Enantioselective synthesis of the C1-C6 and C7-C23 fragments of the proposed structure of iriomoteolide 1a

Synthesis of the C1-C6 and C7-C23 fragments of the proposed structure of iriomoteolide 1a has been accomplished. Key steps include a cross metathesis to form the C15-C16 E olefin and a chelation controlled Grignard addition to form the tertiary alcohol at C14. Notably, 7 of the 9 stereocenters of the proposed structure have been set using various aldol reactions employing metallo enolates of thiazolidinethiones.     

Enantioselective total synthesis of (+)-obtusenyne

A total synthesis of the laurencia metabolite (+)-obtusenyne has been completed. The key steps include a Sharpless kinetic resolution and an asymmetric glycolate alkylation to establish the stereogenic centers adjacent to the ether linkage and a ring-closing metathesis reaction to construct the nine-membered ether without the aid of a cyclic conformational constraint. The synthesis was completed in 20 linear steps from commercially available 1,5-hexadiene-3-ol.     

An Improved Synthetic Preparation of 3-Butenal

A convenient synthesis of 3-butenal from aqueous glyoxal and allyl bromide is described. The preparation readily provides multigram quantities of 3-butenal.     

Enantioselective total synthesis of (+)-SCH 351448

[structure: see text] A stereoselective synthesis of SCH 351448 has been completed. Twelve of the fourteen stereogenic centers were established through chiral enolate reactions, and six key C-C bonds were formed by metathesis reactions.     

Intramolecular photocycloadditions: synthesis of stericallycongested substituted [4.5.5.5] Fenestranes. Models for the total synthesis of laurenene and silphinene

The synthesis of the first example of a fenestrane substituted at opposing ring junctures utilizing an intramolecular photocycloaddition at elevated temperatures as the key step is reported.     

Formal total synthesis of (+)-trehazolin. Application of an asymmetric aldol-olefin metathesis approach to the synthesis of functionalized cyclopentenes

An asymmetric synthesis of the aminocyclopentitol pseudosugar of trehazolin has been completed. The synthesis hinges on an asymmetric aldol-ring closing metathesis strategy to construct the five-membered ring with control of both the relative and absolute stereochemistry.     

An intramolecular Diels-Alder strategy for the asbestinins: enantioselective total syntheses of 11-acetoxy-4-deoxyasbestinin D and asbestinin-12

The enantioselective total syntheses of 11-acetoxy-4-deoxyasbestinin D and asbestinin-12 have been completed. A glycolate aldol reaction provided a diene useful for ring-closing metathesis to form an oxonene, which was ultimately employed as a template to execute a highly stereoselective intramolecular Diels-Alder cycloaddition, forming the hydroisobenzofuran moiety. The absolute configuration of the asbestinin subclass was confirmed via these synthetic efforts.     

Enantioselective synthesis of apoptolidinone: exploiting the versatility of thiazolidinethione chiral auxiliaries

An efficient, enantioselective synthesis of apoptolidinone has been completed, demonstrating the versatility of thiazolidinethione auxiliaries. Three propionate aldol additions and two asymmetric glycolate alkylations function to establish 8 of the 12 stereogenic carbon centers. A cross-metathesis reaction is utilized to assemble the C1-C10 trieneoate fragment and the C11-C28 polypropionate region of the molecule.     

Total synthesis of the proposed structure of briarellin J

The total synthesis of the originally proposed structure of briarellin J is reported in 15 steps from a known compound and in 23 steps from readily available materials. Key reactions include an exo-selective intramolecular Diels-Alder and a substrate-controlled hydroboration. Discrepancies in the spectroscopic data of the synthetic and natural material led to a revision of the assigned structure.     

Enantioselective Total Synthesis of Brevetoxin A: Convergent Coupling Strategy and Completion

A highly convergent, enantioselective total synthesis of brevetoxin A is reported. The development of a [X+2+X] Horner–Wadsworth–Emmons/cyclodehydration/reductive etherification convergent coupling strategy allowed a unified approach to the synthesis of two advanced tetracyclic fragments from four cyclic ether subunits. The Horner–Wittig coupling of the two tetracyclic fragments provided substrates that were explored for reductive etherification, the success of which delivered a late‐stage tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.