Carbenium ion trapping using sulfonamides: an acid-catalysed synthesis of pyrrolidines by intramolecular hydroamination

Cyclisations of homoallylic sulfonamides proceed smoothly via carbenium ion generation using trifluoromethanesulfonic (triflic) acid, the ease of cyclisation being directly related to the ion stability to give good to excellent yields of the corresponding pyrrolidines. Both toluene- and nitrophenyl-sulfonyl groups are suitable for all substrates tested whereas the corresponding carbamates are only useful in cases of tertiary and highly stabilised carbenium ions. Polyene-derived sulfonamides can also be cyclised to the corresponding polycyclic systems in remarkably high yields, in reactions reminiscent of related cascades encountered in terpene biosynthesis.     

Gold(I)-catalyzed intramolecular hydroamination of unactivated alkenes with carboxamides

N-Alkenyl carboxamides undergo gold-catalyzed intramolecular exo-hydroamination to form nitrogen heterocycles in excellent yield.     

Copper(II) acetate promoted intramolecular diamination of unactivated olefins

A concise method for the synthesis of cyclic sulfamides and vicinal diamines is presented. This method is enabled by Cu(OAc)2 and demonstrates a new transformation for this metal. Both five- and six-membered vicinal diamine-containing heterocycles have been synthesized in good to excellent yields, and substrate-based asymmetric induction has been achieved. This is the first reported example of intramolecular diamination of olefins.     

Room temperature palladium-catalyzed intramolecular hydroamination of unactivated alkenes

A mild and facile Pd-catalyzed intramolecular hydroamination of unactivated alkenes is described. This reaction takes place at room temperature and is tolerant of synthetically useful acid-sensitive functional groups. The formation of hydroamination products rather than oxidative amination products is due to the use of a tridentate ligand on Pd which effectively inhibits beta-hydride elimination.     

Platinum-catalyzed intramolecular hydroamination of unactivated olefins with secondary alkylamines

Reaction of benzyl-2,2-diphenyl-4-pentenylamine with a catalytic 1:2 mixture of [PtCl2(H2C=CH2)]2 (2.5 mol %) and PPh3 in dioxane at 120 degrees C for 16 h led to isolation of 1-benzyl-2-methyl-4,4-diphenylpyrrolidine in 75% yield. A number of gamma- and delta-amino olefins underwent intramolecular hydroamination to form the corresponding pyrrolidine derivatives in moderate to good yield. The reaction displayed excellent functional group compatibility and low moisture sensitivity.     

Iridium-catalyzed intermolecular hydroamination of unactivated aliphatic alkenes with amides and sulfonamides

The intermolecular addition of N-H bonds to unactivated alkenes remains a challenging, but desirable, strategy for the synthesis of N-alkylamines. We report the intermolecular amination of unactivated α-olefins and bicycloalkenes with arylamides and sulfonamides to generate synthetically useful protected amine products in high yield. Mechanistic studies on this rare catalytic reaction revealed a resting state that is the product of N-H bond oxidative addition and coordination of the amide. Rapid, reversible dissociation of the amide precedes reaction with the alkene, but an intramolecular, kinetically significant rearrangement of the species occurs before this reaction with alkene.     

Catalytic intramolecular aminoarylation of unactivated alkenes with aryl sulfonamides

Arylethylamines are abundant motifs in myriad natural products and pharmaceuticals, so efficient methods to synthesize them are valuable in drug discovery. In this work, we disclose an intramolecular alkene aminoarylation cascade that exploits the electrophilicity of a nitrogen-centered radical to form a C–N bond, then repurposes the nitrogen atom''s sulfonyl activating group as a traceless linker to form a subsequent C–C bond. This photoredox catalysis protocol enables the preparation of densely substituted arylethylamines from commercially abundant aryl sulfonamides and unactivated alkenes under mild conditions. Reaction optimization, scope, mechanism, and synthetic applications are discussed.

A photochemical assembly of cyclic arylethylamines occurs by cascade radical annulation and desulfonylative rearrangement in N-acyl sulfonamides. This aminoarylation is made possible through judicious design intended to thwart undesired reactivity.     

Gold(I)-catalyzed intramolecular hydroamination of unactivated C==C bonds with alkyl ammonium salts

A mixture of (5)AuCl [ = PCy2[2-(2,6-C6H3(OMe)2)C6H4]] and AgOTf catalyzes the intramolecular hydroamination of unactivated C==C bonds with primary and secondary ammonium salts.     

