Cascade reactions hydrogen-bonding

It is worth mentioning that some precursors easily catalyze the reductive carbonylation of alkynes from the C0/H20 couple. Here, the main role of water is to furnish hydrogen through the water-gas-shift reaction, as evidenced by the co-production of CO2. In the presence of Pd /KI terminal alkynes have been selectively converted into furan-2-(5H)-ones or anhydrides when a high concentration in CO2 is maintained. Two CO building blocks are incorporated and the cascade reactions that occur on palladium result in a cyclization together with the formation of an oxygen-carbon bond [37,38]. Two examples are shown in Scheme 4. 

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

However, their intermolecular addition reactions with alkynes are mostly aimed at synthesizing substituted aLkenes, ° and only very few cascade reactions that are initiated by P radical addition to C = C triple bonds have been reported. Renaud and coworkers developed a simple one-pot procedure for the cyclization of terminal alkynes mediated by dialkyl phosphites (Scheme 2.35). In this radical chain procedure, dialkyl phosphite radicals, (R0)2P =0, undergo addition to the C = C triple bond in 190, which triggers a radical translocation (l,5-HAT)/5-eAO cyclization cascade. The sequence is terminated by hydrogen transfer from dialkyl phosphite to the intermediate 194 and regeneration of P-centered radicals. 

The proposed reaction mechanism is shown in Scheme 6.75. The nitroalkene moiety of bifunctional ortAo-alkyne-substituted nitrostyrenes 159 is activated through hydrogen bonding with catalyst 160 to incorporate the stereoehemieal information in the first AFC reaction. Then the alkyne is activated under gold catalysis to affect the seeond AFC/ring expansion cascade. 

Thromboplastin formation and thrombin elaboration are only steps in a cascade of reactions, which to be successful must convert fibrinogen molecules into fibrin. The conversion of fibrinogen into fibrin involves the splitting of peptide bonds, the release of sialic acid, and the rupture of hydrogen bonds. 

The cyclization mechanism of type 11 terpene cyclases is exemplified by the reaction of the SHC (Scheme 87.19). Important insights into the reaction mechanisms have been obtained from structural data [199, 208]. One of the inner helices of the p-domain of SHC contains a conserved DxD(D,E) motif that is located in the central cavity at the interface between the p- and y-domains. Its central aspartate residue D376 is polarized via hydrogen bonding to an adjacent histidine residue and protonates the double bond of the squalene substrate to initiate the reaction cascade. Conserved aromatic residues stabilize the intermediate cations by cation-tt-interactions. A water molecule is a candidate to act as catalytic base, and this water may also account for the formation of the by-product hopanol. Another bridging water molecule connects D376 to a tyrosine residue and can restore the active site after catalysis by reprotonation of D376. 

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