Saturated nitrogen heterocycles are among the most significant structural components in small-molecule pharmaceuticals. Herein, a protocol for construction of enantiopure 2-azabicyclo[3.1.1]heptane derivatives by stereospecific intermolecular formal cycloaddition aziridines with bicyclo[1.1.0]butanes is described. The reaction run using B(C

Asymmetric synthesis presents many challenges, with the selective formation of chiral bridged polyheterocycles being a notable example. Cycloadditions using bicyclo[1.1.0]butanes (BCB) offer promising solution along those lines, yet, despite significant advances in that emerging area, asymmetric control has remained limited thus far. Here, we describe an organocatalytic, enantioselective formal (3 + 3)-cycloaddition BCBs 1H-indol-3-yl((hetero)aryl)methanol derivatives. This approach enables...

Ynamides are typically more reactive than simple alkynes and olefins. However, a serendipitous observation revealed rare case where the reactivity of exceeds that ynamides. This led to development unique sulfur-radical-triggered cyclization yne-tethered ynamides, which involves attack alkyne by thiyl radical followed with ynamide. A wide range novel 4-thioaryl pyrroles could tolerate common functional moieties N-protecting groups were expediently constructed this strategy. The current method...

Developed is an unprecedented Au(I)-catalyzed syn-1,2-difunctionalization of ynamides with 2-aminobenzonitriles via nitrile activation. The coupling between and explicitly regioselective, providing a straightforward access to 2,4-diamino-substituted quinolines. Density functional theory (DFT) study provides insightful information rationalizes the reaction pathway. It shows how synergy ynamide π-activation σ-coordination by Au(I) catalyst makes cyclization viable.

A three-component Pd-catalyzed coupling of ynamides, aryl diazonium salts, and boronic acids for the synthesis novel triaryl-substituted enamides is described. This transformation represents first example an umpolung regioselective unsymmetrical syn-1,2-diarylation/aryl-olefination ynamides. The moieties salt (electrophile) acid (nucleophile) are explicitly incorporated in electrophilic α- nucleophilic β-position, respectively, ynamide, resulting a single isomer N-bearing tetrasubstituted...

Ynamide, a unique species with inherited polarization of nitrogen lone pair electron to triple bond, has been largely used for the developement novel synthetic methods and construction unusual N-bearing heterocycles. The reaction versatility ynamide on umpolung reactivity, radical reactions asymmetric synthesis have recently reviewed. This review provides an overall scenic view into gold catalyzed transformation ynamides. ynamides reactivity towards nitrogen-transfer reagents, such as...

Abstract π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis complex all-carbon-substituted always draws attention. The difunctionalization unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues. Here we report discovery a regio- stereoselective syn -1,2-dicarbofunctionalization internal alkynes. A cationic Pd-catalyzed...

α-Fluoro-α′-aryl ketones are crucial in pharmaceuticals and agrochemicals. However, synthesizing unsymmetrical α-fluoro-α′-aryl poses regioselective challenges. This study presents a one-pot aryl-oxy-fluorination method for such fluoro-aryl ketones. Using ynamide, aryl boronic acid, F-source under Pd-catalysis, this efficiently produces wide range of valuable with potential applications. Through combination control experiments DFT studies, we proposed reaction mechanism involving situ acetic...

A cationic palladium-catalyzed arylalkenylation of ynamides is presented. The putative keteniminium arylpalladium intermediate likely dictates the regioselective carbopalladation ynamide to form a vinylpalladium species. capture this complex by olefin yields linear conjugated β-alkenyl aminodienes (especially with trans selectivity). transformation features broad scope labile functional group tolerance and makes 42 unusual molecular scaffolds structural diversity. DFT studies provide...

A Pd-catalyzed three-component syn-1,2-arylmethylation of internal alkynes (ynamides/yne-acetates/alkynes) is described. The readily available and bench stable coupling partners iodo-arenes, methyl boronic acid are successfully used in this strategy to access the methyl-containing tetra-substituted olefins; scope broad showing excellent functional-group tolerance. Notably, transformation regio- as well stereoselective. biologically relevant motifs (BRM) bearing iodo-arenes ynamides also for...

An uncommon sulfur → selenium carbon radical transfer process is employed to develop an unprecedented selenyl radical-mediated regioselective cyclization of yne-tethered-ynamides.

