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The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development in carbonyl and carboxyl deoxygenative functionalizations, highlighting some representative and significant contributions in this field. These advances are categorized based on the reactivity patterns of some oxygenated feedstock compounds, including aldehydes, ketones and carboxylic acids. Four types of reactive intermediates arising from aldehydes and ketones during the deoxygenation, namely, bis-electrophiles, carbenoids, bis-nucleophiles and alkyl radical equivalents, are presented, while the carboxylic acids mainly behave as tris-electrophiles when deoxygenated. In each subcategory, selected examples are organized according to the type of bond formation and discussed from a generalized mechanistic perspective.

Cross-coupling reaction between two C-H bonds has become a fundamental strategy in synthetic organic chemistry. With its increasing importance in green chemistry, atom economy, and step economy, its development has sky-rocketed within the last 20 years, with the term "cross-dehydrogenative coupling (CDC)" popularized and progressed by the group of Li and others to describe direct Y-Z bond formations from Y-H and Z-H bonds under oxidative conditions. Among all types of CDC reactions, the C-C bond formations are of prime importance in building up the molecular complexity but their categorization currently remains disarray due to a wide diversity, resulting in frequent display in separate topics. In this Perspective, a contemporary categorization via C-H activation strategies is presented herein, which could be vital for future CDC designs. With this mechanism-based categorization and discussion, we wish that this minireview will help more synthetic chemists gain insight into the design of CDC reactions and inspires more ideas on this topic.

Direct conversion of aldehydes and ketones into alkylboronic esters via deoxygenative borylation represents an unknown yet highly desirable transformation. Herein, we present a one-step and metal-free method for carbonyl deoxy-borylation under mild conditions. A wide range of aromatic aldehydes and ketones are tolerated and successfully converted into the corresponding benzylboronates. By the same deoxygenation manifold with aliphatic aldehydes and ketones, we also enable a concise synthesis of 1,1,2-tris(boronates), a family of compounds that currently lack efficient synthetic methods. Given its simplicity and versatility, we expect that this novel borylation approach could show great promise in organoboron synthesis and inspire more carbonyl deoxygenative transformations in both academic and industrial settings.

A metal-free protocol for accessing both α and δ-carboline derivatives, starting from a common indolylchalcone oxime ester precursor is reported. The reaction involves mild conditions and uses a regiodivergent approach. DDQ is used as a switching agent in selectively generating α and δ-carboline derivatives in good to moderate yields.

Simple and straightforward methods for the synthesis of 2-benzylbenzofuran, 3-substituted 2-benzylbenzofuran, and 2-aryl-nitrochroman derivatives are described. Benzofurans were generated from nitroalkenes by reduction with NaBH4 followed by a Nef reaction and acid-mediated cyclization, whereas 3-substituted 2-benzylbenzofurans were prepared from nitroalkenes by reactions with Grignard reagents followed by a Nef reaction and an acid-mediated cyclization in a one-pot process. The synthesis of chromans involved a Knoevenagel condensation and the 1,4-diazabicyclo[2.2.2]octane (DABCO) assisted cyclization of β-(2-hydroxyphenyl)-nitroethanes and benzaldehydes, also in a one-pot process.

An efficient and straight forward procedure for the syntheses of bicyclic isoxazole/isoxazoline derivatives from the corresponding dimethyl-2-(2-nitro-1-aryl/alkyl)-2-(prop-2-yn-1yl)malonates or dimethyl 2-allyl-2-(2-nitro-1-aryl/alkyl ethyl)malonate is described. High yields and simple operations are important features of this methodology.

An efficient approach for the synthesis of benzo-fused pyridoindolone derivatives via a one-pot copper catalyzed tandem reaction of 2-iodobenzamides with 2-iodobenzylcyanides has been developed. Using this protocol, benzo-fused pyridoindolone derivatives are obtained in high yields in a relatively short period of time under mild reaction conditions. To the best of our knowledge, this is the first approach where one can synthesize free indole N–H benzo-fused pyridoindolones. Also, both indole and pyridone cores are constructed during the course of the reaction. The methodology shows good functional group tolerance and allows synthesis of thiophene-fused pyridoindolones and fused indolobenzonaphthyridone derivatives.

The dual character of benzoquinone is exploited for the synthesis of benzo[a]carbazole derivatives starting from 3-ethylindole derivatives. A diene is generated in situ from the 3-ethylindole derivative with the help of benzoquinone, where it acts as an oxidizing agent. Later it serves as a dienophile and participates in a Diels–Alder reaction with the diene to afford benzo[a]carbazole derivatives.

