Heterodiene cycloadditions: Synthesis and oxidation of pyrano[3,2,b]indoles into spiro derivatives

Tetrahedron.Vol.

53, No. 3, pp. 987-1002,

Copyright

CY CLOADDITIONS:

PYRAN0[3,2d]INDOLES

1996 Elsevier

Pnnted in Great Britain.

PII: SOO40-4020(96)01040-X

HETERODIENE

0

1991

Scw~ce Ltd

All rights reserved

0040.4020/97

$17.00

+ 0.00

SYNTHESIS AND OXIDATION OF

INTO SPIRO DERIVATIVES

Jean-Yves M&our*, Ahmed Mamai, BCatrice Malapel, Philippe Gadonneix

Instttut

Organique et Analytique, assock? au

de Chimie

Orl&ins

C&x

Abstract:

l-Acetyl-2-benzyltdene-2,3-dihydroindol-3-ones

to afford

substituted

pyrano[3&b]indoles;

spirolactones

or to 0x0 acetals

Copyright

1996

0

Elsevier

with

Science

compounds

in the presence

reagents.3-6 dihydropyrans

High

of dihydropyrans;

pressure

also

vinyl

d’OrlCans,

ethers

oxidized,

of boron

and vmyl

using

45067

Jones

thioethers reagent,

to

trifluoride.

considerably

reactions (IEDDA)t,z a well-established

were catalyzed

accelerates

the

of electron rich and a powerful

by Lewis acids and lanthanides

Diels-Alder

or pyridines.

reactions;7,8

the

substituted

Tietze2 reported on asymmetric

using IEDDA in a key step of their synthesis.

has reported on the reactivity of chromones,

with electron-withdrawing

substituents,

in IEDDA reactions with vinyl ether. We wish to report here the synthesis of new pyrano[3,2-blindoles examine their reactivity towards oxidation in order to obtain lactonic derivatives. 2 position of 1-acetyl-lH-indol-3(2H)-onet1~12

aldol condensation

of 1-acetyl-lH-indol-3(2H)-one

with electron-rich

olefins

vinylsulfide

diastereomers

(1) (mixture of E/Z-isomers),

cisltmns,

days

with substituted

(except for 3f,g) (Scheme]).

obtained

and to of the C-

Cycloaddition

was performed

2d

Fax: 33 0238417281 E-mail: [email protected] Dedicated to Professor Wuldemar Adam on the occasion of his 60th birrhdq. 987

to an

reacted as heterodienes

3 as a mixture

of

at 110 “C in a sealed tube

2. The yields were high except for the phenyl vinylsulfide

of 24 h at 110 “C. The keteneacetal

according

(2a), 1-(4-methoxy)benzyloxyethene

(2d) to afford the cycloadducts

(2~) or 1, I-diethoxyethene

at 135 “C instead

benzaldehydes,l3

such as 1-ethoxyethene, 5 I-benzyloxyethene

with a large excess of dienophile

The easy oxidability

can interfere during the oxidation of cyclic ketals 3.

I-Acetyl-2-benzylidene-2,3-dihydroindol-3.ones

(2b), phenyl

1,6-

in the synthesis of carbohydrates.

We have recently described the synthesis of &carboline$ Also recently, Wallaceto

Universttk

has become

these reactions

formed give easy access to carbohydrates9

induction with chiral oxabutadienes

with

were

Diels-Alder

such as enol ethers, with I-oxa-1,3-butadienes

method for the synthesis

6759,

Ltd

The inverse electron demand (LUMOdiene- controlled) dienophiles,

BP

reacted

these

m-CPBA

CNRS,

2. France

2c which needed 6

(I,]-diethoxyethene)

was

highly

988

J.-Y. MBROUR et ~1

nucleophilic

and was the most reactive one. These IEDDA reactions worked only in the presence of a catalytic

amount (5%) of ytterbium salt, Yb(fod)3.3

CH,= Cm’)R3 2 Yb (fad), , 11 O’C t 50

98%

la R’ = 0CH3

3

lb R’ = CH, lc R’=H

Compound

R2

Rt

R’

Yield (%)

mp”C Oil

cis/trans (S)

3a

4-OCH, OBn

H

98

3b

4-CH,

OBn

H

98

113a

81/19

3c

4-CH,

OPMB

H

95

oil

85115

3d

4-OCH, SC,H,

H

53

oil

51143

3e

4-CH,

SC,H,

H

50

oil

62138

3f

4-CH,

OC*H,

OC,H,

92

oil

3g

4-H

OC>H,

OC,H,

75

oil

3h

4-OCH, OC,H,

H

98

oil

3i 4-CH, a major diastereomer cis.

WI5

84116

H 98 125a OC,H, Bn = Renzyl; PMB = 4-methoxybenzyi.

86114

Scheme I The use of methoxyallene diastereomers) Disubstituted

as dienophile

afforded

in only 40% yield due to polymerisation dienophiles

like 2$dihydropyran

(20%). No reaction occurred with vinylidene to its low energy HOMO. I ,4-Benzodioxin

afforded

the cycloadduct

4a

of the methoxyallene the cycloadduct

(ratio

66133 for the two

even at 50 “C (Figure

Sa (Figure

carbonate. The lack of the reactivity of this dienophile

was also unproductive

0' 5a

4a Figure 1

can be due

as dienophile in these cycloadditions.

of&

:&o,

I). 1,2-

I) but in a low yield

Synthesis

For all the cycloadducts endo/exo

configuration

of the anomeric (equatorial).

3a-e,

3h,i the major diastereomers

or respectively

proton

and oxidation of pyrano[3,2-hlindoles

cis/n~ns

Hz and its coupling

The major diastereomer

989

have the same relative configuration.

has been tentatively attributed by examining constants

with the inequivalent

has always a more deshielded

protons

The

the chemical shift

H,,

(axial) and H,,

Hz (6=5.36 ppm VERSUS5.27 ppm for 3a)

indicating an axial position for the ethoxy group but the coupling constant J2+ = 5. I Hz is only slightly inferior to J gsa = 5.9 Hz (minor diastereomer)

3a; the aspect of the signals

for compound

of the Hja and H3, also

depended on the value of the coupling constant, frans or cis, with the Ha (J3e4 = 7.2 Hz, J2a4 = 5.4 Hz) for the presumed

compound

ROESY experiments) pseudo

these two values were close and may be confusing.

indicated connectivities

planarity

of the pyrano

ring has an infhience

reported were not conclusive.

