Synthesis of furo-furans by rearrangement of 4-acetylpyrans

Tetmhedrm VoL 48. No. 28, pi. 58825900,1992

oo4o420192

RiinGnslBW

h8U”O” hZsS Ltd

SYNTHESIS

OF FURO-FURANS

Angela

M.Celli,

Istituto

di

BY REARRANGEMENT

Mirella

Chimica

Scotton*,

Organica,

53100

- Siena

OF 4-ACETYLPYRANS

Alessandro

Piano

$5.00+.00

dei

Sega

Mantellini,

44

(Italy)

(Receivedin UK 18 May 1992)

Key

words:

Abstract

furo-furans,

- The

c bearing

hetero-Diels-Alder

4c

and

6c.

Cycloadducts

3a,

3c

and

7a was

with

7c

4c'easily

vinyl

ether

and

8c. by

of

the

aspects

The

single

of

to

6c

to

stereochemistry crystal

other the

and

5a-c

and

furo[2,3-blfurans

difuro[2,3-b:3',4'of

X-ray

compounds

reaction

and

5,6-dihydro-4H-pyrans

rearranged 5a

la-

l-oxabutadienes

ethyl

functionalized

cycloadducts

determined

Some

the

2a and and

configurations data.

groups

of

noes.

4H-4aB5,6,6a;Sz!etrahydrofuro[2,3-blpyrans

9c

7a,

dlfurans

gave

hetero-Diels-Alder,

reaction

electron-withdrawing

2,3-dihydrofuran 2a-c,

furo-pyrans,

compounds

analysis.

were

5c

established

mechanisms

are

and

Relative by

nOe

discussed.

Introduction

The bony1 the

hetero

Diels-Alder

compounds synthesis In

earlier

2,5-dione,

and of

la

electron-rich

dihydropyran

work and

reaction

by ethyl

one

of

substituted

dienophiles

is

a,R-unsaturated an

attractive

carroute

to

derivatives. of

vinyl

us1 ether

it

was

gave

5883

found the

that

expected

3,4-diacetyl-3-hexencycloadduct

2a

with

5884

A. M. CELLIet al.

a 4-acetylpyran ibly the

to

the

furo[2,3-blfuran

reaction We

yield

was

therefore

tent

of

with

one

this

desired

or

This

structure.

The

3a.

practically

undertook

a

was

labile,

isomerising

rearrangement

was

irrevers-

stereospecific

and

quantitative.

study

in

rearrangement

more

compound

to

gain

some

understanding

$-SCylpyrahS.

other

electron-withdrawing

groups

We

such

as

of

used

la-c 2-4

the

ex-

heterodienes to

obtain

the

4-acylpyrans.

Results

The

reaction

of

2,3-dihydrofuran which

were

acetyl

and

well-known 'H-NMR

gave

4b

ethoxy

one

(coupling

more

easily

of

with in

The

and

vinyl

case,

the

on

4b

and

5b were

not

than

the

former.

This

or

with

structures between

the

reactions5"

nOe

ether

configuration

attributed

Diels-Alder

constants

ethyl

each

trans

tentatively

was

endo-selectivity

lb

cycloadduct

respectively.

groups

cycloadducts

latter

only

5b

and

spectra

The

Z-3-hexen-2,5-dione

basis

and

of the

of

the

confirmed

by

experiments). very

stable

made

their

and

the

decomposed,

purification

diffi-

cult. The 3 and

introduction 4

of

but

also

la

reacted

tive by

the

made

yield.

acidity.

two

heterodiene the

with This On

of

other not

cycloadducts

the

basis

gave of

to rise

spectral

18 R= R’=R”=Ac lbR=R’=H,

only

increased

obtained

2,3-dihydrofuran compound

electron-withdrawing

R”=Ac

lc R= R”= COOEt , R’=Ac

more

give to

rate

stable. cycloadduct

the

rearranged

in

positions

cycloaddition

of

Thus

a rearrangement

data

2al-c

the

the

groups

the 5a

which

in

tetraketone a quantita-

was

product

4b,c

catalyzed was

at-

Synthesis of fin-furans

5885

fOOEt

EtOOC\

tributed

structure

the

of

3,3a-diacetyl-2,7a-dimethyl-3b,4,5,6a-tetra-

hJ-drodifuro[2,3-b:3',4'-dlfuran. the

configuration X-ray

ranged

made

of

analysis

compound

had

The

substitution

the

cycloaddition

reaction

trend

endioic which

two

On

was

undertaken cis-syn-cis

by

X-ray

data

out

of

and

basis

of

than

in

Thus

analysis,

eight

was

that

two of

ester

compound of

la,

for The

and

8c

exo in

cis-syn-cis The

compound adduct the

a mixture

6c

ratio

lc

even

of but

data

the

stable

cycloadduct

established

if

products

stable

other

groups the

6c.

