Highly regio- and syn-diastereoselective synthesis of 4-hydroxy-1,2-alkadienylcarbamates from α-titanatedl 2-alkynylcarbamates and aldehydes1,2

$\text{N}$,$\text{N-}$Diisopropyl 2-alkynyl carbamates 9 are deprotonated by $\text{n}$-butyllithium to form lithium compounds 10. After exchange of the cation, titanium reagents 13 add highly diastereoselective to aldehydes with formation of the title compounds 14. In contrast to metallated 2-alkynyl ethers, the reagents 10 and 13 exhibit high γ-regioselectivity in carbonyl addition reactions, due to the chelating carbamoyl group. The $\text{syn}$-configuration of 14 was deduced from the crystal structure of the urethane derivative 21.     

Total synthesis of (−)-funebrine via Au-catalyzed regio- and stereoselective γ-butyrolactonization of allenylsilane

The stereoselective total synthesis of (−)-funebrine from 2-butyn-1-ol was described. The crucial steps in the synthesis involved the stereoselective enolate Claisen rearrangement of the (S)-α-acyloxy-α-alkynylsilane 8, the Au-catalyzed regio- and stereoselective lactonization of the allenylsilane 7, and the Paal-Knorr pyrrole condensation using an unsymmetrical 1,4-diketone 4b.     

Synthesis and some transformations of bicyclic γ-lactones with a fused cyclopropane ring

Reductive cyclization of 4-hydroxymethyl-5,5-dimethyl(or pentamethylene)-2,5-dihydrofuran-2-ones by the action of sodium tetrahydridoborate gave bicyclic compounds in which the lactone ring is fused to a cyclopropane ring. Hydrolysis of the products with aqueous sodium hydroxide resulted in the formation of the corresponding disodium cyclopropane-1,1-dicarboxylates, which reacted with alkyl halides to produce the diesters. Acid hydrolysis of the fused systems was accompanied by opening of the cyclopropane ring with formation of 4-chloromethyl-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylic acid.     

Application of a one-pot lipase resolution strategy for the synthesis of chiral γ- and δ-lactones

A successful one-pot reduction of γ-ketoesters, δ-ketoesters and lactones to the corresponding 1,4- and 1,5-diols followed by a lipase catalyzed kinetic resolution coupled with hydrolysis to afford optically active diols is described. The synthetic utility of this one-pot method was illustrated by the oxidation of these chiral diols to respective chiral γ-butyrolactone and δ-lactones. Lipase from Pseudomonas cepacia, immobilized on ceramic afforded the product with high enantiomeric excess in good yields under mild reaction conditions. This approach has been used to develop a convenient enantioselective route for several γ- and δ-lactones using achiral and corresponding racemic starting material.     

Diastereoselective synthesis of β- and γ2-muurolene: a carbocationic pathway from mono- to sesquiterpenes

The Lewis acid catalysed addition of the piperityl chlorides6 to isoprene yields adduct7, which undergoes a cis-stereoselective cyclisation to give the diastereoisomeric muurolene monohydrochlorides8. Treatment with potassium tert-butoxide affords β- and γ₂- muurolene 2.     

Total synthesis of (±)-nicolaioidesin B via a highly regio- and diastereoselective Diels–Alder reaction

The total synthesis of (±)-nicolaioidesin B, a natural product that shows preferential cytotoxicity against pancreatic cancer cells under nutrient starvation conditions, is achieved. The key step is a thermally-induced, highly regio- and diastereoselective Diels–Alder reaction between (E)-N-methoxy-N-methylcinnamide and ocimene under solvent-free conditions.     

Asymmetric synthesis via aziridinium ions: exploring the stereospecificity of the ring opening of aziridinium ions and a formal synthesis of (−)-swainsonine

The use of aziridinium ions in two different projects is described. First, the stereospecificity of the ring opening of aziridinium ions with MeNH₂ as a route to chiral diamines has been explored. When the aziridinium ion contained a phenyl or para-methoxyphenyl substituent, stereospecific ring opening occurred. In contrast, switching the para-methoxy group to a para-N,N-dimethylamino group gave a racemic diamine product. Second, starting from N-Boc pyrrolidine, asymmetric lithiation-trapping-ring expansion (via an aziridinium ion) was used to synthesise a piperidine alcohol. In this way, a formal synthesis of (?)-swainsonine was completed.     

A facile synthesis of γ-butenolides via cyclization of 3-alkenoic acids with dimethyl sulfoxide and oxalyl bromide

The combination of dimethyl sulfoxide and oxalyl bromide was used to accomplish the cyclization of 3-alkenoic acids with the aid of a base to afford γ-butenolides, in which bromodimethylsulfonium salt generated in situ was proposed to serve as a Br⁺ source.     

Inclusion complexes of γ-cyclodextrin and carboxyl-modified γ-cyclodextrin with C60: synthesis, characterization and controlled release application via microgels

Carboxyl modified γ-cyclodextrin (CDSA) with a substitution degree of about 9.5 was prepared by the esterification of γ-cyclodextrin (CD) with succinic anhydride in pyridine at 90 °C. The chemical composition and the structure of CDSA were characterized by FT-IR, MALDI-TOF, X-ray diffraction pattern, potentiometric titration and TGA. Modified and native γ-cyclodextrin associate with fullerene (C₆₀) in DMF-toluene mixture resulting 1:1 CDSA:C₆₀ and CD:C₆₀ inclusion complexes. Aqueous solutions of native cyclodextrin, carboxyl-modified cyclodextrin and their inclusion complexes with C₆₀ were used as microgel solvent (or swelling agent) for controlled release application. The release of solutions was induced by shear stress and demonstrated using rheo-optical set-up.     

