Highly stereoselective Saucy-Marbet rearrangement using chiral ynamides. Synthesis of highly substituted chiral homoallenyl alcohols

[reaction: see text] A highly stereoselective Saucy-Marbet rearrangement using chiral ynamides and propargyl alcohols is described here. This rearrangement can be catalyzed by para-nitrobenzenesulfonic acid leading to high diastereoselectivities for a range of different chiral propargyl alcohols and ynamides in a stereochemically intriguing matched, mismatched, or indifferent manner. This provides an excellent entry to highly substituted chiral homoallenyl alcohols.     

2,3]-Sigmatropic rearrangement of ynamides: preparation of α-amino allenephosphonates

α-Amino allenephosphonates were easily prepared in two steps from protected amines, propargyl alcohols, and chlorophosphites. First, ynamides were synthesized from unprotected 1-bromopropargyl alcohols using a copper(II) catalyzed coupling reaction. In the second step, the previously prepared ynamides were transformed directly to allenes through a [2,3]-sigmatropic rearrangement of propargyl phosphites. This efficient method led to the formation of a series of α-amino allenephosphonates with diverse substituents on the amine, the phosphonate, and the allene moieties.     

The first stereoselective Ficini-Claisen rearrangement using chiral ynamides

The first asymmetric Ficini-Claisen rearrangement using chiral ynamides is described. At relatively low temperatures, the Ficini-Claisen rearrangement can be efficiently promoted by p-nitrobenzenesulfonic acid leading to high diastereoselectivity for a range of different allylic alcohols and chiral ynamides. [reaction: see text]     

Efficient Access to Multifunctional Trifluoromethyl Alcohols through Base‐Free Catalytic Asymmetric C−C Bond Formation with Terminal Ynamides

The asymmetric addition of terminal ynamides to trifluoromethyl ketones with a readily available chiral zinc catalyst gives CF₃‐substituted tertiary propargylic alcohols in up to 99 % yield and 96 % ee. The exclusion of organozinc additives and base as well as the general synthetic utility of the products are key features of this reaction. The value of the β‐hydroxy‐β‐trifluoromethyl ynamides is exemplified by selective transformations to chiral Z‐ and E‐enamides, an amide, and N,O‐ketene acetals. The highly regioselective hydration, stereoselective reduction, and hydroacyloxylation reactions proceed with high yields and without erosion of the ee value of the parent β‐hydroxy ynamides.     

Highly stereoselective [2,3]-sigmatropic rearrangement of sulfur ylide generated through Cu(I) carbene and sulfides

A highly stereoselective [2,3]-sigmatropic rearrangement of sulfur ylide generated through Cu(I) carbene and allyl and propargyl sulfides by a double asymmetric induction approach that combines a chiral camphor sultam auxiliary and Cu(I) catalyst with chiral or achiral diimine ligands has been developed.     

The first successful base-promoted isomerization of propargyl amides to chiral ynamides. Applications in ring-closing metathesis of ene-ynamides and tandem RCM of diene-ynamides

[reaction: see text] A highly useful sequence of reactions is described here. These reactions consist of the first successful base-induced isomerizations of propargyl amides to chiral ynamides, applications of these novel ynamides in ring-closure metathesis leading to chiral 2-amidodienes useful for Diels-Alder cycloadditions, and the first successful tandem RCM of diene-ynamides.     

A novel highly stereoselective synthesis of chiral 5- and 4,5-substituted 2-oxazolidinones

A novel highly stereoselective synthesis of chiral mono- and bicyclic 4- and 4,5-substituted 2-oxazolidinones starting from β-keto esters was developed. After bioreduction with S. cerevisiae the resulting homochiral β-hydroxy esters are transformed into their hydrazides. Treatment with NaNO₂/H⁺ then furnishes 2-oxazolidinones in high e.e. (∼99%) and d.e. (>99%). The ring formation proceeds via a highly concerted sextet rearrangement with full retention of configuration at the stereocentres. Enantiopure 1,2-amino alcohols can subsequently be obtained by saponification of the 2-oxazolidinone products.     

