Search

In this Perspective, we describe an emerging type of catalysis that enables the catalytic reversible transfer of chemical entities beyond the well-established transfer hydrogenation reactions. Shuttle catalysis facilitates the transfer of small molecules (e.g., CO, HCN) or reactive intermediates between two substrates in an isodesmic process. In many cases, these often safer processes provide unprecedented synthetic flexibility and complement other catalytic bond-forming and bond-breaking reactions.

The selective deoxygenation of polyols is an important frontier in our ability to transform biomass-derived compounds and other synthetic intermediates. In this Synpacts article, recent approaches using a B(C6F5)3/silane combination to site-selectively deoxygenate polyols are highlighted. First, the work of Gagne and coworkers is discussed. They developed a partial, selective deoxygenation of biologically sourced polyols proceeding through an elegant example of anchimeric assistance. In the second part, we present our recent work describing a catalytic deoxygenation of terminal diols with selectivity for the cleavage of the primary hydroxyl group. This transformation was enabled by the strategic formation of a cyclic siloxane intermediate. 1 Introduction 2 Background 3 Selective Deoxygenation of Carbohydrates 4 Selective Deoxygenation of Terminal Diols at the Primary Position 5 Conclusion

Aryl-substituted amino alcohols are privileged scaffolds in medicinal chemistry and natural products. Herein, we report that an exceptionally simple and inexpensive Fe(II) complex efficiently catalyzes the direct transformation of simple alkenes into unprotected amino alcohols in good yield and perfect regioselectivity. This new catalytic method was applied in the expedient synthesis of bioactive molecules and could be extended to aminoetherification.

Nitriles and alkenes are important synthetic intermediates with complementary reactivity that play a central role in the preparation of materials, pharmaceuticals, cosmetics, and agrochemicals. Here, we report a nickel-catalyzed transfer hydrocyanation reaction between a wide range (60 examples) of alkyl nitriles and alkenes. This strategy not only overcomes the toxicity challenge posed by the use of HCN in traditional approaches, but also encompasses distinct chemical advances, including retro-hydrocyanation and anti-Markovnikov regioselectivity. In a broader context, this work highlights an approach to the reversible hydrofunctionalization of alkenes through thermodynamically controlled transfer reactions to circumvent the use of volatile and hazardous reagents in the laboratory.

The selective deoxygenation of polyols is a frontier in our ability to harness the stereochemical and structural complexity of natural and synthetic feedstocks. Herein, we describe a highly active and selective boron-based catalytic system for the selective deoxygenation of terminal 1,2-diols at the primary position, a process that is enabled by the transient formation of a cyclic siloxane. The method provides an ideal complement to well-known catalytic asymmetric reactions to prepare synthetically challenging chiral 2-alkanols in nearly perfect enantiomeric excess, as illustrated in a short synthesis of the anti-inflammatory drug (R)-lisofylline.

The title procedure under conditions A) renders possible a rapid and successful access to the desired ketones.

The aldehyde-selective oxidation of alkenes bearing diverse oxygen groups in the allylic and homoallylic position was accomplished with a nitrite-modified Wacker oxidation. Readily available oxygenated alkenes were oxidized in up to 88% aldehyde yield and as high as 97% aldehyde selectivity. The aldehyde-selective oxidation enabled the rapid, enantioselective synthesis of an important pharmaceutical agent, atomoxetine. Finally, the influence of proximal functional groups on this anti-Markovnikov reaction was explored, providing important preliminary mechanistic insight.

A Wacker-type oxidation of unbiased alkenes (I) affords the anti-Markovnikov aldehyde products (II) as major products.

The key aspect of the title reaction is the identification of a wide range of directing groups for enabling a regioselective Wacker oxidation of internal alkenes.

A method to synthesize different substituted α-trifluoromethyl acetals via an insertion strategy is developed.

The one-pot two-step procedure affords the desired products, which are of interest in drug development, with complete regioselectivity and high cis-diastereoselectivity.

Electron-donating and electron-withdrawing substrates produce aromatic cyclopropyl esters in good isolated yields of pure trans-products [cf.

Direct access to 3-trifluoromethyl-substituted benzofuranols is presented. The products are obtained in good yields from commercially available salicylaldehydes by using in situ generated trifluoromethyl diazomethane and boron trifluoride as an activator. As shown in a representative example, the products can be transformed into the corresponding trifluoromethyl-substituted benzofurans.

The new approach includes diazotation of trifluoroethylamine (I) followed by ZrCl4-promoted reaction of the resulting trifluorodiazoethane with aldehydes.

Optically active cyclopropanes bearing a trifluoromethyl group are obtained with high enantioselectivities by reaction of styrene derivatives with trifluoromethyl diazomethane generated in situ.

A catalytic decarbonylation reaction for epoxyaldehydes is reported. This reaction may be sequentially used with known asymmetric methods to access optically active mono- and disubstituted terminal epoxides, as illustrated for a key example.

The enantioselective total synthesis of the actin-targeting metabolite (−)-microcarpalide is described. Key steps include ring-closing metathesis (RCM) for the final construction of the 10-membered lactone framework and stereoselective homologation of boronic esters for the insertion of all stereocentres with the desired absolute configuration. In particular, the acidic fragment was prepared in seven steps from a suitable chiral bromomethane boronate by means of two sequential stereoselective homologations to install the two stereocentres with the correct final R stereochemistry, employing (−)-pinanediol as the chiral director. Subsequent elaboration to the required C 7 backbone entailed nucleophilic displacement with a vinyl Grignard reagent, oxidative cleavage of the boronic scaffold and protection–deprotection manipulations. Interestingly, when the tribenzyloxy diene ester resulting from DCC-mediated coupling of the two key synthons was subjected to RCM in the presence of Grubbs' catalyst, the reaction proceeded stereoselectively to yield the desired trans oxecin-2-one, albeit with poor conversion.