Short and Efficient Synthetic Route to Methyl α-Trioxacarcinoside B and Anomerically Activated Derivatives

A 9-step synthetic route to the complex carbohydrate methyl α-trioxacarcinoside B from 2-acetylfuran is described. Anomerically activated forms, including 1-phenylthio, 1-O-(4′-pentenyl), 1-fluoro, and 1-O-acetyl derivatives are also prepared

Anti-Selective Epoxidation of Methyl α-Methylene-β-<i>tert</i>-butyldimethylsilyloxycarboxylate Esters. Evidence for Stereospecific Oxygen Atom Transfer in a Nucleophilic Epoxidation Process

Methyl α-methylene-β-tert-butyldimethylsilyloxycarboxylate esters are found to undergo diastereoselective epoxidation in the presence of potassium tert-butoxide−tert-butyl hydroperoxide to form anti products. In an effort to better understand mechanistic details of the transformation and the basis of diastereoselectivities observed, we studied the epoxidation of substrates with α-methylene groups containing (trans) deuterium labels and discovered that oxygen-atom transfer proceeds with ≥95% stereospecificity in all cases examined. These and other experiments suggest that the mechanism of epoxidation is not distinguishable from a concerted process

Synthesis of (−)-Quinocarcin by Directed Condensation of α-Amino Aldehydes

An enantioselective synthesis of the natural antiproliferative agent quinocarcin was achieved by the directed condensation of optically active α-amino aldehyde intermediates. Condensation of the N-protected α-amino aldehyde 1, prepared in eight steps (19% yield) from (R,R)-pseudoephedrine glycinamide, with the C-protected α-amino aldehyde derivative 2, prepared in seven steps (34% yield) from (R,R)-pseudoephedrine glycinamide, afforded the corresponding imine in quantitative yield. Without isolation, direct treatment of this imine intermediate with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and hydrogen cyanide led to cleavage of the fluorenylmethoxycarbonyl (Fmoc) protective group followed by addition of cyanide (Strecker reaction) to form the bis-amino nitriles 3 as a mixture of diastereomers, in 91% yield. Treatment of the diastereomers 3 with trimethylsilyl cyanide and zinc chloride in 2,2,2-trifluoroethanol at 60 °C led to stepwise cyclization to form the tetracyclic product 4 (42% yield from 1 and 2). The latter intermediate was transformed into (−)-quinocarcin (1) in five steps (45% yield). The yield of quinocarcin was 19% from 1 and 2 (7 steps), and 4% from pseudoephedrine glycinamide (15 steps)

New and Stereospecific Synthesis of Allenes in a Single Step from Propargylic Alcohols

New and Stereospecific Synthesis of Allenes in a Single Step from Propargylic Alcohol

New and Stereospecific Synthesis of Allenes in a Single Step from Propargylic Alcohols

New and Stereospecific Synthesis of Allenes in a Single Step from Propargylic Alcohol

Highly Efficient Methodology for the Reductive Coupling of Aldehyde Tosylhydrazones with Alkyllithium Reagents

Highly Efficient Methodology for the Reductive Coupling of Aldehyde Tosylhydrazones with Alkyllithium Reagent

Practical Syntheses of Enantiomerically Enriched γ-Lactones and γ-Hydroxy Ketones by the Alkylation of Pseudoephedrine Amides with Epoxides and Their Derivatives

Pseudoephedrine amide enolates are shown to undergo efficient alkylation reactions with epoxides as electrophiles. Reactions with monosubstituted epoxides are subject to stereochemical matching such that the pairing leading to the 1,3-syn diastereomer is a highly selective, synthetically useful process, while the pairing forming the 1,3-anti diastereomer is not. Reactions with the 1,1-disubstituted epoxide isobutylene oxide are also highly diastereoselective and synthetically useful, but ethylene oxide exhibits poor diastereoselectivity. As an alternative to the use of ethylene oxide, 2-(tert-butyldimethylsilyloxy)ethyl iodide is shown to undergo highly diastereoselective and efficient alkylation reactions with pseudoephedrine amide enolates. Interestingly, epoxides and alkyl halides are found to attack opposite π-faces of pseudoephedrine amide enolates. The products of each of these alkylation reactions are transformed efficiently into γ-lactones by acidic hydrolysis and into methyl ketones by the addition of methyllithium. The methodology described provides useful procedures for the synthesis of enantiomerically enriched γ-lactones and γ-hydroxy ketones

Heck-Type Arylation of 2-Cycloalken-1-ones with Arylpalladium Intermediates Formed by Decarboxylative Palladation and by Aryl Iodide Insertion

A palladium-catalyzed decarboxylative arylation reaction was shown to produce Heck-type coupling products using a number of different arene carboxylic acid and 2-cycloalken-1-one substrates. The more conventional Heck coupling of an aryl iodide and a 2-cycloalken-1-one reactant was also briefly explored for comparison, where it was found that phosphine-free (Jeffery) conditions afforded the highest yield of product

On the Inherent Instability of α-Amino α‘-Fluoro Ketones. Evidence for Their Transformation to Reactive Oxyvinyliminium Ion Intermediates

α-Amino α‘-fluoro ketones are shown to be inherently unstable intermediates. Evidence is presented that they undergo enolization toward the amino group followed by expulsion of fluoride ion, forming a proposed oxyvinyliminium ion (amino-substituted oxyallyl cation). In protic, nucleophilic media the proposed intermediate is trapped by solvent. In the presence of a reactive diene, [4 + 3] cycloadducts have been isolated. Prior observations concerning fluorinated amino ketones are discussed in light of these findings

Highly Efficient Methodology for the Reductive Coupling of Aldehyde Tosylhydrazones with Alkyllithium Reagents

Highly Efficient Methodology for the Reductive Coupling of Aldehyde Tosylhydrazones with Alkyllithium Reagent