In order to have more information ethyl vinylether

and

on interactions

The major diastereomer

through

space since

the

the different

might be cis and the minor truns based on

[47c+ 2711since the Z-isomer should give the endo (c-is) cycloadduct.

the usual tenets of cycloaddition

we reacted the Z-4-methoxybenzylidene-2,3-dihydroindol-3.onet4

with

3j (80% yield) from an endo process

(Figure 2);

which afforded the expected cis cycloadduct

only a trace amount of the truns diastereomer

is observed

medium (K,CO,

/ethanol/HzO,

3j as a unique

cis diastereomer

= 9.4 Hz). The deacetylation

50°C. lh30, 67% yield) of the major diastereomer which confirms

of 3j is easily

(~5% yield). The cis configuration

assigned using tH NMR (Jzie = 1.8 Hz, J2Ja = 8.2 Hz, Jse4 = 6.8 Hz, J,,

cycloadduct

2Q NMR (NOESY

of the H, with Hga and to a some extend with H3e for the major

of 3a; for H, the presence of the 0CH2 signal with the same chemical shift was disturbing;

cis diastereomer

connectivities

cis-3a;

the cis configuration

in basic

of 3h15 afforded compound

of the major diastereomer

of the

3 obtained from la-c.

3.j

3h

/O

Figure 2

As reported previously

afforded respectively (compound

Id

isomerisation material

the ratio of diastereomers

in the cycloadduct

of the starting material 1 (which was predominantly

stereochemistry

the major cis diastereomer

of 3a, 3d in 85%, 57% yield; even starting from pure Z-isomer

R1 = NOz) gave also a mixture of cis and tram cycloadducts in the mixture, by Lewis acid Yb 3+, of the diastereomeric

1. It has been discussed

by Tietze 1 that isomerisation

reaction

configuration

and the exe or endo nature of the process; (the endo-E-syn-TS

products.

could occur with the possibility

of four transition

3). Some reports3 indicated in these cycloadditions

3. This can be due to an

cycloadducts

of the

cycloaddition

the cis-adduct

3 was not directly related to the

Z) t6,17; for example la (79% Z-isomer)

and/or of the starting

I-oxa-1,3-butadiene states according

and the exo-Z-syn-TS

the formation

during

the

to the E and Z would give

of a 1:l mixture of cisltrans

990

J.-Y. MBROURet al.

The population the coupling position

of the two conformers

constants

of the cis diastereomer

Jasa and Jsa4; for compound

for the 4-phenyl

and the 2-ethoxy

can be discussed by examining the values of

3j the values of these constants

group. A different

behavior

where a decrease of the coupling constants J 23aand Jas4 indicates

indicate

an equatorial

is shown by the other cycloadducts

a significant

contributionla

of the conformer

having the 2-ethoxy and the 4-phenyl group in axial position. (Scheme 2)

dc2J% Scheme 2 Compounds anomeric

3 were slightly different

carbon by TMSCN

(TMSOTf)

in the presence

corresponding

failed in presence

of a non-nucleophilic

the 2-position

hydroxylation in carbohydrate reactions

Treatment

of compound

base as N,N-diisopropylethylamine

in 2-position chemistry

for some years the oxidation

of indolic compounds

was sensitive

of I-substituted-lH-indol-3(2H)-ones. we submitted

the compounds

we have worked on pure diastereomer

diastereomers,

from usual acetals since nucleophilic

of TMSOTf.

attack on the

3 with Lewis acids

also failed to give the

enol ethers.19

We have been exploring process;*0

in reactivity

of indoles

which was an important

towards oxidation

1lvl* Using oxidation procedures

3h,i to a Jones oxidation*lg**

3i

E!%z!?a,

6h

RIzCH~~

R’=OCH3

6i Rl=CH3

\

F

R’

developed

(For the oxidation

cis or tram). We obtained only spirolactones

and not the expected lactones 7h,i (Scheme 3).

&a,

biological

and we have reported on the

6h,i, as single

Synthesis

The cis or truransdiastereomer or trans diastereomer mechanism23

and oxidation of pyrano[3,2-blindoles

of 3h afforded the same unique diasteromeric

of 3i gave the same diastereomeric

(Scheme 4) involving

initial epoxidation.

opening of the pyrano ring generates the intermediate to the Spiro compound

991

lactone 6h; similarly the cis

lactone 6i. These results were consistent

with a

The opening of the oxirane ring with a concomitant

oxonium ion (A). This oxonium ion may evoluate either

8 which is further oxidised to the lactone 6 or to an hydroxyaldehyde

which affords 6

after an oxidation via its hemiacetal. We have also shown that compound 8 gave product 6 under similar Jones oxidation.

3h,i

H30+

6h,i

Scheme 4

This type of Spiro structure was found in some oxindole alkaloids like Horsfiline24 which possess a 3,3Spiro structure; 2,2-Spiro pseudoindoxyl mitragynine

pseudoindoxyl

structure was encountered

Oxidation of 3h,i was also performed of BF3 etherate at room temperature The major diastereomer mixture of diastereomers of compound

pseudoindoxy125

or in

using meraperchlorobenzoic

acid in presence of a catalytic amount

as reported for the oxidation of cyclic acetals into lactones.27

(cis) of 3h afforded the rearranged

ketonic cyclic acetal 8h in 58% yield as a

in the ratio 1:3 and not the lactone 7h. (Scheme 3). Similarly the major diastereomer

3i gave 8i in 68% yield (mixture

afforded, in the same oxidation conditions, plausible mechanism

in tetrahydrocarbazole

alkaloid.26

for this transformation

of diastereomers

1:6). The minor diasteromer

a mixture of products 6h, Sh, 9h approximately of 3h,i into Sh,i was first the epoxidation

(trans)

of 3h

in the same ratio. A of the ethylenic

bond

J.-Y. MBROUR et al.

992

followed

by opening

intramolecular

of the oxirane after complexation

nucleophilic

displacement

(Scheme 5). This mechanism

of the Lewis acid BF3 (oxonium

the two diastereomers

cannot explain the mixture of epimers. Another possibility

pathways proceeding

A direct

which may occur via an attack of the anomeric carbon to afford Sh,i

may differentiate

discrete steps and that the rate-determining

species).

of the starting materials

is simply that the rearrangement

step differs from one diastereomer

3h or 3i but

proceeds via several

to the other one despite both

through an oxonium ion such as A (Scheme 4).

M = BF3-

Sh,i Scheme 5

It is noteworthy single diastereomeric

that the 0x0 acetal 8i (major diastereoisomer)

is oxidized by Jones reagent to the same

0x0 lactone 6i obtained previously.

