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We present a novel synthetic approach for the synthesis of the 1,2,3-triazole core, with a particular focus on the direct and regioselective synthesis of the synthetically more challenging triazoles having additional substituents at the N 2 nitrogen atom. Through treatment of readily accessible geminal diazides with organic hydrazines under mild thermolysis conditions, a broad spectrum of N 2 -alkyl- and N 2 -aryl-1,2,3-triazoles are easily generated. For example, geminal diazides derived from ketoesters, ketoamides, and ketones were converted under the reaction conditions. The product structures were confirmed via NMR as well as single-crystal structure analysis.

Herein, we report a concise and efficient formal synthesis of (+)-hannokinol. Key to this new strategy is the use of a chiral Horner-Wittig reagent, readily available from 2-deoxy-D-ribose, to introduce the chiral 1,3-diol motif.

The synthesis of polyketide natural products has been a captivating pursuit in organic chemistry, with a particular focus on selectively introducing 1,3-polyol units. Among these natural products, Marinomycins A-D have garnered substantial interest due to their exceptional structural features and potent cytotoxicity. In this paper, we present a novel approach for synthesising the monomeric counterparts of Marinomycin A and B. Our method employs a previously established iterative cycle in conjunction with a standardised polyketide building block. Through this strategy, we showcase a promising pathway towards total and partial syntheses of these intriguing natural products.

One of the most useful transformations in the synthetic chemist arsenal is the oxidation of alcohols to their corresponding carbonyl congeners. Despite its seemingly straightforward nature, this transformative reaction predominantly relies on the use of metals or hazardous reagents, making these processes highly unsustainable. To address this challenge, we have developed a sustainable metal-free method for the oxidation of alcohols in continuous flow. Using a solid phase hypervalent iodine catalyst and nBu 4 HSO 5 as a phase transfer catalyst and co-oxidant, primary and secondary alcohols were selectively oxidized to the corresponding carbonyl motifs. This operationally simple continuous-flow set-up is highly robust (15 cycles run without significant catalyst leaching or loss of reaction efficiency), uses green solvents, such as acetonitrile or acetic acid, and is readily scalable., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Aureosurfactin is a novel biosurfactant that exhibits similar surface tension activity to known biosurfactants. In this work, we now report a facile synthesis for aureosurfactin using a bidirectional synthetic strategy. Both enantiomers of the target compound were accessed from the ( S )-building block, derived from the same chiral pool starting material.

The modular synthesis of 1,3-polyols using a chiral phosphine oxide building block is reported. This versatile building block works in a repetitive way for the stereocontrolled synthesis of a tetraol key intermediate, which serves for the first total synthesis of the potentially anti-inflammatory natural product cryptoconcatone D. A new route toward the chiral building block is also presented: Starting from 2-deoxy-d-ribose, the optimized sequence now makes the use of the building block more attractive to practicing chemists again.

