Iodine-induced cyclisations of (E )- and (Z )-3-hydroxy-5-alkenoates: Stereoselective approaches to trisubstituted tetrahydrofurans

Tehahedrcm Letlcrs.Vol. 33. No. 43. pp. 6507-6510.1992 Priited in Great Britain

00404039/92 $5.00 + .OO

Pcrgamon PressLid

IODIRE-DUDDCRD CYCLISATIONS OF @)- NUD @&3-RYDROXY-tULRENOA~

-

AFFROACRESTOTRIS~D~ROFtJRAR8

Frank Bennett.* Simon B. Bedf~rd.~ Kathryn E. J3e.ll,eGany Fent0n.b David W. Knight a* and Duncan Shwp

a Department of Chemistry, University Park, Nottingham, NC7 2RD. UK. -one-Poulenc-Rmer.

M#tmct:-

Central Research, Dagenham. Essex, RMlO 7XS. UK.

Iodoether@cation of lhe (Z)-3-hydroxy-5-alkenoates’

tetr&ydrofirans

8 whereas similar cyclisalfons

hfgefythefod&eirahgd@iians

111.14 and 161.

In the foregoing paper.1 we report that iodine-induced lead. somewhat

4 leads exclusiuely to the h&&W-

of the wrresponding @I-isomers110.IS and 151 glw

une.xpectedly.2 to the tram+disubstltuted

transitlon state 2 wherein the stereochemistry

cyclisations

of 3-silyloxy-5-hexenoic

valerolactones

3. probably

acids 1

ufa a chair-like

of the cycllsation is controlled by. hydrogen bonding between

the carboxylate function and the sflyloxy group.

3

2

1

During these studies. it was obsexved that very small quantities which appeared to be tetrahydrofurans:,

involving loss of the sllyl group. In order to try and maximize related cyclisatlons

of the corresponding

[> 5961of byproducts

were formed

it seemed likely that these weie. formed by a 5-endo-trig process such transformations,

melhyl 3-hydroxy-5-hexenoates.

we have examined

The methyl ester fun&ton was

used as this was expected to prevent lactone formation while the free hydroxyl group should favour THF formation. Herein. we report the unexpected outcomes of such cyclisatlons. When the methyl (ZJ-3-hydroxy-5-alkenoate 13 eq.] in dry acetonitrlle

4a 1 was exposed to iodine 13 eq.] and sodium bicarbonate

at -5 - 0°C for 6Oh. the hydrawy-tetrahydrofuran

6507

Sa 2 was isolated,

following

6508

column

chromatography,

tetrahydrofurans. acetonttie

in 85% yield.

The cyclisation

[l:l].

accompanied

was relatively

the hydroxy-tetrahydrofuran

and Sphenethyl-hydroxy-tetrahydrofurans

by no more than traces

insensitive

to the presence

of less polar

of water:

3-lodo-

from aqueous

Sa was isolated in 70% yield. The corresponding [Sb,c] ’

respectively]. in each case as single diastereoisomers.

were

isolated

in similar

yields

5-ethyl-

187% and

7096

However, yields were much loweT from cyclisations of

the corresponding butyl and benzyl esters [CCL. 30% and 10% respectively].

b)R=Et

&,NfiCO3

CO,Me

COzMe

CH3CN 4

c) R= PhKX$&

5

The structures of these products were proven by the usual spectroscopic while the stereochemistry

and analytical techntques.

was determined largely by NOE studies. The assignment of stereochemjstry

also consistent with those of a related series of trisubslltuted

4-benzoyloxy-tetrahydrofumns.

was

reported by

Williams and his colleagues,3 based upon chemical shift data. For this, we converted the initial pnxluct 5a into the con;esponding benzoate 6.2 [PhCOCl, py] and also into the epimeric benmate 7 2 by a Mitsunobu reaction phCO,H.

PP$.

Et02CN=NC02Ell.4

Both esters exhibited spectral data In line with the Williams

assignments. as well as appropriate NOE data. PhC0.q

PhC0.q Bu

oFCO#e

,,,,a

+,,,,,CO#e 6

7

We next examined coupling the epoxy-ester

cyclisalions

8

of lhe corresponding

9 with vInylaluminium

9

(E)-3-hydroxy-5-alkenoates

‘ate’ complexes

derived from the 1-alkynes 9.’

surprise. these underwent cyclisation under slmllar conditions 13 eq. 12. 3 eq. NaHCO,. rapidly [clh. O’C] and lead instead to the iodo-tetrahydrofurans case, the cycllsations epimerk

were hlghly stereoselecllve:

iodo-tetrahydrofuran,

To our

CH3CN] but more

11 2 in excellent isolated yields. In each

each product was a&ompanied

the slereochemislry

10, obtained by

of which was establlshed

by ~12% of a second

as the 2.5&s

ephners 12.

according to nOe measurements and coupling constant data. The cyclisations water,

although

cyclisations

of the trans-hydroxy-esters

slightly

better

yields

[5-lo%]