Demonstrated herein is an AuI -catalyzed annulation of sulfonyl-protected ynamides with substituted 1,2-benzisoxazoles for the synthesis E-benzo[e][1,3]oxazine derivatives. The transformation involves addition benzisoxazole to gold-activated ynamide, ring expansion fragment provide α-imino vinylic gold intermediate, and 1,2-migration sulfonamide motif masked carbene center deliver respective ring-expanded benzo[e][1,3]oxazine predominant E configuration. A trapping experiment justifies...

The regioselective annulation of unsymmetrical alkynes has always been a focused research topic. A Pd-catalyzed double (i.e., yne-acetates) with aryl diazonium salts for the synthesis substituted naphthalene derivatives is developed. process addresses intrinsic regioselectivity challenges in annulations alkynes. Mechanistic investigations shed light on crucial role acetate-directing groups determining regiochemical reaction outcome.

Reported herein is a <italic>syn</italic>-thioallylation of ynamides incorporating sulfide moiety at the α-position and an allyl group β-position ynamide.

Abstract A three‐component Pd‐catalyzed coupling of ynamides, aryl diazonium salts, and boronic acids for the synthesis novel triaryl‐substituted enamides is described. This transformation represents first example an umpolung regioselective unsymmetrical syn ‐1,2‐diarylation/aryl‐olefination ynamides. The moieties salt (electrophile) acid (nucleophile) are explicitly incorporated in electrophilic α‐ nucleophilic β‐position, respectively, ynamide, resulting a single isomer N‐bearing...

Abstract Presented herein is a gold(I) catalyzed intramolecular tetradehydro‐Diels‐Alder (TDDA) reaction of alkyne‐tethered‐ynamides for the construction structurally complex 2,3‐dihydrobenzo[ f ]indole derivatives. The mechanism regioselective benzannulation was rationalized by means density functional theory (DFT) calculations. Substrates having an aryl group at ynamide terminus are exclusively participating in this TDDA under gold catalysis.

We herein demonstrated a N-hydroxyphthalimide (NHPI)-mediated chemo- and regioselective radical cyclization of yne-dienone with thiols to construct 3-thioaryl bearing [6,6]-fused dihydrochromenone derivatives. This transformation tolerates common functional groups has broad scope. The reaction proceeds via the attack thioaryl alkyne over activated Michael acceptor. TEMPO quenching experiment suggests involvement intermediate. Synthetic versatility 3-thioaryldihydrochromenones is also showcased.

The regioselective hydro-functionalization reaction is a powerful method to convert readily available alkynes into structurally diverse olefins.

A straightforward regioselective intramolecular 6-endo-dig cyclization of yne-tethered ynamide is herein developed. The reaction involves an enolate attack ketene-N,O-acetals, generated in situ from yne-ynamide and methanesulfonic acid, to the alkyne moiety activated by a sulfonium cation. transformation enables access structurally diverse 5-(arylthio)-3,6-dihydropyridin-2(3H)-ones with broad functional group compatibility. recovery S-protecting groups synthetic applications products make useful.

Abstract Ynamides are typically more reactive than simple alkynes and olefins. However, a serendipitous observation revealed rare case where the reactivity of exceeds that ynamides. This led to development unique sulfur‐radical‐triggered cyclization yne‐tethered ynamides, which involves attack alkyne by thiyl radical followed with ynamide. A wide range novel 4‐thioaryl pyrroles could tolerate common functional moieties N‐protecting groups were expediently constructed this strategy. The...

A Pd( ii ) catalyzed syn -symmetrical diarylation of ynamides has been showcased utilizing readily available arylboronic acids as nucleophilic arylating agents.

A straightforward and sustainable approach for the 1,2-addition of propiolic acids to ynamide has led bench-stable sp 2 ( E )-enol-enamides enediynes dienynes.

Abstract The use of ynamides in organic synthesis has gained significant attention due to their ability provide access complex molecular structures through transformations such as 1,2‐difunctionalization and annulation reactions. These reactions enable the formation highly functionalized N‐bearing olefins unusual heterocycles. In this minireview, we present a systematic overview regioselective difunctionalization ynamides. We discuss multi‐component reactions, radical‐triggered...