This

diethyl

the

from

other

slowly was

attribution

tenwas

4a-acetyl-2-methylas

the

struc-

5c.

configuration

alkene

rear-

E-2,3-diacetyl-3-but-

1H-4aB,j,6,7aR-tetrahydrofuro[2,3-b]pyran-3,4-dicarboxylate t.ure

the

ethoxycarbonyl

was

the

establish

possibilities.

One

and

which

to

7a.

case

gave

sufficient

established

by

diethyl

spectral 5c

the

it

the

isolated.

structure

not

groups

2,3-dihydrofuran were

was

configuration

acetyl

analogous.

attributed

confirmed

two

slower

with

the

compound

the

cycloadducts

rearranged. tativelh

lc

this

of

was

acid

The

also

rearranged 60:40. for reacted

easily

Spectral 7c

and with

to data,

give

chiefly

cis-syn-trans ethyl

a mixture

vinyl

nOe for

ether

of

compounds

data,

compound to

yield

7c

confirmed 8c. a

mixture

A. M. Wetal.

of three

compounds

in the

as the cycloadduct

ratio

4c. The

83:13:4.

other

two

The

had

main

the

product

was

identified

furo[2,3-blfuran

structures

3c and 9c respectively.

MO

R

Discussion

NMR and X-ray The group

NMR

is

constant

in

Data spectrum axial

values

coupling

spect

to the ethoxy

the

lished.

relative

in

The

group

4b fact

trans

clearly the

support

on saturation

ethoxy

group

for this

of

the from

C6 chiral

interpretation

3J~5g,H~

and

ethoxy

cowling

of the H6 axial-H5

acetyl the

the

group

reaction

centers

is offered

can

with

re-

mechanism be estab-

by nOe experi-

on both methylene

hydrogens

of the

(2.3 % and 3.7 %) and no nOe on H6. However

we cannot

choose

conformation

of H3 we have noes

that

the presence

be deduced

of C4 and

indicates

35 H5,H6

position

can then

configuration

ments:

between

position:

pathway.

Further

compound

(2.48 and 4.60 Hz) exclude

axial

and

of

A and B:

6Et

A

B

5887

Synthesis of furo-furans

The

relative and

nism,

configuration

also

and

4 we

is

possible

fairly

have

noes to

well

on

(3.4

distance

pendent

of

between

tion

we

111

the

4a

conformation

Dreiding

be on

results:

and

2.1

%

nOe

analysis

deduced

from

irradiation

of

respectively);

terms

and

7a

or

D)

of

compound

= 2.5

r4,4a

the

in

protons

this

and.equation

are

mecha7a

case

it

can

be

[l]

negligible':

111

(C

models

obtain

may

6 r 4a,4 6 r 4a,7a

=

sponding

%

5b

cross-saturation

f4a(4)

The

nOe

quantitative

that

f4a(7a)

compound

from

4a

exploit

provided

written,

of

protons

(r4a,7a)

can

and, 5b:

be

is

a

estimated =

r4a,7a

2.30

constant from

A.

inde-

the

corre-

Applying

equa-

1.

c If to

the

and

4a

3.1

1

the

7a

protons for

cis

and is

thus

we

f4(3) PC-= f4(7a)

Introducing

r3,4 model,

cis

in

2.5

can

the

then

(from

trans

this

the

NOe

distance

Dreiding

are

noes

on

position

is

model

reveals the

4

with

satisfied

that

As on

proton

only

= 2.45

r4,4a

respectively).

analysis

a

A

and

and

if

the

4

r4,4a

=

consequence

irradiation

(12.5%

respect

1.05%

of

the the

3

respec-

write:

12.5

r6

1.05

r63,4

=

pseudo-equatorial

configuration

A".

there

protons,

is

ring,

are

r3,4

tively),

Dreiding

ring

dihydropyran

distance and

furan

2.50

however,

r4 Ls

4,7a

1, this

7a

r3,4

we

obtain

distance

r4,7a should

[21

1.51 -

= be

3.8 4.2

A. 1.

According

to

the

A. M. CELLIef al.

5888

Now,

if the

hydropyran either then

furan

ring,

axial

or equatorial

to the Dreiding as

= 3.3 A).

trans

to the acetyl The

methyl

and H-6a

fore

solved

shown

ORTEP

X-ray

ORTEP

of

on H6a

= 3.8 ff (whereas is axial, to

probably

then the

di-

H4

in

according = 2.9 A

r3,4

Dreiding

in axial

be taken

settled

of a cis

as conclusive. The

Bond

(Fig.1).

be

on saturation

in favor

diffraction.

plot

7a cannot

(3.4%),

evidence

cannot

configuration

plot

are listed The

of

the

structure

(Me group

from

model

position

and

so

distances

and

coupling

of the quaternary

relationship

The

structure

using

problem

between

was

determined angles

there-

is

are

7a

as

listed

in

on both

is shown

data

analysis.

to 7a carbon)

nOe on 3b (0.088)

5c was

of the compounds

3b and

in the case

compound

determined

by

Bond

in Fig.2.

