Abstract Treatment of the readily available (R)-(-)enantiomer of 2-aminobutan-1-ol 1 with sodium hydride followed by benzyl chloride afforded the O-benzyl base (R)-(-)-2. The latter was successfully used for the resolution of racemic α-methylsuccinic and α-bromosuccinic acids, as well as of the racemic α-benzylhemisuccinic esters 8 and 9 resectively.

[reaction: see text] Under standard hydroboration-oxidation conditions, the dihydropyrans 4 underwent a highly stereocontrolled tandem reaction, involving the expected hydration of the double bond together with the reduction of the ketal moiety. This unprecedented transformation gives rise to a short, [4 + 2]-based synthetic route to (+/-)-beta-C-naphthyl-2-deoxyglycosides 5, which allows a significant structural and functional diversity at C-6. We thus described the first synthesis of (+/-)-C-aryl-6-fluoro and -6,6-difluoro olivosides, via the allylic mono- and difluorides produced by regioselective fluorination of, respectively, hydroxyalkyl and oxoalkyl dihydropyran derivatives.

A dithioacetalisation procedure at low temperature using TMSOTf as the promoter is described. This method proved highly efficient for unprecedented transprotection of ketone enol ethers and was successfully applied to polyfunctional sensitive substrates.

Reaction of polysubstituted 2-hydroxyalkyldihydropyrans with DAST led regiospecifically to fluorination at the exocyclic position, except for primary alcohols. Difluorination of carbonylated analogues with deoxo-fluor™ occurred also regioselectively. The unexpected stability and synthetic potential of these new allylic fluorides are discussed.

The synthesis of chiral 1,2,3,5-substituted tetrahydropyrans has been realized via an asymmetric hetero Diels–Alder (HDA) reaction. The key step that involved a trisubstituted chiral enol ether derived from (R)-mandelic acid as the dienophile promoted the creation of three stereogenic centers with a remarkable and unprecedented endo and facial stereocontrol. The hydrogenation of the heteroadduct 2 was optimized by using Pd on charcoal and diisopropylethylamine, leading to a unique isomer. The chiral inductor was cleanly and stereoselectively removed via an acetal reduction, which demonstrated the potential of this methodology for the efficient construction of key intermediate of biologically active molecules.

A convergent synthetic pathway for access to the functionalized (+/-)-9-decanolides is described, using a [4+2] bicyclic heterocycloadduct as the key intermediate. Thus, the exo adduct (+/-)-10 led to the hemiacetal (+/-)-14a via a 4-step sequence. Free radical oxidation of (+/-)-14a by means of iodine and iodosobenzene diacetate under UV light gave the model 9-decanolide (+/-)-15 in 53% yield.

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.

The [4+2] heterocycloaddition reaction between (E)gamma-substituted beta-unsaturated alpha-oxo esters 1a-d and cyclic and acyclic ketone enol ethers 2a-1 afforded heteroadducts 3-5 in high yields when either [Eu(fod)(3)] or SnCl4 were used as the catalyst. With methyl (E)-benzylidenepyruvate (1a), the two catalytic modes displayed divergent stereoselectivities. In the case of the heterocycloaddition of silyl enol ether 2h, X-ray investigations established the relative configurations of the bicyclic adducts 3h and 5h, each obtained as the major isomer with [Eu(fod)3] and with SnCl4, respectively. These assignments provided valuable information concerning the concerted vs, nonconcerted mechanism of these acid-catalysed reactions, With methyl (E)-tert-butoxymethylenepyruvate (1d), the scope of the reaction proved to be restricted to alkyl enol ethers as the dienophiles. In this case, the stereochemical process followed a different pathway, exemplified by the X-ray structure of the adduct 4q, obtained with total stereoselectivity from 1d and 1-methoxycyclohexene (2f) when SnCl4 Was the catalyst.

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.

Under Eu(fod)3-catalyzed conditions, the endo-selective hetero Diels–Alder reaction of (S)-(+)-O-vinyl mandelate with Wang-supported benzylidenepyruvate occurred with a 93/7 facial selectivity that compares well with those observed in solution. In addition, the solid-phase sequence allowed an unprecedented reuse of the catalyst in the presence of excess dienophile in solution.

A new and highly simple method for the synthesis of E-gamma -aryl-alpha -oxobutenoic esters is described. This unprecedented one-step procedure is based on an unexpected nucleophilic reactivity of alkyl pyruvates towards aromatic aldehydes in refluxing dichloromethane, when using catalytic amounts of Cu(OTf)(2) and in the presence of stoichiometric amounts of trimethyl orthoformate in the case of electron-rich aldehydes. Under these conditions, yields obtained are uniformly higher than those obtained by previous multistep procedures.

The syntheses of the diaryls 14 and 21, substituted by two ω-cyanoalkyl chains (one on each ring), are described. Treatment of the unsymmetrical diaryl 14 with NaN(Me)Ph in a Thorpe-Ziegler reaction failed to give any definite product. Under the same conditions the symmetrical diaryl 21 led to an isomeric mixture of dimeric enaminonitriles 24. Mild acidic hydrolysis of the latter yielded the isomeric β-ketonitriles 25, whereas more drastic hydrolytic conditions led to the macrocyclic diketone 26.

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.

The OH groups of Wang resin were esterified with benzylidenepyruvic acid (1) to give the immobilized 1-oxabutadiene 2. The latter reacted with vinyl ethers 3a-h (dienophiles) in the presence of Eu(fod)(3), and the resulting adducts 4a-h underwent reductive cleavage with LiAlH4 to afford the dihydropyrans 5a-h in high (62 to 100%) overall yields. A similar sequence carried out under conventional homogeneous liquid phase conditions led to significantly lower yields. The endo/exo selectivity of the cycloaddition reaction was the same in both cases.

Various chiral N,N-dialkylhydrazines were prepared in four to five steps from (R)-(–)-2-aminobutan-1-ol 6. They reacted with various prochiral ketones, thus giving the corresponding hydrazones. Reduction of the latter by means of LiAlH4 afforded N,N,N′-trisubstituted hydrazines whose d.e.s were in the range 43–100%. Interestingly, LiAlH4 reduction of the four N-trifluoroethylhydrazones 34 and 38–40 yielded the hydrazines 46 and 48–50, respectively, and with d.e.s=100% by 1H and 13C NMR.

A new methodology has been applied to synthesize an isomer of the west part of (+)-ambruticin based on an efficient asymmetric de novo access to the A unit and sequential stereospecific reactions catalyzed by Pd-0 for the construction of the B unit.

Polystereocontrolled access to 4-type heterocycloadducts was consistently improved by using a new 4-oxy-substituted 1-oxabutadiene, methyl (E)-tert-butoxymethylenepyruvate (1c). Obtained in both enantiomeric forms with high diastereomerical purity, these adducts led to diprotected 2,4-dideoxyglucose 10 and gluconolactone 12 in both L and D series in high yields. Epimer ization of (-)-12 via ntramolecular Mitsunobu inversion gave a straightforward access to the lactone moiety (+)-16 of compactin.