Epoxy- and hydroxy-fatty acids are physiologically active lipid mediators which are formed from arachidonic acid and other fatty acids by cytochrome P450 monooxygenase (CYP) catalytic activity. In this study, we investigated the structure-activity relationship of the inhibition of fatty acid-oxidizing CYP by flavonoids. A sum of 65 naturally occurring as well as new flavonoids were synthesized and tested in a multi-enzyme assay. Substituents at C2' and C7-position of the flavone structure caused epoxygenase blockade, while electronegative substituents at C4'-position led to ω-hydroxylase-selective inhibition. We identified 4'-trifluoromethylflavone as a potent and selective compound, inhibiting 20-HETE formation with an IC 50 of 2.8 μM (1.3 μM-6.1 μM) in human liver microsomes. This inhibition is achieved by selective inhibition of CYP4F2 [IC 50 : 0.76 μM (0.42 μM-1.4 μM)], while the other human ω-hydroxylating CYP, CYP4A11, is not affected. The compound is also active in microsomes from rat and mouse liver [IC 50 : 1.4 μM (0.77 μM-2.7 μM) and 0.71 μM (0.24 μM-2.2 μM), respectively]. Moreover, it exhibits moderate permeability properties in PAMPA and CaCo-2 transwell systems (p app : 4.6 ± 0.6 × 10 -6  cm/s and 4.1 ± 0.4 × 10 -6  cm/s, respectively) and is stable to metabolic conversion in vitro. With this inhibitor, we provide a novel tool to selectively investigate the CYP4F2-catalyzed 20-HETE formation and its role in physiology., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Lipoxygenases (ALOX) are lipid peroxidizing enzymes that catalyze the biosynthesis of pro- and anti-inflammatory lipid mediators and have been implicated in (patho-)physiological processes. In humans, six functional ALOX isoforms exist and their arachidonic acid oxygenation products have been characterized. Products include leukotrienes and lipoxins which are involved in the regulation of inflammation and resolution. Oxygenation of n3-polyunsaturated fatty acids gives rise to specialized pro-resolving mediators, e.g. resolvins. However, the catalytic activity of different ALOX isoforms can lead to a multitude of potentially bioactive products. Here, we characterized the patterns of oxygenation products formed by human recombinant ALOX5, ALOX15, ALOX15B and ALOX12 from eicosapentaenoic acid (EPA) and its 18-hydroxy derivative 18-HEPE with particular emphasis on double and triple oxygenation products. ALOX15 and ALOX5 formed a complex mixture of various double oxygenation products from EPA, which include 5,15-diHEPE and various 8,15-diHEPE isomers. Their biosynthetic mechanisms were explored using heavy oxygen isotopes (H 2 18 O, 18 O 2 gas) and three catalytic activities contributed to product formation: i) fatty acid oxygenase activity, ii) leukotriene synthase activity, iii) lipohydroperoxidase activity. For ALOX15B and ALOX12 more specific product patterns were identified, which was also the case when these enzymes reacted in concert with ALOX5. Several double oxygenated compounds were formed from 18-HEPE by ALOX5, ALOX15B and ALOX12 including previously identified resolvins (RvE2, RvE3), while formation of triple oxygenation products, e.g. 5,17,18-triHEPE, required ALOX5. Taken together our data show that EPA can be converted by human ALOX isoforms to a large number of secondary oxygenation products, which might exhibit bioactivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A novel ring expansion based on the readily available 2-azido-2-phenyl-indan-1,3-dione is described. Treatment with primary amines and cesium carbonate in a two-step sequence gives rise to 3-amino-2,3-dihydroisoquinoline-1,4-diones with an unprecedented substitution pattern. The corresponding conversion using amino acid methyl esters leads directly to a novel tricyclic 1,10a-dihydroimidazo-isoquinoline-2,5,10-trione scaffold, a structure that has never been reported before, to the best of our knowledge.

In recent years, the non-covalent interaction of halogen bonding (XB) has found increasing application in organocatalysis. However, reports of the activation of metal-ligand bonds by XB have so far been limited to a few reactions with elemental iodine or bromine. Herein, we present the activation of metal-halogen bonds by two classes of inert halogen bond donors and the use of the resulting activated complexes in homogenous gold catalysis. The only recently explored class of iodolium derivatives were shown to be effective activators in two test reactions and their activity could be modulated by blocking of the Lewis acidic sites. Bis(benzimidazolium)-based halogen bonding activators provided even more rapid conversion, while the non-iodinated reference compound showed little activity. The role of halogen bonding in the activation of metal-halogen bonds was further investigated by NMR experiments and DFT calculations, which support the mode of activation occurring via halogen bonding., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Rubazonic acids are a class of dyes that are long-known, but studies on their syntheses and uses are rare. We now describe an experimentally simple and highly practical one-pot procedure for their synthesis starting from easily accessible 1 H -pyrazol-5(4 H )-ones. This protocol provides direct access to a broad range of the desired rubazonic acid derivatives through oxidative diazidation combined with a reductive work-up, without the need to isolate the potentially hazardous diazido compounds generated en route the target compounds. We also show how more challenging variants of rubazonic acid are efficiently prepared using an alternative two-step procedure and controlled hydrogenation conditions.