X-ray

study.

distances

and

The

angles

3 and 4, respectively.

nOe

bonded

of

molecule

in Tables

be deduced

As

the

the

that H4 is equatorial,

(according

is very

to

with

1 and 2, respectively.

The

noes

offers

but

by

in the

Tables

problem

The nOe obtained

hydrogens,

Me-78

ring

If H4 i

respect

group.

configurational

constants.

[2] r4,7a

= 4.4

furan

with

bl is satisfied

Let us suppose

= 4.0 1).

r4,7a

So the

position

= 2.5

equation

r4,7a

a consequence,

in axial r4,4a

position.

from

model

r4,7a

is

distance

= 2.5 i% and

r3,4

and,

ring

the

6a protons

5b,

from

6c by

irradiation

of the more

of

abundant

on

(0.013),

and on irradiation

of compound

derived On

rearrangement the

it is possible

was

of

a nOe

to apply

can

protons

we obtained

compound

irradiation

of 3b there

methyl

6a there on 6a

was

a

(0.143).

quantitative

ana-

lysis:

f6a(3b)

=

p-efg,(Me)

r 6 Ga,Me

fgb(6a)

I31

6

fgb(Me)

r 6a,3b

From if

these

r3b,6a

distance

equations

it is possible

is

Let

known.

is 2.35 A and

from the equations

r 6 3b,Me 6 r 3b,Ga

=

us

suppose

to extract that

it is independent

[3] and

[4] we have

6a of

r3b,Re

r~~,he and

3b

(4 1

and r6a,Re are

syn or anti

cis:

distances then

structures.

= 3.2 1 and r6a,Me

their Thus

= 3.5 A.

Synthesis of tie-furans

However,

from

the Dreiding

= 3.3-3.5

r3b,Me

structures

the

express

ton).

If 3b and

[3).and

(41,

matched

by

tributed

(Me

6a are

r3b,Me trans

the less

group

bonded

irradiation

of

bonded

abundant to

3b

to

equation

=

independent

trans then

on

the

On

NMR

syn

(the

methyl

pro-

from

equations

distances

7c can

be

are

not

safely

at-

1.5%

for the minor

the compounds

a

6a

and

nOe

on

(0.042)

on

of the methyl

protons

3b

proton

(0.026),

and

methyl

protons

irradiation

of

6a there

on (Me

is

a

write:

E51

of r3b,Me

on

be

compound was

Their

distance

is 3.1

equation

[5] we

by configuration

6a are with

of

lc and

obtained

relative

the protons

cis

r3b,6a

any

structure.

of

vinyl ratio

configuration

the methyls

the methylenes

derivatives

ethyl

in the

have

cis-syn-

= 2.35 A and Thus

the

and

minor

9c, the ethoxy

group

may

assume

a mix-

3:l as deestablished

in position

respectively).

major

ether, ca.

was

of ethoxy

to the

attributed

Let us

to the compound.

products

and major

3c and

If 3b and

is known.

their

from

only

is not compatible

the protons

then

Thus,

is satisfied

between

of

if r3b,6a

are trans,

structure.

= 3.4 A.

integration.

saturation

then

on

(0.031)

distance

reaction

obtained

tion.

structure

have

noes

or anti

r3b,Me

were

9c could

we

the calculation

two rearranged

from

nOe.

are

8c can be attributed

From

by

carbon)

= 2.45 A which

r3b,Me

duced

These

on irradiation

the 3b and 6a protons

for which

of

the closest

f

r63b,Me

3.2 A. This

q

structure

ture

4.3-4.5

is 3.1 1 and,

= 4.6 A.

the

range

for the other

r63b,6a

allows

that

suppose

7a

there

fgb(6a)

r3b,Me

Thus

We can therefore

f3b(Me)

A

distance

r6a,Me

compound,

7a carbon)

nOe on 3b (0.033).

This

structure.

the

= 3.5 A and

rGa,Me

(7c), while

3b or 6a and

their

A and

in

are

to the compound.

For

group

values

between

trans,

= 4.3

distances

structure

have

distances

the distances

any

these

i for the cis-syn-cis same

values

model,

5889

groups

6a, noes (11%

Structures

derivatives, a pseudo-axial

and

3c and In both posi-

A. M. CELLIet al.

Mechanistic

aspects

The

formation

explained

by

the

ring

pyran

or

5c

and

of

the

rearranged

nucleophilic in

attack

attack 2a

compound by

the

of

or

pyran

products

3a,

4-acetyl

group

a

2c,

or

oxygen

on

on

the

the

If

both

this

the

Since that

only

the

carbon The

a

syn

would

of

obtain

the 2a

crystal

of

similar

ethyl From

vinyl the

endo-adduct

of

two

or

the

furan

quite

carbon

of we

conclusion

7a

can

ring

7a as

as

can

6 position system

shown

be of 5a

below:

can

5a

partecipated

in

in

we

a suitable

have

to

position

conclude to

attack

5a.

