α-Methoxy-Benzylmetals : Original Synthesis and Reactivity

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TetrahedronL.utters,Vol. 38, No. 35, pp. 6289-629o, 1997 @ 1997Publisbed by E1sevierScience Ltd All rights reserved. Printed in Great Britain 0040-4039/97$17,00 +0.00 P11so040-4039(97)01410.x

Pergarnon

u-Methoxy-Benzylmetals : Original Synthesis and Reactivity Alain

Krief* and Jamai Bouabaa

Departmentof Chemiatry,Facult6sUniversitaires Notre-Dame dela Paix,61ruede BruxelleaB-5cX30, NAMUR(Belgium)

Abstract: Although I-methoxy-l -methylseleno-toluene is efficiently metallated by KDA, the same compound as well as its higher homologies react with t-butyllithium producing 1-methoxy benzyllithiumsvia the C-Se bond cleavage.These speciesare efficientlyalkylatedby alkyl halides, even the secondary ones and react with THF in the presence of BF3-0Et2 to produce the homologated tatrahydropyranderivative in good yield. 01997 Published by Elsevier Science Ltd.

a- Methoxyalkyl selenides proved to be useful compounds in synthesis allowing, by cleavage of their C-Se bond, the productionof a-methoxyalkylradicals,-cationsand -anionsand of vinyl ethersvia selenoxideelimination reaction.l The presence of a methoxy substituent on the carbon directly attached to the selenium atom in selenides usually inhibits both the H/Li and the C/Se exchange by lithium amides2a or alkyllithiums2b-drespectivelywhich would have led to a-methoxy-a-seleno-alkyllithiums and to a-methoxy-alkyllithiums. The synthesis of the later derivatives was neverthelessachievedlb,d using arenyllithiums,especiallyLiDBB. We now report that I-methoxy-l-methylseleno-toluene 1,which possessesan extra phenyl stabilizing group, is metallated by KDA in THF (1eq., -78°C, 1h) providing 1-methoxy-l -methylseleno-benzylpotassium 2, almost quantitatively.This one is stable at -78°C and reacts efficientlywith a large variety of electrophiles including epoxides and organic halideseven the sec-alkyl-,benzylic-and allylicones (Scheme1). Scheme 1

+=””

KOA,THF,-78”C,Ih

H

1

OMe

d I ‘+ae”a K 2

Entry

E’

a

Me3Si-Cl

Ms$3i

E

b

Oxidopropene

CH2CH(OH)Me

c

mPentyl-Br

rkPentyl

d

i-Propyl-l

i-Propyl

e

PhCH2.Cl

PhCH2

f

AllyI-l

Allyl

(ft E’,THF,-7SSC,0.5

(11)-7Sto zo~c

~wms”””

E

s Product 3a 3b 3C 3d 3e 3f

Yieldin3 08 72 77 9s 98 7.3

l-Methoxy-l -methylseleno toluene 1 also reacts with butyllithiums. Best conditions involve the addition of 1 to a precooled solution of t-butyllithium in THF (-78°C, lh) to provide the a-methoxy-benzyllithium4 by selective cleavage of the C-Se bond (Scheme 2).3 Further alkylation, benzylationand ailylationof 4 delivers 5 in high yield besides trace amount (< 5%) of 6 (Scheme2). ...-—-...-—--------------------------Dedicated Professor D. Seebach at the occasion of his 60th Birthday with great appreciation for his fundamental contribution to Organic Chemistry.

6289

6290

Entry a b c

E’ PhCH2-Cl n-Pentyl-Br Me3Si-Cl

Product Se 5C 5s

E PhCH2 n-Pentyl Me3Si

Yieldin5 86 95 85

It must be recalled that the presenceof an aryl substituenton the a-alkoxyalkylselenide is crucial for the successof this reaction.3b The reaction of t-butyllithium has been successfullyextended to homologous I-methoxy-l -phenyl-l methylseleno-ethane 7 and the resulting organolithium 8 has been reacted with a large variety of electrophiles to produce functionalized methoxy-arylalkane9 in high yields (Scheme 3). It is worthwhile to mention thst the reaction conditions are so smooth that products resulting from the well known Wittig rearrangement of the intermediate amethoxy-benzyllithium8 were never observed.4 Scheme 3

Ph Me

4

SeMe

keuLi, THF, -78QC,1 h

Me

-[

7

Entry a b c d e f

Ffll.i +

E’ Me3Si-Cl Oxidopropene n-Pentyl-Br s-Butyl-Br PhCH2-Cl Allyl-Br

s

oMe 1

Me

E Me3Si CH2CH(OH)Me n-Pentyl s-Butyl PhCH2 Allyl

(i) E’, THF, -78-C, 0.5 h > (11)-78to 25--C

Product 9e 9b 9C 9d 9e 9f

O“e ~

E

+ Me 9

Yieldin 9 100 97 S5 86 90 77

a-Methoxy-benzyllithium 8 does not react, under the experimentalconditions used above, with THF. Nevertheless ring opening of this heterocycle has been efficiently achieved in the presence of boron trifluoride etherate used as Lewisacid catalyst (Scheme4). The resulting &-methoxy-alcohol10 has been successfullycyclised,in acidic media, to the corresponding tetrahydropyran 11 (Scheme 4). In the above five to six membered heterocycle homologation reaction, I-methoxy-l -phenyl-l -methylseleno-ethane7 has played the role of a methyl phenyl carbene.l d Scheme 4

REFERENCESand NOTES 1. (a) Clive, D. L. J.; Yang, W. Chem. Commwr.1996, 1605(b) Krief, A.; Nazih,A.; Hobe, M. TetrahedronLetf. 1995, 36, 8111 (c) Tingoli, M.; Temperini, A.; Testaferri, L.; Tiecco, M. Syrr/ett 1995, 1129 (d) Krief, A.; Hobe, M.; Badaoui, E.; Bousbaa, J.; Dumont, W.; Nazih,A. Syrr/eft1993, 707 and referencescited. 2. (a) Reich, H. J.; Chow, F.; Shah, S. K. J. Amer. Chem. Soc. 1979, 102, 6636 (b) Seebach, D.; Meyer, N.; Beck, A.K. Liebigs Ann. Chem. 1977, 846 (c) Anciaux, A.; Eman, A.; Dumont, W.; Van Ende, D.; Krief, A. Tetrahedron Lett. 1975,1617 (d) Goldsmith, D.J.; Liotta, D.C.; Volmer, M.; Hoekstra, W.; Waykole, L. Tetrahedron 1985, 41, 4873. 3. (a) These conditions are by far more efficient than those involving instead n-or s-butyllithiums which are less chemoselective and offen lead to irreproducible resultsld (b) For unsuccessful reactions involving the parent compound or a-alkylated derivatives.2b-d 4. Tomooka, K.: Nakai. T. J. SvrrthOru. Chem. tbn 1996.54, 1000 (b) Nakai,T.: Mikami. K. OraarricReaction 1994, 46, 106 Paquette, L. A. ed.’John wily & Sons, Chichester (c) Marshall, J~A.‘Comprehensiv~ Organic Synfhesis 1991, Vo/3, 975, Trost, B.; Fleming, L; Pattenden,G. Pergamon Press,Oxford.

(Receivedin UK 18June 1997;accepted11 July 1997)