10 were also relatively insensitive were realized

when

are somewhat surprising as, In general, such electrophilk

dry acetonitrile

to the presence of was used. These

cyclisations of homoallylk

alcohols

6509

with the notable

give very poor yields of tetrahydrofurahs.5 These types of cycltsation

are formally unfavourable

exception

5-en&-trig

of phenylseleno-ethertftcattons,5~6

processes,

which is consistent

I

CO,Me b “““‘:

I al R - Bu f.+74%1 b)R=Et [8’7%1 c) R = F’b(CH& E%l I d) ti = (cRi,,oTBDps COzMe [f=%l

R.,.,,

C%a 11

10

with the

n

R,“,. h0

%,,COaMe

12

0

-

%

COzMe

I

COgMe

generally poor yields obtained.

cyclisations.

trans-iodo-THF conditions,

The cationic

14 2 was Isolated

stereoselective

nature of the reactions

however, means that they cannot really

Two further examples emphasize

explained by assuming

iodonium

ion prior to cyclisation.

especially

the hydroxy-acid

[lo.

the absence

of such reactions

of which appears

iodo-THFs

would be expected to produce

penultimate

telrahydrofurans.

iodolactonisation

In the

of water Is

of the intermediate 15 and

of the hydroxy-ester

[14 and 161 are also consistent particularly

latter

case,

stable carbonium the ‘perhaps

with this ions as the

more

expected

l would result In an eleclron deficient cenlre 6- and not a-to the phenyl ring.

The cychsations rationalized.

of the hydroxyl

to the presence

to allow hydration

leading lo an iodohydrin. 5 The cyclisalions

lb to the corresponding

to the

13 and 151 can be

state 17. This features activation

model as both of these substrates precursors

under the same

by hydrogen bonding with the ester group, in much the same way as the

were directed. 1 The insensllivity

with such an activation,

only the

lactone.s

of the tram

of the transition

in acetonitrile.

15 was reacted

in 65% yield. When the hydroxy-acid

the intermediacy

iodo-lactonisations

consistent

the cationic nature of such

13 was treated with iodine and bicarbonate

cyclisations

function with respect to cyclisation foregomg

16

the iodo-THF 16 2 was formed, ralher than the corresponding

The highly

COaH

15

as exceptions to Baldwin’s rules.’ When the hydroxy-ester

I

COzH

14

13

be considered

Ph

of the (Z)-isomers

leading

Our initial idea that they arose

THF were proven incorrect

to the hydroxy-tetrahydrofurans

da an S,2

displacement

ether, which are well known to be relatively unreactive. from the alkenoates of the hydroxy-THFs

of the corresponding

when a small sample of the lalter was unchanged

conditions. In any event, this is an unlikely displacement,as

4, decomposed 5. Therefore,

the electropbile

we were lead to consider

all-c& iodo-

can be regarded as a p-iodothe epoxtdes

to a mixture which contained

the involvement

so easily

when exposed to the reaction

Other llkely intemlediates.

under, the reaction conditions

are not

derived

only traces

of the ester function

in the

cycltsatton If it Is assumed that the the transltion slate 18 istoo crowded. then attack by the ester group on the iodontum function in conformatlon 19 would lead to the stabilized carbonturn ion 20. ll-apping by water would then lead to the orthoester 21 and thence to iodo-dlol22. cyclisat@n offwhich could again be as&ted by tntramoIecular hydrogen bonding. 1 When a cyclisatlon of the (Z)-alkenoate 4a was worked up atter 3h. a compound correspondmg [‘H NMR ir] to the iodo-dlol[22: R = Bun] was tsolated admked wtth the THF Ea. whtch was completely converted tnto the latter upon exposure to only sodium bicarbonate in acetonttrtle.

I

As the starting hydroxy-alkenoates 4 and 10 are available in optlcally active forms1. the foregoing reactions should be applicable to the elaborallon of chlral trisubstltuted tetrahydrofurans: efforts to exploit and extend these in target synlhesfs are in progress. We are grateful to Dr. I Fleming and Professor T. Ltvinghouse for helpful comments and to Rhone-PoulencRarer and the SERC for financial support under the CASE scheme. REFERENCES 1.

S. B. Bedford. G. Fenton, D. W. Knight and D. Shaw. precedhgpaper.

2.

Sattsfactory analytical and spectroscopic data were obtained for this compound.

3.

D. R Wtlllams. Y. Harlgaya.J. L. Moore and A D’Sa, J. Am. Chem. Sot.. 1984.106.2641.

4.

0. Mttsunobu. S@Jtesfs. 198 1.1.

5.

S. B. Bedford. K. E. Bell, G. Fenton, C. J. Hayes. D. W. Knight and D. Shaw,fbUowfngpaper.

6.

K. C. Nicolaou. Tetmheclmn 1981. 37.4997 and references therein; S. H. Kang. T. S. Hwang. W. J. K&n and J. K. Mm. TefmhaironLeU.. 1991. 32, 4015. and references therein.

7. 8.

J. E. Baldwm. J. Chem. Sot.. Chem Commun.. 1976,734. For a related example of such a cyclisatlon of a hydroxy-acid, see and J. G. Macmtllan, J. Am Chem. Sot.. 1989. 111.3712.

(Received in UK 23 July 1992)

M.

J. Kurth. R L. Beard, M. Olmstead