TMSOTf m-CPBA

BF3

(W,),O * 40%

0

\

CF&OOH

CHO

.

63%

Scheme 6 The use of a stronger Lewis acid like TMSOTf in the oxidation procedure,

instead of BF3, afforded the

Synthesis

keto esters 9h,i in 51% and 60% yield respectively dihydropyran

as single diastereomers

6). The opening

presence of a protonic acid like trifluoroacetic Compounds

which cannot be directly alkylated.29

Another

route to obtain lactones 3a (diastereomer

3i afforded the acetal 1Oi; in

as the result of a formal alkylation in 2-position

lH-indol-3(2H)-one

3a,b. Compound

of compound

acid the unmasked aldehyde28 lli was obtained from 3i.

9i, lOi, lli may be considered

alternative

7h,i was to prepare

cis) in methanol,

13b respectively

under a hydrogen

atmosphere,

in presence

of of

in 37% yield, rather than

(Scheme 7). Using a 100% weight of Pd/C 10% allowed us to obtain the indoline lactol 13a or in 42% and 40% yield as a mixture of diastereomers

be obtained from 12a by hydrogenolysis moiety was in this case particularly

sensitive to hydrogenation

substituent)

was readily transformed

presence

(10% weight),

of 10% PdK

substituent

of low stability. Compound

13a can also

of the benzyl group with a 100% weight of Pd/C (10%). The indole

instead of a benzyloxy

methoxybenzyl

of l-acetyl-

first a lactol by hydrogenolysis

10% (10% weightj was reduced into indoline derivative 12a (one diastereomer)

hydrogenolysed

of the

of the ethylenic

species to the carboxylic acid ester by the peracid (Scheme 6).

In the absence of oxidant, treatment with BF3 etheratelethanol

PdK

(Scheme

ring was, in this case, the first step of the oxidation instead of the epoxidation

bond, followed by oxidation of the carboxonium

compounds

993

and oxidation of pyrano[3,2-blindoles

since compound

3i (with an ethoxy substituent

into the corresponding

in the same conditions

indoline derivative

as for 12a. CA!! or DDQ oxidation

of the 4-

of compound 3c was unfruitful. OBn

OBn

HO

3”i? H

:I

oL

3a 3b

I_\

R’

12a

R’=OCHj

I

R’ = CH,

Hz/Pd

Scheme 7

In summary we have extended the [47t + 27~1cycloaddition one to different dienophiles

and prepared spiroindolic

compounds

of 1-acetyl-2-benzylidene-2,3-dihydroindol-3which were interesting intermediates.

12i in

J.-Y. MBROUR et al.

994

EXPERIMENTAL

PART

Melting points were determined recorded on a Perkin Elmer tetramethylsilane expressed

using a Kofler apparatus hot stage and were uncorrected.

1330. lH-NMR

as the internal standard

spectra were recorded

for solutions

in deuteriochloroform

on a Bruker AM 300 (300 MHz) and coupling

in Hertz. Mass spectra were obtained using chemical

ionisation

IR spectra were

(ammonia)

constants

on a Nermag

with were IO-1OC

apparatus.

IEDDA Reactions. General Procedure 1 (1.9 mmol) were dissolved

Compounds

in CH,Cl,

(2 ml) and vinylether

2 (1.5 ml) in presence

of

Yb(fod)3 (0.095 mmol); the mixture was heated in a sealed tube at 110 “C during 24 h (2a, 2b), at 135 “C during 6 d for 2c or at 90 “C for 20 h for 2d. Evaporation chromatographed

of the solvent under vacno gave an oil which was

on a silica gel column (230/400 mesh) using CH2C12/petroleum

of two diastereomers

ether 1: I as eluent; a mixture

was obtained; (see Scheme I, Table 1).

5-Acetyl-2-methoxy-4-(4-methoxyphenyl)-3-methylene-3,4-dihydro-2H-pyrano[3,2-b]indole Methoxyallene

(1.5 g, 21.4 mmol) was reacted on compound

50 “C during IO d in presence chromatographed diastereomers

of Yb(fod),

la (293 mg, 1 mmol) in CH,CI,

(32 mg, 0.030 mmol). After evaporation,

on a silica gel column (eluent: CH$l$petroleum

(1 ml) at

the residue was twice

ether 1:l) giving an oil as a mixture of

(ratio 66:33); yield: 145 mg (40%). IR (film): v=l68O(C=O) cm-t.

Major diastereomer:

lH-NMR (CDC13) : 6=2.41(s, 3H, CH,), 3.24(s, 3H, COCH,),

5.29, 5.33, 5.42(4s, 4xlH,

lH, J=l.4, 7.3, Hg), 7.98(d, IH, J=7.3, Hg).

Minor diastereomer:

(CD+)

tH-NMR

5.18, 5.31, 5.32(4s, 4xlH,

: 6=2.38(s, 3H, CH3), 3.55(s, 3H, COCHj), 3.72(s, 3H, OCH& 4.88,

HZ, H,, =CH,),

7.30(m, 2H, H7, HS), 755(dd, Anal. Calc. for C,,H21N0,:

6.76(d, 2H, J=8.8, H3’, HS’), 6.94(d, 2H, J=8.8, HZ’ , He), 7.20-

IH, J=2.0, 8.0, Hg), 7.93(d, lH, J=8.1, He). MS (U/NH,)

la (200 mg, 0.68 mmol) with dihydropyran

on a silica gel column (eluent: CH2C12/petroleum cm-t.

5,6]pyrano[3,2-blindole

(Sa).

(2 g, 24 mmol) were heated at 140 “C in presence

(40 mg, 0.038 mmol) during 8 d. After evaporation

IR (KBr): v=1695(C=O)

: m/z = 364(M+l)+.

C, 72.71; H, 5.82; N, 3.85. Found: C, 72.90; H, 5.67; N, 3.91.

6-Acetyl-5-(4-methoxyphenyl)-2,3,4,4a,S,lla-hexahydropyrano[3’,2’: Compound

3.69(s, 3H, OCHj), 5.18,

H,, H,, =CH,), 6.70(d, 2H, J = 8.8, H,’ ) HSn), 6.99(d, 2H, J=8.8, Hz* 3He’), 7.22-

7.33(m, 2H, H7, H8)~7.58(dd,

of Yb(fod),

(4a).

under vucuo the residue was chromatographed

ether 3: 1); yield:62 mg (24%). mp=149 “C (ethanol/water).