Ring-opening reactions of MCPs with sulfonamides promoted by metal triflate Lewis acids

The reaction of aromatic MCPs with sulfonamides catalyzed by Lewis acids affords the corresponding ring-opened homoallylic sulfonamides in good yields and the reaction of aliphatic MCPs with sulfonamides gives the corresponding pyrrolidine derivatives under the same conditions. Through deuterium-labeling experiments, we found that the reaction process is involved with the rearrangement of a cyclopropylcarbinyl cation and a nonclassic carbonium ion.     

Rh(III)-catalyzed oxidative olefination of N-(1-naphthyl)sulfonamides using activated and unactivated alkenes

Rhodium(III)-catalyzed oxidative olefination of N-(1-naphthyl)sulfonamides has been achieved at the peri position. Three categories of olefins have been successfully applied. Activated olefins reacted to afford five-membered azacycles as a result of oxidative olefination-hydroamination. Unactivated olefins reacted to give the olefination product. 2-fold oxidative C-C and C-N coupling was achieved for allylbenzenes.     

Gold(I)-catalyzed intra- and intermolecular hydroamination of unactivated olefins

Ph3PAuOTf catalyzes efficient intra- and intermolecular hydroamination of unactivated olefins with sulfonamides.     

Gold(I)-catalyzed domino ring-opening ring-closing hydroamination of methylenecyclopropanes (MCPs) with sulfonamides: facile preparation of pyrrolidine derivatives

Reaction of methylenecyclopropanes 1 with sulfonamides produces the corresponding pyrrolidine derivatives 3 in moderate to good yields under the catalysis of Au(I) via a domino ring-opening ring-closing hydroamination process.     

Et2Zn-catalyzed intramolecular hydroamination of alkynyl sulfonamides and the related tandem cyclization/addition reaction

Intramolecular hydroamination of alkynyl amides was effected by a catalytic amount of Et2Zn (20 mol %) to form indole derivatives, and a tandem cyclization/nucleophilic addition procedure involving reaction of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient approach to C3-substituted indole derivatives when an excess of Et2Zn (120 mol %) was used.     

Vinyl carbocations: solution studies of alkenyl(aryl)iodonium triflate fragmentations

Generation of vinyl cations is facile by fragmentation of alkenyl(aryl)iodonium trifluoromethanesulfonates. Kinetics and electronic effects were probed by (1)H NMR spectroscopy in CDCl(3). Products of fragmentation include six enol triflate isomers in addition to iodoarenes. The enol triflates arise from direct reaction of a triflate anion with the starting iodonium salts as well as triflate reaction with rearranged secondary cations derived from those salts. G2 calculations of the theoretical isodesmic hydride-transfer reaction between secondary vinyl cation 7 and primary vinyl cation 6 reveal that cation 6 is 17.8 kcal/mol higher in energy. Activation parameters for fragmentation of (Z)-2-ethyl-1-hexenyl(3,5-bis-trifluoromethylphenyl)iodonium triflate, 17e, were calculated using the Arrhenius equation: E(a) = 26.8 kcal/mol, Delta H(++) = 26.2 kcal/mol, and Delta S(++) = 11.9 cal/mol x K. Added triflate increases the rate of fragmentation slightly, and it is likely that for most beta,beta-dialkyl- substituted vinylic iodonium triflates enol triflate fragmentation products are derived from three competing mechanisms: (a) vinylic S(N)()2 substitution; (b) ligand coupling (LC); and (c) concerted aryliodonio departure and 1,2-alkyl shift leading to secondary rather than primary vinyl cations.     

Gold(I)-catalyzed intramolecular hydroamination of alkyne with trichloroacetimidates

[reaction: see text] A study on the gold (I)-catalyzed intramolecular hydroamination of trichloroacetimidates derived from propargyl and homopropargyl alcohols is described. In the presence of 2-5 mol % of cationic Au(I) complex, a variety of trichloroacetimidates undergo efficient hydroamination under an exceptionally mild condition. An orthogonality of the current catalytic protocol with those using a stoichiometric electrophile as well as a preliminary synthetic application as a stable precursor of 2-acylamino-1,3-diene has been demonstrated.