Divergent synthesis of benzene derivatives: Brønsted acid catalyzed and iodine-promoted tandem cyclization of 5,2-enyn-1-ones.

Highly substituted benzene derivatives, including alkoxy-, iodoalkoxy-, and diiodo-substituted benzenes, can be selectively synthesized via Brønsted acid catalyzed and iodine-promoted tandem carbocyclization respectively. This reaction involved a direct process for C-C bond formation from 5,2-enyn-1-ones, and different reaction systems (Brønsted acids/electrophiles with solvents) afforded different substituted benzenes. Furthermore, the halogenated moiety and alkoxy group can be readily introduced into the benzene in a position which has not been easily obtained previously.

Palladium-catalyzed divergent reactions of 1,6-enyne carbonates: synthesis of vinylidenepyridines and vinylidenepyrrolidines.

A method for preparing five- or six-membered heterocyclic compounds from enyne carbonates via palladium catalysis was developed. Enyne carbonates were transformed into 3-vinylidene-1-tosylpyridines 2 in the presence of PdI(2) as the catalyst. Using Pd(dba)(2) as the catalyst, 3-vinylidene-1-tosylpyrrolidines 3 were obtained. Further functionalizations of compounds 3 were carried out in a one-pot manner.

Brønsted acid catalyzed cyclization of hydroxylated enynes: a concise synthesis of five-membered heterocycles.

A mild and direct pathway for the formation of five-membered heterocyclic compounds from hydroxylated enynes has been developed. In this reaction, hydroxylated enynes were selectively transformed into five-membered heterocyclic compounds 2, with an allene moiety at the 3-position, in the presence of F(3) CSO(3) H (0.1 mol %). When R(1) , R(2) =Ph, diphenylvinyl-2,3-dihydro-1H-pyrrole (2 y) was obtained. With HSbF(6) (5 mol %) as the catalyst, polycyclic skeletons 3 and 4 with adjacent stereocenters were obtained. When R(1) =H and R(2) =styrene, 1,3-dienyl-2,5-dihydro-1H-pyrrole (6 as) was formed. This Brønsted acid catalyzed domino process involves the formation of an allene carbocation intermediate, which can be readily trapped by olefins to give various novel five-membered heterocyclic skeletons.

Sc(OTf)3-catalyzed synthesis of indoles and SnCl4-mediated regioselective hydrochlorination of 5-(arylamino)pent-3-yn-2-ones.

Highly substituted indole derivatives bearing alkyl and aryl moieties can be prepared by Sc(OTf)(3)-catalyzed Friedel-Crafts alkenylation of 5-(arylamino)pent-3-yn-2-ones. In addition, a method for regioselective hydrochlorination of 5-(arylamino)pent-3-yn-2-ones mediated by SnCl(4) in moderate to good yields (up to 84%) has been developed. The resulting exclusive Z-selectivity of the C-Cl bond can be further exploited using cross C-N coupling reactions.

Iodine-induced regioselective C-C and C-N bonds formation of N-protected indoles.

A mild, metal-free, and environmently benign iodine-promoted regioselective C-C and C-N bonds formation of N-protected indole derivatives giving 2,3'-biindoles 2 and 4-(1H-indol-2-yl)morpholines 4 is successfully demonstrated. Various bioactive 2,3'-biindoles and 4-(1H-indol-2-yl)morpholines, bearing electron-rich to moderately electron-poor substituents, can be prepared in moderate to good yields.

Platinum/scandium-cocatalyzed cascade cyclization and ring-opening reaction of tertiary amines with substituted salicylaldehydes to synthesize 3-(aminoalkyl)coumarins.

The synthesis of 3-(aminoalkyl)coumarins starting with a platinum/scandium-cocatalyzed oxidative dehydrogenation of α,ß-C(sp(3))-H bonds of tertiary amines in the presence of ambient oxygen followed by reactions with substituted salicylaldehydes is revealed. The in situ formed enamines reacted with various salicylaldehydes, which resulted in the development of a one-pot synthetic protocol involving aldol reaction, cyclization, and then ring-opening.

Pd(0)-catalyzed [1,5]-sigmatropic hydrogen shift of propargylic esters toward substituent naphthylamines.

A novel and convenient carboannulation method for the synthesis of highly substituted naphthylamine derivatives has been developed though a Pd(0)-catalyzed [1,5]-sigmatropic hydrogen shift and cyclization reaction of propargyl esters.