‘H-NMR (CDCI-,) : &1.60-1.82(m,

4H, CH,CH,),

2.09(m, lH, Haa), 2.41(s,

3H, COCH3), 3.70(s, 3H, OCH,), 3.70(m, lH, OCH,), 4.02(m, lH, OCH,), 4.31(s, lH, HS), 5.32(d, IH, J=2.2,

Synthesis

HI,,),

6.Wd,

2H, J=8.8,

8.0, Hlo), 7.99(d,

H,,, Hs~), 6.92(d,

lH, J=8.0,

995

of pyrano[3,2-blindoles

2H, J=8.8,

H7). MS (CVNH,)

6.14; N, 3.71. Found: C, 72.90;

Table 1. Compounds

and oxidation

Hz’, Hg), 7.23-7.33(m,

2H, Hg, Hg), 764(dd,

: m/z=378 (M + I)+. Anal. Calc. for Cz3Hz3N04:

lH, J=1.5, C, 73.19;

H, 5.99; N, 3.91.

3 Prepared

680a

Diastereomer

Z=O)

H3, J=2.4, J=6.8, J=13.5),

cis: 2.24(dt, lH, H3, J=5.1, J=13.5), 2.32(s, 3H, AC), 2,50(ddd,

J=11.9), 4.59(t,

3.69(s,

3H, OCH3),

lH, H4, J=6.0), 5.36(dd,

4.58 and 4.86(2s,

2xlH,

lH,

OCH2,

lH, H2, J=2.4, J=5.1), 6.67(d, 2H, Hg’,

H5’, J=8.7), 6.90(d, 2H, H2’, H6’, J=8.7), 7.06-7.32(m,

7H, Harom),

7.57(d, lH,

H9, J=6.5), 8.04(d, lH, H6, J=S.O). Diastereomer

2.00(ddd,

trms:

lH, H3, J=2.2,

J=7.1, J=13.8),

2.29(s,

3H, AC),

2.44(dt, lH, H3, J=5.6, J=13.8), 3.71(s, 3H, OCH3), 4.59(t, lH, H4, J=6.3), 4.67 et 4.92(2s,

2xlH,

0CH2,

J=11.9),

5.27(dd,

lH, H2, J=2.2, J=5.6), 6.76(d, 2H, Hg’,

H5’, J=8.7), 6.94(d, 2H, H2’, H6’, J=8.7), 7.06-7.32(m,

7H, Ha,,,),

7.57(d, lH,

H9, J=6.5), 8.04(d, lH, H6, J=B.O). 680b

Diastereomer

C=O)

AC), 2.51(ddd,

cis: 2.24(s, 3H, CH3), 2.25(dt,

lH, H3, J=2.2, J=7.35, J=14.0),

J=12.5),

lH, H4, J=6.2), 5.36(dd,

4.61(t,

H5’, J=8.1),

6.96(d,

Diastereomer

3H, AC), 2.46(dt,

4.64 and 4.87(2s,

2.32(s, 3H,

2xlH,

OCH2,

7.05-7.33(m,

7H, H7, H8, Harom),

8.05(d, IH, H6, J=8.1).

trans: 6=2.01(ddd,

CH3), 2.29(s,

4.59 and 4.88(2s,

lH, H2, J=2.2, J=5.1), 6.88(d, 2H, Hg’,

2H, H2’, H6’, J=S.l),

7.57(d, lH, H9, J=S.l),

lH, H3, J=5.1, J=13.5),

2xlH,

lH,

H3, J=2.2,

J=6.6,

lH, Hg, J=5.9, J=13.2),

OCH2, J=12.5), 5.27(dd,

2H, H2’, H6’, J=8.1), 7.15-7.33(m,

7H, Ha,,,),

J=13.2),

4.62(t,

2.26(s,

3H,

lH, H4, J=6.2),

lH, H2, J=2.2, J=5.9), 7.04(d, 7.57(d, lH, H9, J=7.3),

8.05(d,

lH, H6, ]=7.3). iC

690a

Diastereomer

C=O)

AC), 2.45(ddd, J=6.6),

cis: 2.17(dt,

lH, H3, J=5.9, J=13.9), 2.21(s, 3H, CH3), 2.28(s, 3H,

lH, H3, J=2.2, J=7.3, J=13.9), 3.69(s, 3H, OCH3), 4.55(t, lH, H4,

4.64, 4.87(2d,

2xlH,

0CH2,

J=11.7),

5.30(dd,

lH,

6.72(d, 2H, H3”, H5”, J=8.8), 6.83(d, 2H, H3’, H5’, J=S.l), J=8.1), 7.02(d, 2H, H2”, H6”, J=8.8), 7.15-7.30(m,

H2, J=2.2,

J=5.9).

6.93(d, 2H, H2’, H6’.

2H, H7, H8), 7.55(dd,

lH, H9.

J=6.6, J=2.2), 8.02(d, lH, H6, J=7.3). Diastereomer 2.29(s, 4.85(2d, J=5.9),

3H,

tram:

2xlH, 6.80(d,

lH,

OCH2, J=11.7), 2H, H3:

H2’, H6’, J=S.l), 7.57(dd,

1.99(ddd,

AC), 2.42(dt,

lH, H3, J=2.2, J=7.3, J=13.9), H3, J=5.9,

3.74(s,

2.26(s, 3H, CH3), 3H, OCH3),

4.61(t, lH, H4, J=6.6), 5.25(dd,

H5”, J=S.l),

7.20-7.33(m,

J=13.9),

lH, H2, J=2.2

6.91(d, 2H, Hg’, H5’, J=S.l),

2H, H7,

H8),

7.23(d,

lH, H9, J=7.3, J=1.5), 8.06(d, lH, H6, J=7.3).

2H,

4.57,

7.04(d, 2H

H2”, H6”, J=8.1)

12(M+l)+

H,

J.-Y.

996

Id

MBROUR et al.

