Palladium catalysis addition

Four-membered heterocycles can be formed by the addition of isocyanides to 1,3-dipoles (80AG(E)45) and by the reaction of carbon monoxide with -haloamines, with the aid of palladium catalysis (Scheme 10) (79CC699). 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

Application of the largest dendritic catalyst 8 (Figure 4.15) in a continuous process showed activity over 15 exchanged reactor volumes (Figure 4.16). The decrease in activity caused by wash out was calculated to be only 25% (retention of ligand 98.1%). The drop in activity was therefore ascribed to the decomposition of the palladium catalyst. Addition of membrane material to batch catalysis experiments did not change the conversion showing that this was not the cause of decomposition. 

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 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. 

Butylallene, which fails to react with (PhSe)2 under palladium catalysis, undergoes the diselenide addition upon photo-irradiation (Equation (80)).215 Using the (PhS)2/(PhSe)2 binary system, introduction of two different chalcogen elements into allenic C=C bond is also viable (Equation (81)). 

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. 

Aside from alkoxycarbonylations, hydroxycarbonylations in the presence of water to yield allenic carboxylic acids [15] (93, Y = OH) and aminocarbonylations in the presence of amines to give the analogous amides [139] (93, Y = NRR ) have also been carried out, respectively (Scheme 7.13). These products of structure 102 can also be obtained if using the propargylamines 101 with R1 = Ph or R3 Z H as starting materials (Scheme 7.15) [140]. Additionally, hydroxycarbonylations, also termed carboxyla-tions, are successful without palladium catalysis by reaction of propargyl halides and carbon monoxide in the presence of nickel(II) cyanide under phase-transfer conditions [141, 142]. 

Highly branched ethene-methyl acrylate polymers. The cationic palladium diimine complexes are remarkably tolerant towards functional groups, although the rates decrease somewhat when polar molecules are added. In ETM catalysis addition of polar molecules or monomers kills the catalyst and therefore it was very interesting to see what the new palladium catalysts would do in the presence of polar monomers. Indeed, using methyl acrylate a copolymerisation... 

Scheme 59. Different modes of addition of MegXsi-Y reagents onto the double bond in bicyclopropylidene (1) under palladium catalysis [149]...

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

Recently, Fu and coworkers have shown that secondary alkyl halides do not react under palladium catalysis since the oxidative addition is too slow. They have demonstrated that this lack of reactivity is mainly due to steric effects. Under iron catalysis, the coupling reaction is clearly less sensitive to such steric influences since cyclic and acyclic secondary alkyl bromides were used successfully. Such a difference could be explained by the mechanism proposed by Cahiez and coworkers (Figure 2). Contrary to Pd°, which reacts with alkyl halides according to a concerted oxidative addition mechanism, the iron-catalyzed reaction could involve a two-step monoelectronic transfer. 

Alkylation and deprotection of N-protected aminomethylphosphonate esters 6 are shown in Scheme 6. The nitrogen is protected as the imine derived from benzophenone or a benz-aldehyde, and a variety of conditions are used for deprotonation and alkylation (Table 2). The benzaldehyde imine of aminomethylphosphonate can be deprotonated with LDA and alkylated with electrophilic halides (entries 1 and 2). For the best yields, saturated alkyl bromides require an equivalent of HMPA as an additive. 36 Allylic esters can be added to the carbanion with palladium catalysis (entries 3-7). 37,38 For large-scale production, phase-transfer catalysis appears to be effective and inexpensive (entries 8-12). 39,40 ... 

In the palladium-catalyzed addition of allylstannanes to allyl acetates, complete allyl inversion of the allylstannane is observed.137 Symmetrical coupling is also possible, for example, by treatment of cinna-myl acetate with hexa-n-butyldistannane.137 In this reaction, cinnamyl tri-n-butylstannane is generated in situ by Pd catalysis and it then couples with the allyl acetate with allyl inversion (equation 32). 

The copper-catalysed asymmetric conjugate addition of dialkylzinc leads to homo-chiral zinc enolates.28 These intermediates have been trapped in situ with activated allylic electrophiles, without the need for additional palladium catalysis (Scheme 3). 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

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