A new synthetic route toward the tetrazole core is described, which is based on a general fragmentation pattern that was found in a range of compounds featuring geminal diazido units. Through a simple two-step procedure, the synthesis of structurally diverse target compounds containing a tetrazole, such as tetrazoloquinoxalinones, benzoylaryltetrazoles, tetrazolotriazinones, and tetrazoloazepinones, was easily accomplished, starting from broadly accessible substrates (i.e., oxindoles, diarylethanones, pyrazolones, and phenanthrols). The initial oxidative diazidation reaction with iodine and sodium azide under mild conditions is followed by the thermal fragmentation under microwave irradiation, leading to the tetrazole products. Noteworthy, an experimental solution is presented in which the potentially hazardous diazide intermediates are not isolated and the concentration of crude reaction mixtures containing diazides is not required to achieve the tetrazoles in good yields., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Diazidated malonamides derived from amines and diazidated diethyl malonate react with lithiated alcohols through nucleophilic substitution reactions where azide acts as an unconventional leaving group. This deazidoalkoxylation leads to the formal construction of N, O-acetals, and the remaining azide functionality is a useful entry point for further functionalizations through, for example, standard cycloaddition chemistry. Thus, the presented chemistry provides an easy route toward densely functionalized molecules: Amines, alcohols, and alkynes can be attached onto the small malonate core unit in a sequential manner.

The synthesis of previously unknown 3,3-diazidooxindoles as synthetically useful derivatives of isatins was accomplished through the direct oxidative diazidation of 2-oxindoles. The method yielded the diazido compounds from the starting oxindoles under mild and simple conditions with NaN 3 and iodine, in good yields. The notable reactivity of this new class of compounds toward primary and secondary nucleophilic amines is also described, which gives access to either 4-imino-3,4-dihydroquinazolin-2(1 H)-one derivatives or cyanophenylureas.

Objective: The purpose of this study was to identify factors that predict parent satisfaction (PS) with their child with autism spectrum disorder (ASD)'s visit to a hospital emergency department (ED) or urgent care (UC) center., Methods: Parents recruited through a national database whose child (3-21 years; N = 378) with ASD had been treated in an ED/UC center within the previous 3 years completed an anonymous on-line questionnaire. They answered questions about whether they were satisfied overall with the visit and the care provided, their demographics, patient characteristics, their expectations and preparation for the visit, and the ED/UC center experience itself, including their observations of staff interpersonal and communication skills (ICSs) and behaviors, and whether the patient was disruptive (D). Multiple correspondence analysis (MCA) was used to demonstrate the relative effects of individual variables on PS., Results: Among the 10 most important determinants of PS with the visit were the 9 assessed staff ICS behaviors. These were followed by shorter than expected waiting time and the patient not being disruptive (ND) during the visit. PS was not associated with any of the 3 measures of patient disability severity (ASD subtype, communicative competence, or restrictiveness of educational placement), whether the patient is hyperreactive to sensory stimuli, reason for the visit, or parent's education., Conclusion: PS with an ED/UC center visit when the patient has autism depends mostly on the quality of staff interactions with the patient and family. It is important for ED/UC center administrators to ensure that staff understand how to interact and communicate effectively with patients with ASD and their families.

The degradation of geminal diazides is described. We show that diazido acetates are converted into tetrazoles through the treatment with bases. The reaction of dichloro ketones with azide anions provides acyl azides, through in situ formation of diazido ketones. We present experimental and theoretical evidence that both fragmentations may involve the generation of acyl cyanide intermediates. The controlled degradation of terminal alkynes into amides (by loss of one carbon) or ureas (by loss of two carbons) is also shown.