The development of structure-activity relationships (SARs) relating to the function of a biological protein is often a long and protracted undertaking when using an iterative medicinal chemistry approach. High throughput screening of ECLiPS®(Encoded Combinatorial Libraries on Polymeric Support) libraries can be used to simplify this process. In this paper we illustrate how a large ECLiPS library of 26,908 compounds, based on a tricyclic core structure, was used to define a multitude of SARs for the oncogenic target, farnesyltransferase (FTase). This library, FT-2, was prepared using a split-and-pool approach in which small molecules are constructed on resin that contains tag/linker constructs to track the synthetic process [1-5]. Highly defined SARs were produced from this screen that enhanced our understanding of FTase binding site interactions. The pivotal compounds culled from this library were potent in both cell-free and cell-based FTase assays, selective over the closely related enzyme, geranylgeranyltransferase I (GGTase I), and inhibited the adherent- independent growth of a transformed cell line.

Farnesyltransferase inhibitors identified from an ECLiPS® library were optimized using solution-phase synthesis. X-ray crystallography of inhibited complexes was used to identify substructures that coordinate to the active site zinc. The X-ray structures were ultimately used to guide the design of second-generation analogs with FTase IC50s of less than 1.0 nM.

In order to fully explore structure-activity relationships at the 1- and 2-positions of the piperazine core of tricyclic farnesyltransferase inhibitors, an 11,718-member ECLiPS library was synthesized and screened in a farnesyltransferase scintillation proximity assay. A detailed description of the library and analyses of the screening data will be provided.

New and stereoselective syntheses of (1,2,3/4)-, (1,2/3,4)-, (1,4/2,3)-, and (1,2,4/3)-cyclohexanetetrols (1, 2, 3, and 4 respectively) are described. The known syn and anti 1,4-cyclohex-2-enediols 9 and 10 were used as starting materials. Diols 9 and 10 were allow to react with OsO4 to directly form 3 and 1 respectively. Diols 9 and 10 were epoxidized with MCPBA, which yielded 4 and 2 after acid catalyzed epoxide opening.

Treatment of secondary amines with a (dimethoxybenzoin)carbonylimidazolium salt provides dimethoxybenzoin carbamates that can be deprotected photochemically.

A polyaza cleft was synthesized and shown to bind 1,2- and 1,3-cyclohexanediols and 1,3-2-cyclohexanetriol in chloroform.

A method has been developed to spatially define the immobilization of proteins on surfaces using the classic avidin-biotin link, for which a wide variety of biochemical reagents are commercially available. A derivative of biotin bearing a photoremovable nitrobenzyl group (MeNPOC-biotin) has been prepared in a form suitable for simple linkage to biomolecules and surfaces. It has been used to functionalize bovine serum albumin (BSA) to form MeNPOC-biotin-BSA, which can then be coated onto glass. On photolithographic patterning of the surface, biotins are freed in the irradiated areas, permitting avidin to be localized at the irradiated sites. Subsequent addition of a biotinylated molecule permits its site-specific localization. Patterning of a biotinylated antibody and dye-labeled avidins or streptavidin using this reagent has been demonstrated by fluorescence microscopy.

In order to maximize the applications of advanced optical techniques for immunoassay it is critical that one can analyze multiple analytes simultaneously. One method of creating a multiple analyte sensor is to pattern antibodies against ligands of interest onto distinct regions of a single waveguide for fluorescence immunoassay. To achieve protein patterning, we are using a photolabile protected biotin with the caging moiety MeNPOC, (methyl nitropiprionyloxy carbonyl). The biotin molecules within a given region are selectively deprotected by exposure to ultraviolet light and subsequently bound to streptavidin. Incubation with a biotinylated antibody results in a functionalized region on the surface. This paper characterizes the method for immobilizing caged biotin onto the wave guide surface. Two surface biotinylation methods were examined silane coupling via aminpropyl triethoxy silane to a biotin-MeNPOC ester, and adsorption of biotin-MeNPOC conjugated bovine serum albumin. Using an I-125 label, protein surface densities have been determined for streptavidin bound to protected and deprotected surfaces. In addition, the duration of ultra-violet light exposure was evaluated to assess the ultimate effect on bound protein. The ability of an antibody bound within a patterned region to detect its corresponding analyte was determined.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.