determined that out

by

X-ray

only

the

reached

be

and

products.

is

of

deduce

carried

2a

stereospecific

groups

carbon

structure

cycloadduct

rearranged

is

acetyl

the

so

the

two

rearrangement

6 of

side A

the

the

groups

configuration,

other

and

we

one

the

7c

5a.c

acetyl

attack,

on

and

furo[2,3-blpyran

acyl

2 a,c

7a,

3c,

the

analysis

acetyl

re\,ealed

group

on

the

between

la

rearrangement.

for

the

cycloadduct

etherl. reaction 5c

and

between the

exe

lc

and

adduct.

2,3-dihydrofuran 6c.

The

former

we

isolated

showed

the

both aoetyl

5891

Synthesis of furo-furans

group

cis

to the

exo-adduct

6c slowly

7c and

8c. The

rearrangement

In this

ity. It

can

be

attacks the

case

cis

carbonyl

oxygen

the

In

la.

were

can

of

the

spectrum

fact

isolated

of

the

derived two

raw

from

rearranged

and their

slower of

rise

to the

the

by

rearranged

traces

in the

pyran

the

of

of

intermediate

7a

on

of acid-

former

ring

both

rear-

cases.

6c

first

9c.

Then,

sides

of

the

ether

the

7c and 8c. lc

and

was so high

material.

The

less

ethyl

that

vinyl

it was not even

rearrangement

stereospecific

compounds,

formation

than

carbonium

between

lc are

give

to a mixture

giving

compounds

reaction

not

accelerated

atom

at C-4

attack

the

was

oxygen

group

did rise

was

rate of the exo-adduct

the cycloadducts of

the

ring to give

case

rearrangement NMR

that

and

gave

rearrangement

carbonyl

tetrahydrofuran

in the

the

supposed

the

In

ring

The

rangeeent. products

tetrahydrofuran

3c and

9c,

can be explained

seen

reactions

than

in the

of

in the case ratio

75:25,

as for compounds

7c and

8c. The

cycloaddition

dihydrofuran withdrawing fully

was

tion

lb with

slower,

expected,

much

groups.

as

in contrast

Moreover,

stereospecific, Compounds

of compound

giving

hydrogen

atom

in position

pathways

to yield

but, 4, the

a mixture

ether

lb

has

or with

less

the behavior

2,3-

electron-

of lc,

it was

only.

the acetyl

possibly

vinyl

since

with

one cycloadduct

4b and 5b seem to have

for the rearrangement,

ethyl

due

group

in a suitable

to the presence

cycloadducts

prefer

to

posi-

of a mobile

follow

different

of products.

Experimental

Unless 782

otherwise

stated,

spectrophotometer

spectra strument shifts

were

recorded

(60 MHz) (J in Hz)

Proton-Proton

samples

are

pulse

reported

were

were

XL-200

with

with

from gated

on

bromide

a Perkin-Elmer pellets;

'II NMR

a Hitachi-Perkin-Elmer

FT spectrometer

downfield

measured

recorded

in potassium

solutions

for CDC13

or a Varian

noes

nOe difference Silica

using

IR spectra

(200 MHz);

internal

in-

chemical

tetramethylsilane.

decoupling

techniques

using

sequences.

gel plates

(Merck

F2.54) and

silica

gel

60

(Merck

70-230

mesh)

5892

A.M.Ceuretal.

were

used

for analytical

phy,

respectively.

were

evaporated Starting

cited:

la2,

General

Extracts

over

and

for

sodium

column

sulphate

chromatograand

solvents

were

prepared

by

the

literature

procedures

lb3 and lc4.

Procedure

for Cycloadditions

la-c

up (see Table

were

When

the excess

heated

the

reagent

with

starting

an

excess

material

was removed

had

under

of

ethyl

vinyl

disappeared

vacuum

ether

or

(TLC

or NMR

and the residue

worked

5).

5 - Cycloaddition

Heterodiene

dried

TLC

in vacua.

2,3_dihydrofuran.

