Palladium catalysis group

Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

CH2=C(OBn)CH2F, PdCl2(COD), CH3CN, it, 24 h, 89-100% yield. Protic acids can also be used to introduce this group, but the yields are sometimes lower. A primary alcohol can be protected in the presence of a secondary alcohol. This reagent also does not give cyclic acetals of 1,3-diols with palladium catalysis. 

In the first chapter, N. M. Ahmad and J. J. Li (Pfizer, Ann Arbor, USA) discuss the use of palladium in quinoline synthesis, thus filling an important gap in a recent monograph on the uses of palladium catalysis in heterocyclic synthesis authored by the same group. This is followed by an account of pyrimidine-pyridine interconversions by H. C. van der Plas (Wageningen University, The Netherlands) the immense variety of heterocyclic chemistry is illustrated by the large number of diverse strategies for such transformations. 

The synthesis of thiepins 14 was unsuccessful in the case of R1 = i-Pr,79 but if the substituents in the ortho positions to sulfur arc /erf-butyl, then thiepin 14 (R1 = t-Bu R2 = Me) can be isolated in 99% yield.80 Rearrangement of diazo compound 13 (R1 = t-Bu R2 = H), which does not contain the methyl group in position 4, catalyzed by dimeric ( y3-allyl)chloropalladium gives, however, the corresponding e.w-methylene compound. The thiepin 14 (R1 = t-Bu, R2 = H) can be obtained in low yield (13 %) by treatment of the diazo compound with anhydrous hydrogen chloride in diethyl ether at — 20 C.13 In contrast, the ethyl thiepin-3,5-or -4,5-dicarboxylates can be prepared by the palladium catalysis method in satisfying yields.81... 

Allyl sulphones can be converted to dienes by alkylation and elimination of sulphinic acid under basic conditions (equation 64)105. Several vitamin A related polyenes have been synthesized following this two-step protocol (Table 10)106. The poor leaving-group ability of the arylsulphonyl group requires treatment with strong base for elimination. However, elimination of the allylsulphonyl group takes place readily under palladium catalysis (equation 65)107. Vinyl sulphones can be converted to dienes via Michael addition, alkylation with allyl halides and elimination of sulphinic acid sequence (equation 66)108. 

The palladium-catalyzed arylation of 2-phenylphenols and naphthols shows an interesting feature of arylation of C-H bonds, leading to the formation of an (aryl)(aryloxy)palladium(n) intermediate.65,65a,65b The phenolates are suitable as precoordinating groups. The reaction of 2-hydroxybiphenyl with an excess of iodobenzene occurs regioselectively at the two ortho-positions of phenyl group under palladium catalysis (Equation (57)). In the case of 1-naphthol, the peri-position is phenylated (Equation (58)). 

The intramolecular arylation of sp3 C-H bonds is observed in the reaction of l-/ r/-butyl-2-iodobenzene under palladium catalysis (Equation (71)) 94 94a 94b The oxidative addition of Arl to Pd(0) gives an ArPdl species, which undergoes the electrophilic substitution at the tert-butyl group to afford the palladacycle. To this palladacycle, another molecule of Arl oxidatively adds, giving the Pd(iv) complex. 

The formation of an s/Z-hybridized C—P bond is readily achievable using the Michaelis-Arbuzov reaction. Such an approach is not applicable to form heteroaryl C—P bonds in which the carbon atoms are sp2 hybridized, whereas palladium catalysis does provide a useful method for Csp2—P bond formation. The first report on Pd-catalyzed C—P bond formation was revealed by Hirao et al. [134-136]. Xu s group further expanded the scope of these reactions [137, 138], They coupled 2-bromothiophene with n-butyl benzenephosphite to form n-butyl arylphosphinate 161 [137]. In addition, the coupling of 2-bromothiophene and an alkylarylphosphinate was also successful [138], For the mechanism, see page 19-21. 

The group of allyl-based linkers was developed by Kunz et al. [49] Linkers of the general allyl type are particularly valuable, because they are removable under almost neutral conditions using palladium catalysis and are orthogonally stable towards the commonly used acid and base-labile protecting groups (Tab. 3.2). 

Thioxylation has also been achieved using palladium catalysis, and reaction of 5-iodo-2,4-dimethoxypyrimidine 202 with the arylthiopropyne 201 occurred with loss of the propyne unit and replacement of the iodine by the arylthio group <2000TL7259, 2001T5885>. 

The intramolecular palladium catalyzed ring closure of the tetrahydro-isoquinoline derivative depicted in 8.41. led to the formation of the aporphine derivative in good yield, which was then converted into racemic aporphine in three steps. In the ring closing step 20 mol% palladium acetate and 40 mol% tricyclohexylphosphine were used as catalyst. The removal of the hydroxyl group was also achieved by palladium catalysis through its conversion to triflate and the subsequent reduction with ammonium formate in the presence of palladium acetate and dppf.53... 

Several new leaving groups have been discovered recently which merit special discussion. Allyl sul-fones, surprisingly, function as substrates for palladium catalysis.86 As the sulfone group had previously been proven to be able to stabilize an adjacent carbanion, this result allowed allyl sulfones now to be considered as synthons for 1,1- and 1,3-dipoles (equation 10). That is, the allyl sulfone can be used alternately as a nucleophile and electrophile, greatly extending its synthetic utility. 

Aniline nucleophiles readily participate in this type of ring-closure process under palladium catalysis (Pd(OAc>2, BINAP, and CS2CO3 in hot toluene) without resort to protecting groups when an aryl iodide is used <2005T61>. 

As described in Section III.1.4.1.1, the catalytic direct arylation reactions of aromatic compounds occurs effectively via C-H bond cleavage when the substrates are appropriately functionalized. On the other hand, various five-membered heteroaromatic compounds involving one or two heteroatoms, even without a functional group, are known to undergo arylation, usually at their 2- and/or 5-posi-tion(s), on treatment with aryl halides under the action of palladium catalysis. The coupling has recently been developed significantly [1, 2]. Representative examples with some mechanistic discussion are summarized in this section. 

Stannaries have become prominent in multifunctional anchoring groups. A polymer-bound tin hydride 41 has been used to hydrostannylate alkynes under the action of palladium-catalysis to give polymer-bound alkenylstannanes 42. These alkenyl stannanes have been employed in intermolecular [45] and intramolecular Stille reactions [46]. Alkenylstannanes can also undergo protonation to give alkenes 44 in a traceless fashion. This linker is therefore multifunctional (Scheme 6.1.12). 

The iodyl group (I02) is a good nucleofugue. Under mild conditions, the conversion of several iodylarenes into benzoic acids was realized in good yields, via carbonylation. Carbon monoxide was used at atmospheric pressure and 40-50°C, in aqueous sodium carbonate, with palladium catalysis [9] ... 

Halides react with carbon monoxide in the presence of a source of a second alkyl group, with palladium catalysis, to give ketones as shown in equation 148. 

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