AgBF4 catalyzed regio- and stereoselective synthesis of trans α-vinyl-β-amino esters via asymmetric addition of siyl dienolate to sulfinylimines

AgBF₄ catalyzed Mannich-type reactions of siyl dienolate with chiral aryl-substituted (S)-N-tert-butanesulfinylimines has been developed. A class of chiral trans α-vinyl-β-amino esters was obtained in moderate to excellent yields (up to 93%), good diastereoselectiveties (up to 92:8 dr), and complete α-site regioselectivity.     

Diastereoselective and enantioselective synthesis of 4′-aza analogues of 2′,3′-dideoxynucleosides

A diastereo- and enantioselective synthesis of 4′-aza analogues of 2′,3′-dideoxynucleosides has been designed by the strategy of the 1,3-dipolar cycloaddition reaction of a Vasella-type nitrone. The reaction leads to (1′R)- and (1′S)-4′-aza analogues of 2′,3′-dideoxythimidine and fluorouridine, in enantiomerically pure forms.     

Enantioselective organocatalytic Friedel-Crafts alkylation reaction of indoles with 5-hydroxyfuran-2(5H)-one: access to chiral γ-lactones and γ-lactams via a Ugi 4-center 3-component reaction

5-Hydroxyfuran-2(5H)-one 1, a readily available renewable resource, was used as an electrophile in the Friedel-Crafts alkylation of indoles catalyzed by a diphenylprolinol silyl ether. Moderate catalyst loading was achieved because of the high reactivity of 5-hydroxyfuran-2(5H)-one 1 in this process. Reduction of the Friedel-Crafts adduct (FC adduct) afforded indoyl lactones in high yield and enantioselectivity. Moreover, the FC adduct was used as a chiral synthon in a diversity-oriented synthesis, as illustrated by its successful engagement in a 4-center 3-component Ugi reaction (U-4C-3CR) to afford chiral five-membered lactams in high yield and enantioselectivity.     

An alkaloid-mediated desymmetrization of meso-anhydrides via a nucleophilic ring opening with benzyl alcohol and its application in the synthesis of highly enantiomerically enriched β-amino acids

The cinchona alkaloid-mediated opening of prochiral cyclic anhydrides in the presence of benzyl alcohol leading to optically active hemiesters is described. Structurally diverse anhydrides are converted into their corresponding benzyl monoesters with either enantiomer being obtained with up to 99% e.e. by using quinine or quinidine as the directing additive. A simple aqueous work-up protocol permits the isolation of the products in analytically pure form and the recovery of the alkaloids almost quantitatively. These hemiesters can be converted to N-protected β-amino esters by means of Curtius degradation of the corresponding acyl azides. Subsequent cleavage of both protecting groups by a single reaction step leads to the free β-amino acids in excellent yields. The efficiency of this procedure is demonstrated by the short asymmetric synthesis of the fungicide cis-pentacin delivering the amino acid with >99.7% enantiomeric excess.     

Radical cyclization of α-bromo aluminum acetals onto alkenes and alkynes (radic[Al] process): a simple access to γ-lactols and 4-methylene-γ-lactols

An efficient preparation of γ-lactols and methylene-γ-lactols is described. Highly acid-sensitive lactols are prepared in a concise manner by using a radical cyclization of aluminum acetals. The precursors for the radical reactions are readily prepared from allyl or propargyl alcohols and α-bromo acids. Functionalization of the resulting γ-lactols and methylene-γ-lactols can be achieved following isolation, leading to synthetically useful building blocks, such as 1,4-diols, 1,4-dienes, γ-lactones, and polysubstituted tetrahydrofurans.     

Palladium-catalyzed coupling of haloalkynes with allyl acetate: a regio- and stereoselective synthesis of (Z)-β-haloenol acetates

A Pd-catalyzed coupling of haloalkynes with allyl acetate has been reported, providing a convenient method for the stereoselective synthesis of (Z)-β-haloenol acetates in good yields. The synthetic utility of this method is demonstrated by the formation of functionalized enol acetates via the Suzuki-Miyaura or Sonogashira coupling of the resulting (Z)-β-haloenol acetate products.     

Diastereoselective synthesis of aliphatic α,α-difluoro-β3-amino esters via a sonocatalyzed Reformatsky reaction

(R)-2-Phenylglycine ethyl ester was found to be a cheap and effective auxiliary for the preparation of aliphatic α,α-difluoro-β(3)-amino esters via a Reformatsky reaction performed under sonication conditions. The products were obtained in good to high yield and ≥96:4 dr, thus providing a new stereoselective route to this under-represented class of compounds. A facile one-pot removal of the phenylglycine moiety and concomitant Boc protection subsequently afforded the corresponding Boc-protected β(3)-amino esters in excellent yield.