Medium-Sized Oxacycles Research Articles

Intermolecular Oxonium Ylide Mediated Synthesis of Medium-Sized Oxacycles

Detailed in this account are our efforts toward efficient oxacycle syntheses. Two complementary approaches are discussed, with both employing chemoselective allyl ether activation and rearrangement as the key step. Vinyl substituted oxiranes and oxetanes provide a single step access to dihydropyrans and tetrahydrooxepines. Oxiranes proved to be poor substrates, while oxetanes were slightly better. An alternative approach using substituted allyl ethers proved successful and addressed the limitations encountered in the ring expansions.

Synthesis of Heterocycle-Annulated Medium-Sized Oxacycles and Lactone Derivative by Intramoleculer Heck Reaction

An efficient and convergent methodology for the highly strained medium-sized oxacyclic compounds and lactone derivatives has been developed via palladium-catalyzed intramoleculer Heck reaction.

Highly enantioselective carbon–carbon bond formation by Cu-catalyzed asymmetric [2,3]-sigmatropic rearrangement: application to the syntheses of seven-membered oxacycles and six-membered carbocycles

A concise route for the syntheses of enantioenriched functionalized scaffolds of medium-sized oxacycles and carbocycles employing the chiral auxiliary-mediated Cu-catalyzed ylide formation/[2,3]-sigmatropic rearrangement as a key step was developed.

Enantioselective Synthesis of Functionalized Medium-Sized Oxacycles

Enantioselective routes to functionalized, seven-, eight-, and nine-membered oxacycles that are amenable to further elaboration have been developed. Salient features of the methodology include highly diastereoselective and regioselective transformations of an ephedrine-derived epoxy morpholinone to functionalized precursors of the oxacycles. The ephedrine scaffold exerts remote stereocontrol in the functionalization of the appended oxacycle. [reaction: see text]

Novel “Protecting Group-Dependent” Alkylation−RCM Strategy to Medium-Sized Oxacycles: First Total Synthesis of (−)-Isoprelaurefucin

[reaction: see text] A novel "protecting group-dependent" alkylation strategy was developed for complementary diastereoselective syntheses of alpha,alpha'-syn- and alpha,alpha'-anti-bis-alkenes 2 and 3, which represent ring-closing metathesis (RCM) substrates for medium-sized oxacycles. This principle has been applied to a stereoselective and concise total synthesis of (-)-isoprelaurefucin (4) in 14 steps in 12% overall yield from known epoxide 8.

Base‐Catalyzed endo‐Mode Cyclization of Allenes: Easy Preparation of Five‐ to Nine‐Membered Oxacycles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Base-Catalyzed Endo-Mode Cyclization of Allenes: Easy Preparation of Five- to Nine-Membered Oxacycles

A reliable and efficient procedure for constructing five- to eight-membered oxacycles has been developed. Allenes with both a phosphoryl group and a suitable delta-hydroxyalkyl side chain at the C1-position underwent an endo mode ring-closing reaction to give five- to seven-membered oxacycles. Changing the phosphoryl group to a phosphono functionality facilitated the preparation of eight-membered congeners. Introduction of a cis double bond to the alkyl side chain of the starting allenes made possible the easy formation of medium-sized oxacycles, such as the dihydrooxocin and tetrahydrooxonin frameworks, regardless of the electron-withdrawing group (POPh2, PO(OEt)2, SOPh, and SO2Ph) at the C1-position.

Ring-Closing Metathesis in the Synthesis of Large and Medium-Sized Oxacycles. Application to the Synthesis of Polyoxygenated Macrocycles.

Ring-closing olefin metathesis (RCM) catalyzed by Grubbs's ruthenium benzylidene complex 1 is applied to the synthesis of unsaturated rings ranging in size from seven to thirteen members in trans-fused polyether systems. Reaction occurs with great efficiency in the cyclization of oxepene and oxocene rings, but as ring size increases, yields drop. The influence of the final double bond position is also studied. Better yields and milder reaction conditions are observed when an additional oxygen atom is introduced on the diene. This feature has promoted the application of this reaction to the synthesis of polyoxygenated macrocycles (with sizes ranging from 15 to 21 members), with excellent results.