Negishi E. 2002 Handbook of organopalladium chemistry for organic synthesis / 0973 993

2 RM Pd cat., Oxidant

III.2.20 Palladium-Catalyzed Homocoupling of Organic Electrophiles or Organometals

MARTIN KOTORA and TAMOTSU TAKAHASHI

A. INTRODUCTION

Although homocoupling can be catalyzed or mediated by a number of main group metals as well as transition metals, Pd-catalyzed processes are receiving special attention. Taking into account the specific properties of palladium and its compounds, it is not surprising that they have been used extensively for homocoupling of a wide variety of organic derivatives under mild reaction conditions.

Generally, the homocoupling can be classified into the following two groups: (i) coupling of organic electrophiles (halides, triflates, etc.) and (ii) coupling of organometallic compounds (lithium, boron, silicon, tin, mercury, etc.). The former process uses Pd0 as the catalytically active species and requires the presence of reductants (amines, phosphines, zinc, electrons, etc.) in the reaction mixture to keep the catalytic cycle going. On the other hand, the latter process uses PdII as the catalytically active species and requires the presence of oxidants (CuCl2, peroxides, oxygen, etc.) (Scheme 1).

The aim of this section is to focus on the synthetic scope of Pd-catalyzed homocoupling as well as recent advances in this area.

B. Pd-CATALYZED COUPLING OF ALKENYL, ARYL,

AND ALKYNYL ELECTROPHILES

B.i. Homocoupling Reactions

Generally, homocoupling of aryl and alkenyl halides has been the most widespread. Other halide derivatives, such as alkyl or alkynyl halides, have seldom been used. This is either because of problems during homocoupling (alkyl halides may easily undergo dehydrohalogenation) or because the homocoupled product (diynes) could be obtained by more convenient methods. Nonetheless, a rare example of homocoupling of alkyl halides catalyzed by palladium chloride in the presence of hydrazine as the reductant was published[1]; however, this procedure is of limited synthetic value (Scheme 2).

One of the first papers dealing with homocoupling of sp2-C halides was a mechanistic study of Pd-catalyzed dimerization of aryl iodides in the presence of trialkylamine as the

Handbook of Organopalladium Chemistry for Organic Synthesis, Edited by Ei-ichi Negishi ISBN 0-471-31506-0 © 2002 John Wiley & Sons, Inc.

973

Scheme 2

reductant.[2] A considerable improvement of yields was achieved when the same reaction was conducted in the presence of triphenylarsine in DMF at 140 °C.[3] A number of unsubstituted aryl halides (bromide and iodides) gave reasonable yields of the corresponding biaryls (Scheme 3). A system composed of palladium acetate, tetraalkylammonium halide, and a base (amine, potassium carbonate) in DMF has found wide application. This system was used for homocoupling of phenyl halides (Scheme 4) and for 1,8-diiodonaph- thalene to afford a mixture of diiodobinaphthalene and perylene (Scheme 5). Diiodobinaphthalene in a separate reaction was intramolecularly cyclized to perylene.[4]

This system was later used for a systematic study of homocoupling of variously substituted aryl and heteroaryl bromides.[5],[6] The authors conducted a number of experiments to find the best conditions for homocoupling of various aryl halides. The influence of the base (K2CO3, amines) and the reductant (isopropanol) was studied. It was demonstrated

Scheme 3

5 mol % Pd(OAc)2,

Scheme 4

or at 105 °C in toluene. I: 5 mol % Pd(OAc)2, 1 equiv K2CO3, DMF/H2O, isopropanol; II: 5 mol % Pd(OAc)2, 1 equiv Et3N, DMF, isopropanol; III: 5 mol %Pd(OAc)2, 1 equiv Et3N, DMF; IV: 5 mol % Pd(OAc)2, 1 equiv K2CO3, DMF/H2O; V: 5 mol % Pd(OAc)2, 1 equiv (i-Pr)2NEt, DMF, isopropanol; VI: 5 mol % Pd(OAc)2, 1 equiv (i-Pr)2NEt, DMF, VII: 5 mol % Pd(OAc)2,

1 equiv (i-Pr)2NEt, toluene, isopropanol.

b GC yield. Isolated yields are given in parentheses.

aFor details see Table 1.

bGC yield. Isolated yield are given in parentheses.

Aryl triflates were homocoupled to biaryls in the presence of zinc[14],[15] or under electroreductive conditions.[15],[16] In some cases, the former method gave better yields of the biaryls, whereas in others the latter method was more successful (Table 5). It is noteworthy that in the case of the electroreductive formation of biaryls from chloroaryltriflates the coupling proceeded through the cleavage of the C —OTf bond leaving the halogen moiety intact.

In one case arylsulfonyl halides were used to prepare biaryls. The reaction was catalyzed by a palladium complex in the presence of titanium tetraisopropoxide (Scheme 9).[17] This procedure is convenient for the preparation of halogen-substituted biaryls, because the homocoupling proceeds through cleavage of the C — SO2Cl bond.

a GC yield. Isolated yields are given in parentheses.

Scheme 8

TABLE 3. Preparation of Biaryls from Aryl Halides Using Sodium Formate, Pd/C, and Surfactant in Sodium Hydroxide Liquor a

aAryl halide ( 0.1 mol), sodium formate (6.8 g), Pd/C (2 g), surfactant (4 g), 32% sodium hydroxide liquor, 95 °C.

bIsolated yield.

a GC yield.

Scheme 9

aPd catalyst: I = Pd(PPh3)4; II = PdCl2(PPh3)2.

bIsolated yield.

Homocoupling of vinyl halides is a possible pathway to obtain 1,3-dienes; however, this option has not been developed synthetically. A rare example is Pd-catalyzed interand intramolecular homocoupling of vinyl bromides in the presence of a stoichiometric amount of triphenyl phosphine and an excess of potassium carbonate.[18],[19] The yields of the intermolecular coupling of vinyl bromides are from moderate to high and depend on the substrate (Scheme 10). The intramolecular coupling gives high yields of the corresponding exocyclic 1,3-dienes (Scheme 11). Also, Pd-catalyzed homocoupling of vinyl chloride to butadiene was reported.[20]

B(OH)2

76

aReaction conditions: 4.7 mol % Pd(OAc)2, 1.3 equiv Na2CO3, air(O2), 20 °C.

bHPLC yield.

Vinylsilanes were one of the first organometallics used in the Pd-catalyzed homo coupling reaction with CuCl2 as an oxidant (Scheme 13).[22] Similar reaction conditions were used for the homocoupling of dienyl, trienyl, and tetraenylsilanes to afford the corresponding polyenes (Scheme 14).[23]

So far, the most intensive homocoupling studies were conducted with trialkylstannyl derivatives. Alkyl-, alkenyl-, aryl-, and alkynylstannanes have been homocoupled to give the corresponding dimers. There is no report of homocoupling of n-alkylstannanes, but cyclopropyltributylstannanes were easily coupled in the presence of a catalytic amount of a palladium complex to the corresponding biscyclopropanes in good yields (Scheme 15).[24]

One of the first papers dealing with Pd-catalyzed homocoupling of alkenylstannanes utilized t-butylhydroperoxide as an oxidant. The reaction gave good yields of the corresponding dimers; however, in some cases, stereochemistry of the double bond was lost. It was also demonstrated that this methodology is suitable for the homocoupling of arylstannanes (Table 7).[25]

Scheme 13