It is shown how imidazolinones are reduced by trichlorosilane in a highly enantioselective fashion when treated with a novel Lewis base organocatalyst that is based on a 2,2'-bispyrrolidine core. Under mild reaction conditions and with low catalyst loading the hydrosilylation reaction provides a broad range of chiral imidazolidinones with various structural motifs including sterically demanding substituents, alkyls and aryls.

A mild and convenient protocol for the oxidative cleavage of 1,3-diketone compounds is described. Under metal-free conditions, the method converts the 1,3-dicarbonyls into amides when treated with (nBu 4 N)N 3 and iodine in the presence of an amine at room temperature. Using this method, a range of 1,3-dicarbonyls with various structural motifs including sterically demanding substituents and ordinary functional groups were easily fragmented, and it is demonstrated that cyclic 1,3-dicarbonyls can be directly transformed into acyclic diamides through ring-opening. Initial mechanistic studies show that diazidation of the enol form is followed by nucleophilic substitution with the amine.

A concept for site selective acylation of poly-hydroxylated substrates is presented where polymer-supported catalysts are employed: catalytically active DMAP units were combined with a library of small molecule peptides attached to the solid phase with the goal to identify substrate-optimized catalysts through library screening. For selected examples, we demonstrate how the optimized catalysts can convert "their" substrate with a markedly enhanced site-selectivity, compared to only DMAP. Due to the solid support, product purification is significantly simplified, and the peptidic catalysts can be easily reused in multiple cycles while conserving its efficiency.

An operationally simple protocol for the rapid and efficient construction of highly substituted 3-hydroxypyridines is presented. The thermally induced cyclization of easily constructed geminal diazides derived from β-ketoesters having an additional olefin moiety affords the title compounds in yields up to 97% under reagent-free conditions. The new method allows for the synthesis of preparative quantities of material. Additionally, the synthetic utility of the pyridine products for the synthesis of valuable heterocycles is described.

The acylation of alcohols catalyzed by N,N-dimethylamino pyridine (DMAP) is, despite its widespread use, sometimes confronted with substrate-specific problems: For example, target compounds with multiple hydroxy groups may show insufficient selectivity for one hydroxyl, and the resulting product mixtures are hardly separable. Here we describe a concept that aims at tailor-made catalysts for the site-specific acylation. To this end, we introduce a catalyst library where each entry is constructed by connecting a variable and readily tuned peptide scaffold with a catalytically active unit based on DMAP. For selected examples, we demonstrate how library screening leads to the identification of optimized catalysts, and the substrates of interest can be converted with a markedly enhanced site-selectivity compared with only DMAP. Furthermore, substrate-optimized catalysts of this type can be used to selectively convert "their" substrate in the presence of structurally similar compounds, an important requisite for reactions with mixtures of substances., (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

A versatile process for the construction of 1,3-polyols, a key structural element of polyketide-type natural products, is presented. The modular synthesis strategy involves the iterative chain elongation with novel four-carbon building blocks to access all possible stereoisomers of a growing 1,3-polyol chain. These chiral building blocks are designed to install four carbon atoms with two stereogenic centres by performing only four experimentally simple steps per elongation cycle, thus making these building blocks attractive for the realization of a universal platform from which to access a diverse range of polyketidic molecules.

A range of geminal bis- and tristriazoles are presented. These rare and hardly studied compound classes were easily synthesized using ethyl 2,2-diazido-3-oxobutanoate as the common starting point. Firstly, CuAAC-reaction with an alkyne afforded the corresponding deacetylated bistriazoles. Upon further azidation yielding azidomethylenebistriazoles, a second CuAAC-functionalization then led to the creation of the geminal tristriazole compounds.