Table

preparative were

heterodienes

Compounds

check),

and

Ether

Reactions

"C

Time

(h)

Products

% Yield

x,ya

la

X

36

28

la

Y

55

6

lb

X

60

lb

Y

lc lc

a x = Ethyl

Compound The 5a

and

revealed

2a

89

5a t 7a

54:36

50

2b

80

85

29

5b

90

X

60

40

2c t

Y

55

8

vinyl

3c t 9c

83:13:4 32:49:6:4

5c t 6c t '7c t 8c

y = 2,3-dihydrofuran.

ether;

la and 2,3-Dihydrofuran NMR 7a.

spectrum

of the

Preparative

TLC

5a as the faster

residue with

running

showed

the

presence

ether/petroleum

of

ether

3:l

band and la as the slower

Z-Methyl-3,4,4-triacetyl-dH-4aa,5,6,7aa-tetrahydrofuro[2,3-b]furan, oil;

IR

(neat)

1730,

4.4-3.8(m,2H,H6,H6'),

1710,

162O(vs)

2.7-3.l(m,lH,H4a),

cm-';

NMR

6:

two as

products eluent

band. 5a:

5.56(d,lH,J=4.8,Hia),

2.17(s,3H,Me),

2.29(s,6H,2xMe),

5893

Synthesisoffuro-furans

2.12(s,3H,Me),

1.7-lB9(m,2H,H5,H5')

H 6.77;

C 63.05,

found:

ppm. Anal.calcd

for Cl4Hl805:

C 63.16,

H 6.71.

3,3aa-Diacetpl-2,7aa-dimethyl-3ba,4,5,6aa-tetrahydrodifurof2,3-b:3',4'-dl 7a:

furan,

NMR

6:

mp

145-148°C

(cyclohexane);

5.95(d,lH,J=6.4,H6a), 2,34(s,3H,MeCO),

H5'), lH,H4)

1.45

63.16., H 6.77;

Compound

lb

The

ether

found:

and

residue

1:l.

The

vinyl

was

band was a mixture

3.79(m,lH,H3b),

ppm.

1710,

lH,J=3.05,H3),

by preparative band

was

of E and Z starting

NMR

the

TLC

1.04(t,3H,J=7.08,Me)

Compound

The

lb

and

for

with

Cl4Hl805:

residue

2b and

H3),

oil;

2b: and

4.60,

IR

(neat):

H6),

4.51(brd,

3.34-3.49(m,lH,CH2-O),

1.68-le79(m,2H,H5,H5'),

was

sublimed

1670

cm-';

NMR

and

at

room

1.59(brd,3H,J=l.g5,Me-2),

temperature

Compound

and

with

residue

1:2. The the

Diethyl

ethyl

was

faster

stereoisomer

6:

and

0.05mm.Hg

to

give

vinyl

IR

4.43(brd,lH,J=5.4,

3,02(brd,lH,J=5,7,H4),

1.7-1.92(m,2H,H5tH5'),

2.45-2.57

1.62(s,3H,Me-2)

ppm.

ether

purified running 9c.

oil;

56:

5.25(d,lH,J=4.1,H7a),

16.9,H6tH6'),

2.07(s,3H,MeCO),

ether

3.06-3.13(m,

5b.

(m,lH,H4a),

The

slower

ppm.

3.79(dd,ZH,J=8.0

lc

the

alkene.

4a-rlcetyl-Z-methyl-4H-4aa,5,6,7aa-tetrahydrofuro[2,3-b]pyran,

1705,

C

2,3-dihydrofuran

the cycloadduct

(neat):

(m,

ether/petroleum

cycloadduct

6: 4.84(dd,lH,J=2.48

3.60-3.75(m,lH,CH2-O),

lli,H4), 2.01(s,3H,MeCO),

3.54(m,lH,

ether

running

1690 cm-';

cm-l;

1.75-1.95

Anal.calcd

4a-AcetJ71-4H-5,6-dihydro-6R-ethoxy-2-methylpyran,

1720,

16OO(vs)

H 6.88.

purified

faster

1680,

2.11(s,3H,Me-2),

1.42(s,3H,Me-5)

C 63.42,

ethyl

1700,

3.87(m,lH,H5),

2,36(s,3H,MeCO),

(m,lH,H4'),

:

IR

by preparative band

The

slower

was

the

band

TLC

rearranged was

the

with

ether/petroleum

compound

cycloadduct

3c

together

2c.

2,6aa-dimethyl-5R-ethoxy-3a,4,5,6a-tetrahydrofuro[2,3-bJfuro-3,

3an-dicarboxylate,

3c:

oil;

IR (neat):

1730,

1720,

1680,

1610 cm-';

NMR 6:

A. M. CELUet al.

5.17(dd,lH,J=4.2 (m,lH,0CH2

acetal),

14.1, H4), MeGa),

and 7.6, H5),

2.44

(dd,lH,J=4.2

Jaa-dicarboxylate, esters),

(m,SH,JxMe

9c,

oil

1720,

oil,

(purified 1690,

Compound

5.27(d,lH,J=5.3,H5), acetal),

sublimation NMR

6:

2.27(s,3H,Me-2),

1.23(t,6H,J=7.8,2xMe

eluent

was

and

solved

gave,

(s,3H,

4.05-4.25(m,4H,

3.41-3.48(m,lH,0CH2

acetal),

1.47(s,3H,Me-6a),1,05-1.30

at

5O'C,

0.02

4.88(dd,lH,J=2.4

mmHg), and

IR

2.20(dd,lH,J=7.0 esters),

(neat):

7.O,H6),

3.49-3.64(m,lH,0CH2),

4.08-

2.51(dd,lH,

and 13.3, H5'),

l.l9(t,3H,J=7,3,Me

by preparative

in

order

of

TLC with

mobility,

2.19

acetal).

