Palladium-Catalyzed Intramolecular α-Arylation of Aliphatic Ketones

4!!9

pp.

Vol.

Pergarnon

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PIISO040-4039(97)01787-5

Palladium-Catalyzed Intramolecular ct-Arylation of A1iphatic Ketones

ResearchFoundationItsuuLaboratory 2-28-10Tamagaw~Setagaya-ku,Tokyo158,Japan

10 mol%ofPdCl(Ph3P) in the presence of 3 q of Cyclizstion reactionof 5 — 10 C~CO~inhotTHPortolueneafforded bridged orSPUOmrpmmdsfl — ~c in tl~ to mod~t Yiel*. @21

EIsevier Science Ltd.

In the precedingpaper,we reporteda newprocedurefor preparationof heteroarornaticphenolderivatives using a palladium-catalyzedintramolecularcyclizationreactionof 1 to form 2 ‘ This reaction comprizesa s constitutes an coupling reaction between an aryltriflate and a methyl ketone functionality, and intramolecularversionofthe ct-arylationreactionof alphaticketones,whichhasbeenwidelystudied.2’3In view of the high yield conversionof 1 to 2 w sttied extensivestudiesto explore applicabilityof our reaction conditionsto a generalreaction,3 to 4. In the literatures,thesetypesof intramolecularreactionswerereported by Sakan,~ Semrnelhack,2b,kand most rwent]y by Snider~d TfO N {r

1

I o

PdC12(Ph3P)2

CS2C03 Ph3P .{$ benzene reflux

h /

2

d~d

OH

3

4

For the cyclizationreactionof 5-10 (Table),suitableconditionswerefoundto be heatingofa substrate in tolueneor THF in the presenceof 10mol%of PdC12(Ph3P)2 and 3 eq. of CS2C03underan Ar atmosphere. Additionof Ph3Pwas unneccesary. 2-Bromobenzyl-substituted cycloalkanones5,6, and 7 affordedbridged compounds and 13, whereascycloalkartones8–10having2-bromophenethyland 3-(2-bromophenyl)1 propylsubstituentsaffordedspiroderivatives14– 16. Amongthesereactionproducts, obtainedin goodyields(entries2, 3,4, and 5). Whenthereactiongavetheproducts115and 16in onlymodest yields,considerableamountsof debrorrtocompounds17and21 wereproducedas by-products(entries1 and6). Occasional enones18and 20 wereobtainedin traceamountsas by-products. Probablythesewete formedby palladium-catalyzeddehydrogenationof theketonederivatives.In entries1 and4, inseparablereacdonmixtures of and 17,and 14 and 19 wereonceconvertedintomixturesof ethyleneacetals,followedby separationand acidhydrolysisto give pure 11 and 14. Generallyspeaking,ourreactionconditionsusinga palladiumcatalyst and CS2C03workedwellfor the cyclizationof 3 to 4.

7581

7582

Table CylizationReactionwith 10mol%PdCl+Ph3P)2and 3 eq. of CS2C03underAr Atmosphere Entry

Solvent Temp. Time

substrate

‘a 2

TI#

6’

3

4

16h

T#

100”C 13h

TH#

100”C 14h

TH#

100”C 14h

07

, :’ &

0

8

Yield

Product

d,1

0

I C@

0

26%

o

O

19%

17 0

61%

& , I &

m

11

,471%

0!?0

18

d“

19

2%

2%

Br

5

6

d

1 h

reflux

&

9

0

TI#

&

8 I

1 o

100”C 14h a

a: Ina sealedtube. b: Containedtrace

1

o

2

‘4%

1 2

1 o

REFERENCES 1. Mttratake,H.; Hayakawa,A.; Natsume,M. cx-Arylation of ketones:a) Ueda,N.;Tokuyama,T.; Sakan,T. Bull.Chem.Soc. c b) Semmelhack, M. F.; Stauffer, R. D.; Rogerson, T. D. Semmelhack,M. F.; Bargar,T. M J d Kosugi,M.; Suzuki,M.; e H J Hagiwara,I.; Goto,K.; Saitoh,K.; Migita,T. Chem. ~ Kosugi,M.;Hagiwara,I.;&uniyAT.; Migita,T. J g Kosugi,M.;Hagiwara,I.; Sumiya,T.; Migit%T. i McCague,R.; h) Urabe,H.; Kuwajima,I. j K Kuroda,R.; Leclercq,G.; Stoessel,S. J Chem. 1987, 1007-1010. k) Barton,D. H. R.; Donnelly,D. M. X.; Finet, J.-P.; Stenson,P. H. Finet,J.-P.; Stenson,P. H. 1)Donnelly,D. M n) m) Hou, D.; Mas, J. L. U S o P.; Pandey,G.; Krishna,A.; Girija,K.; Karthikeyan,M. p B B M J Portoghese,P. S. their a) Bruggink,A.;McKillop,A. b) Semmelhack,M. F.; Chong,B. P.; Stauffer,R. D.; Rogerson,T. D.; Chong,A.; Jones,L. D. Am. 1975,97,2507-2516.c) Uno,M.; Seto,K.; Takahashi,S. J d) Uno, M.; Seto,K.; Ueda,W.; Masuda,M.; Takahashi,S. Synthesis ~ Ciufolini,M. A.; 1985,506-508.e) Kobayashi,T.; Tanaka,M. g Ciufolini,M A.;Qi, H-B.;Browne,M. E.J. Browne,M. E. 1988,53,4149-4151.h) Dell’Erba,C.; Novi,M.;Petrillo,G.; Tavani,C.; Bellandi,P. i Lloris, M. E.; Abramovitch,R. A.; Marquet,J.; Morenomanas,M. j Donnelly,D. M. X.; FinetJ.-P.; Rattigan,B. A. J k) Okuro,K.;Furuune,M.;MittrajM.; Nomura,M.J. S

Julia, S.; Huynh,C.; Olivie,J. 2