1 → 6 oxygen transposition of a cyclohex-2-enone

The 1 → 6 transposition can be achieved by 6-hydroxylation, reduction to the $\text{cis}$-diol, cyclic carbonate formation, and reduction with sodium cyanoborohydride-tetrakis(triphenylphosphine)palladium(o) -tetrahydrofuran.     

A stereoselective synthesis of (R)-5-hydroxy-3-(4-methoxyphenethyl)cyclohex-2-enone,towards total synthesis of Prelunularin

A first chiral strategy for synthesis of (R)-5-hydroxy-3-(4-methoxyphenethyl) cyclohex-2-enone reported. Key transformation includes Barbier allylation, ionic hydrogenation, Jeffery reaction, Katsuki Sharpless asymmetric epoxidation, reductive opening of epoxide and ring closing metathesis.     

A novel highly stereoselective synthesis of chiral 5- and 4,5-substituted 2-oxazolidinones

A novel highly stereoselective synthesis of chiral mono- and bicyclic 4- and 4,5-substituted 2-oxazolidinones starting from β-keto esters was developed. After bioreduction with S. cerevisiae the resulting homochiral β-hydroxy esters are transformed into their hydrazides. Treatment with NaNO₂/H⁺ then furnishes 2-oxazolidinones in high e.e. (∼99%) and d.e. (>99%). The ring formation proceeds via a highly concerted sextet rearrangement with full retention of configuration at the stereocentres. Enantiopure 1,2-amino alcohols can subsequently be obtained by saponification of the 2-oxazolidinone products.     

Asymmetric synthesis of β-substituted alcanoic acids via highly stereoselective conjugate additions of organocopper compounds to chiral enoates

Conjugate additions of organocopper compounds RCu·.BF₃ to encates of sulfonamide-shielded alcohols 1x and 1n quite generally proceed with > 99% ee and > 90% yield.     

Kinetic resolution of chiral cyclohex-2-enones by rhodium(I)/binap-catalyzed 1,2- and 1,4-additions

The feasibility of kinetic resolutions of racemic monosubstituted cyclohex-2-enones by Rh/binap-catalyzed reactions was investigated. 1,2-Addition of AlMe(3) to the 5-substituted derivatives furnished allylic alcohols in the matched case, while the less reactive enantiomers were either left over or transformed into trans-3,5-disubstituted cyclohexanones in parallel or sequential 1,4-additions. Altogether, these represent regiodivergent reactions on racemic mixtures. In contrast, 1,4-addition of aryl groups led to inferior results since either catalyst or substrate control dominated.     

Synthesis of chiral allenes from ynamides through a highly stereoselective Saucy-Marbet rearrangement

A highly stereoselective Saucy-Marbet rearrangement using chiral ynamides and propargyl alcohols is described here. This rearrangement can be catalyzed by para-nitrobenzenesulfonic acid and leads to high diastereoselectivities for a range of different chiral propargyl alcohols and ynamides in a stereochemically intriguing matched, mismatched or indifferent manner. The stereoselective Saucy-Marbet rearrangement of ynamides provides an excellent entry to highly substituted chiral homo allenyl alcohols.     

A highly stereoselective synthesis of chiral alpha-amino-beta-lactams via the Kinugasa reaction employing ynamides

A highly stereoselective synthesis of chiral alpha-amino-beta-lactam through an ynamide-Kinugasa reaction is described. In addition, a mechanistic model is illustrated here to rationalize the observed diastereoselectivity, which depends on both the initial [3 + 2] cycloaddition step and the subsequent protonation for which both are highly selective.     

Origins of aryl substituent effects on the stereoselectivities of additions of silyl enol ethers to a chiral oxazolinium ion

Density functional theory calculations are reported that reveal the role of aromatic interactions in the additions of aryl-substituted silyl enol ethers to a chiral oxazolinium ion. Aryl-substituted silyl enol ethers give the opposite diastereomer of the adduct than do aliphatic silyl enol ethers, due to a combination of attractive cation-π and CH-π interactions, reduced steric repulsion, and lower torsional strain in the more "crowded" transition state.     

2,3a,5,6,7,7a-Hexahydro-3h,4h-benzothiophene-3,4-dione and cyclopenta [b]-tetrahydrothiophene-3,4-dione enolate anions as synthetic equivalents to cyclohex-2-enone and cyclopent-2-enone c-2-carbanions.

An efficient procedure for α-alkylation of cyclohex-2-enone and cyclopent-2-enone involving a base-promoted tandem of retrograde Dieckmann-Michael reactions of the C-alkylated derivatives of the title heterocycles is presented.     

