An efficient and simple method for synthesis of 2,2-disubstituted-2H-chromenes by condensation of a phenol with a 1,1-disubstituted propargyl alcohol using BF3·Et2O as the catalyst

An efficient and simple method for the synthesis of 2,2-disubstituted-2H-chromenes by one-step cyclocondensation of a phenol with a variety of 1,1-disubstituted propargyl alcohols using BF₃·Et₂O as the catalyst is described.     

Synthesis of o-Carboranyl Containing Esters of Pentavalent Phosphorus Acids

Abstract

A new method for the synthesis of o-carboranyl containing phosphoric, phosphonic and phosphinic acid esters, where the o-carboranil group is in the ester group, has been developed. The propargyl esters of these acids were prapared in two ways: by the reaction of phosphorus acid salts with propargyl chlorid and by interaction of propargyl alcohol with acid chlorides in the presence of Et₃N. The propargyl esters have been converted into carboranyl containing compounds upon treatment with decaborane and dimethyl aniline     

Unprecedented Transformation of Thioglycosides to Their Corresponding 1‐O‐Acetates in the Presence of HClO4‐SiO2 §

An unprecedented conversion of thioalkyl/aryl glycoside to the corresponding 1‐O‐acetates has been described using acetic anhydride and HClO₄‐SiO₂ at rt. Although this transformation does not play an important role in the oligosaccharide synthesis in comparison to its reverse transformation, this gives useful information in selecting the reaction condition for the synthesis of oligosaccharides. The yields were excellent in all cases.     

Synthesis of 3‐Heteroaryl‐Substituted Tetrahydrofurans from the Baylis–Hillman Adducts of Heteroarylaldehydes by n‐Bu3SnH‐Mediated 5‐exo‐trig Vinyl Radical Cyclization

The synthesis of 3‐heteroaryl‐substituted tetrahydrofurans from the propargyl derivative of Baylis–Hillman adducts of heteroaryl aldehydes by n‐Bu₃SnH‐mediated 5‐exo‐trig vinyl radical cyclization in high yield is reported.     

Enantioselective synthesis of phomallenic acid C, an inhibitor of FAS II pathway

Enantioselective synthesis of phomallenic acid C, an inhibitor of bacterial FAS II pathway, was successful. Allenyldiyne structure was constructed by a direct anti-S_N2′ coupling of propargyl mesylate with diynylindium in the presence of palladium catalyst. Enantiomeric purity was determined by Ohrui-Akasaka method to be 83%ee.     

Cyclopenta[g]quinazolinone-based inhibitors of thymidylate synthase targeting α-folate receptor overexpressing tumours: synthetic approaches to 4-{N-[(6RS)-2-hydroxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoic acid

An advanced intermediate for the synthesis of cyclopenta[g]quinazolinone-based antifolates such as (6RS)-CB300945 was prepared by a convergent methodology. The oxo-functionality required for the formation of the C-6-N-10 bond in 4 was introduced in the initial steps of the synthesis, then the tricyclic ring was constructed and finally the propargyl group was introduced using the (propargyl)Co₂(CO)₆⁺ complex without the need to protect the N-3-H or 2-hydroxymethyl functionalities.     

Enantioselective synthesis of phomallenic acid C by In- and Pd-mediated anti-SN2′ coupling

Enantioselective synthesis of phomallenic acid C, an inhibitor of bacterial FAS II pathway, was succeeded. Allenyldiyne structure was constructed by a direct anti-S_N2′ coupling of propargyl mesylate with diynylindium in the presence of palladium catalyst. Enantiomeric purity was determined by Ohrui-Akasaka method to be 96% ee.     

Carbon tether rigidity as a stereochemical tool directing intramolecular radical cyclizations

The phenyl group incorporated into a carbon tether provides for the synthesis of 1,5-cyclodecadiynes with 95-100% d,l-diastereoselectivity due to intrinsic conformational constraints and preorganization of the Co₂(CO)₆-complexed propargyl intermediates.     

