Cycle-specific catalysts

Combination of the Hantzsch ester mediated transfer hydrogenation together with chlorine (116) or fluorine (117) electrophiles allows for the formal addition of HCl or HF aaoss a double bond in a catalytic asymmetric manner (Scheme 48) [178], Within this paper the reactions were further refined by the use of two cycle-specific secondary amines which effectively operated independently within the same reaction mixture. Impressively, this allowed access to either diastereoisomer of the product depending upon the absolute configuration of the catalyst used in the second step of the sequence. 

This observation was not so obvious on coke yields because the coke production is a contribution of mnltiple mechanisms and reactions. Thus, the coke yields are quite similar, probably because the catalytic coke is decreased while the contaminant coke is increased. The coke remarks are also observed on the CPS samples taking into account that the dehydrogenation degree is not strongly affected by the extended ReDox cycles, becanse the lower catalysts decay is limiting the effect of the required mass of catalyst (C/0 ratio). Thus, the small decrement of the coke yield on the CPS samples is possibly related to the descent of the catalyst (less specific area) leaving less available space for coke adsorption and less activity for catalytic coke production. It is clear that prolonging the deactivation procednres is not beneficial as far as the metal effects are concerned. 

Perhaps the most important point in these studies was the discovery that two discrete amine catalysts could be employed to enforce cycle-specific selectivities (Scheme 3.18) [20]. Conceptually, this achievement demonstrates that these cascade-catalysis pathways can be readily modulated to afford a required... 

These recent findings indicate overall that the ligand that remains on the metal affects the energetics of the catalytic cycle, specifically olefin coordination, and the accessibility of the metallocyclobntane stmcture, the properties of the phosphane ligand control initiation rates, and thus how much of the catalyst can enter the catalytic cycle. The results of these carefiil analyses (Table 2) are sure to germinate the next generation of efficacious olefin metathesis catalysts. 

Tn 1955 Pines and Schaap (1) discovered that toluene was alkylated by ethylene in the presence of sodium or potassium metal or, more specifically, their organometallic derivatives. This reaction requires a high temperature (about 200°C) and considerable olefin pressure the organometallic catalyst is essentially insoluble in the reaction medium. The catalyst cycle—for example, in the side-chain ethylation of toluene— involves a benzyl carbanion which adds to ethylene to form a primary alkyl carbanion. The latter immediately abstracts a proton from the excess toluene reactant to form n-propylbenzene and to reform the energetically-favored benzylic anion in a catalytic cycle. 

Scheme 7.45 Tandem conjugate hydrogen-transfer/electrophilic fluorination using cycle-specific imidazolidinone catalysts.

MacMillan and co-workers [79] pioneered the development of entirely organo-catalyzed cascade reactions. In his seminal report, iminium-catalyzed Friedel-Crafts reactions were followed by enamine-catalyzed a-chlorinations (Scheme 13.40). In this same report, an iminium-catalyzed conjugate reduction was followed by an enamine-catalyzed a-chlorination (not shown). In both of these cascade reactions, a single catalyst was used for both the iminium- and enamine-mediated reactions. Alternatively, MacMillan demonstrated that it was possible to use one catalyst for an iminium-catalyzed conjugate reduction and a different catalyst for an enamine-catalyzed a-fluorination (Scheme 13.40) [79]. Such cycle-specific cascade reactions allow access to both the anti (shown) and syn diastereomers of the product simply by using the opposite enantiomer of the catalyst for one of the two reactions in the cascade. 

Mac Millan and coworkers reported a multicatalytic approach by using a catalyst combination of imidazolidinone 8 and proline (Scheme 12.10). The cycle-specific Friedel-Crafts alkylation-amination of enals was studied with different nucleophilic components. For instance, the reaction of 1-methylindole as a Jt-nucleophile with the catalyst combination containing L-Pro (20 mol%) and 8 (10 mol%) provided the iyn-1,2-aryl amination adduct 23 with excellent yield (94%) and stereocontrol (syn/anti 14 1, ee 99%). Access to the corresponding anti isomer 24 was achieved by... 

Complex molecules have also been synthesized by sequential use of the orga-nocatalytic a-amination of aldehydes by azodicarboxylates catalyzed by some of the systems shown above and by other reaction processes, such as the Passerini reaction [40], Homer-Wadsworth-Emmons olefination [41], Wittig olefination [42], and allylation reaction followed by a ring-closing metathesis [43], In addition, the combination of catalysts in cycle-specific organocascade processes [44] has allowed the synthesis of chiral complex molecules with good results. 

Transfer hydrogenation followed by alkylation of oc,P-unsaturated aldehydes mediated by a combination of cycle-specific catalysts of 115 and ent-196 was also developed [135]. 

It is believed that monofunctional imidazolidinones are optimal for iminium catalysis but without the necessary structural features to participate in bifunctional enamine catalysis (e.g., activation of electrophiles via electrostatic interaction). Conversely, proline has proved to be an enamine catalyst for which bifunctional activation is a standard mode of operation aCTOss a variety of transformation types, yet it is generally ineffective as an iminium catalyst with enals or enones. Therefore, a combination of imidazoUdinone and proline may provide a dual-catalyst system that could fully satisfy the chemoselectivify requirements for cycle-specific catalysis [136]. 

In addition to imininm-initiated cascade reactions, two of the steps in enamine-activated cascade reactions can also be enforced by cycle-specific catalysis. It is well known that diphenylprolinol silyl ether catalyst 34 is optimal for diverse enamine-mediated transformations to fnmish prodncts with high enantioselectivities. However, similar to imidazolidinone catalysts, it proved to be less effective or ineffective for bifunctional enamine catalysis. Cycle-specific catalysis via an aza-Michael/Mannich sequence by combining 34 and either enantiomer of proline was thus developed to generate 206 in about 60% yields with excellent diastereo- and enantioselectivities (Scheme 1.89) [139]. 

In 2005, Huang et al. reported a tandem asymmetric conjugate reduction-fluorina-tion reaction by an efficient combination of iminium and enamine catalysis using two distinct secondary amine catalysts [16]. This method offered direct access to chiral multifunctionalized aldehydes from P-substituted enals and electrophilic florinated reagents in a biomimetic way (Schane 9.13). The diastereoselectivity of the products varied depending on the catalyst combination (Scheme 9.14). The chemistry presented here demonstrated for the first time the power of the multicatalysis process for control of the product diastereoselectivity based on the cycle-specific catalysis concept. 

Catalysis (qv) refers to a process by which a substance (the catalyst) accelerates an otherwise thermodynamically favored but kiaeticahy slow reaction and the catalyst is fully regenerated at the end of each catalytic cycle (1). When photons are also impHcated in the process, photocatalysis is defined without the implication of some special or specific mechanism as the acceleration of the prate of a photoreaction by the presence of a catalyst. The catalyst may accelerate the photoreaction by interaction with a substrate either in its ground state or in its excited state and/or with the primary photoproduct, depending on the mechanism of the photoreaction (2). Therefore, the nondescriptive term photocatalysis is a general label to indicate that light and some substance, the catalyst or the initiator, are necessary entities to influence a reaction (3,4). The process must be shown to be truly catalytic by some acceptable and attainable parameter. Reaction 1, in which the titanium dioxide serves as a catalyst, may be taken as both a photocatalytic oxidation and a photocatalytic dehydrogenation (5). 

Organic chloride and cycle diluent specifications are less critical since the flows are significantly less. The organic chloride specifications must prevent gross contamination as weU as the potential of soHds that would lead to plugging. The cycle diluent must also be free of gross contamination as weU as significant catalyst poisons such as sulfur (170). 

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