Regioselective nucleophilic ring-opening reaction of chiral epoxyallyl alcohols: a ready access to the pyran core of macrolactin 3

Herein we report the synthetic strategy towards the pyran core of macrolactin 3 via Sharpless epoxidation, titanium(IV) mediated regioselective ring-opening reaction of epoxyallyl alcohol/epoxy alcohol and oxa-Michael addition as the key steps.     

Tandem intramolecular oxa-Michael addition/decarboxylation reaction catalyzed by bifunctional cinchona alkaloids: facile synthesis of chiral flavanone derivatives

Bifunctional cinchona alkaloids were used to catalyze a tandem intramolecular oxa-Michael addition/decarboxylation reaction of alkylidene β-ketoesters 1, providing a series of flavanone derivatives with up to 97% yield and 93% ee.     

Stereoselective synthesis of anti-1,4-diols by a BH3.THF-mediated rearrangement of 1,2-disubstituted cyclobutenes

A new stereoselective rearrangement of cyclobutylboranes, obtained by the hydroboration of 1,2-disubstituted cyclobutenes, provides anti-1,4-diols with good-to-excellent diastereoselectivity. The mechanism of the rearrangement is discussed based on theoretical calculations.     

A modified approach to the phomoidrides: synthesis of a late-stage intermediate containing a key carbon quaternary stereocenter

A previously developed approach to the synthesis of the phomoidrides has been modified to incorporate all necessary carbon atoms prior to the key tandem carbonylation/Cope rearrangement reaction. This modification necessitated the synthesis of a challenging all-carbon quaternary stereocenter, which in turn rendered ineffective several reactions from the original synthesis. An oxidative radical cleavage of a spirocyclopropane ring system was developed that accomplishes the synthesis of the quaternary center, and a regioselective double hydroboration reaction was devised that provides an alternate approach to a key sequence of functional group interconversions, where the originally developed route was found to be ineffective.     

Zinc-mediated synthesis of 3-alkynyl-3-hydroxyindolin-2-ones by addition of iodoalkynes to isatins

An efficient and economical method was developed for synthesis of 3 alkynyl-3-hydroxyindolin-2-ones by addition of iodoalkynes to isatins using zinc dust.     

Stereoselective synthesis of novel C-azanucleoside analogues by microwave-assisted nucleophilic addition of sugar-derived cyclic nitrones

A series of C-azanucleoside analogues were synthesized by microwave-assisted nucleophilic addition of electron-rich hetero-aromatics to sugar-derived cyclic nitrones, and followed by reduction and deprotection. The nucleophilic addition afforded the 2′,3′-trans isomer as the dominant by the favorite exo attack and showed high stereoselectivity in polar solvent.     

Scope and limitations of the synthesis of functionalized quinolizidinones and related compounds by a simple precursor approach via addition of lithium allylmagnesates to 2-pyridones and RCM as key steps

The scope and limitations of the simple synthesis of functionalized quinolizidin-4-ones by chemoselective N-alkenylation of NH pyridin-2(1H)-ones (2-pyridones), regioselective addition of lithium allyl(di-n-butyl)magnesates(1-) to N-alkenylpyridin-2(1H)-ones, followed by ring closing metathesis (RCM) is described. A number of functionalizations introduced into quinolizidin-4-one rings demonstrated the high prospect of the strategy proposed in scaffold synthesis. Their extension to the syntheses of pyrido[1,2-a]azepin-4-one and pyrido[1,2-a]azocin-4-one derivatives as well as to spiro-fused compounds is also presented.     

Enantioselective synthesis of nitrocyclopropanes via conjugate addition of bromomalonate to nitroalkenes catalyzed by Ni(II) complexes

A novel one-pot methodology for the catalytic enantioselective synthesis of highly functionalized nitrocyclopropanes promoted by chiral nickel complexes is developed. The treatment of bromomalonates with nitroalkenes under the mild reaction conditions afforded the corresponding Michael adducts which cyclizes to controlled reaction conditions with excellent diasteroselectivities (>99 de) and enantioselectivities (up to 99% ee).     

Uncatalyzed Michael addition of indoles: synthesis of some novel 3-alkylated indoles via a three-component reaction in solvent-free conditions

Synthesis of some novel 3-alkylated indoles via an uncatalyzed Michael addition of indoles using three components in one-pot solvent-free conditions is reported. The mechanism was established by performing the reaction in two steps. The reaction was also studied in different solvents and an important solvent effect was noticed.     

Organocatalytic synthesis of dipyrromethanes by the addition of N-methylpyrrole to aldehydes

The reaction of aldehydes with N-methylpyrrole carried out in the presence of catalytic pyrrolidinium tetrafluoroborate at room temperature affords the corresponding dipyrromethanes and minor amounts of tripyrranes. This new, mild, and convenient process represents the first organocatalytic synthesis of dipyrromethanes. The products are obtained in chemical yields similar to those obtained with existing methods, which, however, require either a much larger excess of heterocycle (when aldehydes are employed as starting materials), or more drastic reaction conditions (when aldehyde equivalents are used as starting materials) than those employed here. A mechanism is proposed to explain the course of this reaction.     

An efficient synthesis of 3-(guaiazulene-1-yl)succinimides by addition of guaiazulene to maleimides

A facile,efficient synthesis of 3-(guaiazulen-1-yl)succinimides was developed by Michael-type addition of guaiazulene to maleimides in the presence of p-toluenesulfonic acid under mild reaction conditions.     