Synthesis of functionalized N-triazolyl maleimides

An easy and mild two-step one-pot reaction allowed the synthesis of functionalized N-triazolyl maleimide. Next, the addition of propargyl alcohol and propargyl amine to the N-acyliminium ion mediated by Lewis acid, In(OTf)₃, allowed the introduction of a second 1,2,3-triazol ring at position 5 of the amide. The products in both reactions were achieved in moderate to good yields.     

Rh(I)-catalyzed allenic Pauson-Khand reaction: first construction of the bicyclo[6.3.0]undecadienone ring system

The Rh(I)-catalyzed Pauson-Khand reaction of allenynes afforded the bicyclo[6.3.0]undecadienones as well as their benzo and furo derivatives. In addition, a novel [RhCl(CO)₂]₂-catalyzed [2,3]-sigmatropic rearrangement of the sulfinic ester species of propargyl alcohols was developed.     

Mono- vs. di-fluorous-tagged glucosamines for iterative oligosaccharide synthesis

Fluorous-tagged protecting groups are attractive tools for elongating carbohydrate chains in oligosaccharide synthesis. To eliminate the accumulation of failed sequences during automated oligosaccharide synthesis conditions, an additional C₈F₁₇ ester derived protecting group was attached to the glycosyl donor to better retain the desired doubly tagged glycosylation product on fluorous solid-phase extraction (FSPE) cartridges. Initial studies show that the double-fluorous-tagging strategy offers a robust enough separation using a commercial FSPE cartridge using simple gravity filtration to separate the desired product from the singly fluorous-tagged starting materials and their decomposition products. In addition, removal of the fluorous acetate and its by-products after sodium methoxide treatment and neutralization required only dissolution of the desired sugar in toluene and subsequent removal of the toluene layer from the denser fluorous by-products.     

Synthesis of α-trifluoromethyl unsaturated acids and derivatives

A one pot synthesis of α-trifluoromethyl unsaturated acids via a [3,3]-sigmatropic rearrangement of allyl (or propargyl) fluorovinyl ethers is described. By proto- and iodolactonization, these acids lead to the corresponding trifluoromethylated lactones.     

Total Synthesis of (±)-Corymine

The first total synthesis of the hexacyclic indole alkaloid (±)-corymine is described. Starting from the readily available N-protected tryptamine, the title compound was achieved in 21 steps in 3.4 % overall yield. Key steps of the synthesis include: a) the addition of a malonate to a 3-bromooxindole to afford 3,3-disubstituted oxindole, b) the formation of a 12-membered cyclic enol ether by intramolecular O-propargylation, immediately followed by propargyl Claisen rearrangement to provide the α-allenyl ketone stereospecifically, c) DMDO oxidation to install a hydroxy group in a highly stereoselective manner, and d) the SmI₂-mediated reductive C−O bond cleavage to remove the α-keto carboxyl group.     

One-pot synthesis of highly substituted tetrahydrofurans from activated propargyl alcohols using Bu3P

General and robust synthesis of highly functionalized tetrahydrofuran ring was accomplished with activated propargyl alcohol and reactive Michael acceptors in the presence of catalytic Bu₃P.     

Anhydrous CeCl3 catalyzed C3-selective propargylation of indoles with tertiary alcohols

Anhydrous CeCl₃ was successfully used as catalyst for the synthesis of several 3-propargyl indoles in good yields through the reaction of indole with propargyl alcohols in nitromethane.     

Total Synthesis of (±)‐Corymine

The first total synthesis of the hexacyclic indole alkaloid (±)‐corymine is described. Starting from the readily available N‐protected tryptamine, the title compound was achieved in 21 steps in 3.4 % overall yield. Key steps of the synthesis include: a) the addition of a malonate to a 3‐bromooxindole to afford 3,3‐disubstituted oxindole, b) the formation of a 12‐membered cyclic enol ether by intramolecular O‐propargylation, immediately followed by propargyl Claisen rearrangement to provide the α‐allenyl ketone stereospecifically, c) DMDO oxidation to install a hydroxy group in a highly stereoselective manner, and d) the SmI₂‐mediated reductive C−O bond cleavage to remove the α‐keto carboxyl group.     