Geminal diazides constitute a rare class of compounds where only a limited number of methods are available for their synthesis. We present the reaction of 1,3-dicarbonyl compounds (as exemplified by malonates, 3-oxoesters, and 1,3-diketones) with molecular iodine and sodium azide in aqueous DMSO providing a general access to geminal diazides. A broad range of geminal diazides with various structural motifs including sterically demanding substituents and ordinary functional groups were synthesized, and it was shown that the diazidation of 1,3-dicarbonyls can be selectively achieved even in the presence of other 1,3-dicarbonyls with substituents at 2-position. Additionally, several diazides were studied regarding their thermal stability.

This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide (2) and tetraazidomethane (105) is described in separate sections.

Two new gold(I)-catalyzed cascade reactions of 4-hydroxy- and 4-silyloxy-1,5-allenynes are disclosed, offering access to a variety of mono- and bicyclic, polyunsaturated carbonyl compounds. The diverse reactivity observed for the investigated allenyne system is controlled by the nature of the unsaturated substrate: Allenynes bearing a free hydroxyl group engage in what is likely an oxycyclization/allene-ene carbocyclization cascade, while their silylated analogues are converted through a carbocyclization/pinacol-type rearrangement process.

Phosphane and N-heterocyclic carbene ligated gold(I) chlorides can be effectively activated by Na[Me3NB12Cl11] (1) under silver-free conditions. This activation method with a weakly coordinating closo-dodecaborate anion was shown to be suitable for a large variety of reactions known to be catalyzed by homogeneous gold species, ranging from carbocyclizations to heterocyclizations. Additionally, the capability of 1 in a previously unknown conversion of 5-silyloxy-1,6-allenynes was demonstrated., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Three simple methods for the synthesis of geminal triazides are described: Starting from 1) 3-oxocarboxylic acids, 2) iodomethyl ketones, or 3) terminal olefins, a range of triazidomethyl ketones can be constructed under mild oxidative reaction conditions by the use of IBX-SO3 K, a sulfonylated derivative of 2-iodoxybenzoic acid (IBX), and NaN3 as an azide source. This is the first report of representatives of this novel class of triazide compounds: Despite their high nitrogen content, the geminal triazides are easy to handle, even when preparative-scale syntheses are performed. (Caution: These procedures still require protective measures!) The triazides are now broadly available for further studies regarding their properties and reactivity. Furthermore, we show how the method can be used to provide α-azidoesters, which are potential building blocks for amino acids., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This article presents recent progress in the conversion of propargyl vinyl ethers into heterocyclic scaffolds and how this goal can be reached in a diversity-oriented approach. The article also includes examples of transformations of propargyl vinyl ethers where the propargyl vinyl ether moieties are formed in situ. Furthermore, related reactions transforming propargyl vinyl amines to heterocycles are discussed.

The electrophilic cyclization of 3-silyloxy-1,5-enynes and 3-silyloxy-1,6-enynes was investigated. In the presence of N-iodosuccinimide (NIS), the title compounds are transformed under metal-free conditions into five-membered carbocycles with all-carbon stereogenic centers following a sequence of iodonium activation of the triple bond, carbocyclization, and pinacol-type 1,2-shift.

Background: The aims of the present study were to examine the association between a common serotonin transporter gene (SLC6A4) polymorphism 5-HTTLPR/rs25531 with severity of attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptoms., Methods: Mothers and teachers completed a validated DSM-IV-referenced rating scale for ADHD and ASD symptoms in 118 children with ASD., Results: Analyses indicated that children with at least one copy of the S or L(G) allele obtained significantly more severe maternal ratings of hyperactivity (p=0.001; ηp(2)=0.097) and impulsivity (p=0.027; ηp(2)=0.044) but not inattention (p=0.061; ηp(2)=0.032), controlling for ASD severity, than children homozygous for the L(A) allele. Conversely, mothers' ratings indicated that children with L(A)/L(A) genotype had more severe ASD social deficits than S or L(G) allele carriers (p=0.003; ηp(2)=0.081), controlling for ADHD symptom severity. Teachers' ratings though consistent with mothers' ratings of hyperactivity and social deficits were marginally significant (p=0.07/p=0.09). There was some evidence that the magnitude of parent-teacher agreement regarding symptom severity varied as a function of the child's genotype., Conclusion: The 5-HTTLPR/rs25531 polymorphism or its correlates may modulate severity of ADHD and ASD symptoms in children with ASD, but in different ways. These tentative, hypothesis-generating findings require replication with larger independent samples., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Despite attracting tremendous interest over the last few decades, the field of electrophilic cyclizations is still continuously and rapidly developing. Particularly, metal-free reactions that involve the activation of an alkyne using electrophilic halogen sources are powerful tools in the repertoire of synthetic chemists. This brief overview highlights recent progress in C-C bond-forming halocyclizations allowing for the reaction of alkynes with carbon-nucleophiles. Primarily guided by the type of carbon nucleophile, methods are categorized as the addition of arene, malonate, and olefin nucleophiles.