1690”

Diastereomer

C=O)

J=2.9, J=7.3, J=14.4), 4.66(t, lH, H4, J=7.3), 5.62(dd,

cis: 2.19-2.29(m, lH, Hg), 2.32(s, 3H, AC), 2.76(ddd,

lH, H3,

lH, H2, J=2.9, J=S.l),

6.75(d, 2H, H3’, H5’, J=S.S), 6.95(d, 2H, H2’, Hg’, J=B.B), 7.99(d, lH, H6, J=S.S), 7.20.7.60(m, BH, H7, H8, H9, SPh). Diastereomer

truns: 2.19-2.29(m, lH, Hg), 2.36(s, 3H, AC), 2.4%2.60(m, lH,

H3), 3.71(s, 3H, OCH3), 4.65(t, lH, H4, J=5.1), 5.48(dd, lH, H2, J=2.9, J=8.86), 6.77(d, 2H, H3’, H5’, J-8.8), 6.95(d, 2H, H2’, Hg’, J=S.S), 7.20-7.60(m, BH, H7, H8, H9, SPh), 8.02(d, lH, H6, J=8.8) Le

69Ob

Diastereomer

C=O)

2.77(ddd, lH, H3, J=2.9, J=7.3, J=13.9), 4.66(t, lH, H4, J=7.3), 5.61(dd, lH, H2,

cis: 2.17.2.30(m, lH, Hg), 2.25(s, 3H, CH3), 2.31(s, 3H, AC),

J=2.9, J=8.8), 6.91(d, 2H, H3’, H5’, J=S.l), 7.01(d, 2H, H2’, Hg’, J=S.l), 7.197.60(m, BH, H7, H8, H9, SPh), 7.98(d, lH, H6, J=S.l). trarzs: 2.17-2.3(m,

Diastereomer 2.49-2.59(m,

lH,

H3), 4.66(t,

6.92(d, 2H, H3’, H5’, J=S.l),

lH, lH,

H3), 2.25(s,

H4, J=7.3),

3H, CH3),

5.48(dd,

lH,

7.04(d, 2H, H2’, Hg’, J=S.l),

2.35(s,

3H, AC),

H2, J=2.9,

7.19-7.60(m,

J=B.B), BH, H7,

H8, H9, SPh), B.Ol(d, lH, H6, J=S.O).

690a

1.10 and l.l1(2t,

2x3H, 2xCH3, J=7.3), 2.04(dd, lH, H3, J=7.0, J=13.6), 2.24 and

C=O)

2.26(2s, 2x3H, AC, CH3), 2.54(dd, 6.90(d, 2H, H3’, H5’, J=S.l),

lH, H3, J=8.4, J=13.6), 4.57(t, lH, H4, J=7.7),

7.01(d, 2H, H2’, Hg’, J=B.l),

7.19-7.31(m,

2H, H7,

H8), 7.59(d, lH, H9, J=B.l), 8.02(d, lH, H6, J=S.l).

k

.690a

1.09 and l.l3(2t,

C=O)

3H, AC), 2.57(dd,

2x3H, 2xCH3, J=7.3), 2.09(dd, lH, H3, J=8.4, J=13.6), lH, H3, J=7.0, J=13.6),

3.46-3.82(m,

lH, H4, J=7.3), 7.00-7.35(m, 7H, H7, Hg

Harom),

2x2H, 2xOCH2),

380(M+l)+

2.23(s, 4.64(t,

7.61(d, lH, H9, J=7.0),

B.OO(d,lH, H6, J=B.l). ‘j

i400a

Diastereomer

NH)

J3a3e=13.6), 2.47(ddd,

cis: 1.29(t, 3H, CH, J=7.3), 2.27((m, lH, Hg,, J2sa=8.2, J~~4’9.4, lH, Hze, JzJe= 18, J3e4=6.8, J~~3~=13.6), 3.82 (m, IH,

OCH2), 4.11(s, 3H, OCH3), 4.17 (m, lH, OCH2), 4.33(dd, lH, H4, J~~4’6.8, J3a4=9.4), 5.31(dd, lH, H2, J~3~=l.8, J2sa=8.2), 7.15(d, 2H, H2’, Hg’, J=S.l), ]7.05-7.20(m, Ic = CH$O,

6H, Harom, NH); 7.63(d, lH, Harom, J=S).

a film, b KBr.

l-Acetyl-3’-(4-methoxyphenyl)-2’,3’,4’,S’-tetrahydrospiro[indole-2(3~)-2’-furan]-3,S’-dione Compound

3hs as a single trans or cis diastereomer

(6h).

(1 IO mg, 0.3 mmol) was dissolved

in acetone (3 ml)

at 0 “C; Jones reagent21 was dropwise added till all 3h has reacted (circcc 30 min). Excess of the oxidant was destroyed

with isopropanol;

the solution was filtered on celite and evaporated;

water and CH,C12 and the organic layer was dried over MgSO,; chromatographed

on

a silica

gel

column

(eluent:

evaporation

CH2C12/petroleum

the residue was treated with in vucuo left an oil which was

ether

5:l);

yield:44mg

(4270),

Synthesis

mp=70 “C. IR (KBr): v= ISlO(C=O), 3.OO(dd, lH, J=l2.5,

and oxidation of pyrano[3,2-blindoles

997

173O(C=O), 168O(C=O) cm-l. IH-NMR (CDCI,) : 6=2.5.5(s, 3H, CH,),

16.9, H4.). 3.65(s, 3H, OCH,), 3.68(dd,

IH, 5=8X, 16.9, H4’), 4.49(dd,

IH, J=8.8, 12.5,

H3’), 6.63(d, 2H, J=8.8. H3”, HS,,), 6.97(d. 2H, J=8.8, HZ”, Hs.e), 7.04(t, IH. J=7.3, HS), 7.39(d, lH, J=7.3, H7), 7.56(t,

lH, J=7.3, Hg), 8.14(d,

IH, J=8.1, H,).

I%-NMR

(CDCI,)

: 6=25.8(CH,),

32,O(C4’), 45.3(C3’),

96.O(C2), 1 13&C3”, C5”), 117.1(C7), 120.O(C3a), 124.1 (C4), 124.2(C 1‘I), 124,9(C5), 129,2(C2”,

55.O(OCH$,

C6”), 138.9(C6),

152.6(C7a),

158.8(C4”), 168.9(C=O C5’). 172.9(C=O AC), 194.4(C=O C3). MS (Cl/NH,)

:

m/z=352 (M +I)+. Anal. Calc. for CZ0H,7NOs: C, 68.37; H, 4.88; N, 3.99. Found: C, 68.62; H. 4.68; N, 3.92.

l-Acetyl-3’-(4-methyIphenyl)-2’,3’,4’,5’-tetrahydrospiro[indole-2(3~),2’-furan]-3,S’-dione Same procedure v=l SlO(C=O),

as described

(6i).

for 6h starting from 3i5; yield:61%. mp=62 “C (ethanol/water).

