An efficient asymmetric synthesis of grenadamide

The cyclopropane containing natural product grenadamide has been prepared in six steps using (R)-5,5-dimethyl-oxazolidin-2-one as a chiral auxiliary for asymmetric synthesis. Key synthetic steps include the use of the β-hydroxyl group of a syn-aldol product as a ‘temporary’ stereocentre to control the facial selectivity of a directed cyclopropanation reaction, as well as the use of phenylethylamine as a nucleophile for the direct aminolysis of an N-acyl-oxazolidin-2-one intermediate.     

An efficient asymmetric oxidation of sulfides to sulfoxides

The Sharpless reagent (Ti(OiPr)₄ + 1 mol eq. diethyl tartrate (DET) + 2 t-BuOOH) modified by addition of one mol eq. H₂O gives a new homogeneous reagent which cleanly oxidizes sulfides into sulfoxides in dichloromethane. The best results were obtained for the stoichiometry Ti/DET/H₂O/t-BuOOH = 1:2:1:2. The e.e. observed ranged from 4 to 93% with the highest beeing observed in the case of methyl p-toly] sulfoxide.     

An efficient asymmetric synthesis of manzacidin C

A brief synthesis of manzacidin C based on a chiral silane-promoted diastereo- and enatioselective acylhydrazone-alkene [3 + 2] cycloaddition reaction has been achieved. This synthesis is the first synthesis of any of the manzacidins wherein the C(4) and C(6) stereocenters are established in a single highly stereoselective step.     

An efficient, general asymmetric synthesis of carbocyclic nucleosides: application of an asymmetric aldol/ring-closing metathesis strategy

A general and efficient synthesis of carbocyclic and hexenopyranosyl nucleosides has been developed. The strategy combines three key transformations: an asymmetric aldol addition to establish the relative and absolute configuration of the pseudosugar, a ring-closing metathesis to construct the pseudosugar ring, and a Trost-type palladium(0)-mediated substitution to assemble the pseudosugar and the aromatic base. Carbovir, abacavir, and their 2'-methyl derivatives as well as hexenopyranosyl nucleoside analogues have been prepared by this sequence.     

An efficient copper-catalyzed synthesis of anilines by employing aqueous ammonia

Under the catalysis of CuI/2-carboxylic acid-quinoline-N-oxide, the cross coupling reactions between aryl iodides or bromides and aqueous ammonia proceed very well to afford N-unprotected aniline derivatives in excellent yields. This inexpensive catalytic system shows great functional group tolerance and excellent reaction selectivity.     

An efficient enantioselective synthesis of florfenicol via asymmetric aziridination

An efficient enantioselective synthesis of florfenicol is accomplished in 44.7% overall yield from commercially available p-(methylsulfonyl)benzaldehyde. Key features of this synthesis are the asymmetric aziridination reaction mediated by the Wulff’s catalyst in situ derived from (R)-VANOL and diastereoselectively ring-opening of (2S,3S)-fluoroaziridine 13.     

An efficient large-scale synthesis of gemcitabine employing a crystalline 2,2-difluoro-α-ribofuranosyl bromide

An efficient large-scale synthesis of gemcitabine was achieved without chromatography or fractional crystallization. The key steps include stereospecific conversion of a novel β-ribofuranosyl phosphate into a highly crystalline α-ribofuranosyl bromide and coupling of the α-ribofuranosyl bromide and trimethylsilyl cytosine to produce a β-nucleoside. p-Phenylbenzoyl group was introduced for the protection of one of hydroxy groups in order to enhance the crystallinity of intermediates. Continuous removal of trimethylsilyl bromide, generated during the coupling reaction, by distillation from the reaction medium substantially enhanced the β-selectivity of the crucial coupling reaction.     

An efficient oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones employing ferric chloride hexahydrate-methanol: synthesis of naturally occurring 4-alkoxy-2-arylquinolines

A simple, inexpensive and efficient oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones has been carried out by employing FeCl₃·6H₂O-methanol under mild conditions. This method has been investigated for the synthesis of an endothelin receptor antagonist, benzofuro[3,2-b]pyridine core structure.     

