Stereoselective synthesis of substituted dienes by the double ortho ester Claisen rearrangement

This letter shows the highly stereoselective synthesis of substituted (E)-1,3-dienes from substituted propargylic diols via the double ortho ester Claisen rearrangement. The cyclohexyl-substituted diene undergoes thermal Diels-Alder cycloaddition with maleic anhydride to produce the corresponding bicyclic diester in highly stereoselective manner.     

Synthesis of the diazatricyclic core of the marine alkaloids madangamines

A new approach to synthesize the madangamine core structure is described. The synthesis involves intramolecular N,O-acetalization of the keto-aminophenol which allows rapid construction of the 2-azabicyclo[3.3.1]nonane skeleton with a quaternary carbon center at C4. This strategy also demonstrates the utility of such approach in the stereoselective construction of the central diazatricyclic core found in the madangamine alkaloids.     

An asymmetric synthesis of (+)-desoxoprosophylline

An efficient synthesis of (+)-desoxoprosophylline is described. The key steps in the reaction sequence include the preparation of an N-Cbz-sulfilimine from the corresponding sulfoxide using the Burgess reagent, regio- and stereoselective hetero-functionalization of an alkene using the pendant sulfilimine as the nucleophile and a stereoselective amidomercuration to form the cis-2,6-disubstituted piperidine ring.     

Formal total synthesis of (±)-magellanine

Formal total synthesis of magellanine is described. Key features in the synthesis were stereoselective Ireland-Claisen rearrangement and intramolecular Pauson-Khand reaction of exo-cyclic enynes.     

Stereoselective synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol

A highly stereoselective total synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol is described. Key steps involved in this synthesis are diastereoselective zinc allylation, azido-olefin cyclization and reductive amination followed by cyclization which effectively constructed the indolizidine ring. This contributes a unique approach to the synthesis of indolizidine alkaloids that offers the advantages of brevity and relatively high overall yields.     

Enantioselective total synthesis of (−)-tetrahydrolipstatin using Oppolzer’s sultam directed aldol reaction

A highly practical and concise stereoselective total synthesis of (−)-tetrahydrolipstatin is achieved using Oppolzer’s sultam directed aldol reaction as the key step.     

Gold(I)-catalyzed [4+2] cycloaddition of N-(hex-5-enynyl) tert-butyloxycarbamates

A study concerning the gold(I)-catalyzed transformation of N-(hex-5-enynyl) tert-butyloxycarbamates is described. The mild conditions employed allow the moderately efficient but stereoselective synthesis of a range of bicyclic carbamates following a formal [4+2] cycloaddition process.     

Stereoselective synthesis of (−)-allosedamine and (1R,3R)-HPA-12 from β-p-toluenesulfonamido-γ,δ-unsaturated sulfoxide

A stereoselective synthesis of (−)-allosedamine and HPA-12 is disclosed. The key steps of the synthesis include the diastereoselective synthesis of a β-sulfonamido unsaturated sulfoxide, elaboration of a bromohydrin via intramolecular sulfinyl group participation and a ring-closing metathesis reaction for the construction of the piperidine ring of allosedamine.     

Stereoselective synthesis of (−)-microcarpalide

A highly convergent and efficient synthesis of (−)-microcarpalide, a 10-membered lactone displaying remarkable microfilament disrupting activity is described. Ring-closing metathesis and Sharpless asymmetric dihydroxylations are the key steps. Our strategy highlights the application of novel hydroxy lactone precursors for the stereoselective synthesis of (−)-microcarpalide.     

An efficient synthesis of semiplenamide C

Semiplenamides are anandamide-like fatty acid amide metabolites previously isolated from a marine cyanobacterium that display a range of biological activity. Novel syn-aldol/dehydration methodology has been developed for the stereoselective synthesis of the core (E)-α,β-unsaturated amide functionality of this class of natural product, and employed for the efficient synthesis of semiplenamide C.     

