Stereoselective Iodolactonization Research Articles

Synthesis of seven-membered lactones by regioselective and stereoselective iodolactonization of electron-deficient olefins.

A regio- and stereoselective iodolactonization of internal electron-deficient olefinic acids has been reported, which provides a straightforward access to a series of multi-functionalized seven-membered lactones containing two consecutive chiral centers. The ester substituents on the olefins played a key role in achieving high regioselectivity. This result was proved through experiments and DFT calculations.

Synthesis and Reactivity of Oxazinoindolones via Regioselective 6‐exo‐dig Iodolactonization

An efficient protocol for the facile construction of 3,4‐dihydro‐10‐iodo‐3‐iodomethylene‐[1,4]‐oxazino[4,3‐a]indol‐1‐ones has been developed by using a regio‐ and stereoselective iodolactonization reaction. Subsequent palladium cross‐coupling reactions of 3,4‐dihydro‐10‐iodo‐3‐iodomethylene‐[1,4]‐oxazino[4,3‐a]indol‐1‐ones readily afforded functionalized oxazinoindolones.

Stereoselective Iodolactonization of 4‐Allenoic Acids with Efficient Chirality Transfer: Development of a New Electrophilic Iodination Reagent

A highly stereoselective iodolactonization of 4-allenoic acids with a new sterically demanding electrophilic iodination reagent to afford optically active γ-butyrolactones has been developed. The reaction shows high efficiency of axial chirality transfer and excellent Z/E selectivity and has been applied to the synthesis of chiral cis-β,γ-disubstituted γ-butyrolactones to give very high diastereomeric and enantiomeric excess values. The reaction has been successfully utilized in the synthesis of naturally occurring compounds (+)-cis-whisky lactone and (+)-cis-3-methyl-4-decanolide.

Regio- and diastereoselective fluorination of alicyclic β-amino acids

A regio- and stereoselective approach to fluorinated β-aminocyclohexene or cyclohexane esters has been developed, starting from a bicyclic β-lactam (1). The procedure involves six or seven steps, based on regio- and stereoselective iodolactonization, lactone opening and hydroxy-fluorine exchange. The method has been extended to the synthesis of fluorinated amino ester enantiomers.

ChemInform Abstract: Highly Stereoselective Iodolactonization of 4,5‐Allenoic Acids — An Efficient Synthesis of 5‐(1′‐Iodo‐1′(Z)‐alkenyl)‐4,5‐dihydro‐2(3H)‐furanones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly Stereoselective Iodolactonization of 4,5‐Allenoic Acids—An Efficient Synthesis of 5‐(1′‐Iodo‐1′(Z)‐alkenyl)‐4,5‐dihydro‐2(3H)‐furanones

Highly Stereoselective Iodolactonization of 4,5‐Allenoic Acids—An Efficient Synthesis of 5‐(1′‐Iodo‐1′(<i>Z</i>)‐alkenyl)‐4,5‐dihydro‐2(3<i>H</i>)‐furanones

Stereoselective Synthesis of the Macrocyclic Core of (-)-Salicylihalamides A and B

Stereoselective synthesis of the macrocyclic core of salicylihalamides A and B is described. The synthetic strategy features stereoselective iodolactonization, Sharpless asymmetric epoxidation, Mitsunobu esterification, and ring-closing metathesis.

An Efficient Stereoselective Synthesis of 4,5‐trans‐1,5‐cis‐3‐Oxabicyclo[3.1.0]hexan‐2‐ones via the Iodolactonization of Alkylidenecyclopropyl Esters.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Monomers for Preparation of Amide-Linked RNA: Asymmetric Synthesis of All Four Nucleoside 5‘-Azido 3‘-Carboxylic Acids

[reaction: see text] Recent discovery of RNA interference as an efficient and naturally occurring mechanism of gene regulation has reinvigorated the interest in chemically modified RNA. For potential in-vivo applications small interfering RNAs require chemical modifications to fine-tune the thermal stability and increase the cellular delivery and potency and in vivo half-life of the RNA duplexes. From this perspective, amides as neutral and hydrophobic internucleoside linkages in RNA are highly interesting modifications for RNA interference. Amides are remarkably good mimics of the phosphodiester backbone of RNA and can be prepared using a relatively straightforward peptide coupling chemistry. However, the progress in the field has been hampered by the shortage of efficient methods to synthesize the monomeric building blocks for such couplings, the nucleoside amino acid equivalents. Herein, we report enantioselective synthesis of 5'-azido 3'-carboxylic acid derivatives of all four natural ribonucleosides. The key transformations in our synthesis are a double asymmetric ene reaction and a stereoselective iodolactonization that form the basic carbon skeleton of the modified ribose. Standard nucleoside synthesis is followed by a short and highly efficient protecting group manipulation to give the enantiomerically pure (>98%) title compounds in 9-10 steps and 15-19% overall yields starting from small achiral molecules. The present results are a significant improvement over our first-generation racemic synthesis and compare favorably with the previously reported synthesis from nucleoside and carbohydrate precursors.