A stereoselective synthesis of a chiral anthracyclinone AB-synthon from a carbohydrate precursor

Reaction of tetralinol 5 with phenylboronic acid removed the isopropylidene group with concomitant formation of phenylboronate 12. Oxidation of the latter with PCC gave keto-ester 13, a key intermediate in the synthesis of enantiopure anthracyclinones. Attempts at cleavage of the isopropylidene group in 5 by the usual procedures led first to substitution and epimerization at the benzylic position, then removal of the acetonide followed by formation of the cyclic ether 11a as the final product.     

A chiral Ag-based catalyst for practical, efficient, and highly enantioselective additions of enolsilanes to alpha-ketoesters

A Ag-based chiral catalyst promotes efficient and highly enantioselective aldol additions of ketone-derived enolsilanes to alpha-ketoesters in the presence of a readily available amino acid-based ligand and commercially available AgF2. alpha-Ketoester substrates may bear alkyl, alkenyl, and aryl substituents; reactions proceed to >98% conversion to afford the desired tertiary alcohols in 61->98% isolated yield and 60-96% ee. In contrast to previously reported approaches, highest enantioselectivities are observed with sterically demanding substrates, and reactions can be carried out in undistilled solvent, in air with as little as 1 mol % catalyst.     

A highly diastereoselective vinylogous Mannich condensation and 1,4-conjugate addition of (Z)-propenyl cuprate in the synthesis of an influenza neuraminidase inhibitor

A practical synthesis of neuraminidase influenza inhibitor, A-322278, has been developed. Asymmetry is introduced into the synthesis by an enzyme mediated ester hydrolysis. A highly diastereoselective vinylogous Mannich condensation reaction of N-Boc-2-tert-butyldimethylsilyloxypyrrole (TBSOP) and an N-(triphenylmethylsulfenyl)imine proceeds under thermodynamic control to assemble the framework. A significant temperature dependent rate difference for the transfer of (Z)- and (E)-propenyl moieties from a cuprate reagent during a 1,4-conjugate addition was observed. A very selective addition of cyanide to an N-acyliminium intermediate was employed to control the final stereocenter.     

a highly stereoselective synthesis of carbocyclic compounds by the michael induced intramolecular alkylation a stereocontrol of extracyclic chiral centers

Three, five, six, and seven-membered carbocyclic compounds, some of which contain an extracyclic chiral center, were synthesized highly stereo-selectively by the Michael induced intramolecular alkylation.     

One-pot and stereoselective synthesis of 2,3-dihydro-1,5-benzodiazepin-2-one with a phosphanylidene or phosphono-succinate substituent

The one-pot synthesis of 2,3-dihydro-1,5-benzodiazepins-2-one bearing phosphanylidene (ylide) or phosphono-succinate substituent is described. In this four-component reaction, benzodiazepine derived from condensation of o-phenylenediamine and diketene is trapped with the trialkyl phosphite-dialkyl acetylenedicarboxylate zwitterion. In the presence of H₂O, the ylide functional group is hydrolyzed to the corresponding phosphonate. The configuration of the products is selective and only one of the two possible rotamers or diastereomers is formed exclusively in high yield.     

Lipase-mediated resolution of 4-TMS-3-butyn-2-ol and use of the mesylate derivatives as a precursor to a highly stereoselective chiral allenylindium reagent

[reaction: see text]. An improved procedure for the resolution of 4-trimethylsilyl-3-butyn-2-ol has been developed. The mesylate derivatives of the resolved alcohols have been found to undergo highly enantio-, regio-, and diastereoselective additions to aldehydes, leading to homopropargylic alcohol adducts.     

Sequential nucleophilic addition/intramolecular cycloaddition to chiral nonracemic cyclic nitrones: a highly stereoselective approach to polyhydroxynortropane alkaloids

Two new polyhydroxylated nortropane analogues closely related with Calystegines have been prepared in excellent chemical yields and complete selectivity. A synthetic strategy based on consecutive nucleophilic allylation, oxidation, and intramolecular dipolar cycloaddition was developed. The formation of key intermediate cycloadducts were observed to take place through the recently confirmed thermally induced 2-aza-Cope rearrangement of nitrones.     

A short and highly stereoselective synthesis of α-(2-aminothiazolyl)-C-nucleosides

A short route to novel α-(2-aminothiazolyl)-C-nucleosides has been developed. The key step was the high diastereoselective reduction of the hemiacetal intermediates using L-Selectride, which afforded the corresponding R-diols in quantitative yields. These diols were converted, after C4-C1 ring closure and protecting groups cleavage, to their corresponding free α-C-nucleosides.