As discussed in Sect. I.2,reductive eliminationis one of only a few to several basic pat- terns permitting the formation of various types of single bonds in organic compounds in- cluding C—C, C—H, C—X, where X is N, O, or a related heteroatom, and even bonds between two heteroatoms. Reductive elimination is thought to be an important microstep in Pd-catalyzed cross-coupling. In this Part, these Pd-catalyzed cross-coupling reactions leading to the formation of C—C (Sect. III.2), C—H (Sect. III.3.1), C—N and C—O (Sects. III.3.2and III.3.3), as well as C—M (Sect. III.3.4) bonds are discussed. It should be noted, however, that reductive elimination occurs in many other types of Pd-catalyzed reactions as well, and it is discussed throughout this Handbook. Thus, for example, the Heck reaction (Part IV) must involve regeneration or Pd(0) complexes via reductive elimination of H(X)Pd(II) complexes, and a similar reduction of Pd(II) species must oc- cur in the Tsuji – Trost reaction (Part V). Reductive elimination is also a critical step in the generation of organic acyl derivatives from acylpalladium intermediates with con- comitant two-electron reduction of Pd(II) complexes (Part VI), while it is well accepted that reductive elimination to form the C—H bond is the product-forming step in various Pd-catalyzed hydrogenations (Part VII). So, the scope of reductive elimination of Pd(II) complexes is far wider than that in Pd-catalyzed cross-coupling. With this understanding, however, our attention in this Part will be focused on Pd-catalyzed cross-coupling leading to the formation of C—C, C—H, C—N, C—O, and C—M bonds within the context of cross-coupling.
Cross-coupling between organometals (R1M) and organic electrophiles (R2X) is un- doubtedly one of the most straightforward methods for the formation of carbon – carbon bonds (Scheme 1). As discussed in Sect. I.1, the use of Grignard reagents and organolithi- ums without involving any transition metal catalysts was first introduced many decades ago. Both stoichiometric and catalytic use of Cu[1],[2] revolutionized the art of cross- coupling mainly during the 1960s and 1970s. Most notably, organic electrophiles contain- ing Csp2—X and Csp—X bonds became usable and useful in cross-coupling. Over the past three decades Ni- and Pd-catalyzed cross-coupling, the latter in particular, has substan- tially improved and expanded the cross-coupling methodology. The historical evolution of Pd-catalyzed cross-coupling is discussed in Sect. I.1, and many reviews are available on this topic.[3]–[17] The narrow definition of cross-coupling presented above may be
Handbook of Organopalladium Chemistry for Organic Synthesis, Edited by Ei-ichi Negishi ISBN 0-471-31506-0 © 2002 John Wiley & Sons, Inc.
R M + R X R R
expanded so as to include H, N, O, and other heteroatom groups, as well as metals and metal-containing groups in R1or R2in Scheme 1.
The relationships between the cross-coupling reaction shown in Scheme 1and some other related reactions should briefly be discussed here. Whether or not one should con- sider those Pd-catalyzed reactions in which M is H in Scheme 1, such as the Heck reaction with alkenes and the Sonogashira reaction with alkynes, as cross-coupling reactions is largely a matter of semantics or a personal preference. For mainly historical and practical as well as somewhat vague mechanistic and other chemical reasons, the Heck alkene hy- drogen substitution reaction is discussed mostly in Part IV as a representative carbo- palladation reaction. On the other hand, the Sonogashira and related Heck-type alkyne hy- drogen substitution reactions are discussed in this section in part because ammonium or copper acetylides are considered to serve as R1M in these reactions. In contrast, no such species derived from alkenes are considered for the Heck alkene substitution. It should, however, be noted that, even if discrete acetylide anions are involved as actual reactive species in the alkyne substitution, they may still undergo the Heck-type non-redox addi- tion–elimination process suggested as early as 1978[3](Scheme 2). Furthermore, it is not unreasonable to consider some of the more genuine cross-coupling reactions, such as the reaction of preformed alkynylmetals with organic halides (Sect. III.2.8.2) and the conju- gate substitution reaction (Sect. III.2.15) shown in Scheme 2, as non-redox carbometalla- tion–elimination reactions. Irrespective of their mechanistic details, however, these are genuine examples of Pd-catalyzed cross-coupling reactions discussed in this Part.
R1M + R2X cat. PdLn R1 R2 + MX Scheme 1
R1C CM (or H) + R2X
cat. PdLn
R1C CM (or H) + R2PdLnX M (or H)
R2 R1
XLnPd R1C CR2 + M (or H)PdLnX R1M
X2PdLn
R1PdLnX
C C X
C O
R1 C X
C PdLnX
C O R1 C C C O + X2PdLn
Scheme 2
The Tsuji–Trost allylation of enolates can be viewed as a variant of Pd-catalyzed cross-coupling involving allylic electrophiles (Sects. III.2.9and III.2.10). In recognition of the widely accepted mechanism involving a nucleophilic attack by enolates at the -allyl ligand of an allylpalladium derivative on the side opposite to Pd, however, it is discussed separately in Part Vtogether with the Wacker and related reactions, which are
also thought to involve nucleophilic attack on -ligands of Pd -complexes. However, the same mechanistic interpretation cannot be applied to most of the other Pd-catalyzed - substitution of enolates and related compounds including -arylation and -alkenylation.
These reactions are therefore viewed as Pd-catalyzed cross-coupling reactions and discussed in Sect. III.2.14.1(Scheme 3).
Various Pd-catalyzed carbonylation reactions have often been referred to as carbonyla- tive cross-coupling reactions (Scheme 4). However, these reactions involving the forma- tion of two C—C bonds with incorporation of CO clearly display a pattern of chemical transformation that is different from Scheme 1. So, these reactions are discussed in Parts VIand VIII. On the other hand, Pd-catalyzed acylation with acyl halides and related derivatives are examples of the reaction represented by Scheme 1, where R2is acyl, and they are therefore discussed in this Part (Sect. III.2.12.1), even if CO may be used to prevent decarbonylation.
C C O
X cat. PdLn Part V (Sect. V.2)
C C O
the Tsuji−Trost reaction
RX, cat. PdLn
Part III (Sect. III.2.14.1) R C C O
R = aryl, alkenyl, etc.
M
Scheme 3
R1M + R2X CO, cat. PdLn R1COR2 Part VI
R1M + R2COX CO, cat. PdLn R1COR2 Part III (Sect.III.2.12.1)
Scheme 4
Finally, most Pd-catalyzed hydrogenation reactions are discussed in Part VII. How- ever, Pd-catalyzed hydrogenolysis of organic halides and related electrophiles can be viewed as Pd-catalyzed cross-coupling of organic electrophiles with hydrides. The corresponding reactions of metal-centered nucleophiles have also been developed.
Although these reactions are closely related to hydrogenation and related reduction reactions discussed in Part VII, those that are discussed in Part VIIgenerally involve addition of metal–hydrogen and metal–metal bonds to alkenes and alkynes, displaying different patterns of chemical transformation. These two discrete patterns are shown in Scheme 5.
As discussed above, distinctions among many closely related reactions and processes are often vague and somewhat arbitrary. Some are based on chemical and mechanistic
reasonings, but many other factors including historical and semantic ones have also been taken into consideration. After all, inasmuch as many Pd-catalyzed reactions involve more than one microstep and are hence multidimensional, some compromises are neces- sary in any unidimensional arrangement of Pd-catalyzed reactions.