Palladium catalysed cascade cycloaddition reactions. General concepts and illustrative examples.

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TetmkdxmLam, Vol.34,No. 1.pp.153454 1993 RinWdinGrMtBrihin

Palladium Catalysed Cascade Cgcloaddition Reaations. General Concepts and Illustrative Examples. Ronald

Grigg,*ra

Peter

Kennewell,b

Andrew

Teasdalea

and

Visuvanathar

Sridharana. a School of Chcxnistryy. Leeds University,LeedsL.S29JT. b: Roussd Scia~tificIMitute. Kingfh

Abstractz A gettad polhdhn

Drive;SwindmtSN3 5BZ

catalyscd cydmtldition strategyislroposed involving inital oxidi&vc - additbn of dkyl

-, atyl - and vinyl - halides to Pd(0) followed intemtokcu&r cdqdadation

and subsequentintramolecular

carbopaUadesionlctuiingtoringffamation.Euunplcsof5-and6- tingfonnationarcgivcn.

The recent literahue illustrates that palladium catalysts a~ capable of a wide range of cycliaethm processes1 This prompts us to propose a new general scheme for palladium catalysed cascade cycloaddition reactions that is both flexible and ,tide ranging in concept, potential ring sizes, and applications. These pmcesses can be repxesentcdas the combination of %tarW molecule, which comprks a vinyl -, aryl -. allylic - or henzylic - halW&uith

one or more accepmr molecules

(alkene. alkyne, die@. Soax potential startermolecules a& shown in the Table (note that regiochemical diversity is aften possible though in practise this is unlikely to be a problem)

Table.

l- or 2 - C component

StarterComponents for catalytic cascade cychddition.

2-C component

t

2 - C or 3-C component

R

3-or4-C component

(X = Br, I, OTI, Nz+etc)

[3+2] - Procemes. The aryl starter molecule (1) ( 5:l En: isomer mixture) reacts (anisole, 1WC. 18h) with diphenyl acetylene using catalyst system A3 to give the fulvene (3) @O%)as a 5:l z(E isonxf mixnue via the vinylpalladium

intemxdiate (2).

153

(6)

(5)

Aryl iodide (1) and norbomcnc react (M&N, 8OT) using catalyst system B3to give (4) (5:1 z/e) (82%). Tbc stem&dexpuimenlx. WM

of (4) was establishal by n.0.c. adies ambid

with decoupling

(1) was mmcd with mcthylcnc cycloprojmne as tb8 2x- component using

~~syaCtmB3the~~compri#damixam!of(6)(5:1Z/B)(3246)wdCI)(5:1Pn)(309b). Thus although the [3+2]- process is xqiospccific

p - hydride etimination in intcrmalh

(5)

~withcycliMbbato(6)even~ghunfavolaableringstraineccuarmla&sincI).

.Br

(‘I

~hcvinylb~nni&s(8)and(1O), (1o)givcs(11)(62%)usinglc-

functieau3-C

H

HA

colqmats.

WheaKJilCtCdWithlldOmWB

Thus (8) giver (9) (46’k) and iaboiliIlgaa%oai~

155

using cacalystsystemC.Tbe~chemistryob(9)and(ll)~establishedbyn.O.e.aadiesin conjunction with decoupling experiments. l&donaphthaknc also funcdow as a 3-C compooeat and undeqow palMum catalysal q&add&n

@MF,l20%

36h) to diphenylacuyknc using catalyst

system c3 to givc(l2) (45%)

Related studieson fulvcnc formation have mcendy been mportcd5 and Chiusoli has q&cd

exampleofa no&mew

an

annulation6.

[2+2+1] - Process. Two moles of acenaphthylene mact (anisole, 12W’C ) with B bmmostyrcne(l3) (I- C component) using catalyst system A3 to give the ethylene

cyclapcntanc

(14) (50%). The stcrcuchemistry of (14) was established by n.0.e. studies. A related example asthc2%-canponcnthashccnmported~

rmployingn~

Ph +

t h

Br

(13)

[4+21- Procena 2 - Ally1 bromobcnzcnc (15) functions as a 4 - C component and reacts (C& 8ooc, 16h) with no&omcne using catalyst system A3to give a 1. 2:4 mixtlne (51%) of(M) and (17).

(15)

(16)

(17)

156

Tht benzylic bmmide (18) m~cts (CgHg, 80°C. 18h) with m

ushqcatalystsystemB

60givea2:1-ZJEmixtlllc(64%)of(19).Tbcprocerswa9reputedintkepasCenceofTlOAc(2 mol)affcaded Z-(19) (50%) as a single sm.

Further examples &these and mlated process

axe under study We thank the SERC. Leeds University and Roussel for support.

References 1.

La.,

Grigg, R., Sridharan, V., and Sukirthalingam..Tertahedron

1991. a

3855-3858;

Negishi. E.-I.; Pure Appl.Chem.. 1992, de 323-324, Meyer, F.E.; Parsons, P.J.. and dehneijere, A., J.Org.Chem., 1991, ti

6487-6488. (Poly)cyclisation

- anion eapture:

Grigg,R.; Sukirthalingam. S., and Sridharan. V., Tetrahedron L&t., 1991.2 refs. therein; &gg. Polycyclisation:

R.; Sridharan, V.. Sukirthalingam, Meyer, F.E.; de Meijere,A..

Sridharan,V., and Sukirthalingam,

2545-2548 and

S., ibid, 1990, a

Synletr.,

1991, 771-778;

S., Tetrahedron Lerr., 1991, &

1343-1346; Grigg.R.,

3855-3858; Negishi,

E.-I.; Hawing, S., Owczarczyk. Z., Mohamud, M. and Ay, M. ibid, 1992, j& 3253-3256; Trost.B.M.9 Shi Y., J.Am..Che+w. 2.

, 1991, u

701-703.

Halidenlgybtnplaccdbytriflate~~~specieslolownto~~facile~ve-~~ to Pd(0). Alternatively alkynes can function as starter molecules via addition of I-IF%%e.g. Trost. B.M., Rise.F.E., J.Am.Chem.Soc., 1987. u14, 3161-3163.

3.

All the catalysts used 10 molab Pd(OAc)2 and 20 mol% PPh3 but them was a variation in base and in some cases other additives were present. Catalyst A used KOAc (2 mol) as base. Catalyst system B used K2CO3(2 mol) as a base together with Et4NCl(l

mo1)4. Catalyst

system c used TlOAc(2 mol) as base. 4.

The use & R4NCl to speed up palladium catalysed intermolecular nactions was introduced by

5.

Jeffery. See Jeffery, T.; Tetrahedron fen, 1991.2 2121-2124. and earlier papers. Lee, C.M.; Tobias, B., and Holmes, J.M., J.Am.Soc., 1990 , 9330-9336; Heck, R.F.; Silverberg, L.J., J.Organomet.Chem., 1991.4(14,411~20.

6.

Catellani, M.; Chiusoli, G.P., and Sagarabotto, P., J.Organomet.Chem., 311-319.

7.

See: Brown, S.; Clarkson,S., Grigg, R., and Sridharan, V., accompanying paper.

(Received in UK 16 October 1992)

1982. 244,