Cycle-specific catalysis

Scheme 7.46 Cycle-specific catalysis in several tandem processes initiated by conjugate hydrogen-transfer reaction.

In 2005, MacMillan et al. disclosed the concept of cycle-specific catalysis, wherein each cycle in a tandem reaction is moderated by a different chiral... 

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]. 

SCHEME 1.89 Aza-Michael/Mannich cascade by cycle-specific catalysis. 

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. 

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... 

Simmons B, Walji AM, MacMillan DWC (2009) Cycle-Specific Organocascade Catalysis Application to Olefin Hydroamination, Hydro-oxidation, and Amino-oxidation, and to Natural Product Synthesis. Angew Chem Int Ed 48 4349... 

Scheme 12.10 Olefin aryl- and alkylamination by cycle-specific ca-ganocascade catalysis.

Simmons, B., Walji, A. M., Mac Millan, D. W. C. (2009). Cycle-specific organocascade catalysis appheation to olefin hydroamination, hydro-oxidation and amino-oxidation and to natural product synthesis. Angewandte Chemie International Edition, 48,4349-4353. 

Cycle-specific cascade catalysis in natural product synthesis... 

Iminium-enamine cycle-specific cascade catalysis... 

Cycle-Specific Cascade Catalysis in Natural Product Synthesis... 

As mentioned above, the development of elegant approaches based on cascade catalysis, which was inspired by nature s biosynthetic proficiency for the rapid synthesis of molecular complexity, has been considered as a new tool for target-oriented synthesis. The implementation of cycle-specific cascade catalysis also provides a... 

Enamine (/Dienamine)-Iminium Cycle-Specific Cascade Catalysis... 

The enamine (/dienamine)-iminium cycle-specific cascade catalysis is an important constituent of amine-catalyzed cascade reactions [10]. This strategy has been explored extensively and also applied to natural product synthesis. One such example is the total synthesis of dihydrocorynantheol, which was first isolated from the bark of Aspidosperma marcgravianum in 1967 [29]. This indole alkaloid is a member of the corynantheine and was found to exhibit antiparasitic, antiviral, or analgetic activities, which have attracted considerable attention from the synthetic community. Among those reported total syntheses, Itoh et al. developed a Mannich-Michael cascade reaction catalyzed by L-proline 52 for the total synthesis of ent-dihydrocorynantheol 54 (Scheme 3.8) [30], The cascade reaction of 3-ethyl-3-buten-2-one 51 with dihydro-P-carboline 50 catalyzed by 30mol% of (S)-proline afforded the tetracyclic core structure 53 in 85% yield. Excellent stereoselectivity was achieved in this cascade reaction (99% enantiomeric excess and almost complete diastereomeric control). Therefore, this organocascade reaction could lead expeditiously to construction of the core structure, which enabled the authors to accomplish the total synthesis of enl-dihydrocorynantheol 54 in just five steps. 

By merging a transition metal-catalyzed reaction with an organocatalytic cascade sequence into a cycle-specific cascade catalysis, Simmons et al. developed a new... 

Simmons B, Walji AM, MacMillan DWC. Cycle-specific organocascade catalysis application to olefin hydroamina-tion, hydro-oxidation, and amino-oxidation, and to natural product synthesis. Angew. Chem. Int. Ed. 2009 48(24) 4349-4353. 

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). 

The function of enzymes is to accelerate the rates of reaction for specific chemical species. Enzyme catalysis can be understood by viewing the reaction pathway, or catalytic cycle, in terms of a sequential series of specific enzyme-ligand complexes (as illustrated in Figure 1.6), with formation of the enzyme-substrate transition state complex being of paramount importance for both the speed and reactant fidelity that typifies enzyme catalysis. 

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