PDF《Pure》

Pure Appi.

Chem., Vol. 50, pp. 691―701. 00334545/78/08010691 $02.OO/O Pergamon Press Ltd. 1978. Printed in Great Britain. ? TUPAC NEW APPLICATIONS OF PALLADIUM IN ORGANIC SYNTHESES Richard F. Heck Department of Chemistry, University of Delaware, Newark, Delaware 19711, U.S.A. Abstract ― The palladium catalyzed vimylic substitution reaction with organic halides is a new and useful method for producing carbon―carbon bonds. FL R \ /

1 "Pd" \ /

1 + - RX+ C=C +RN > CC +RNHX /\

3 /\

3 The reaction is useful with aryl, heterocyclic, benzylic, and vinylic bromides and iodides. The most useful reactions are with bromides in which cases a triarylphosphine is required with the palladium catalyst. The best phosphine to employ for a specific synthesis can now be predicted based upon knowledge of how the phosphines influence vinylic substitution rates and side reactions forming phosphonium salts and palladium metal. Essentially all common functional groups can be tolerated by the reaction under the same conditions with the exception of cx,―unsaturated ketones and aldehydes. These react normally in the form of their acetals or ketals, however. Reactions proceed well with conjugated or isolated double bonds with mono―, di― and often tn―substituted olef ins, generally in a stereospecific manner. A syn addition of the organopalladium compound to the olef in followed by a syn elimination of the palladium hydride is observed. The direction of addition of the organopalladium complex to the olef in depends upon the substituents present. Both steric and electronic influences have been observed. The direction of addition is dominated by steric effects;

the organic group always adds, at least mainly, to the least substituted carbon of the double bond. Electron withdrawing substituents on the double bondS generally cause exclusive addition of the organic group to the olefinic carbon not having the substituent. With electron donating groups, some addition to the carbon carrying the substituent is usually observed. For about ten years we have been investigating the chemistry of organopalladium compounds. We have been mainly concerned with mono―organopalladium(II) species, RPdL2X, where L is a ligand and X is a halide or acetate ion. Initially these complexes were prepared by exchange reactions of main group organometallics, principally mercurials, with palladium(II) salts (chloride or acetate). While this method works well, it suffers from the major disadvantage RHgC1 + PdC12 + 2L ―> RPdL2C1 + HgCl2 that many desirable main group organometallics are not easily accessible and even when they are they must be used in stoichiometric amounts in the synthesis of organic compounds. We, therefore, have turned to another method of preparation, the reaction of organic halides with either finely divided palladium metal or more frequently palladium(O) phosphine complexes. RX + Pd(PR) ―> RPd(PR)2X + (n―2)PR The chemistry of the mono―organopalladium compounds has turned out to be extremely varied, unique in many respects, and of great potential use in the area of organic syntheses. In our own work, for example, we have found eight new reactions of synthetic value, all of which (with the possible exception of the last one which has not yet been studied in much detail) can be carried out catalytically with a wide variety of aryl, vinylic, heterocyclic, and benzylic bromides and iodides in good to excellent yields. These reactions are: (1) Carboalkoxylation RX + CO + R1OH + RN Pd RCO2R1 + RNH+X

692 RICHARD F. HECK (2) Amidation RX + CO + R1R2NH + RN "Pd" > RCONR1R2 + RNH+X (3) Formylation RX + CO + H2 + RN Pd RCHO + RNH+X (4) Ethynylic Substitution RX + HCSCR' + RN "Pd" RCECR1 + RNH+X (5) Reduction RX + HCO2RNH+ "Pd" > RH + CO2 + H20 + RNH+X (6) Vinylic Substitution + + RN "Pd" > R + RNH+X (7) A Beta Substituted Ketone or Aldehyde Synthesis px + + RN "Pd" > + RNH+X (8) Dienylation + + RN "Pd" > R+ RNH+X There are, of course, many other known reactions discovered in other laboratories which also involve RPdL2X complexes. Of the eight reactions we have been concerned with, the most generally useful one appears to be the vinylic substitution, (6). Reactions (7) and (8) are really just variations of this one. This reaction has received most of our attention in the past few years and is the subject I will concentrate on in this lecture. The mechanism of the vinylic substitution is not kmown in detail. We have been working on this problem for some time, however, various chemical complications have made progress very slow. In any case, we have good evidence to suggest that the mechanism, at least, is close to the following: R CHC