IR (KBr):

173O(C=O). 1685(C=O) cm-l. IH-NMR (CDCI?) : 6= 2.1 l(s, 3H, CH,), 2.53(s, 3H. COCH,),

2.97(dd. IH, J=l2.9,

17.6, H4’), 3.65(dd, III, J=8.8, 17.6, H4.)>4.49(dd, IH, J=8.8, 12.9, H3,), 6.87(d. 2H. J=8.1,

H,,,, HS*,), 6.9l(d, 2H, J=8.1. H,,‘, H,,,), 7.00(t, IH, J=7.3, HS), 7.35(d, IH, J=7.3, H7), 7.53(dt, IH, J=2.5, 8.1, Hb), 8.1 l(d, IH, 5=8X, H4). Anal. Calc. for C2~~H1,N04: C. 71.63; H. 5.1 1; N, 4.18. Found: C, 71.72; H, 5.28; N, 4.03.

l-Acetyl-5’-ethoxy-3’-(4-methoxyphenyl)-2’,3’,4’,S’-tetrahydrospiro[indole-2(3~),2’-furan]-3-one Compound and m-CPBA temperature.

3h (250 mg, 0.685 mmol) was dissolved in CH,C12 (3.5 ml); BF,, Et,0

(142 mg, 0.822 mmol) were successively

Ether (25 ml) was added, then the mixture was sequentially

ml), saturated NaHC03

(0.04 ml, 0.33 mmol)

was stirred 2 h at room

treated with aqueous 5% Na2S0,

(10 ml) and brine ( 10 ml). The organic layer was dried over MgSO,

The obtained residue was chromatographed diastereomers

added and the solution

(Sh).

were obtained

and evaporated.

on a silica gel column (eluent: petroleum ether /CH,Cl,

in the ratio 1:3; yield:149 mg (58’%,) mp=l40

(15

“C (ethanol),(major

3:7). Two isomer). IR

(KBr): v=172O(C=O), 1675(C=O) cm-l. Major diastereomer: 3H, CH,), 3.37(dt,

IH-NMR (CDCI,)

: 6=1.2l(t, 3H, J=7.0, CH,), 2.24(dd, IH, J=l3.3, J=7.3, H,‘), 2.69(s,

IH, J=6.6, 13.3, Hq’), 3.58(dq,

J=7.0, 9.7, OCH,), 4.19(dd,

IH, J=7.0, 9.7, OCH$,

3.59(s. 3H, OCH,),

3.86(dq,

IH, J=7.3, 13.3, H3e), 5.63(d, IH, J=6.6, HSt), 6.55(d, 2H, J=9.0, H3”, H,,,), 6.91(t,

IH, J=7.3, HS), 6.93(d, 2H, J=9.0, H,,,, He’.), 7.27(d, IH, J=7.3, H7), 7.44(t, IH, .l=7.3, Hg). 8.4l(d, H4). ‘3C-NMR (CDCI,): 6=14.9(CH,). 113.8(C3”, C5” PhOMe),

IH,

1 l8.4(C7),

34.6(C4’), 46.5(C3’), 55,0(OCH3). 64.l(OCH,), 12l.O(C3a), 123.4(C4), 124.l(C5).

IH, J=9.0.

lOO.O(C2), 104.6(C5’),

124.4(Cl” PhOMe),

128.8(C2”, C6”),

137.5(C6), 153.4(C7a). 158.9(C4”), 17O.l(C=O ), 198.O(C=O C3). Minor diastereomer:

IH-NMR

(CDC13) : 6=1.24(t, 3H, J=7.0, CH3), 2.53(m,

3.04(dt, IH, J=7.3, 13.2, H,,), 3.59(s, 3H, OCH,), OCH$, 4.14(dd,

3.63(dq,

IH, H4’), 2.54(s, 3H, CH3),

IH, J=7.0, 9.5, OCH;?), 3.86(dq,

IH, J=7.0, 9.5,

IH, J=7.3, 13.2, H3’), 5.69(dd, IH. J=5.1, 7.3, HS,), 6.54(d, 2H, J=8.8, H,,‘, H,,,), 6.92(t, IH,

J.-Y. MI~ROUR et al.

998

J=7.3, H5), 6.94(d, 2H, J=8.8, Hz*,, He”), 7.30(d, IH, J=8.1, H7), 7.45(t, IH, J=8.1, He), 8.13(d large, IH, Hd). MS (CI/NH$

: m/z=382 (M + I)+. Anal. Calc. for C,,H,,NO,:

C, 69.28; H, 6.08; N, 3.67. Found: C, 69.47; H,

5.95; N, 3.83.

l-Acetyl-5’-ethoxy-3’-(4-methylphenyl)-2’,3’,4’,5’-tetrahydrospiro[indole-2(3H),2’-furan]-3-one Same procedure

as described

for 8h starting from the major diastereomer

obtained in the ratio 1:6; yield=68%,

mp=l16

(8i).

of 3i. Two diastereomers

“C (ethanol), (major diastereomer

were

). JR (KBr): v=172O(C=O),

167O(C=O ) cm-t. tH-NMR (CDCl,) : 6=1.20(t, 3H, J=7.3, CH,), 2.07(s, 3H, CH,), 2.24(dd, lH, J=13.2, 7.3,

Major diastereomer:

Ha,), 2.69(s, 3H, CH,), 3.40(dt, lH, J=5.9, 13.2, H4’), 357(dq, OCH,), 4.21(dd,

lH, J=7.3, 9.5, OCH,), 3.85(dq, lH, J=7.3, 9.5,

lH, J=7.3, 13.2, Hjs), 5.62(d, IH, J=5.9, Hg’), 6.80(d, 2H, J=8.0, H,jj , HStt), 6.89(t, IH, J=7.3,

HS), 6.90(d, 2H, J=8.0, H,‘!, H,,‘), 7.26(d, lH, J=7.3, H7), 7.42(t, IH, J=8.1, H6), 8.41(d, lH, J=8.8, H4). Minor diastereomer: 3H, CH,),

tH-NMR (CDCI,) : 6=1.24(t, 3H, J=7.3, CH& 2.09(s, 3H, CH,), 2.55(m, lH, H4e), 2.55(s,

3.07(dt,

lH, J=7.3, 13.2, HA’), 3.63(dq,

lH, J=7.3, 9.5, OCH*), 3.86(dq,

lH, J=7.3, 9.5, OCH$,

4.18(m, IH, H31), 5.70(dd, lH, J=4.4, 7.3, HS*). 6.80(d, 2H, J=8.1. H,‘*, Hg”), 6.92(t, lH, J=7.3, HS), 6.90(d, 2H, J=8.1, Hz”, Hg”), 7.30(d, IH, J=7.3, H7), 7.42(dt, lH, J=1.5, 7.3, H6), 8.41(d large, lH, H4). Anal. Calc. for C22H23N04: C, 72.31; H, 6.34; N, 3.83. Found: C, 72.54; H, 6.42; N, 3.89.

