Oxetanes: Recent Advances in Synthesis, Reactivity and Medicinal Chemistry

The 4-membered oxetane ring has been increasingly exploited for its behaviors, i.e. influence on physicochemical properties as a stable motif in medicinal chemistry, and propensity to undergo ring opening reactions as a synthetic intermediate. These applications have driven numerous studies into the synthesis of new oxetane derivatives. This review takes an overview of the literature for the synthesis of oxetane derivatives, concentrating on advances in the last 5 years up to the end of 2015. These methods are clustered by strategy for preparation of the ring (Sections 3 and 4), and further derivatisation of preformed oxetane-containing building blocks (Sections 5-7). Examples of the use of oxetanes in medicinal chemistry are reported, including a collation of oxetane derivatives appearing in recent patents for medicinal chemistry applications. Finally examples of oxetane derivatives in ring opening and ring expansion reactions are described

Seven-membered Rings Through Metal-free Rearrangement Mediated By Hypervalent Iodine.

A versatile and metal-free approach for the synthesis of carbocycles and of heterocycles bearing seven- and eight-membered rings is described. The strategy is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (PhI(OH)OTs). Reaction conditions can be easily adjusted to give ring expansion products bearing different functional groups. A route to medium-ring lactones was also developed.201475-9

Enantioselective Organocatalytic Four-Atom Ring Expansion of Cyclobutanones: Synthesis of Benzazocinones

International audienceAn enantioselective Michael addition-four-atom ring expansion cascade reaction involving cyclobutanones activated by a N-aryl secondary amide group and ortho-amino nitrostyrenes has been developed for the preparation of functionalized eight-membered benzolactams using bifunc-tional aminocatalysts. Taking advantage of the secondary amide activating group, the eight-membered cyclic products could be further rearranged into their six-membered isomers having a glutarimide core under base catalysis conditions without erosion of optical purity, featuring an overall ring expansion-ring contraction strategy

Visible-light photocatalytic intramolecular cyclopropane ring expansion

Described herein is a new visible-light photocatalytic strategy for the synthesis of enantioenriched dihydrofurans and cyclopentenes by an intramolecular nitro cyclopropane ring expansion reaction. Mechanistic studies and DFT calculations are used to elucidate the key factors in this new ring expansion reaction, and the need for the nitro group on the cyclopropaneThe Spanish Government (CTQ2015-64561-R, CTQ2014-59544-P) and the European Research Council (ERC-CG,contract number:647550) are acknowledge

Synthesis of fluvirucins and their aglycons, the fluvirucinins

Fluvirucins are bioactive macrolactam glycosides isolated from actinomycetes. This review gives an overview of this family of natural products, covering isolation, biological activities, biosynthesis, and total synthesis. The synthesis of fluvirucins and their aglycons, the fluvirucinins, is presented, paying special attention to the synthetic strategy and stereochemical aspects. 1 Introduction 2 Isolation, Biological Activity, and Biosynthesis 3 Synthetic Approaches 3.1 Closure of the 14-Membered Ring by Ring-Closing Metathesis 3.2 Closure of the 14-Membered Ring by Macrolactamization 3.3 Construction of the 14-Membered Ring by Aza-Claisen Ring Expansion 4 Conclusio

A direct route to cyclic organic nanostructures via ring-expansion metathesis polymerization of a dendronized macromonomer

Cyclic organic nanostructures were prepared via ring-expansion metathesis polymerization of a dendronized norbornene macromonomer. The strategy provides a direct, efficient route to nanoscale rings in a single operation. AFM imaging confirmed toroidal features having diameters of ca. 35−40 nm

Phosphorus Bearing Substrates in Ring Expansion Reactions

A variety of substituted phosphonium salts, phosphorus ylides and phosphonates were studied to assess their utility in ring expansion reactions. The strategy involved formation of fused ring systems whose ring strain could be exploited to accomplish ring expansion to medium sized rings. β-Alkoxy vinylphosphonium salts were found to be unreactive with species such as the dimethylsulfoxonium methylide anion, Simmons-Smith type reagents. and carbenes in attempts to produce cyclopropyl phosphonium salts. C-Alkylation of β-keto phosphorus ylides using haloalkanes bearing terminal groups that could be converted and reacted with the B-carbonyl, was also examined as a method for accessing strained rings bearing electron donating alkoxy groups and electron withdrawing phosphorus substituents. The presence of C-alkylated phosphonium salt products was detected by NMR analysis of crude reaction mixtures for diiodomethane and dibromoethane, but synthetically useful yields were not obtained except for the reaction with methyl iodide. Alkynyl phosphonates, however, were found to be adequate substrates for cycloaddition with enamines to yield ring expanded products. This represents the first ring expansion via cycloaddition of alkynyl phosphonates. The reactivities of enamines derived from pyrrolidine or morpholine were compared in the cycloaddition‘ Efficiency in formation of seven and eight member rings from the enamines of cyclopentanone and cyclohexanone were thus examined. The unsaturated medium sized rings thus obtained were probed for their utility in Michael addition. This method may provide access to the basic framework of a number of natural products found to have biological activity

Last millennium northern hemisphere summer temperatures from tree rings: Part I: The long term context

Large-scale millennial length Northern Hemisphere (NH) temperature reconstructions have been progressively improved over the last 20 years as new datasets have been developed. This paper, and its companion (Part II, Anchukaitis et al. in prep), details the latest tree-ring (TR) based NH land air temperature reconstruction from a temporal and spatial perspective. This work is the first product of a consortium called N-TREND (Northern Hemisphere Tree-Ring Network Development) which brings together dendroclimatologists to identify a collective strategy for improving large-scale summer temperature reconstructions. The new reconstruction, N-TREND2015, utilises 54 records, a significant expansion compared with previous TR studies, and yields an improved reconstruction with stronger statistical calibration metrics. N-TREND2015 is relatively insensitive to the compositing method and spatial weighting used and validation metrics indicate that the new record portrays reasonable coherence with large scale summer temperatures and is robust at all time-scales from 918 to 2004 where at least 3 TR records exist from each major continental mass. N-TREND2015 indicates a longer and warmer medieval period (∼900–1170) than portrayed by previous TR NH reconstructions and by the CMIP5 model ensemble, but with better overall agreement between records for the last 600 years. Future dendroclimatic projects should focus on developing new long records from data-sparse regions such as North America and eastern Eurasia as well as ensuring the measurement of parameters related to latewood density to complement ring-width records which can improve local based calibration substantially

Methanol-Driven Oxidative Rearrangement of Biogenic Furans - Enzyme Cascades vs. Photobiocatalysis

The oxidative ring expansion of bio-derived furfuryl alcohols to densely functionalized six-membered O-heterocycles represents an attractive strategy in the growing network of valorization routes to synthetic building blocks out of the lignocellulosic biorefinery feed. In this study, two scenarios for the biocatalytic Achmatowicz-type rearrangement using methanol as terminal sacrificial reagent have been evaluated, comparing multienzymatic cascade designs with a photo-bio-coupled activation pathway.Peer reviewe