Gold(I)-catalyzed propargyl Claisen rearrangement

Homoallenic alcohols are prepared from propargyl vinyl ethers using a trinuclear gold(I)-oxo complex, [(Ph3PAu)3O]BF4, as a catalyst for propargyl Claisen rearrangement at room temperature. The gold(I)-catalyzed reaction is effective for a diverse collection of propargyl vinyl ethers, including substrates containing aryl and alkyl groups at the propargylic position, and hydrogen, aryl, and alkyl substituents at the alkyne terminus. Tertiary propargyl vinyl ethers can be employed in the reaction, at slightly elevated temperatures, to afford tetrasubstituted allenes. Importantly, the rearrangement of 1,2-disubstituted vinyl ethers proceeds with excellent diastereoselectivity, and the rearrangement of chiral nonracemic propargyl vinyl ethers proceeds with excellent chirality transfer to furnish enantioenriched allenes.     

Highly stereoselective synthesis of novel alpha-haloenamides via a mild and efficient hydrohalogenation of ynamides

A highly stereoselective preparation of novel chiral (E)-alpha-haloenamides under mild conditions utilizing magnesium halide salts is described. This unexpected mild and efficient hydrohalogenation reaction highlights another synthetic utility of ynamides. [reaction: see text]     

Mo-Au combo catalysis for rapid 1,3-rearrangement of propargyl alcohols into alpha,beta-unsaturated carbonyl compounds

The combination of Mo and cationic Au catalysts dramatically accelerated the rearrangement of diverse propargyl alcohols, which includes a short reaction time, mild conditions, and high product yields. A practical application to the highly challenging primary propargyl alcohols and the N-alkynyl amides is achieved.     

Nickel-catalyzed regio- and stereoselective hydrophosphinylation of internal ynamides with H-phosphinates

A method for the catalytic hydrophosphinylation of internal ynamides with H-phosphinates has been developed for the first time. The protocol employing the catalyst generated from NiBr₂ and PPh₃ could be applied to several types of ynamides and H-phosphinates, affording (E)-β-aminovinylphosphinates in a highly regio- and stereoselective manner.     

Asymmetric Synthesis of Chiral 1,4‐Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines

A highly enantioselective synthesis of 1,4‐enynes is described that proceeds through an organocatalytic reaction between propargyl alcohols and trialkenylboroxines. Our strategy relies on acid‐mediated generation of the carbocationic intermediate from propargyl alcohols followed by enantioselective alkenylation with trialkenylboroxines. A range of chiral 1,4‐enynes were obtained in moderate to good yields with high levels of enantioselectivity. Use of a highly acidic chiral N‐triflyl phosphoramide catalyst, which has two distant Lewis basic oxygen atoms, was found to be crucial for both high reactivity and selectivity in the present reaction.     

Synthesis of N,4-diaryl substituted β-lactams via Kinugasa cycloaddition/rearrangement reaction

The methodology of construction of N,4-diaryl substituted β-lactam framework, based on the Kinugasa cycloaddition/rearrangement sequence is presented. The series of protected chiral propargyl alcohols was treated with diaryl nitrones to afford mainly the cis-I adduct, providing direct access to the highly-functionalized azetitidin-2-one derivatives with a well-defined stereochemistry. Under the optimized reaction conditions, the unprotected chiral propargylic alcohols were also found to be suitable precursors of β-lactams. The absolute configuration of adducts was determined by CD or HPLC-CD technique, which was shown to be reliable method of determination of the configuration at C-4 of 4-aryl-substituted azetidin-2-ones. Epimerization of the cis adduct to the respective trans isomer could be easily done by the oxidation of hydroxyl group next to the four-membered β-lactam ring to the ketone, followed by a base-mediated epimerization of the malonyl fragment.     