Rugulactone is a dihydro-α-pyrone isolated from the plant Cryptocarya rugulosa in 2009. It has been reported to display IkB kinase (IKK) inhibitory activity, as well as antibiotic activity in several strains of pathogenic bacteria. However, its biological targets and mode of action in bacteria have not yet been explored. Here we present enantioselective syntheses of rugulactone and of some corresponding activity-based protein profiling (ABPP) probes. We found that the ABPP probes in this study are more potent than rugulactone against Staphyloccocus aureus NCTC 8325, S. aureus Mu50, Listeria welshimeri SLCC 5334 and Listeria monocytogenes EGD-e, and that molecules of this class probably exert their antibacterial effect through a combination of targets. These targets include covalent inhibition of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMPP) kinase (ThiD), which is an essential component of the thiamine biosynthesis pathway in bacteria. This represents the first example of a small-molecule inhibitor of ThiD., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The total synthesis of (+)-cyperolone, an eudesmane-derived sesquiterpenoid from Cyperus rotundus, is described. The de novo synthesis was accomplished via a 15 step sequence starting from (R)-(-)-carvone. The synthetic route features a platinum-catalyzed cycloisomerization to rapidly construct the bicyclic core from a 3-silyloxy-1,5-enyne intermediate., (© 2012 American Chemical Society)

An operationally simple, direct azidation of 1,3-dicarbonyl compounds has been developed. The reaction proceeds readily under ambient conditions using sodium azide and an iodine-based oxidant such as I(2) or 2-iodoxybenzoic acid (IBX)-SO(3)K/NaI. In particular, the latter method, as a new and well-balanced oxidizing agent, shows excellent functional group tolerance and substrate scope and thus allows access to a variety of tertiary 2-azido and 2,2-bisazido 1,3-dicarbonyl compounds that would be more difficult to access by using traditional methods. Because the azide-containing products easily undergo 1,3-dipolar cycloaddition with alkynes, our report represents a novel route to analogues of sensitive complex molecules., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two cats, two paths: two novel domino reactions starting from 6-hydroxy-2-alkyl-2-alkynylcyclohexanones have been discovered. While redox-neutral platinum catalysis gives rise to furans through a sequence of cyclization, 1,2-shift, and Grob fragmentation, oxidative copper catalysis provides an entry to bicyclic 2,3-dihydrofurans. Upon cyclization and oxidation, an unusual benzilic acid rearrangement can take place in this case., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The catalyzed synthesis of 1,2-dihydropyridines starting from easily accessible propargyl vinyl ethers was realized. The reaction sequence involving a transition metal-catalyzed propargyl-Claisen rearrangement, a condensation step, and a Brønsted acid-catalyzed heterocyclization furnishes the highly substituted heterocycles in moderate to excellent yields. Additionally, a practical one-pot protocol toward 1,2-dihydropyridines and 2H-pyrans starting from propargylic alcohols was developed.

