Tetrahedmn Lams. Vo1.31, No.9.p~ 1271-1274.1990 PhtdilIonUBtitGI

oo4o-m9l90 $3.00 + .oo eergamm Press pk

IJNIJSUAL 1,24416RATION IN OR6ANOALlMINIlM CHEMISTRY,

PROm)TED BY BF3.0Et2.'

Alex Alexakis* , Jezia Hanaizi, Denis Jachiet, Jean-F. Normant

Laboratoire de Chimie des Clrgano616ments, associi au CNRS (UA 473) Tour 44-45 Universiti P. et M. Curie, 4 Place Jussieu, F-75005 Paris

Loic Toupet

Laboratoire de Physique Cristalline, Universiti de Rennes Campus Beaulieu, 35042 Rennes, France

Abdaact. Lithium cLd.g&opyanyl on dihyd/Lo&anyl tioqanoa4uminafezl neact with cyclohexene LF .0&i

oxide 04 benpldehgde in Me puence o,?Z not 09 nuc.LeopL!ic a&a& 20 a[fTond pnsduct I, but bg I,2

mi&z.t& OC a mbntieni ,?nom A! 20 the O(-cwzbon, with WrKomitcuLt neackion with fhe eCect/rophile on fhe k-canbon, giving n&e ito pwxiuct .?

We have recently described the BF3 promoted opening of epoxides by R2CuCNLi2*

reagents. and R4A1Li3

In the course of these studies we were interested by the use of acyl anions

equivalents as nucleophiles. Ganem reported the reaction of O(-ethoxy vinyl lithium with

cyclohexene oxide, in the presence of BF34. The analogous reaction with the lithium anion

of dihydropyran, however, failed completely in our hands. Turning to the cuprate reagent

proved also unsuccessful. Finally the alanate reagent reacted smoothly, but gave a totally

unexpected product :

This new product, obtained in 78% yield, was identified as 2. In the absence of BF3.0Et2

no reaction at all takes place. No trace of the normal product 1 was detected. Moreover,

although 2 possesses four stereogenic centers, only two diastereomers, 2A and 28 were

observed, in a 78122 ratio. The two isomers could be separated by column chromatography

and the structure of the major one, 2A (the less polar), was fully characterized by X-ray

crystallography. 28 differs from 2A only the different relationship5.

1271

1272

X-ray structure of 2

The formation of 2 can be accounted for by a 1,2-migration of a methyl group from

aluminium to carbon. In contrast to the usual 1,2-migration in organoboron chemistry6

where the adjacent leaving group is expelled, we observe here an electrophilic attack on

the epoxide :

40 4

5

That we end

folowed by

position.

Y Me/ Me

up with a new organometallic reagent, was demonstrated by deuterolysis (MeOO,

020) which gave deuterated 2( > 95% deuterium incorporation) in the C-l

Such a 1,2-migration is quite unexpected in organoaluminum chemistry 6b,7 . To our

knowledge, only three other examples have been reported*. A closely related migration, but

without concomitant trapping of the electrophile, was also recently reported by Kociensky

et& with mixed alkyl dihydropyranyl cuprates9.

This unusual reaction occurs also with aldehydes. In the absence of 8F3.0Et2 no reaction

takes place, although Z-lithio dihydropyran reacts normally :

OH

1273

3 is obtained as a mixture of only two diastereoisomers (58/42) though four of them are

theoretically predictible. Attempted reactions with acetals or methyl iodide gave

intractable mixtures or no reaction at all.

On the other hand, among the other metallated enol ethers, only dihydrofuran reacted in

the same manner as dihydropyran. The reaction with cyclohexene oxide is even more highly

diastereqselective. It is also possible to transfer other groups than Me if other

triorganoaluminium reagents are used5.

R-AIR’2

Li 00 I

0 -zJJ-J+!PJ--J R’=Me R : Me 4 91 9 55%

R’ = iBu R : iFlu 5 86 14 46%

R’ = iBu R : Pent& 6 89 11 37%

The obtention of 5 is quite remarkable since it is known that i&r-Al< is split off into

isobutene and H-Al< in the presence of a Lewis acid such as BF3 3,6b

. We did not observe

any product where R is H. On the other hand the formation of 6 is expected in light of the

normal transferability order in organoaluminium chemistry 6b,lO . In the case of an alkynyl

group (from Pent-CHC-A1Me2) or a hydride (from M-AliBu2) less than 10% of the wished

product is obtained.