A short approach to the synthesis of the ritonavir and lopinavir core and its C-3 epimer via cross metathesis

A short synthesis of hydroxyethylene dipeptide isostere, a core unit of the HIV-protease inhibitors ritonavir and lopinavir, its C-3 epimer and C₂ symmetric diamino diol is described. The crucial aspects of the synthesis are self-cross metathesis and exploitation of C₂-symmetric of the metathesis product 8 to obtain the required skeleton.     

Stereoselective synthesis of highly enantioenriched 3-methyl-2-cyclohexen-1-ones possessing an asymmetric quaternary carbon as C-4 or C-6: a sugar template approach

The 1,4-addition of the enolate generated from α-methylated acetoacetate incorporated at C-4 of methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-α-d-glucopyranoside to methyl vinyl ketone, followed by aldol condensation of the resulting 1,4-addition product under two base-mediated conditions, provided 4-O-functionalized d-glucose derivatives with high diastereoselectivity. These products install a 3-methyl-2-cyclohexen-1-one-4- (or -6-) carboxylic acid as the O-4 ester, in which C-4 or C-6 is an asymmetric quaternary carbon. Removal of the sugar template from those aldol condensation products provided synthetically useful 3,6-dimethyl-2-cyclohexen-1-one-6-carboxylic acid and 3,4-dimethyl-2-cyclohexen-1-one-4-carboxylic acid derivatives both in high enantioenriched forms.     

Diastereoselective synthesis of dihydroindolizin-3(2H)-one derivatives via catalytic sulfur-Michael addition triggered intramolecular tandem sequence

A diastereoselective synthesis of functionalized dihydroindolizidine derivatives bearing sulfur moiety was reported with high stereoselectivity via a catalytic sulfur-Michael addition triggered intramolecular aldol-type tandem sequence. This protocol allowed to readily access trans- and cis-dihydroindolizidine products in high yields with moderate to excellent diastereoselectivities under the optimized mild reaction conditions, which also can be easily transformed into various substituted functionalized pyridines incorporating β-quaternary carbon centers.     

Pd-catalyzed addition of boronic acids to vinylogous imines: a convenient approach to 3-sec-alkyl substituted indoles

A convenient approach to 3-sec-alkyl substituted indoles was developed via palladium-catalyzed addition of arylboronic acids to vinylogous imines generated in situ from sulfonylindoles under mild conditions.     

Sequential one-pot method for oxy-Michael addition,Heck coupling,and degradation followed by condensation: facile synthesis of 2-benzoxepin-3(1H)-ones

A sequential one-pot intermolecular oxy-Michael addition, intermolecular Heck coupling, and intramolecular degradation (retro-oxy-Michael addition) followed by condensation method has been developed for the synthesis of interesting 2-benzoxepin-3(1H)-ones. Significantly, the 2-benzoxepin-3(1H)-ones form the core quantum of biologically vital natural products. The initial oxy-Michael addition and Heck coupling steps involve a straight forward construction of C–O and C–C bonds, whereas, the final condensation step follows a novel mechanistic path via intramolecular degradation, double bond isomerization, and intramolecular condensation. Notably, a remarkable solvent effect has been observed in-order to promote the final intramolecular condensation.     

Access to the nicotine system by application of a guanidine-catalyzed asymmetric Michael addition of diphenyliminoacetate with 3-pyridyl vinyl ketone

A guanidine-based chiral organocatalyst was successfully applied to the Michael addition of diphenyliminoacetate to pyridyl vinyl ketone as a key reaction for the construction of the nicotine system.     

On the synthesis of β-bromohydrine ethers via intermolecular alkoxyl radical addition to bicyclo[2.2.1]heptene

Primary, secondary, and tertiary alkoxyl radicals add exo-selectively to the olefinic π-bond in bicyclo[2.2.1]heptene to afford exo-2-alkoxybicyclo[2.2.1]hept-3-yl radicals, which are trapped with BrCCl₃ preferentially from the endo face to furnish β-bromohydrine ethers in 23-67% yield.     

A general approach to the synthesis of enantiopure 19-nor-Vitamin D(3) and its C-2 phosphate analogs prepared from cyclohexadienyl sulfone

A synthesis of enantiopure 19-nor-Vitamin D(3) and its C-2 substituted cyclic phosphate analogs is achieved via in situ trapping of an α-sulfonyl anion with a CD-ring allyl chloride and 1,2-eliminative desulfonylation exploiting the basic properties of TBAF. The A-ring is prepared via anti-selective dithiane addition to vinyl sulfone and LiBH(4) mediated sequential bis reduction of an epoxy vinyl sulfone.     

Asymmetric synthesis of 3-substituted 3,4-dihydroisocoumarins via stereoselective addition of laterally lithiated chiral 2-(o-tolyl)oxazolines to aldehydes followed by diastereomer-selective lactonization

Lateral lithiation of (S)-4-isopropyl-2-(o-tolyl)oxazoline in diethyl ether followed by the reaction with aldehydes in the presence of TMEDA produced the addition products with stereoselectivities up to 84% de. Utilization of TMEDA as a ligand is essential for the good selectivity. Rationale for the stereoselectivity is proposed based on ab initio calculation of the lateral lithio species. The major (S,S)-products lactonized faster than the minor (S,R)-products to the corresponding 3,4-dihydroisocoumarins under acidic conditions. Thus, (3S)-3,4-dihydroisocoumarins were obtained in good optical purities up to 97% ee by sequential application of these matched stereoselective reactions.