Synthesis of five- and six-membered dihalogenated heterocyclic compounds by electrophile-triggered cyclization.

Highly substituted dihalogenated dihydrofurans, dihydropyrroles, and dihydro-2H-pyrans bearing alkyl, vinyl, aryl, and heteroaryl moieties can be prepared in good to excellent yields (up to 99%) by allowing 1,4-butyne-diol, 4-aminobut-2-yn-1-ol, and pent-2-yne-1,5-diol derivatives to react with different electrophiles (I(2), IBr, and ICl) at room temperature. Both halogen atoms generated from electrophiles were used effectively. The resulting halides can be further exploited by using palladium-catalyzed coupling reactions. The presence of trace amount of water is essential for this electrophilic cyclization.

Platinum-catalyzed Michael addition and cyclization of tertiary amines with nitroolefins by dehydrogenation of alpha,beta-sp3 C-H bonds.

A mild platinum-catalyzed oxidative dehydrogenation of alpha,beta-C(sp(3))-H bonds of tertiary amines in the presence of ambient oxygen is revealed, and the in situ formed enamines subsequently reacting with various nitroolefins resulted in the development of two one-pot synthetic protocols involving Michael addition-elimination and Michael addition-cyclization. By using different functionalized nitroolefins compatible with the current oxidative conditions, two types of structurally divergent products, trisubstituted enamines and chromano[2,3-b]piperidines, could be expediently accessed, respectively.

Platinum-catalyzed cross-dehydrogenative coupling reaction in the absence of oxidant.

A third strategy for cross-dehydrogenative coupling reaction has been reported via platinum-catalyzed sp(3) C-H and sp(3) C-H coupling reaction in the absence of oxidant. Nitroalkanes as well as dialkyl malonate derivatives, beta-keto esters and malononitrile are active participants in this coupling reaction. Both cyclic and acyclic non-activated simple ketones are good reactants in this reaction.

Selective functionalization of sp(3) C-H bonds adjacent to nitrogen using (diacetoxyiodo)benzene (DIB).

A PhI(OAc)(2) mediated selective functionalization of sp(3) C-H bonds adjacent to a nitrogen atom has been reported. When piperidine derivates were used, direct diacetoxylation of alpha and beta sp(3) C-H adjacent to a nitrogen atom were observed to afford various cis-2,3-diacetoxylated piperidines. On the other hand, tetrahydroisoquinoline derivatives gave various alpha-C-H functionalized products in the presence of PhI(OAc)(2). Nitroalkanes, dialkyl malonates, and beta-keto ester are active participants in this coupling reaction. Meanwhile, alpha-amino nitriles can also be obtained by oxidative coupling of amines with malononitrile.

Platinum-catalyzed cycloisomerization reaction of 1,6-enyne coupling with rearrangement of propargylic esters.

A platinum-catalyzed cycloisomerization of 1,6-enyne coupling with the rearrangement chemistry of propargylic ester has been developed. Most probably, under platinum catalysis, propargylic ester undergoes the 1,3-acyloxy migration to afford metal allene intermediate, which is followed by the Diels-Alder-type reaction. 1,3-Acyloxy migration is the key step during the transformation.

Synthesis of isoquinoline derivatives via Ag-catalyzed cyclization of 2-alkynyl benzyl azides.

Ag-catalyzed cyclization of 2-alkynyl benzyl azides offers a novel and efficient method for the synthesis of substituted isoquinoline. The reaction proceeds smoothly in moderate to good yields and tolerates considerable functional groups. The reaction conditions and the scope of the process are examined, and a plausible mechanism is proposed.

Gold-catalyzed tandem cyclization/Friedel-Crafts type reactions toward furan derivatives.

A simple and convenient synthetic approach to furan derivatives 4 has been developed via gold-catalyzed tandem cyclization/Friedel-Crafts type reactions.

Synthesis of 3,4-dihalogenated furan-2-(5H)-ones by electrophilic cyclization of 4-hydroxy-2-alkynoates.

Functionalized 3,4-dihalogenated furan-2(5H)-ones can be readily prepared in moderate to good yields by treating 4-hydroxy-4-arylbut-2-ynoate derivatives with ICl, IBr, and I(2). Both halogen atoms of the electrophile are incorporated in the product. The resulting halides can further afford polycyclic aromatic compounds using known palladium-catalyzed coupling reactions.