Toward the ideal synthesis. New transition metal-catalyzed reactions inspired by novel medicinal leads

Abstract

Studies in our laboratory are directed at the advancement of synthesis, biology, and medicine. This lecture will focus on new transition metal-catalyzed reactions that have been inspired by biologically potent targets such as phorbol and Taxol® and by the more general interest in producing syntheses that are concise, efficient, cost- and resource-effective, environmentally benign, quick, and simple to conductin essence, ideal. A special emphasis in our program is placed on new transition metal-catalyzed reactions that, in the absence of catalyst, would be forbidden or difficult to achieve. We have thus far reported the first examples of intramolecular metal-catalyzed [4+2], [5+2], and [4+4] cycloadditions, reactions that produce 6-, 7-, and 8-membered rings, respectively. Recent advances in our [5+2] cycloaddition studies will be presented, including new catalysts for relative and absolute stereochemical control. We will also describe recyclable catalysts that can be used in water, thereby minimizing cost and environmental concerns about solvent waste streams. New multicomponent reactions will also be presented. Finally, we will report a new [6+2] cycloaddition that produces an 8-membered ring.

Supersilyl Protective Groups in Aldol Reactions

“…In this vein, the concept of ''step economy'' has recently been invoked as a means of assessing the overall efficiency of a synthesis simply by evaluating the number of steps required to complete a target [61][62][63].…”

Organocatalytic Asymmetric Direct CH Functionalization of Ethers: A Highly Efficient Approach to Chiral Spiroethers

“…[4] Among the reported transformations, intramolecular redox processes for the direct functionalization of C sp 3 ÀH bonds that are a to heteroatoms are important for the synthesis of structurally diverse amine and ether derivatives. [5] Furthermore, since the pioneering work of Kim and co-workers, [6] there have many good results reported in the area of intramolecular redox processes for the direct enantioselective C sp 3 À H functionalization at positions a to nitrogen atoms.…”

“…Notably, in order to measure the ee value, the initial aldehyde product 2'' was subjected in situ to a Wittig reaction to give the corresponding unsaturated ethylester 2 a. [10] The presence of a counterion that is more weakly coordinating than ClO 4 À would lead to an iminium ion with enhanced electrophilicity (Scheme 1), thus accelerating the hydride shift. The weakly coordinating anions, BF 4 À and SbF 6 À , have been effective for many catalytic reactions.…”

“…[10] The presence of a counterion that is more weakly coordinating than ClO 4 À would lead to an iminium ion with enhanced electrophilicity (Scheme 1), thus accelerating the hydride shift. The weakly coordinating anions, BF 4 À and SbF 6 À , have been effective for many catalytic reactions. [11] Therefore, substrate 1 a was treated with 7 (the hydrochloride salt of 6) together with either AgBF 4 or AgSbF 6 (Table 1, entries 7 and 8).…”

Cycle‐Specific Organocascade Catalysis: Application to Olefin Hydroamination, Hydro‐oxidation, and Amino‐oxidation, and to Natural Product Synthesis

“…[1] Recently, our laboratory disclosed the concept of organocascade catalysis, [2][3][4] a new chemical paradigm that combines two modes of catalyst activation (iminium and enamine catalysis) into one mechanism, thereby allowing the rapid conversion of simple achiral starting materials into stereochemically complex, single-enantiomer products (! 99 % ee, Scheme 1 a).…”