7c was

purified

repeated

preparative

TLC

from

traces

ether/petroleum

the

7c and 8c, and the cycloadduct

products

of the

in the same mixture

ether

cycloadduct

6c,

the

5c. diastereoisomer

anti

8c

of solvents.

4a-acetyl-Z-methyl-4H-4aa,5,6,7aa-tetrahydrofuro[2,3-b]furan-3,4R-

dicarboxylate,

6c:

oil;

(m,lH,HS'),

IR

(neat):

2.36(s,3H,Me-2),

1720,

2.11(s,3H,MeCO),

1.21(t,3H,J=7.6,Me

for C16H2207:

1735,

1680,

4.14(q,2H,J=7.6,CH2-ester),

5.87(d,lH,J=5.3,H7a), CH2 ester),

C 58.89;

ester), H 6.75;

1610

cm-';

1.78-2.0(m,lH,

1.14(t,3H,J=7.6,Me

found:

'H NMR

3.65-4.09(m,6H,

C 58.44;

H5),

6

H4atH6+ 1.5-

ester).

1.7

Anal.

H 6.76.

2,7aa-dimethyl-3a,3ba,4,5,6aa,7a-hexahydrodifuro[2,3-~~:3',~'-dl

Diethyl

furan-3,3aa_dicarboxylate, 6:

(s,3H,Me-2),

3H,J=7.2,

7c: oil;

5.64(d,lH,J=3.8,H6a),

1.60

Me ester)

TR (neat):

4.1-4.3(m,

3.16(dt,lH,J=3.8

8.5 and 16.2,H5'), 2.24

1.52

ppm.

2.20(s,3H,Me-2),

cm-',

Compound

1 ; NMR

6:

3.79-3.95(m,lH,0CH2),

residue

rearranged

calcd

(s,3H,Me-2),

and

lc and 2,3_dihydrofuran

The

Diethyl

NMR

by

1620

and 13.3,H5),

(s,3H,Me-CO),

with

2.79(dd,lH,J=7.5

t acetal).

4.26(m,4H,2xCH2),

as

t acetal)

2.26

3.76-3.92

4a-Acetyl-4H-5,6-dihydro-6a-ethoxy-Z-methylpyran-3,4-dicarboxyl-

2c,

J=2.4

esters

and 14.1,H4),

esters

Diethyl

1:3

and 14.1, H4'),

3.61-3.78(m,lH,OCH2

3.01(dd,lH,J=5.3

1740,

acetal),

ester),

2,6aa-dimethyl-5a-ethoxy-3a,4,5,6a-tetrahydrofuro[2,3-b]furo-3,

Diethyl

ate,

3.52-3.66(m,lH,0CH2

1.05-1.30(m,9H,3xMe,

2xCH2

4.05-4.26(mS4H,2xCH2,CH2

(s,3H,Me-7a),

ppm. Anal.calcd

1730,

5H, 2xCH2tH5),

and 9.2,H3b), 1.23

1715,

Me ester),

C 58.89;

1600

I.Ol(dd,lH,J

2.15-2.24(m,2H,

(t,3H,J=7.2,

for C16H2207:

1680,

cm-

=

H4+H-I'), 1.22

H 6.75;

(t,

found:

Synthesis of furo-fimns

C 58.57;

H 6.79,

Diethyl

2,7aa-dimethyl-3a,3ba,4,5,6aR,7a-hexahydrodifuroC2,3-b:3',4'-d]

furan-3,3aa_dicarboxylate, cm -1;

NMR

6:

(m,lH,H3b), 1.3(m,6H, Diethyl

8c: oil;

5.98(d;lH,J=5.2,H6a),

5c:

and

mp

65-68°C

16.9,H6),

(cyclohexane);

or

Me-4),

1.19(t,3H,J=5.9,Me

found:

X-Ray

Structure

Single

C 58.52;

1610

3.45-3.65

1.43(s,3H,Me-7a),

1.15-

were

Cell

reflections.

The weighting

temperature

standard

Compound

and

9.5,H4a),

Anal.calcd

examined

deposited

were

1690,

1625

3.96(dd,

2.34(s,3H,Me-2

or

1.25(t,3H,J=5.9,

for Cl6H2207:

with

was

from O=

C 58.89;

H

and

X-ray angle

where

difof 25

o(Fo)

is

from the diffractom-

and

equivalent

parameters

isotropic

the Cambridge

setting

reflection

temperature and

the

crystalliza-

CAD4

[o~(Fo)J-~,

parameters

observed

by slow

an Enraf-Nonius

for each

parameters of

with

used

Positional

a list

7a, obtained

determined

deviation

anisotropic

positional and

5c and

scheme

statistics.

atoms,

been

ester).

parameters

factors,

atoms,

hydrogen

1720,

1.69-1.85(m,2H,H5tH5'),

of compounds

fractometer.

counting

1740,

Analysis

crystals

the individual

IR

H 6.69.

from cyclohexane,

isotropic

of carbon

temperature

calculated

and oxy-

parameters

structure

Crystallographic

of

factors

Data Centre.