3-[(1-Acetyl-3-oxo-2,3-dihydroindol-2-yi)(4-methoxypheny~)]propanoic Compound

3h (310 mg, 0.85 mmol) was dissolved

was added dropwise

in CH,Cl,

(4 ml). TMSOTf (0.08 ml, 0.042 mmol)

at -25 “C; mCPBA (176 mg, 1 mmol) was then added. After 1 h, the mixture was treated

with ether (20 ml) and washed with 5% aqueous sodium thiosulfate drying over MgSO, silica gel column

acid Ethyl Ester (9h).

and evaporation

under wzcuo of the organic layer, the residue was chromatographed

(eluent: CH2Clz/petroleum

yield:51% (oil). JR (film): v=1715(C=O), 2.61(s, 3H, COCH,),

(15 ml) and saturated NaHCO,.

ether 3: 1). Only one diastereomer

167O(C=O) cm-t. tH-NMR (DMSO-d6)

was obtained;

After on a

m=165 mg,

: 6=1.26(t, 3H, J=7, CH,),

3.08(m, lH, CH,), 3.54(m, lH, CH2), 3.67(s, 3H, OCH,), 4.03(m, lH, CH), 4.18(dq, 2H,

J=2.6, 7.0, OCH,), 4.91(d, IH, J=4.3, Hz), 6.69(d, 2H, J=8.6, H3’, HS’), 6.99(d, 2H, J=8.6, HT, H6), 7.15(t, lH, J=7.3, HS), 7.53(d, lH, J=7.7, H,), 7.61(t, IH, J=7.7, H6), 8.17(d large, lH, H4). Anal. Calc. for C~~H,,NOS: C, 69.28; H, 6.08; N, 3.67. Found: C, 69.54; H, 6.22; N, 3.69.

3-[(l-Acetyl-3-oxo-2,3-dihydroindol-2-yl)(4-methylphenyl)]propanoic Compound v=1725(C=O),

9i was similarly obtained

from the major diastereomer

171O(C=O), 167O(C=O) cm-t. tH-NMR

CH,), 2.48(s, 3H, CH&

2.96(m,

acid Ethyl Ester (9i).

(DMSO-d6)

of 3i; yield: 60% (oil). JR (film):

: 6=1.13(t, 3H, J=7, CH,), 2.04(s, 3H,

IH, CH,), 3.40(m, lH, CH,), 3.93(m,

lH, CH), 4.05(dq,

2H, J=2.0, 7.0,

Synthesis

OCH,), 4.SO(d, lH, J=4.3, H2), 6.75-6.85(m, H7), 7.47(t,

999

and oxidation of pyrano[3,2-blindoles

4H, H2,, H,,, H,!, H6’), 7.0l(t,

lH, J=7.3, Hg), S.OO(d large, IH, H4). MS (U/NH,)

IH, J=7.3, HS), 7.39(d, lH, J=7.7,

: m/z=366

(M + I)+. Anal. Calc. for

C22H23N04: C, 72.31; H, 6.34; N, 3.83. Found: C, 72.46; H, 6.22; N, 3.91.

l-Acetyl-2-[3,3-diethoxy-l-(4-methylphenyl))propyl]-2,3-dihydroindol-3-one The cis diastereomer

of 3i (100 mg, 0.287 mmol) was dissolved

(lOi).

in ethanol (20 ml) and BF3.Et20

ml, 0.285 mmol) was added and the mixture stirred at reflux for I h. Evaporation which was treated with aqueous NaHC03 dried over MgS04 and evaporated CHzCl$petroleum

(DMSO-d6) : 6=1.12(t, 3H, J=7.0, CH$ 3H, COCH,),

of the solvent leaves a residue

(25 ml) and extracted with CH2C12 (25 ml). The organic layer was

in vacua. the residue was chromatographed

ether 5: I); yield:42mg

(0.035

on a silica gel column (eluent:

(40% ); oil. JR (film): v=l705(C=O), l.l4(t,

167O(C=O) cm-t.

t H-NMR

3H, J=7.0, CH& 2.03(s, 3H, CH& 2.20(m, IH, CH,). 2.39(s,

2.5S(m, lH, CH,), 3.30-3.70(m, 5H, 2xCH2, CH), 4.57(d, IH, J=4.4, Hz), 6.7l(d, 2H, J=S.l, H3’,

HS’), 6.79(d, 2H, J=S.l, H,,, He,), 6.89(t, IH, J=7.3, HS), 7.3l(t,

IH, H6, J=7.9), 7.37(d, lH, J=7.3, H7), 8.20(d

large, IH, Hb). MS (CJ/NH3) : m/z=396 (M + l)+. Anal. Calc. for C24H,,N04:

C, 72.89 H, 7.39; N, 3.54.

Found: C, 72.70; H, 7.55; N, 3.37.

3-[(1-Acetyl-3-oxo-2,3-dihydroindol-2-yl)(4-methy~phenyl)]propanal

(lli).

The cis isomer of 3i (120 mg. 0.344 mmol) was dissolved in a mixture TFA-H@THF

(4 mU2.5 mU2.5

ml) and the mixture was stirred 1 h at 25°C. Ether (20 ml) was then added followed by a solution of saturated NaHCO,;

the two layers were separated

and the organic layer was dried over MgS04.

vacua, the residue was chromatographed

on a silica gel column (eluent: CH,Cl,);

(film): v=1715(C=O),

tH-NMR

3.17(m, IH, CH$,

167O(C=O) cm-l.

(DMSO-d6)

After evaporation

yield:7lmg

in

(63%); oil. JR

: 6=2.05(s, 3H, CH,), 2.5 I(s, 3H, COCH&

3.54(m, IH, CH,), 4.05(m, lH, CH), 4.77(d, lH, J=4.7, Hz), 6SO(d, 2H, J=S.S, H,‘, Hs’),

6.83(d, 2H, J=S.S, H2’, H6’), 7.02(t, IH, J=7. I, H5), 7.40(d, lH, J=7.9, H7), 7.4S(t, lH, J=7.9, H6), S.O2(d broad, IH, HJ), 9.70(s, IH, CHO). Anal. Calc. for C,oHtgNO,:

C, 74.75; H, 5.96; N, 4.36. Found: C, 74.56; H, 5.81;

N, 4.49.

5-Acetyl-2-henzyloxy-4-(4-methoxyphenyl)-3,4,4a,9b-dihydro-2~-pyrano[3,2-~]indole Compound

3a (major diastereomer)

(10 mg) was introduced.

cm-t.

tH-NMR

in MeOH (6 ml) and Pd/C 10%

The mixture was stirred 8 h under a hydrogen atmosphere

filtration on celite and evaporation, Only one diastereomer

(90 mg, 0.21 mmol) was dissolved

(12a).

the residue was chromatographed

at room temperature.

on a silica gel column (eluent: CH,CI,).

was obtained; yield:38 mg (37%) mp=14S”C (ethanol/HzO).