An efficient,asymmetric synthesis of pipecolic acid and 2-alkyl pipecolic acids

Both (R)- and (S)-pipecolic acids and their 2-alkyl derivatives have been synthesized via diastereoselective alkylations of (R)-5-phenylmorpholin-2-one 5.     

An efficient asymmetric synthesis of furofuran lignans: (+)-sesamin and (−)-sesamin

An efficient synthesis of (+)-sesamin 1a and (−)-sesamin 1b is described. The key reactions include highly stereoselective aldol condensation of piperonal 7 with the dianion of chiral oxazolidinone 8, followed by intramolecular ring cyclization of aldol product 11 in high yield.     

A short and efficient asymmetric synthesis of komaroviquinone

An asymmetric total synthesis of komaroviquinone (1), which is a natural product isolated from Dracocephalum komarovi and shows novel potent trypanocidal activity, was achieved in five steps from the known starting materials. The synthetic route is shorter and more efficient than the reported methods and also useful for the scale-up synthesis.     

An enantioselective strategy to macrocyclic bisindolylmaleimides. An efficient formal synthesis of LY 333531

[reaction: see text]. The ability to employ a bromo alcohol as a nucleophile in a palladium-catalyzed dynamic kinetic asymmetric transformation leads to an efficient synthesis of a selective PKC inhibitor under clinical development.     

An efficient strategy for the synthesis of 1-chloroethyl phosphates and phosphoramidates

[reaction: see text] A versatile, efficient, and simple method for the preparation of various 1-chloroethyl phosphates and phosphoramidates is described. The protected chlorophosphates or phosphoramidates are synthesized to the vinyl derivative under mild conditions, followed by conversion to the chloroethylidene phosphate or phosphoramidate by dry HCl gas, resulting in good to excellent yields. 1-Chloroethyl phosphates and phosphoramidates are excellent building blocks for the synthesis of novel ethylidene-linked phosphate prodrugs.     

Convergent asymmetric synthesis of (+)-aureothin employing an oxygenase-mediated resolution step

Need an enzymatic push? The desymmetrization of α,α'-dimethoxy-γ-pyrone allows the convergent and rapid preparation of the complete carbon skeleton of (+)-aureothin. The final step in the synthesis of the target molecule is the regiodivergent parallel kinetic resolution promoted by cytochrome P450 monooxygenase AurH to deliver the enantiopure natural product.     

An asymmetric synthesis of L-pyrrolysine

An efficient asymmetric synthesis of the 22nd amino acid L-pyrrolysine has been accomplished. The key stereogenic centers were installed by an asymmetric conjugate addition reaction. A Staudinger/aza-Wittig cyclization was used to form the acid-sensitive pyrroline ring. Pyrrolysine was synthesized in 13 steps in 20% overall yield.     

An efficient route to the synthesis of symmetric and asymmetric diastereomerically pure fullerene triads

A new synthetic route based on the stepwise functionalisation of fullerene cages allows the facile formation of linear, diastereomerically pure triads incorporating two different fullerene cages linked by an organic spacer group. The critical coupling step of two fullerene cages via activation by N,N′-dicyclohexylcarbodiimide was systematically investigated to reveal that the yield of the coupling is maximised in o-dichlorobenzene at high concentrations of the reactant fullerene nucleophile, while in more polar solvents or at lower concentrations of reactants the formation of unwanted side-products (such as guanidine-, N-acylurea- and anhydride-functionalised fullerenes) is favoured. The resultant triads possess an atypically good solubility for this class of compound, which enabled full detailed characterisation by ¹H and ¹³C NMR, IR and UV–vis spectroscopies and by MALDI-TOF mass spectrometry.     

An efficient one-pot asymmetric synthesis of biaryl compounds via Diels-Alder/retro-Diels-Alder cascade reactions

[reaction: see text] A single-step chirality transfer method for the synthesis of axially chiral biaryl compounds by construction of the second aromatic ring via a Diels-Alder/retro-Diels-Alder cascade reaction is reported. This methodology should find broad application in the synthesis of natural products and asymmetric catalysts.     

An efficient synthesis of 2-alkylpyridines using an alkylation/double decarboxylation strategy

We have discovered a novel route for synthesising 2-alkylpyridines by exploiting the decarboxylation of pyridyl malonate esters. Herein we report the synthesis of a number of examples and describe how the reaction was discovered.