The yield of these last experiments is lower, than in the dihydropyran series. ln fact the

major by-products are ring-opened derivatives, exactly as it happens in organoboron

chemistry6. This ring-opened product 7 is the sole observed when, BF3,0Et2 is added in the

absence of any electrophile :

.-+ i-~e~~is i-8U~~H 46% BFj.OEl2

Al - i-Bu 1

i-Bu I i-Bu

ln such a reaction, Kocienski obtained higher yield with Cu in place of A19.

The new reaction disclosed herein seems, thus, more efficient with pyrans with than

furans. It may find many applications in more functionalized dihydropyrans where the high

diastereoselectivity in the formation of two new carbon-carbon bonds is useful.

1274

Typical prodedure for 2 : A solution of 2-lithiodihydropyran (15 mmol) is prepared

according to ref. 11 in a mixture of THF (3 ml) and pentane (II ml). After cooling to

-78“C, Me3A1 is added (15 mmol, 6.3 ml of a 2.38 M solution in hexane), followed by Et20

(20 ml). A clear solution is obtained at -20X. This solution is cooled again to -7fl'X and

cyclohexene oxide (0.98 g, IO mmol) in Et20 (20 ml) is introduced, followed by dropwise

addition of BF3.0Et2 (1.26 ml, 10 mmol) in Et20 (IO ml). The reaction is exothermic, and

kept around -60% for 30 mn. Methanol is added (IO ml), the solution stirred 1 h at 0°C

and finally aqueous NaOH (6 ml of a 10 N solution) is introduced. After stirring for 1 h

at room temperature, the mixture is partitioned, extracted with Et20 and worked up 12

normally. Flash chromatography on Si02 (cyclohexane : Et20 = 1 : I) gave 1.2 g of 2A and

356 mg of 28.

References and Notes :

I)

2)

3)

4)

5)

6)

7)

8)

91

This work was presented by A. Alexakis at the Royal Society meeting "The influence of

Organometallic Chemistry on Organic Synthesis : Present and Future", London, 24-25

Feb. 1988. The proceedings of this meeting were published in : Phil. Trans. R. Sot.

Lond. A 326 (1988) 557 --

a/ Ghribi, A. ; Alexakis. A. ; Normant, J.F. : Tetrahedron Lett. (1984) 25 3075 - b/ Alexakis, A. ; Jachiet, 0. ; Normant, J.F. : Tetrahedron (1986) 42 5607

Alexakis, A. ; Jachiet, 0. : Tetrahedron (1989) 45 6197 - Eis, M.J. ; Wrobel, J.E. ; Ganem, B. : J. Am. Chem. Sot. (1984) 106 3693 - For sake of conveniance, only one enantiomer is shown. The numbering of carbons is the

crystallographic one. The structure of the minor isomer 26

spectroscopy ('H, 13C, COSY, NOISY).

a/ Cragg, G.M.L. : "Organoboranes in Organic Synthesis", Marcel

1973

b/ Negishi, E.1. : "Organometallics in Organic Syntheses", John

New York, 1980

c/ Levy, A.B. ; Schwartz, S.J. : Tetrahedron Lett. (1976) 2201

d/ Suzuki, A. : in "Topics in Current Chemistry" p. 67, Vol.

1983

was assigned by NMR

Dekker Inc., New York,

Wiley 5 Sons,

112, Springer Verlag,

Mole, T. ; Jeffery, E.A. : "Organoaluminium compounds", Elsevier, Amsterdam, 1972

a/ Hoberg, H. : An g Chem. lnt. Ed.'Engl. (1966) 2 513 .

b/ Negishi, E.I. ; Akiyoshi, K. : J. Am. Chem. Sot. (1988) 110 646

c/ Miller, J.A. : J. Org. Chem. (1989) 54 998 - a/ Kocienski, P. ; Wadman, 5. : J. Am. Chem. Sot. (1989) 111 2363 - b/ Kocienski, P. ; Dixon, N.J. : Synlett (1989) 52

IO) Zweifel, 6. ; Miller, J.A. : Org. Reac. (1984) 23 375

II) Boeckman, R.K. ; Bruza, K.J. : Tetrahedron (1981) x 3997

12) The crystallographic data have been deposited with the British Document Supply Centre

as supplementary publication.

(Received in Fmncc 13 November 1989)