Direct synthesis of terminally “clickable” linear and hyperbranched polyesters

1,3‐Dipolar cycloaddition of an organic azide and an acetylenic unit, often referred to as the “click reaction”, has become an important ligation tool both in the context of materials chemistry and biology. Thus, development of simple approaches to directly generate polymers that bear either an azide or an alkyne unit has gained considerable importance. We describe here a straightforward approach to directly prepare linear and hyperbranched polyesters that carry terminal propargyl groups. To achieve the former, we designed an AB‐type monomer that carries a hydroxyl group and a propargyl ester, which upon self‐condensation under standard transesterification conditions yielded a polyester that carries a single propargyl group at one of its chain‐ends. Similarly, an AB₂ type monomer that carries one hydroxyl group and two propargyl ester groups, when polymerized under the same conditions yielded a hyperbranched polymer with numerous “clickable” propargyl groups at its molecular periphery. These propargyl groups can be readily clicked with different organic azides, such as benzyl azide, ω‐azido heptaethyleneglycol monomethylether or 9‐azidomethyl anthracene. When an anthracene chromophore is clicked, the molecular weight of the linear polyester could be readily estimated using both UV–visible and fluorescence spectroscopic measurements. Furthermore, the reactive propargyl end group could also provide an opportunity to prepare block copolymers in the case of linear polyesters and to generate nanodimensional scaffolds to anchor a variety of functional units, in the case of the hyperbranched polymer. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3200–3208, 2010     

Synthesis of Xylan-Click-Quaternized Chitosan via Click Chemistry and Its Application in the Preparation of Nanometal Materials

For the high-valued utilization of hemicelluloses and for realizing the controllable synthesis of NPs, this paper’s aim is to combine xylan, chitosan and nanometal materials at the same time. In this research study, firstly, propargyl xylan was synthesized via nucleophilic substitution reaction between xylan and propargyl bromide in NaOH solution. On the other hand, a tosyl group was introduced onto the 6th position of synthesized quaternized chitosan (QCS), and the azide group replaced the tosyl group to obtain 6-amido-QCS (QCS-N₃). The synthesis conditions of the above reactions were optimized. Subsequently, the novel xylan-click-QCS polymer was obtained via click reaction between terminal alkyne groups on the xylan chains and azide groups on QCS. Then, AgNPs and AuNPs were synthesized by adopting the xylan-click-QCS polymer as the reducing and stabilizing agent, and the reaction conditions were optimized to obtain well-dispersed and highly stable nanoparticles. There were two kinds of Ag nanomaterials, with diameters of 10~20 nm and 2~5 nm, respectively, indicating the formation of Ag nanoclusters, except for Ag nanoparticles, in this reaction. The diameter of the synthesized AuNPs was 20~30 nm, which possessed a more uniform size distribution. The Ag nanoclusters with a smaller size (2~5 nm) could inhibit MCF-7 cell proliferation effectively, indicating their application potential in cancer therapy. The study gives a new approach to the high-value utilization of biopolymers.     

Copper‐Catalyzed Highly Stereoselective Trifluoromethylation and Difluoroalkylation of Secondary Propargyl Sulfonates

It is challenging to stereoselectively introduce a trifluoromethyl group (CF₃) into organic molecules. To date, only limited strategies involving direct asymmetric trifluoromethylation have been reported. Herein, we describe a new strategy for direct asymmetric trifluoromethylation through the copper‐catalyzed stereospecific trifluoromethylation of optically active secondary propargyl sulfonates. The reaction enables propargylic trifluoromethylation with high regioselectivity and stereoselectivity. The reaction could also be extended to stereospecific propargylic difluoroalkylation. Transformations of the resulting enantiomerically enriched fluoroalkylated alkynes led to a variety of chiral fluoroalkylated compounds, thus providing a useful protocol for applications in the synthesis of fluorinated complexes.     

Direct access to CF3-propargyl amines and conversion to difluoromethyl imines

Trifluoromethyl aldimines reacted with acetylides in toluene at −78 °C to provide propargyl amines in good yields. From a chiral trifluoromethyl aldimine, the propargyl amines were obtained with excellent diastereoselectivities (de >98%). Trifluoromethyl propargyl amines could be further converted into difluoromethyl imines under basic conditions.