A short stereoselective synthesis of (+)-boronolide

A short and stereoselective synthesis of (+)-boronolide via oxidative functionalization of an olefin using a pendant sulfinyl group is described. Diastereoselective allylation was performed using Keck’s protocol and the lactone moiety was prepared by ring closing metathesis.     

Efficient total synthesis of (+)-curcuphenol via asymmetric organocatalysis

The catalytic enantioselective synthesis of (+)-curcuphenol is described herein. This approach involves the use of an organocatalytic alkylation of m-anisidine, a diazotation/Sandmeyer reaction of the amine and a Negishi-type coupling with dimethylzinc. This versatile strategy allows for the rapid synthesis of other members of this class of natural products.     

A process for the rapid removal of dialkylamino-substituents from aromatic rings. Application to the expedient synthesis of (R)-tolterodine

A range of N,N-dialkylanilines have been successfully converted to the parent substituted benzenes by a novel two-step pathway. The products are obtained in good yields and optical purity of adjacent stereocenters is maintained. This technology has been applied toward the synthesis of (R)-tolterodine.     

Enantioselective synthesis of 1-deoxy-d-gulonojirimycin from a phenylglycinol-derived lactam

Cyclocondensation of (R)-phenylglycinol with appropriately γ-substituted δ-oxo acid derivatives provides bicyclic lactams from which the enantioselective synthesis of 1-deoxy-d-gulonojirimycin has been reported.     

Straightforward enantioselective synthesis of (+)-ancistrofuran

This paper reports the straightforward enantioselective synthesis of (+)-ancistrofuran starting from a readily available enantiopure building block. A stereofacial directed diastereoselective addition of an organocerate for the installation of the required stereogenic center served as the key step. In addition, the efficient conversion of an intermediate hydroxy aldehyde to the one-carbon homologated cyanide was developed. The sequence was achieved by the mild formation of a cyanohydrin and the subsequent one-pot two-step Barton-McCombie double deoxygenation of the hydroxyl groups.     

A short and efficient stereoselective synthesis of the polyhydroxylated macrolactone (+)-aspicillin

[structures: see text] A short and efficient synthesis of the polyhydroxylated macrolactone (+)-aspicilin 1 using a stereoselective lithium perchlorate mediated addition of allyltributyltin to the equatorially disposed carboxaldehyde of 3 (derived from (R',R',R,S) butane diacetal protected butane tetrol 2) as the key step is described. Terminal group manipulation and Masamune-Roush olefination using phosphonate ester 4 followed by macrocyclization via ring closing metathesis afforded the natural product after partial hydrogenation and global deprotection.     

A short enantioselective synthesis of (−)-chloramphenicol and (+)-thiamphenicol using tethered aminohydroxylation

An efficient enantioselective synthesis of (−)-chloramphenicol (1) and (+)-thiamphenicol (2) is described. These antibiotics have been synthesized from commercially available 4-nitrobenzaldehyde and 4-(methylthio)benzaldehyde, respectively, using tethered aminohydroxylation and Sharpless asymmetric epoxidation as the chirality inducing steps.     

Straightforward stereoselective synthesis of polyfunctionalised cyclohexenols using a multicomponent approach

An intramolecular Ugi 5-centre-4-component reaction (U-5C-4CR) followed by a palladium-catalysed ring-opening has been employed to transform oxabicycloheptene-based β-amino acids into two families of regioisomeric polyfunctionalised cyclohexenols. The whole process is completely stereoselective and enantiomerically pure products are obtained in high overall yields.     

A new, enantioselective synthesis of (+)-isolaurepan

A highly enantioselective synthesis of 2,6-syn-disubstituted tetrahydropyrans from commercially available tri-O-acetyl-d-glucal, based on a thermal Claisen rearrangement, allows enantioselective synthesis of (+)-isolaurepan when combined with a ring expansion reaction using trimethylsilyldiazomethane.     

Divergent synthesis of (+)-tanikolide and its analogues employing stereoselective rhodium(II)-catalyzed reaction

In this study, we described the divergent synthesis of (+)-tanikolide and its analogues, such as (4S)- and (4R)-hydroxytanikolides, and nortanikolide, employing a stereoselective dirhodium(II)-catalyzed reaction to construct the quaternary chiral center of tanokolides. The key steps involve (a) a dirhodium(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement, (b) an N-heterocyclic carbene-catalyzed ring-expansion lactonization of tetrahydrofurfural, or (c) an oxidative cleavage of tetrahydrofuran-5-methanol to γ-lactone using a 2-iodobenzamide catalyst. This route would provide high flexibility for analogue synthesis because the long side chain can be introduced at a later stage in the synthesis.     

First enantioselective synthesis of (−)-neplanocin F

(−)-Neplanocin F, the natural isomer of a component of the neplanocin family was enantioselectively synthesized starting from d-γ-ribonolactone. The synthetic approach was based on the preparation of a suitable carbocyclic precursor bearing three hydroxyl groups orthogonally protected. The key steps of the synthesis were the regioselective protection of a secondary allylic alcohol over a homoallylic one and the coupling of the nucleobase with a triflate intermediate.     