7a mw 266.29

C14H1805 Monoclinic, 2622(6)

1665,

3.9-4.3(m,5H,H5+2xCH2-estei-s),

2.80(dt,lH,J=3.7

2.25(s,3H,Me-2

6.75;

have

1710,

2xMe esters).

Me ester),

gen

1725,

4R-acetyl-2-methyl-4H-4aa,5,6,7aa-tetrahydrofuro[2,3-blfuran-3,4a-

lH,J=8.5

eter

(neat):

2.18(s,3H,Me-2),

cm-';- NMR 6: 5.53(d,lH,J=7.3,H7a),

Me-4),

IR

3.7-4.3(m,6H,2xCH2,H5+H5'),

2.0-2.3(m,2H,H4tH4'),

dicarboxylate,

tion

5895

a = 23.53(3),. b = 9.61(l),

A3, Qc

chromated 1148

= 1.349

Mo-Ka, Unique

intensities

were

reflections

with

A=

g.cms3,

0.71069

1330(I)

Z = 8, F(000)

A), p(Mo-Ka)

reflections corrected

c = 12.07(2)

in for

were

the

used

= 1136

and

5'629<50'

Space were

polarization

for structure

106.15(10)',

q

(20-C,

= 0.62 cm-'.

range

Lorentz

A, R

solution

graphite group

mono-

C2/c.

collected.

effects.

V=

The

and refinement

The 694

A.M.Ca.uetal.

5896

Table1

Ebnd

Figure

. Bond lengths(A)

Bond

0(1)-C(2)

1.36t2)

C(4Mx.5)

1.50(2)

O(l)-C(7a)

1.48(2)

C(5)-O(6)

1.48(2)

C(Z)-c(3)

1.36(2)

O(6)-C(6a)

1.43(2)

c(2b-W)

1.48(2)

C(6a)-0(7)

1.45(2)

C(3bC(34

1.56(2)

O(7)-Ct7a)

1.40(2)

C(3)-C(9)

1.40(2)

C(7a)-C(l5)

1.50(2)

C(3a)-C(3b)

1.51(z)

C(9)-C(lO)

1.52(3)

C(3a)-C(7a)

1.56(2)

C(9)-O(11)

1.22(2)

C(3aHXl2)

1.47(Z)

C(l2)-C(l3)

1.55(3)

C(3b)-C(4)

1.56(2)

C( 13)-0(

C(3b)-C(6a)

1.50(2)

1. ORTEP plot

of compound

7a.

14)

Figure

1.19t2)

2. ORTEP plot

of compound

Sc.

Synthesis of furo-furans

5S97

Table 2. Bond angles(deg)

116(l)

108(l)

114(l)

108(l)

113(l)

108(l)

132(l)

108(l)

108(l)

111(l)

132(l)

106(l)

119(l)

106(l)

115(l)

121(l)

98(l)

108(l)

117(l)

107(l)

110(l)

109(l)

10411)

120(l)

110(l)

121(2)

118(l)

119(l)

106(l)

121(l)

103(l)

122(l)

106(l)

116(l)

101(l)

and were solved

corrected

by direct

hydrogen were

atoms.

introduced

groups

were

bon atoms used

once

methods 9 . Successive All

atoms,

atoms.

of the residual

refined. Final

electron

solved 8 . The structure

had been Fourier

synthesis

except

positions;

in the Fourier

isotropically

for all oxygen

tuation

hydrogen

in calculated

located

were

the structure

those hydrogen

difference

map;

Anisotropic

R = 0.096, density

of

was

revealed the

atoms

acetyl

groups,

of

acetyl

the

all hydrogen

temperature

Rw = 0.074. 0.31 eAm3.

The

was

all non-

and

car-

factors

were

maximum

fluc-

A.M.CEuretal.

Compound

5c

C16H2207

mw 326.34

Triclinic,

a = 8.06(l),

75.99(8),

7 = 83.19(8)',

= 348

(20-C,

Cm -1.

