Ketones carbopalladation

The carbopalladation of allylamine with malonate affords the chelating complex 510, which undergoes insertion of methyl vinyl ketone to form the amino enone 511[463]. The allylic sulfide 512 has the same chelating effect to give the five-membered complex 513 by carbopalladation[463.464]. 

Recently, synthesis of aryl ketones by a combination of palladium-catalyzed C-H activation of arenes and intermolecular carbopalladation of nitriles has been reported (Equation (119)).474... 

The aminopalladation and subsequent carbonylation proceed smoothly. The aminopalladation of one of the double bonds of allene 129 generates 130, and CO insertion affords the ester 131 [96]. The carbopalladation of the optically active N-vinyl carbamate 132 with malonate afforded 133. Then CO insertion and trapping with vinylstannane produced the ketone 134 with 95% de, which was converted to 135 [97]. 

Transmetallation of silyl enol ethers of ketones and aldehydes with Pd(II) generates Pd(II) enolates, which are usefull intermediates. Pd(II) enolates undergo alkene insertion and -elimination. The silyl enol ether of 5-hexen-2-one (241) was converted to the Pd enolate 242 by transmetallation with Pd(OAc)2, and 3-methyl-2-cyclopentenone (243) was obtained by intramolecular insertion of the double bond and -elimination [148], Formally this reaction can be regarded as carbopalladation of alkene with carbanion. Preparation of the stemodin intermediate 246 by the reaction of the silyl enol ether 245, obtained from 244, is one of the many applications [149]. Transmetallation and alkene insertion of the silyl enol ether 249, obtained from cyclopentadiene monoxide (247) via 248, afforded 250, which was converted to the prostaglandin intermediate 251 by further alkene insertion. In this case syn elimination from 250 is not possible [150]. However, there is a report that the reaction proceeds by oxypalladation of alkene, rather than transmetallation of silyl enol ether with Pd(OAc)2 [151]. 

In 1997, Hashmi et al. observed the Pd-catalyzed homodimerization of 1,2-allenyl ketones affording2-substituted4-(4 -oxo-2 -alken-2 -yl)furans (Scheme 31) [23]. The reaction may proceed via intramolecular oxypalladation involving the carbonyl oxygen, leading to the formation of furanylpalladium intermediate 69, followed by intermolecular carbopalladation with a second molecule of 1,2-allenyl ketone. Protonation of the C-Pd bond in 70 afforded the product 66 and regenerated Pd(II) (Scheme 32). 

C.i.a. Four-Centered Processes. The carbopalladation of a C,C multiple bond with a carbon-palladium single bonds is the key step in the catalytic cycle of the standard Heck reaction, the intermolecular version of which has been used extensively since its discovery for the functionalization and derivatization of aryl and alkenyl halides, as well as alkenyl triflates or the more reactive nonafiates, which are readily available from the corresponding ketones (Scheme 2) (Sect. IV.2.1.2). 

In contrast to the diverse insertion chemistry of vinylpalladium intermediates discussed in Sects. IV.3 and IV.5, the reactions of vinylpalladium complexes with electrophiles had not been reported until recently. Although a single report on the annulation of the o-mer-curio benzaldehyde with diphenylacetylene into the corresponding indenols and inde-nones catalytic in palladium and stoichiometric in copper had been communicated in 1992, the more synthetically useful protocol for the catalytic version of this type of transformation remained unknown until 1999. In this section the intermolecular carbopalladation of alkynes with aryl halides followed by the intramolecular trapping of the formed vinylpalladium species with ketones, aldehydes, and nitriles will be discussed. 

B. CARBOPALLADATION OF ALKYNES FOLLOWED BY TRAPPING WITH KETONES. 

The feasibility of such a sequential process was accidentally discovered in 1989 in an unsuccessful attempt to achieve cyclic acylpalladation (Sect. VI.4) of la (Scheme 1) with 40 atm of CO, 1.5 equiv of NEtj, and 4 equiv of MeOH in the presence of 3 mol % of Pd(PPh3)4 at 100 °C. Whereas none of the desired cyclic acylpalladation product 2a was formed, the reaction gave an unexpected carbopalladation product 3a in 42% yield along with an uncyclized premature esterification product 4a formed in 28% yield. Similarly, lb provided 3b and 4b in 18% and 42% yields, respectively, rather than the desired 2b (Scheme 1). Since formation of seven-membered ketones via cyclic acylpalladation has never been observed, the results are perhaps not surprising. Later optimization of the reaction conditions including the use of 1 atm pressure of CO has... 

As in the cases of termination by lactonization and lactamization, some specially structured alkenes, such as norbomene and related alkenes, can participate in intermolecular carbopalladation-carbonylative ketonization tandem processes. In the reactions shown in Scheme 22, the acylpalladium intermediates undergo intramolecular acylpalladation with arenes to provide ketones. ... 

The reactivity observed with acetylenic ketones is more complex and the two iodoalkynyl ketones 14 and 15 behave in a different way (Scheme 12). Thus, the phenyl ketone 14 undergoes carbopalladation of the triple bond followed by a reductive elimination, furnishing the exo-alkylidenecyclopentane derivative 16. On the other hand, the methyl ketone 15 undergoes, after carbopalladation, a subsequent Michael addition, leading to the ketone 17 in 52% yield. 

The Pd(II)-catalysed 5-exo-dig carbocyclization of the alkynyl ketone (49) to produce (50) has been rationalized by DFT calculations, which suggest that the reaction proceeds via enolization assisted by (AcO)2Pd, followed by intramolecular alkyne carbopalladation, Z E isomerization, and protiodepalladation. ... 

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