(DMSO-d6)

: 6=1.63-l.Sl(m,

3.72(s, 3H, OCH,), 4.54(d, lH, J=l2.0,

2H, CH,),

After

1.74(s large, 3H, COCH,),

OCH,), 4.85(dd, lH, J=5.1, J=S.6, H&,

JR (KBr): v=l66O(C=O) 3.22-3.3l(m,

4.95(d, IH, J=l2.0,

IH, H4), OCH&

J.-Y. MBROUR et al.

I 000

5.10(t, IH, J=5.1, H,), 5.92(d, IH, J=8.6, Hgn), 6.86(d, 2H. J=8.6, H3’, Hgs), 6.98(t, IH, J=7.7, H7) , 7.06(d, 2H, J=8.6, H,,,H,O, 7.20(t, lH, J=7.0, Hx), 7.257.38(m,

SH, Harom), 7.42(d, lH, J=7.7, H9), 7.88(d large, IH, H6).

: m/z=430 (M + I)+. Anal. Calc. for C27H27N04: C, 75.50 H, 6.34; N, 3.26. Found: C, 75.37; H,

MS (CVNH$ 6.16; N, 3.40.

S-Acetyl-2-hydroxy-4-(4-methoxyphenyl)-3,4,4a,9b-tetrahydro-2~-pyrano[3,2-~]indole Compound

(13a).

3a (710 mg, 1.66 mmol) was dissolved in presence of Pd/C( 10%) (700mg) in MeOH (23 ml)

under a hydrogen atmosphere

of at room temperature.

After 8 h the mixture was filtered and evaporated;

obtained solid was washed twice with ethyl acetate (2 ml). Two diastereomers yield:240 mg (42%). mp=214 “C (mixture of diastereomers). Major diastereomer:

)H-NMR (DMSO-d6)

: 6=1.60-1.75(m,

were obtained in the ratio 1:2;

IR (KBr): v=3280(0-H),

163O(C=O) cm-t.

IH, H3), 1.77(s large, 3H, COCH,),

J=6.6, 14.0, H3), 3.66(s, 3H, OCH,), 3.68(m, IH, H4), 4.83(t, IH, J=8.1, H,,), 4.93(m, J=8.l, H&,

the

2.04(dt, IH,

IH, Hz), 5.63(d, IH,

6.73(d, 2H, J=8.8, H,,, HSa), 7.03(m, IH, H7), 7.05(d, 2H, J=8.8, Hz’, H6#), 7.24(t, IH, J=8.1, Hs),

7.32(d, IH, J=7.35, H9), 7.80(d large, IH, Hg). Minor diastereomer:

i H-NMR (DMSO-d(1) : 6=1.60-l .75(m, 2H, CH,). I .77(s large, 3H, COCH,), 3.27(m, I H,

H4), 3.69(s, 3H, OCH,), 4.78(dd, IH, J=5.1, 8.8, H&,

5.19(m, IH, Hz), 5.78(d, lH, J=8.8, Hgh), 6.79(d, 2H,

J=8.8, H,,, HS’), 7.03(m, IH, H7), 7.08(d, 2H, J=8.8, Hz*, He’), 7.19(t, IH, J=S.l, Hx), 7.37(d, IH, J=7.3, Hg), 7.85(d large, IH. H6). Anal. Calc. for C2uH2,N04:

C, 70.78; H, 6.24; N, 4.13. Found: C, 70.65; H, 6.15; N,

4.27.

5-Acetyl-2-hydroxy-4-(4-methylphenyl)-3,4,4a,9b-tetrahydro-2~-pyrano[3,2-~]indoie Compound

3b was treated as described

for compound

l:2); yield:40%, mp=210 “C (mixture of two diastereomers). Major diastereomer:

IH-NMR (DMSO-d6)

(13b).

13a and two diastereomers IR (KBr): v=3280(0-H),

were obtained

1630(C=O)cm-t.

: 6=1.60- I .75(m, IH, H3), I .69(s large, 3H, COCH,),

J=6.6, 14.7, H3), 2.20(s, 3H, CH,), 3.68( m, IH, H4), 4.84(t, lH, J=8.7, H&, J=8.7, Hgn), 6.46(d, IH, J=4.4. OH), 6.94-7.lO(m,

(ratio

4.91(m,

2.04(dt, I H,

IH, Hz), 5.64(d, IH,

5H, Hz,, H,,, H,,, He,, H7), 7.33(d, lH, J=7.3, Hy), 7.34(t,

lH, J=7.7, Hg), 7.82(d broad, lH, H,). Minor diasteromer:

rH-NMR (DMSO-d6)

CH,), 3.25(m, IH, H4), 4.78(dd, J=3.7, OH), 6.94-7.10(m,

:6=1.60-1.75(m,

IH, J=5.1, 8.7, H&,

2H, CH,),

1.69(s large, 3H, COCH3), 2.24(s, 3H,

5.23(m, IH, H2), 5.79(d, IH, J=8.7, H,h), 6.47(d, IH,

5H, Hz’, H,,, H,‘, H6,, H,), 7.34(t, IH, J=7.7, Hs), 7.37(d, IH, J=7.4, Hg), 7.83(d

large, IH, He). MS (WNH,)

: m/z=324 (M + I)+. Anal. Calc. for C,oH,,N07:

Found: C, 74.40; H. 6.38; N, 4.24.

C, 74.28 H, 6.55; N, 4.33.

Synthesis

and oxidation of pyrano[3,2-hlindoles

1001

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The configuration

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Z has been attributed

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18 I - 186.

according

to 2D NMR NOESY

experiments

The structure cis of the major diastereomer

16.

The configuration

of 3h has been precedently

wrongly attributed as truns.5

213~1~ of l-acetyl-2-benzylidene-2,3-dihydroindol-3-ones

the IH-NMR spectra and more particularly

has been attributed

the chemical shift of the CH,CO

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in acetone-d6

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15.

examining

1750-1756.

An, Z.W.; Catellani, M.; Chiusoli, G.P. J. Organomet. Chem. 1990,397, C31-C32.

by

at 1.94 ppm

J.-Y. MBROUR et al.

1002

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We thank one of the referees for suggesting this mechanism

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(Received in Belgium 25 July 1996; accepted 6 November 1996)

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