Since its discovery by Christoph Hartmann and Victor Meyer in 1893, 2-iodoxybenzoic acid (IBX) has emerged as a rather ubiquitous oxidant for organic synthesis. The past decade has seen the development of a large variety of applications that go far beyond the simple oxidation of alcohols. This Review is concerned with the synthetic potential of IBX, with particular emphasis on uncommon reactivity patterns and novel fields of application., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gold catalysis has emerged as one of the most dynamic fields in organic synthesis. Only recently, more and more domino processes, for which gold pre-catalysts were found to be outstandingly effective, were paralleled by employing iodine electrophiles in place of gold compounds. This review highlights how, in certain cases, iodonium activation can match gold-catalyzed reactions to construct identical product scaffolds. Likewise, processes are discussed where mostly identical starting materials are transformed into diverse frameworks depending on whether gold or iodonium activation was used to trigger the reaction.

The catalytic enantioselective S(N)2' displacement of (Z)-allylic trichloroacetimidates catalyzed by the palladium(II) complex [COP-OAc](2) is a broadly useful method for the asymmetric synthesis of chiral branched allylic esters. A variety of experiments aimed at elucidating the nature of the catalytic mechanism and its rate- and enantiodetermining steps are reported. Key findings include the following: (a) the demonstration that a variety of bridged-dipalladium complexes are present and constitute resting states of the COP catalyst (however, monomeric palladium(II) complexes are likely involved in the catalytic cycle); (b) labeling experiments establishing that the reaction proceeds in an overall antarafacial fashion; (c) secondary deuterium kinetic isotope effects that suggest substantial rehybridization at both C1 and C3 in the rate-limiting step; and (d) DFT computational studies (B3-LYP/def2-TZVP) that provide evidence for bidentate substrate-bound intermediates and an anti-oxypalladation/syn-deoxypalladation pathway. These results are consistent with a novel mechanism in which chelation of the imidate nitrogen to form a cationic palladium(II) intermediate activates the alkene for attack by external carboxylate in the enantiodetermining step. Computational modeling of the transition-state structure for the acyloxy palladation step provides a model for enantioinduction.

A broadly useful catalytic enantioselective synthesis of branched allylic esters from prochiral (Z)-2-alkene-1-ols has been developed. The starting allylic alcohol is converted to its trichloroacetimidate intermediate by reaction with trichloroacetonitrile, either in situ or in a separate step, and this intermediate undergoes clean enantioselective S(N)2' substitution with a variety of carboxylic acids in the presence of the palladium(II) catalyst (R(p),S)-di-μ-acetatobis[(η(5)-2-(2'-(4'-methylethyl)oxazolinyl)cyclopentadienyl-1-C,3'-N)(η(4)-tetraphenylcyclobutadiene)cobalt]dipalladium, (R(p),S)-[COP-OAc](2), or its enantiomer. The scope and limitations of this useful catalytic asymmetric allylic esterification are defined.

The first total synthesis of (+)-chloriolide, a 12-membered macrolide from Chloridium virescens (var. chlamydosporum), was accomplished in a longest linear sequence of 20 steps from commercial materials in 7% overall yield.

The first total syntheses of polyrhacitides A and B, secondary metabolites from Chinese medicinal ants, were accomplished via an iterative approach to the 1,3-polyol motif. For the construction of all stereogenic centers, the catalytic asymmetric Overman esterification was utilized.

On activation with catalytic amounts of gold(I) complexes, 3-silyloxy 1,6-enynes can react through two alternative pathways. In one, a cascade reaction consisting of carbocyclization and subsequent pinacol rearrangement takes place. In the second pathway, a heterocyclization is followed by a Claisen rearrangement. The reaction outcome differs depending on the substitution pattern of the 3-silyloxy 1,6-enynes and, more importantly, the electronic properties of the gold-bound phosphane ligand.

A combination of gold(I) complexes and amine bases catalyzes the 5-exo-dig cyclization of formyl alkynes. This direct alpha-functionalization of aldehydes with unactivated alkynes does not involve the use of preformed enol equivalents.