Metabolic engineering of flavonoid biosynthesis in apple by genetic transformation

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Ir-catalyzed diastereoselective isomerization of primary allylic alcohols

Efficient enantioselective isomerizations of prochiral allylic alcohols have been independently reported by our group and others in recent years. However, diastereoselective isomerization with chiral substrates had been barely documented. Herein, we have first conducted catalyst-directed diastereoselective isomerization with enantioenriched allylic alcohols using both enantiomers of catalyst. Good yields, perfect dr and excellent ee were commonly obtained. Later, we evaluated steroidal allylic alcohols in the catalyst-directed diastereoselective isomerization for the stereocontrolled installation of C20, the first tertiary stereocenter of the acyclic domain in steroid derivatives. Following a uniform yet modular synthetic route to prepare a variety of steroidal allylic alcohols, a range of allylic alcohols were employed in the diastereoselective isomerization. (R)-Catalyst provided indifferently access to the natural C20-(R) and unnatural C20-(S) configurations. The scope of our method was further highlighted through structural diversification in the side chain and within the polycyclic domain of advanced and complex steroidal architectures

Catalyst-Directed Diastereoselective Isomerization of Allylic Alcohols for the Stereoselective Construction of C(20) in Steroid Side Chains: Scope and Topological Diversification

The stereoselective construction of C20 in steroidal derivatives by a highly diastereoselective Ir-catalyzed isomerization of primary allylic alcohols is reported. A key aspect of this strategy is a straightforward access to geometrically pure steroidal enol tosylate and enol triflate intermediates for subsequent high yielding stereoretentive Negishi cross-coupling reactions to allow structural diversity to be introduced. A range of allylic alcohols participates in the diastereoselective isomerization under the optimized reaction conditions. Electron-rich and electron-poor aryl or heteroaryl substituents are particularly well-tolerated, and the stereospecific nature of the reaction provides indifferently access to the natural C20-(R) and unnatural C20-(S) configurations. Alkyl containing substrates are more challenging as they affect regioselectivity of iridium-hydride insertion. A rationale for the high diastereoselectivities observed is proposed for aryl containing precursors. The scope of our method is further highlighted through topological diversification in the side chain and within the polycyclic domain of advanced and complex steroidal architectures. These findings have the potential to greatly simplify access to epimeric structural analogues of important steroid scaffolds for applications in biological, pharmaceutical, and medical sciences

Organometallic Complexes of Iridium

This chapter is an update to the earlier Science of Synthesis contribution (Section 1.6) that covers literature from 1999 to the first half of 2013. While Section 1.6 provided a fantastic overview of the different types of organometallic complexes of iridium and their preparation, this contribution aims at focusing more on their applications in homogeneous catalysis

Steric Parameters in the Ir-Catalyzed Regio- and Diastereoselective Isomerization of Primary Allylic Alcohols

The iridium-catalyzed diastereo- and regioselective isomerization of primary allylic alcohols using Crabtree's catalyst or sterically modified analogs is reported. The importance of the size of the substituents on either the substrates or the catalysts has been rationalized by linear free energy relationships

Iridium-Catalyzed Selective Isomerization of Primary Allylic Alcohols

This Account presents the development of the iridium-catalyzed isomerization of primary allylic alcohols in our laboratory over the past 8 years. Our initial interest was driven by the long-standing challenge associated with the development of a general catalyst even for the nonasymmetric version of this seemingly simple chemical transformation. The added value of the aldehyde products and the possibility to rapidly generate molecular complexity from readily accessible allylic alcohols upon a redox-economical isomerization reaction were additional sources of motivation. Certainly influenced by the success story of the related isomerization of allylic amines, most catalysts developed for the selective isomerization of allylic alcohols were focused on rhodium as a transition metal of choice. Our approach has been based on the commonly accepted precept that hydrogenation and isomerization are often competing processes, with the latter being usually suppressed in favor of the former. The cationic iridium complexes [(Cy3P)(pyridine)Ir(cod)]X developed by Crabtree (X = PF6) and Pfaltz (X = BArF) are usually considered as the most versatile catalysts for the hydrogenation of allylic alcohols. Using molecular hydrogen to generate controlled amounts of the active form of these complexes but performing the reaction in the absence of molecular hydrogen enabled deviation from the typical hydrogenation manifold and favored exclusively the isomerization of allylic alcohols into aldehydes. Isotopic labeling and crossover experiments revealed the intermolecular nature of the process. Systematic variation of the ligand on the iridium center allowed us to identify the structural features beneficial for catalytic activity. Subsequently, three generations of chiral catalysts have been investigated and enabled us to reach excellent levels of enantioselectivity for a wide range of 3,3-disubstituted aryl/alkyl and alkyl/alkyl primary allylic alcohols leading to β-chiral aldehydes. The combination of the isomerization reaction with enamine catalysis in a sequential process gave access to α,β-chiral aldehydes in high diastereomeric ratio and excellent enantioselectivity. Catalyst-controlled diastereoselective isomerization of stereochemically complex steroid scaffolds has been achieved, giving access indifferently to derivatives with the natural and unnatural C20 configuration, a long-standing challenge in the field. Structural diversification at close proximity of the reactive site and within the polycyclic domain served to further demonstrate the generality and the potential of the method. Models based on quadrant diagrams enabled rationalization of the high levels of enantio- and diastereocontrol obtained in the isomerization of allylic alcohols

Well-defined transition metal hydrides in catalytic isomerizations

This Feature Article intends to provide an overview of a variety of catalytic isomerization reactions that have been performed using well-defined transition metal hydride precatalysts. A particular emphasis is placed on the underlying mechanistic features of the transformations discussed. These have been categorized depending upon the nature of the substrate and in most cases discussed following a chronological order

Efficient Generation of <i>ortho</i>-Quinone Methide: Application to the Biomimetic Syntheses of (±)-Schefflone and Tocopherol Trimers

An efficient method using silver oxide-mediated oxidation for the synthesis of <i>ortho</i>-quinone methides has been developed and applied to the biomimetic syntheses of novel trimeric natural products, (±)-schefflone and tocopherol trimers. Further studies of the critical trimerization as well as substrate scope and limitations are also reported