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is completed in six steps in overall yields of 8% for eleutherin and 14% for allo-eleutherin. The synthetic strategy features an efficient combination of the Dötz annulation reaction with a chiral alkyne and an oxa-Pictet Spengler reaction as the keys steps in the stereodivergent synthesis of (+)-eleutherin and (+)-allo-eleutherin. The synthesis of (S)-(+)-2-(2′-hydroxypropyl)-5-methoxy-1,4-naphthoquinone entails the formal synthesis of (+)-nocardione B.     

A stereoselective synthesis of (+)-gonyautoxin 3

An asymmetric synthesis of the paralytic shellfish poison (PSP), (+)-gonyautoxin 3, is described. A unique, Rh-catalyzed amination reaction provides rapid access to the heteratom-rich, tricyclic core of the toxin, which is common to more than 30 related natural products. The completed route should facilitate the preparation of other naturally occurring PSPs and designed analogues thereof.     

A short and stereoselective synthesis of (±)-aristeromycin

A new Stereoselective three-step total synthesis of (±)-aristeromycin starting from readily available 1-hydroxymethyl-3-cyclopentene is described.     

A stereoselective total synthesis of (−)-seychellene

A stereoselective total synthesis of the tricyclic sesquiterpene (−)-seychellene, starting from (R)-carvone via (R)-3-methylcarvone has been accomplished, employing a combination of intermolecular Michael addition-intramolecular Michael addition sequence, a stereoselective hydrogenation, and an intramolecular alkylation reaction.     

Efficient total synthesis of (+)-exo-, (−)-endo-brevicomin and their derivatives via asymmetric organocatalysis and olefin cross-metathesis

The catalytic enantioselective synthesis of (+)-exo-, (−)-endo-brevicomin and their derivatives is described herein. This approach involves the use of the organocatalyzed asymmetric α-aminoxylation of aldehyde, in situ indium mediate allyation and olefin cross-metathesis. This versatile strategy allows for the rapid synthesis of other members of this class of natural products.     

Enantioselective synthesis of (+)-anatoxin-a via enyne metathesis

A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed by a series of nine chemical operations and in 27% overall yield from commercially available d-methyl pyroglutamate (12). The strategy featured the application of a new protocol for the diastereoselective synthesis of cis-2,5-disubstituted pyrrolidines bearing unsaturated side chains and an intramolecular enyne metathesis to provide the bridged bicyclic framework of 1. Thus, d-methyl pyroglutamate (12) was converted in five steps to 32, which underwent facile enyne metathesis to deliver the bicyclic diene 33. Selective oxidative cleavage of the less substituted carbon-carbon double bond in 33 followed by deprotection furnished (+)-anatoxin-a (1).     

A short synthesis of (+) and (−)-falcarinol

A short, practical synthesis of the bis-acetylenic natural product falcarinol 1 is reported. This method relies on the alternate functionalisation of bis-trimethylsilylbutadiyne 10. This may be achieved in one-pot, however, better yields were obtained more conventionally. Lipase mediated enzymatic kinetic resolution of the racemic adduct in an organic solvent afforded (+)-1 in 97% enantiomeric excess. The analogous process performed with racemic 3-acetoxy falcarinol 11 under aqueous conditions gave (−)-1. Oxidation of 1 with Dess-Martin periodinane gave falcarinone 2.     

A stereoselective and short total synthesis of the polyhydroxylated gamma-amino acid (-)-detoxinine,based on stereoselective preparation of dihydropyrrole derivatives from lithiated alkoxyallenes

Based on our earlier results employing lithiated methoxyallene 2 as C(3) building block and imines 3 for the synthesis of dihydropyrrole derivatives 5, we have investigated chiral imines 6, 10, and 15 as electrophilic components. Combined with lithiated alkoxyallenes, these imines provide the corresponding primary adducts and finally the dihydropyrrole derivatives 8, 12, 17, 20, and 22 in good yields and with high to excellent syn selectivities. This stereochemical outcome is interpreted as a result of alpha-chelate control. Treatment with hydrochloric acid converted syn-8 and syn-12 into bicyclic compounds 9 and 13, whereas under more mildly acidic conditions adduct syn-17 was transformed into diol syn-18. The total synthesis of the uncommon gamma-amino acid (-)-detoxinine could be achieved by starting from (S)-malic acid, which was converted into imine 15 in four steps. Lithiated benzyloxyallene added to imine 15 and efficiently furnished the crucial dihydropyrrole derivative syn-22. The hydrogenolysis of this compound did not directly provide the protected triol 29 as anticipated, but a stepwise protocol made the triol available in a fairly satisfactory manner. A second crucial step of the synthesis was the selective oxidation of 29, which could be achieved by employing platinum dioxide and oxygen. The resulting bicyclic lactone 30 was smoothly transformed into enantiopure (-)-detoxinine. Thus, a fairly short synthesis of this natural product based on a lithiated alkoxyallene could be performed, demonstrating the potential of these intermediates for syntheses of interesting functionalized heterocyclic compounds.     

A stereoselective synthesis of (+)-L-733,060 from ethyl (R)-(+)-2,3-epoxypropanoate

An asymmetric synthesis of neurokinin substance P receptor antagonist (+)-L-733,060 starting from enantiomerically pure ethyl (R)-(+)-2,3-epoxypropanoate (ethyl glycidate) is described. The synthesis relies on a diastereoselective reductive amination, regioselective intramolecular epoxide opening, and in situ cyclization as the key steps.