Activation, selective phosphonium salts

Interestingly, various phosphonium salts have been applied [13] as constituents of palladium catalysts for hydrodimerization of butadiene and isoprene about the same time when the results of Kuraray were disclosed. These were obtained by quatemization of aminoalkylphosphines with methyl iodide or HQ (Ph2P-R-NH2 type compounds are known to yield phosphonium salts with these reagents). Although the catalysts prepared in situ from [PdCU] were reasonably active (TOF-s of 10-20 h ) the reactions always yielded complex product mixtures with insufficient selectivity towards the desired 1,7-octadienyl derivatives. 

A selection of commercially available phosphonium salts suitable for the activation of carboxylic acids in the presence of amines is sketched in Figure 13.5. Phosphonium salts such as those shown in Figure 13.5 do not react with amines, and are well suited for preparing amides on insoluble supports, with either the amine or the acid linked to the support (Table 13.5). Solutions of these reagents in dry DMF are quite stable and can be used even after standing at room temperature for several days [84]. BOP, one of the first phosphonium salts used for peptide synthesis [85], leads to the formation of mutagenic HMPA, and should therefore be replaced by the less hazardous PyBOP [86],... 

A series of catalytic cycles are examined to test the catalyst recycling. As a result, the catalyst (BrBu3PPEG6000PBu3Br) keeps high catalytic activity and selectivity after five cycles. Hence, immobilization of a phosphonium salt on a soluble polymer (e.g. PEG) could provide an alternative pathway for realizing homogeneous catalyst recycling. 

The ruthenium complex-catalyzed hydroformylation of 1-alkene was first examined by Wilkinson s group. Ru(CO)3(PPh3)2/phosphine catalysts were found to have moderate catalytic activity [35-37]. Ru3(CO)i2 [38] and anionic hydridocluster complexes such as [NEt4][Ru3H(CO)ii] [39] have also been shown to have catalytic activity. In molten phosphonium salt, Ru3(CO)i2/2,2 -bipyridine has high catalytic activity [40]. The Ru3(CO)i2/l,10-phenanthroline catalyst in N,N-dimethylacetamide (DMAC) shows excellent activity and selectivity for u-aldehydes (Eq. 11.10) [41]. 

In contrast, the use of cobaltocenium bis(diphenyl)phosphine 3 results in increased activity and selectivity toward the n-aldehyde [23]. In an alternative approach, Rh2(OAc)4 was used as the catalyst in a phosphonium salt melt [24]. 

Sardnaxanthin (230), a Cso-carotenoid containing two cyclic y end groups with an additional Cs-unit was first prepared as a racemate [100], For the synthesis of the optically active compound the C20 + C10 + C20 = C50 strategy was chosen. For the synthesis of the C2o-phosphonium salt 231, the key building block of the synthesis, camphoric acid (144) was selected as starting material [101] (Scheme 51). 

A number of cycloaddition reactions involving allene derivatives as dienophiles have been recorded. Allene itself reacts only with electron-deficient dienes but allene carboxylic acid or esters, in which a double bond is activated by conjugation with the carboxylic group, react readily with cyclopentadiene to give 1 1 adducts in excellent yield. For example, the allene 12 gave, with very high yield and selectivity, the cycloadduct 13, used in a synthesis of (-)-P-santalene (3.19). An allene equivalent is vinyl triphenylphosphonium bromide, which is reported to react with a number of dienes to form cyclic phosphonium salts. These can be converted into methylene compounds by the usual Wittig reaction procedure (3.20). 

By using this methodology, a new and useful procedure for macrocyclization of linear peptides has been advanced. The side chains of natural amino acids, such as tyrosine, lysine, and histidine, were allowed to react intramolecularly with pendant carboxamide derivatives of pyridine A-oxides, which were selectively activated by the phosphonium salt, PyBroP (Scheme 18) [44]. The reaction proved to be mild, rapid, and efficient with a potentially large substrate scope. A great deal of examples can be demonstrated, including a novel aza-analogue of the ring system of vancomycin. 

Tanaka and his associates demonstrated for the first time how to use non-volatile ionic liquids (ILs) as solvents in palladium-catalyzed carbonylations [163], In the case of alkoxycarbonylation of bromobenzene, higher yields were obtained when 1-butyl-3-methylimidazolium tetrafluoroborate [bmim][BF4] was used as the reaction medium compared with standard conditions. And the selectivity for the monocarb-onylation of iodobenzene with t -PrOH or Et2NH was significantly enhanced by [bmim][BF4]. After separation of the products, the solvent-catalyst system was easily recycled and exhibited catalytic activity up to seven times. Since then the replacement of traditional solvents with quaternary ammonium halides, imidazoli-um- or pyridinium-derived ILs has gained increasing importance [164—173]. Recently, the phosphonium salt IL trihexyl(tetradecyl)phosphonium bromide has proven to be an effective reaction medium for various carbonylation reactions of aryl and vinyl bromides or iodides under mild conditions (Scheme 2.17) [174]. 

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