affording an 3 such as I. The reactive species in the cycloaddition may in fact be a Lewis

The results

described

sulfate

but yields

immonium

1,3-dienes

and reproducibility

cleavage

fluorideb

in synthesis Me

afforded

sulfonamides

such as the SES 697

can be effected the bicyclic

of indolizidine

under mild 8 5.

lactam 9 alkaloids.

tfSES

I

BF3-Et,0 Me

MgSO4 PhMelCH,CI,

Me

-3oOc (SES= MeJSiCH2CH2S02-)

We are currently

56%

Me

MeO&(CH&CHO

exploring

extensions

and applications

of the methodology

described

here.

3039

TABLE. Diels-Alder Cycloadditions of in situ Generated N-Tosyl lminesa Entrv

Isolated Yield

ProductIs)

Diene

Aldehvde

Me 63%

Me(CH&CHO

1

(CHzkM~

Me Me

60%

[email protected]&CHO

2

Me Me 3

75%

PhCHOb Me

63%

EtCHO

4

Me

5

PhCHOb

60%

6

EtCHO

61%

7

EtCHO

8

EtCHO

73%

9

Me(CH&.CH0

74%

68%

(1.5:1)

IO

EtCHO

fJ-jEt

Me a see General b reaction

Experimental

conducted

’ stereochemistry

Procedure by ‘H NMR

Me

NOEDS

+yEt

Me (1:l)

at 0°C

established

+

44%

3040

General

Experisental

was added

Procedure.

200 mg of MgS04

toluenesulfonamide added

stirred

(0.3 mmol.

extracted

After

The 1,3-diene

The reaction

product

yields

was diluted

Acknowledgment. support.

with

We are grateful

For reviews

2.

see:

Weinreb,

to the National for obtaining

1987.

(c)

S.M.

Act. Chem. Res.

Larsen,

Albrecht,

4.

Melnick,

5.

Krow,

P.A.

NOESY

1965, 98,

M.J.;

G.; Rodebaugh,

R.; Marakowski,

Weinreb,

7.

The N-sulfinyl

Direct with

gel.

for financial

for NOEDS

spectra.

and Notes

R.R.

S.

Tetrahedron

1982, 38, 3087.

in Organic

Synthesis,"

Adv. Heterocvcl.

P.A.; Parker,

Pobare, B.

W.F.

Chem.

1768.

D.T.

(b)

Boger,

Academic

Press,

1987, 3,

Grieco,

245.

(d)

Lett.

1964, 97, 483.

Ber.

S.M.

Tetrahedron

P.A.; Larsen,

J. Org. Chem.

Tetrahedron

Chem.

J.; Ramey.

S.D.

1988, 53, 3325,

1986, 27,

Albrecht,

1975.

R.; Kresze, G.

see:

1988, 29, 3891.

Tetrahedron 1717.

1974, 30. 2977.

Tetrahedron aldehydes

K.C.

Lett.

1975, 1,

Tetrahedron

Lessen,

Krow, G.R.;

T.A.; Demers,

was prepared of:

of compounds generally

J.P.

Lett.

Krow,

1973, 1899.

G.R.;

Pyun, C.:

For cycloadditions Henz, K.J.;

Tetrahedron

from Me3SiCH2CH2S02NH2

Kim, Y.H.;

Shin, J.M.

like 5 via Die&z-Alder

does not work well:

in "Alkal'oids:

New York;

T.: Singer,

(Received

dried

TLC on silica

with N-acyl

Szczepanski,

S.W.

using

Tetrahedron reactions

Edwards,

0.E.;

Lett.

1986, 21, 2099.

the N-sulfinyl

1985, 3,

Lett.

3821.

of 1,2-dehydropyrrolidin-2-one Greaves,

A.M.;

Sy, W.-W.

1988, 66, 1163.

R.B.

John Wiley,

J.

D.M.;

procedure

formation

and

1888.

compound

1,3-dienes

Herbert,

W.N.

from enolizable

S.M.; Demko,

Can J. Chem.

10. Hori,

Speckamp,

1985, 0,

bis-imidazole

S.D.;

R.; Marakowski,

Rodebaugh,

6.

Grieco,

A.J.; Weinreb,

W.A.;

J. Org. Chem.

for 3

1985, 18, 16.

G.; Mlakar,

Freyer,

derived

solution

was

1431.

Zunnebeld,

imines

solution

was stirred

20 mL of H20,

(CA-34303)

and Dr. A. Freyer

J. Am. Chem. Sot. 1985, 107,

P.A.; Larsen,

R.; Kresze,

NaHC03 with

by preparative

Institute

Methodology

T.; Hibino,

1986, 51, 3553.

Grieco,

Chem. Ber.

9.

Kametani,

S.D.; Grieco,

was purified

Cancer

S.M.; Staib,

Diels-Alder

Orlando,

3658.

8.

Weinreb,

Weinreb.

J. Org. Chem.

3.

(a)

S.M. "Hetero

layer was washed

mixture

in the Table.

We thank Dr. A. Benesi

D.L.;

cap

N-Sulfinyl-p-

and the resulting

10 mL of saturated

The product

References

1.

by syringe

The organic

in vacua.

are shown

with a syringe

of argon.

(0.2 nm101) was added and the reaction

mixture

and concentrated

an atmosphere

fitted

in 2 mL of dry CH Cl and this solution was 2 2 the mixture to -30°C, the aldehyde (0.5 mmol) and

cooling

with 40 mL of ethyl acetate.

over MgS04 Isolated

flask.

under

25 mL flask

was dissolved

0.037 mL) were added sequentially

for 5 min.

h at -3O'C.

2-necked

and 3 mL of dry toluene

(0.3 xunol, 65 mg)l'

to the reaction

BP3eEt20

To an oven-dried,

in

USA

Chemical

S.P.; Sharpless, 22

and Biological

Perspectives";

Pelletier,

1985; vol. 3, p. 241.

March

K.B.

1989)

J. Org. Chem.

1978, 42, 1456.

S.W.,

Ed.;