The regio- and stereochemical course of reductive cross-coupling reactions between 1,3-disubstituted allenes and vinylsilanes: synthesis of (Z)-dienes

In investigations aimed at exploring the potential of disubstituted allenes in stereoselective synthesis, we report studies that explore the reductive cross-coupling reaction of vinylsilanes with a range of substituted allenes. Regiochemical control is attained by employing allenic alkoxides, where the proximal heteroatom dictates the site-selectivity in a process that proceeds by net formal metallo-[3,3] rearrangement (directed carbometalation/elimination). Stereoselectivity in these reactions is complex, with both the nature of allene substitution and relative stereochemistry of the substrate impacting the stereoselective generation of each alkene of a substituted 1,3-diene.     

Stereoselective synthesis of tetrazole CB92834, a potent retinoid compound

An improved, convergent synthesis of CB92834 is relying on a Suzuki cross-coupling reaction and easily allows multigram-scale preparation of the compound. The approach features three highly stereoselective steps.     

Novel approach to the synthesis of perhydropyrazino[1,2-a]pyrazine derivatives from amino alcohols

2,4,7-Trisubstituted hydrogenated pyrazino[1,2-a]pyrazines as potential β-turn mimetics were prepared for the first time in a stereoselective synthesis from hexahydro[1,2,3]triazolo[1,5-a]pyrazines.     

Total synthesis of (+)-anamarine

An enantiospecific total synthesis of polyhydroxy δ-pyrone natural product (+)-anamarine is accomplished. The main features of the synthesis include the stereoselective reduction of the ketone obtained by the desymmetrization of the bis-dimethyl amide of tartaric acid and further elaboration involving asymmetric Brown's allylation and ring closing metathesis.     

Stereoselective synthesis of C1-C5 and C4-C5 linked deoxy disaccharides via a ring closing metathesis protocol

The stereoselective synthesis of C-C linked deoxy disaccharides by a short and efficient route is described. An RCM strategy was adopted for the assembly of the required ring skeleton on the sugar unit, while OsO₄ was used to introduce the vic-diol unit.     

Rapid construction of polycyclic ring systems from aromatics: stereoselective synthesis of the carbon framework of vinigrol

The stereoselective syntheses of the tricyclic core structure of vinigrol and highly functionalized polycyclic molecules from 5-bromo-2-methoxyphenol in five synthetic steps are reported. Intramolecular and intermolecular Diels–Alder reactions and tandem oxy-Cope/ene reactions are the key steps in the synthesis.     

Application of oxetane ring opening toward stereoselective synthesis of zincophorin fragment

A stereoselective synthesis of the C1–C11 fragment of zincophorin was achieved by using an intramolecular oxetane ring opening reaction as the key step. The oxetane moiety was synthesized by employing a desymmetrization protocol developed at our group and a non-Evans syn aldol as the key steps toward the synthesis.     

Acid catalyzed rearrangement of vinyl and ketene acetals

Substituted vinyl and ketene acetals undergo smooth oxygen-to-carbon rearrangement with a catalytic amount of TMSOTf to afford chain-extended ketones or esters, respectively. The developed procedure has been applied to the stereoselective synthesis of C-glycosides from the corresponding anomeric vinyl ethers.     

Vinylogous N,N-dimethylaminomethylenation of 3-[(1-substituted)ethylidene]-oxindoles with N,N-dimethylformamide dimethylacetal

An efficient stereoselective synthesis of various 3-(3-dimethylaminoprop-2-enylidene)oxindoles has been disclosed. The compounds were synthesized via a vinylogous N,N-dimethylaminomethylenation at the γ-position of 3-[(1-substituted)ethylidene]oxindoles with DMF-DMA.     

Studies toward the synthesis of salinosporamide A, a potent proteasome inhibitor

An α-methylenepyrrolidinone bearing all the functionalities and relative configurations of an advanced intermediate in the synthesis of salinosporamide A and analogues has been synthesized from methyl pyroglutamate through regio- and stereoselective N-methylnitrone cycloaddition.