An Efficient Stereoselective Synthesis of 4,5-trans-1,5-cis-3-Oxabicyclo[3.1.0]hexan-2-ones via the Iodolactonization of Alkylidenecyclopropyl Esters

[reaction: see text] A highly stereoselective iodolactonization of alkylidenecyclopropyl esters with iodine or N-iodosuccinimide (NIS) in aqueous CH3CN to afford 4,5-trans-1,5-cis-3-oxabicyclo-[3.1.0]hexane-2-ones is described. The reaction is very general, accommodating a wide range of substituents. A plausible mechanism that explains the essential role of water in this reaction is proposed.

Enantiospecific Synthesis of the Phospholipase A2 Inhibitor (‐)‐Cinatrin B.

The first enantiospecific synthesis of phospholipase A2 (PLA2) inhibitor (−)-cinatrin B (2) from the d-arabinose derivative 9 is described. The spirolactone system was formed by an Ireland−Claisen rearrangement of the allyl ester 8 followed by hydrolysis and stereoselective iodolactonization. The stereoselectivity of the rearrangement was controlled by the asymmetry in the allylic alcohol fragment. Ester (S)-8 gave the desired rearrangement product 7 and the epimer 13 in high yield as a 73:27 ratio, respectively. The final stereocenter at C2 was introduced via a chelation-controlled addition of the Grignard reagent derived from trimethylsilylacetylene to α-hydroxy ketone 6. Transformation of the terminal alkyne into the methyl ester 21 followed by acetal hydrolysis and selective lactol oxidation afforded cinatrin B methyl ester (22). Base hydrolysis and acid-induced relactonization then gave (−)-cinatrin B (2).

Enantiospecific synthesis of the phospholipase A2 inhibitor (-)-cinatrin B.

The first enantiospecific synthesis of phospholipase A2 (PLA2) inhibitor (-)-cinatrin B (2) from the D-arabinose derivative 9 is described. The spirolactone system was formed by an Ireland-Claisen rearrangement of the allyl ester 8 followed by hydrolysis and stereoselective iodolactonization. The stereoselectivity of the rearrangement was controlled by the asymmetry in the allylic alcohol fragment. Ester (S)-8 gave the desired rearrangement product 7 and the epimer 13 in high yield as a 73:27 ratio, respectively. The final stereocenter at C2 was introduced via a chelation-controlled addition of the Grignard reagent derived from trimethylsilylacetylene to alpha-hydroxy ketone 6. Transformation of the terminal alkyne into the methyl ester 21 followed by acetal hydrolysis and selective lactol oxidation afforded cinatrin B methyl ester (22). Base hydrolysis and acid-induced relactonization then gave (-)-cinatrin B (2).

ChemInform Abstract: Synthesis of Non‐Peptide Scaffolding Domains via a Totally Stereoselective Iodolactonization Protocol.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Asymmetric Synthesis of α‐Amino Acids Through α‐Iodination of Chiral Unsaturated Carboxamides and Stereoselective Iodolactonization.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of non-peptide scaffolding domains via a totally stereoselective iodolactonization protocol

Exposure of the chiral, non-racemic, allylic ester 7 to LDA/MSCl provides acid 8 and subsequent iodolactonization of 8 provides one lactone ( 9) with total stereoselectivity. X-ray analysis of the corresponding α-methylbenzylamides of 8 and 9 confirmed the absolute stereochemistry of the trans-anti-trans lactone ( 9). The synthesis is completed by treatment of 9 with the enolate of t-butyl acetate affording tetrahydrofuranyl derivative 12.

Asymmetric synthesis of α-amino acids through α-iodination of chiral unsaturated carboxamides and stereoselective iodolactonization

Abstract The α-iodination reaction of chiral enamides 1 possessing (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine as a chiral auxiliary proceeded with high diastereoselectivity in the presence of I 2 and s-collidine. The chiral iodides 2 thus obtained were converted to the α-BocNH-amides 3 without epimerization. The subsequent iodolactonization afforded trans-lactones 4 with a relatively high selectivity.

Stereoselective iodolactonization of acyclic unsaturated 3-hydroxyacids

A stereoselective method for preparing 3-hydroxy-4-alkyl-γ-lactones is reported. iodolactonization of 3-hydroxy-4-alkenoic acids produces predominantly the thermodynamically less stable 3,4-cis products, which undergo methanolysis to threo -epoxyalcohols.