Microwave assisted synthesis of enantiomerically pure allylboronates

Stable allylboronates with a stereogenic centre α to the boronic ester moiety represent versatile reagents for stereoselective synthesis of homoallylic alcohols. Use of microwave irradiation in desilylation and sigmatropic rearrangement reactions allows rapid synthesis of α-chiral allylboronates utilized in the highly diastereo- and enantioselective synthesis of (Z)-configured homoallylic α-hydroxy esters by allyl additions to ethyl glyoxylate.     

Regio- and stereoselective homolytic hydrostannylation of propargyl alcohols and ethers with dibutylchlorostannane

The Et3B-initiated reaction of gamma-unsubstituted propargyl alcohols with dibutylchlorostannane (Bu2SnClH) at low temperature gave (Z)-vinylstannanes with high regio- and stereoselectivity. The corresponding alkyl propargyl ethers also underwent regio- and stereoselective homolytic hydrostannylation with Bu2SnClH; however, the regioselectivity was not so high as that with the propargyl alcohols.     

Stereocontrolled construction of tetrasubstituted tetrahydrofurans: synthesis of 2,5-anhydro d-glucitol

A highly stereoselective construction of 2,3,4,5-tetrasubstituted tetrahydrofurans has been accomplished by an unusual intramolecular 5-endo-tet cyclization of 2,3-epoxy alcohols involving hydroxyl nucleophile. The method has been utilized for the synthesis of 2,5-anhydro d-glucitol through two different approaches starting from the chiral molecule, l(+)-diethyl tartarate or from the non-chiral compound, allyl bromide or cis-but-2-ene-1,4-diol. This synthetic method is a useful example of 5-endo-tet cyclization of 2,3-epoxy alcohols.     

Asymmetric indium-mediated synthesis of homopropargylic alcohols

A method for the enantioselective synthesis of homopropargylic alcohols using indium under Barbier-like conditions is reported herein. Both aromatic and aliphatic aldehydes were successfully converted to the corresponding homopropargylic alcohols in good yield and high enantiomeric excesses using propargyl bromide, indium, and (1S,2R)-(+)-2-amino-1,2-diphenylethanol as a chiral auxiliary.     

Synthesis of new β-hydroxy amide ligands and their Ti(IV) complex-catalyzed enantioselective alkynylation of aliphatic and vinyl aldehydes

Three new chiral β-hydroxy amide ligands were synthesized via the reaction of benzyl chloride and amino alcohols derived from l-tyrosine. The titanium(IV) complex of chiral ligand 8b was found to be an effective catalyst for the asymmetric alkynylation of aliphatic, vinyl and aromatic aldehydes. The propargyl alcohols were obtained in highly enantiomeric excesses (up to 96% ee) under optimized conditions.     

Syntheses of vinylindoles via a Brønsted acid catalyzed highly regio- and stereoselective cis-hydroarylation of ynamides

A highly regio- and stereoselective Brønsted acid-catalyzed coupling of ynamides and indoles is described. This process is the equivalent of hydroarylation of ynamides and leads to the efficient syntheses of vinylindoles. Diels-Alder reaction between the vinylindoles and DMAD afforded carbazole derivatives in good yields.     

Diastereoselective formation of 2-fluoro-2-trifluoromethyl-3,4-alkadienamides from propargyl alcohols and hexafluoropropene-diethylamine adduct (PPDA)

Treatment of propargyl alcohols (1) with hexafluoropropene-diethylamine adduct (PPDA) affords N,N-diethyl-2-fluoro-2-trifluoromethyl-3,4-alkadienamides (2) that are produced by the Claisen rearrangement of intermediary 2-alkynyl 1-(N,N-diethylamino)-2,3,3,3-tetrafluoro-1-propenyl ethers. Starting from propargyl alcohols bearing a triple bond at the terminal position, the corresponding products (2) were formed with a high stereoselectivity.