Influence of polyoxometalate ligands on the nature of high-valent transition metal nitrido species. A theoretical analysis of experimentally known and unprecedented compounds

The electronic structure of group 6-8 transition metal (TM) nitrido derivatives [PW(11)O(39){TM(VI)N}](4-) is studied computationally and the potential reactivity of the polyoxoanions is discussed. The observed electrophilic reactivity for the Ru(VI) nitrido derivative is rationalized from frontier molecular orbital analysis. When we move to the left or down in the periodic table (TM = Os, Tc, Re, Mo and W) the electrophilic character of the polyoxometalate decreases or the cluster should be better regarded as a nucleophile. The DFT analysis of the redox properties suggests that the still unknown high-valent Mn(VI)N and Fe(VI)N units could be stabilized by the porphyrin-like ligand [PW(11)O(39)](7-) and their electronic structure indicates that these anions should have a high potential reactivity towards nucleophiles.     

Asymmetric Organocatalysis: The Emerging Utility of α,β‐Unsaturated Acylammonium Salts

Although acylammonium salts are well‐studied, chiral α,β‐unsaturated acylammonium salts have received much less attention. While these intermediates are convenient synthons, which are readily available from several commodity unsaturated acids and acid chlorides, and possess three reactive sites, their application in organic synthesis has been limited because of the lack of appropriate chiral Lewis bases for their generation. In recent years, the utility of chiral, unsaturated acylammonium salts has expanded considerably, thus demonstrating the unique reactivity of this intermediate leading to the development of a diverse array of catalytic, asymmetric transformations including organocascade processes. This Minireview highlights the recent and growing interest in these intermediates which might spark further research into their untapped potential for asymmetric organocascade catalysis. A cursory comparison is made to related unsaturated iminium and acylazolium intermediates.     

Concise total synthesis of (+/-)-salinosporamide A, (+/-)-cinnabaramide A, and derivatives via a bis-cyclization process: implications for a biosynthetic pathway?

4-Alkylidene-beta-lactones (hetero ketene dimers) and alpha-amino acids are useful precursors for total syntheses of the beta-lactone-containing proteasome inhibitors salinosporamide A, cinnabaramide A, and derivatives. A key step is a nucleophile-promoted, bis-cyclization of keto acids that simultaneously generates the gamma-lactam and beta-lactone of these natural products. This reaction sequence may have implications for the biosynthesis of these natural products.     

Total synthesis of (-)-belactosin C and derivatives via double diastereoselective tandem mukaiyama aldol lactonizations

[reaction: see text] The enantioselective synthesis of (-)-belactosin C and derivatives was accomplished in a concise manner employing the tandem, Mukaiyama aldol-lactonizaton (TMAL) process. One approach involved a distal double diastereoselective TMAL reaction with a dipeptide glyoxamide, whereas a second approach involved amide coupling of a dipeptide with a beta-lactone carboxylic acid, obtained via the TMAL process employing a chiral silyl ketene acetal. Notable improvements in diastereoselectivity were achieved in a proximal double diastereoselective TMAL process.     

Diastereoselective synthesis of tetrahydrofurans via mead reductive cyclization of keto-beta-lactones derived from the tandem Mukaiyama aldol lactonization (TMAL) process

The development of a diastereoselective, three-step strategy for the construction of substituted tetrahydrofurans from alkenyl aldehydes based on the tandem Mukaiyama aldol-lactonization process and Mead reductive cyclization of keto beta-lactones is reported. Stereochemical outcomes of the TMAL process are consistent with models established for Lewis acid-mediated additions to alpha-benzyloxy and beta-silyloxy aldehydes while reductions of the five-membered oxocarbenium ions are consistent with Woerpel's models. Further rationalization for observed high diastereoselectivity in reductions of alpha-silyloxy 5-membered oxocarbenium ions based on stereoelectronic effects are posited. A diagnostic trend for coupling constants of gamma-benzyloxy beta-lactones was observed that should enable assignment of the relative configuration of these systems.     

Cyclopropanations of olefin-containing natural products for simultaneous arming and structure activity studies

Cyclopropanations of alkene-containing natural products that proceed under mild conditions are reported for simultaneous arming and structure-activity relationship studies. An alkynyl diazo ester under Rh(II) catalysis is employed for cyclopropanations of electron-rich olefins while an alkynyl sulfonium ylide is used for electron-poor olefins. This approach enables simultaneous natural product derivatization for SAR studies and arming (i.e., via alkyne attachment) for subsequent conjugation with reporter tags (e.g., biotin, fluorophores, photoaffinity labels) for mechanism of action studies including cellular target identification and proteome profiling experiments.     

Dyotropic Rearrangements of Fused Tricyclic β-Lactones: Application to the Synthesis of (-)-Curcumanolide A and (-)-Curcumalactone

Dyotropic rearrangements of fused, tricyclic β-lactones are described that proceed via unprecedented stereospecific, 1,2-acyl migrations delivering bridged, spiro-γ-butyrolactones. A unique example of this dyotropic process involves a fused bis-lactone possessing both β- and δ-lactone moieties which enabled rapid access to the core structures of curcumanolide A and curcumalactone. Our current mechanistic understanding of the latter dyotropic process, based on computational studies, is also described. Other key transformations in the described divergent syntheses of (-)-curcumanolide A and (-)-curcumalactone from a common intermediate (11 and 12 steps from 2-methyl-1,3-cyclopentanedione, respectively), include a catalytic, asymmetric nucleophile (Lewis base)-catalyzed aldol-lactonization (NCAL) leading to a tricyclic β-lactone, a Baeyer-Villiger oxidation in the presence of a β-lactone, and highly facial-selective and stereocomplementary reductions of an intermediate spirocyclic enoate. The described dyotropic rearrangements significantly alter the topology of the starting tricyclic β-lactone, providing access to complex spirocyclic cyclopentyl-γ-lactones and bis-γ-lactones in a single synthetic operation.     

A diastereoselective, nucleophile-promoted aldol-lactonization of ketoacids leading to bicyclic-β-lactones

An improved, tandem acid activation/aldol-lactonization process is described. This more practical protocol shortens reaction times for the construction of bicyclic β-lactones from ketoacids and implements the use of commercially available reagents p-toluenesulfonyl chloride (p-TsCl) as activator and 4-dimethylaminopyridine (4-DMAP) as nucleophilic promoter (Lewis base). Substrates with β-substituents, with respect to the carboxylic acid, consistently showed excellent levels of diastereoselectivity during the bis-cyclization event.     

Resampling time series using missing values techniques

Several techniques for resampling dependent data have already been proposed. In this paper we use missing values techniques to modify the moving blocks jackknife and bootstrap. More specifically, we consider the blocks of deleted observations in the blockwise jackknife as missing data which are recovered by missing values estimates incorporating the observation dependence structure. Thus, we estimate the variance of a statistic as a weighted sample variance of the statistic evaluated in a “complete” series. Consistency of the variance and the distribution estimators of the sample mean are established. Also, we apply the missing values approach to the blockwise bootstrap by including some missing observations among two consecutive blocks and we demonstrate the consistency of the variance and the distribution estimators of the sample mean. Finally, we present the results of an extensive Monte Carlo study to evaluate the performance of these methods for finite sample sizes, showing that our proposal provides variance estimates for several time series statistics with smaller mean squared error than previous procedures.