Space 2495

grafite group

Unique

b = 10.31(2), V = 818(2)

monochroeated

were

corrected

reflections

with

I&30(1)

solved

corrected

atoms.

and not

refined.

gen

atoms.

residual

gc = 1.325

Mo-Ka,

in

the

a = 70.65(7),

gcmW3,

a = 0.71069

range

for Lorents

A),

6 =

2 = 2, F(000)

p(Mo-Ka)

were

used

for

once the structure

All hydrogen

Final

electron

Anisotropic R

= 0.096,

density

atoms

structure

= 0.64

Fourier

were

= 0.070.

factors The

solution

synthesis

introduced

were

maximum

used

Bond

0(1)-C(2)

1.34(l)

C(6)-O(7)

1.47(l)

O(l)-C(7a)

1.51(l)

0(7bC(7a)

1.38(l)

C(2bCt3)

1.30(l)

C(9bO(lO)

1.24(l)

C(2)-C(8)

1.52(l)

C(9)-O(ll)

1.35(l)

C(3bCf4)

1.56(l)

O(llbC(12)

1.43(l)

C(3)-C(9)

1.45(l)

C(l2bCtl3)

1.46(l)

C(4)-C(4a)

1.54(l)

C(14bO(lS)

1.20(l)

C(4)-C(14)

1.53(l)

C(l4bC(l6)

1.54(l)

C(4)-C(l7)

1.51(l)

C(l7)-Of181

1.19(l)

C(4abC(5)

1.53(l)

C(17)-O(l9)

1.32(l)

C(4a)-C(7a)

1.50(l)

0(19bC(20)

1.47(l)

C(SbC(6)

1.51(l)

C(20)-C(21)

1.47(l)

1495

was

all nonpositions

for non-hydro-

fluctuation

Wh

The

refinement

structure

in calculated

was 0.48 effm3.

Lene;th

and

The

revealed

Table 3 . Bond lengths(A)

Bond

collected.

effects.

solved 8 . The

had been

temperature Rw

5',<26,(50' were

and polarization

methods 9 . Successive

by direct

hydrogen

h3,

A,

Pl. reflections

intensities

and were

c = 10.77(2)

of

the

5899

Synthesisof furo-furans

Table 4.

Bond andes(deg)

Angle(d-4

hzle(deg)

118.6( 7)

106.0(7)

105.4(7)

109.3(7)

127.0(8)

104.5(6)

127.6(8)

107.8(8)

122.5(8)

128.3(9)

121.6(7)

112.8(7)

115.6(7)

118.9(8)

107.6(6)

120.3(7)

108.2(6)

110.3(7)

107.9(6)

124.0(8)

106.5(6)

117.3(7)

108.4(7)

118.6(8)

117.9(7)

123.7(g)

116.3(7)

112.8(8)

115.8(7)

123.4(9)

101.9(7)

115.1(7)

102.4(7)

106.7(7)

108.7(7)

~11

ca!culations

Personal

System

2/80

were with

analytical

approximation

dispersion

corrections

were produced

performed SHELX-76 for

the

for all

by the program

on set

atomic

the atoms

ORTEPl'.

an

IBM

of

personal

programs

scattering from

computer

10 ,

factors

which and

model uses

the

anomalous

ref. 11. The molecular

plots

A. M. CELLIet al.

Acknowledgment This Chimica

research

Fine

was

funded

by

the

e Secondaria

(Italy).

G.; Donati,

D,; Cini,

National

Research

Council,

Progetto

References

1.

Adembri, 1980,

2.

Celli,

A.M.;

Lampariello,

Can. J.Chem.,

1982,

3.

Wilfiams,P.D.;

4.

Adembri,

5,

1983, W.

Noggfe,

8.

Walker,

9,

Burls,

Press:

M.

Can.J.Chem.,

New

Maier,

G.M.

Reactions

Scotton,

M.

46, 4143. A.M.;

in Organic

Lett.,

C.K.

The nuclear

SHELX

Tables

dcta

M.;

Scotton,

Synthesis;

1985,

M. Gazz.

Pergamon

86, 2065 and

Overhauser

Crystallogr.,

Calcarano,

D, J.Appl.Cryst., 76, Program

of Cambridge,

U.K.,

Tennessee,

R.E.

D.D.

Camalli,

International migham,

R.;

effect;

Academic

1971.

R.; Viterbo,

12. Johnson,

1981,

A.; Celli,

M. Tetrahedron

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York.

M.C.;

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N.; Stuart,

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S.;

therein.

J.H.;

10. Sheldrick,

11.

Scotton,

1990.

R.R.;

references

Chimichi,

C.; Camparini,

Cycloaddition

Oxford.

Schmidt,

L,R+;

E. J.Org.Chem.,

G.; AnseImi,

Carruthers,

7.

R.;

60, 1327.

LeGoff,

Chim.Ital.,

Press: 6.

R,; Nesi,

58, 1645.

Sect.A,

1983,

G.; Giacovazzo, 1989,

C.;

67, Polidori,

2605. G.;

22, 389.

for Crystal

Structure

Determination,

1976.

for

K-Ray

Crystallvgrayhy;

Kynoch

Press:

Bir-

1874; ~01.4. ORTEP,

USA.

1971.

Report

ORAL

3791, Oak

Ridge

National

Laboratory,