Xu-Heng Yang

Copper‐Catalyzed Intramolecular Oxidative 6‐exo‐trig Cyclization of 1,6‐Enynes with H2O and O2

Transition-metal-catalyzed cyclization of 1,n-enynes has attracted significant interest because of their synthetic utility, and it is now used as a rapid and powerful approach to prepare cyclic derivatives in organic synthesis. In particular, these cyclization transformations are highly efficient and atom economical, and provide opportunities to discover new reactions. Despite considerable progress in the field, the development of mild 1,n-enyne cyclization routes using inexpensive catalytic materials to construct new, complex compounds remains a challenge. Copper catalysts are widely used in organic synthesis; however, examples of coppercatalyzed 1,n-enyne cyclizations are rare and all reports to date focus on the use of Cu salts. The key obstacle to Cu catalysts is that they have a far stronger affinity for alkynes than alkenes, 4a–d] which results in the addition of more nucleophilic reagents (often H2O, amines, acids, and alcohols) rather than alkenes to alkynes. 4] Although this obstacle does not favor the classical 1,n-enyne cyclization reaction, it may facilitate 1,n-enyne cyclizations that include the simultaneous introduction of other more nucleophilic reagents and alkenes to alkynes. After a series of trials, we found that Ce(SO4)2 facilitated CuCl2-catalyzed oxidative 6-exo-trig cyclization of enynes with H2O for preparing 1,4-naphthoquinones using O2 as an oxidant and a reactant under mild reaction conditions (Scheme 1a). The method is the first example of using a Cu catalyst for the oxidative cyclization of enynes, in which 1,4-naphthoquinones are constructed by the incorporation of two oxygen atoms from molecular oxygen and water into the organic framework of the product. Quinones, particularly 1,4-naphthoquinones, are valuable synthetic intermediates, and important structural units found in numerous natural products, pharmaceutical molecules (most notably Vitamin K), and functional materials (dyes and pigments). The traditional route to 1,4-naphthoquinones is the oxidation of substituted naphthols, naphthyl amines, or naphthalenes. However, this method often furnishes products in low to moderate yields, and has low functional group compatibility. Owing to these drawbacks, several powerful alternative methods have arisen, including (Scheme 1b): 1) the Diels–Alder reaction of substituted 1,3dienes with preexisting quinones (path a), 2) the reaction of alkynes with metal carbonyls (path b), 3) thermo cycloisomerization of cyclobutenones (path c), and 4) the annulation of Fischer carbene complexes with alkynes (path d). As shown in Scheme 1, we herein describe an efficient example of achieving 1,4-naphthoquinones by catalytic oxidative 6-exo-trig cyclization of enynes with H2O and O2 using a simple and inexpensive copper salt as the catalyst. (Scheme 1). Our investigation began with the reaction of (E)-3phenyl-1-(2-(2-phenylethynyl)phenyl)prop-2-en-1-one (1a) with CuCl2 and O2 in THF at 80 8C; however, only a trace amount of the target 6-exo-trig cyclization product 2a was observed (Table 1, entry 1). Substrate 1 a could be successfully cyclized with 10 mol% CuCl2 and 1 atm O2 at 80 8C, thus affording the desired product 2 a in 42% yield, using DMF as the solvent (entry 2). It is noteworthy that the yield is reduced to 38% using air instead of O2 (entry 3). The yield was increased to 60% when the reaction was carried out in DMA Scheme 1. Routes to substituted 1,4-naphthoquinones. DMA=dimethylacetamide, LG = leaving group.

Rhodium-Catalyzed Synthesis of Isoquinolines and Indenes from Benzylidenehydrazones and Internal Alkynes

A new route is presented for the selective assembly of isoquinolines and indenes by rhodium-catalyzed tandem cyclization of benzylidenehydrazones with internal alkynes. This method involves the selective cleavage of the N-N bond and the C═N bonds and is dependent on the substituents of the benzylidenehydrazone.

Iron Catalyzed Oxidative Coupling, Addition, and Functionalization

We cover the achievements and thought process that have emerged as a result of the recent use of iron salts as catalysts for the oxidative coupling, addition, and functionalization on constructing C−C bonds, C−N bonds, C−O bonds, C−S bonds, and C−P bonds. These transformations concomitantly require a stoichiometric oxidant to activate the catalyst: The low‐cost and ubiquity of peroxides is often used as a result of their high oxidative reactivity, resulting in the widespread utilizations of iron catalysis through the initiation of radical processes. Here, we summarize the formation of diverse chemical bonds by using iron oxidative catalysis strategies, including 1) the oxidative coupling strategy and 2) the oxidative addition and functionalization strategy. The oxidative coupling strategy focuses on the formation of one chemical bond in a single reaction, whereas the oxidative addition and functionalization strategy includes the transformations that construct at least two chemical bonds.

Palladium-catalyzed cyclocarbonylation of arynes with methyl allyl carbonates: selective synthesis of 1H-inden-1-ones.

A selective protocol for the synthesis of 2-methylene-3-substituted-2,3-dihydro-1H-inden-1-ones and 2-benzylidene-2,3-dihydro-1H-inden-1-ones has been developed via palladium-catalyzed cyclocarbonylation reactions of arynes with allyl carbonates and carbon monooxide (CO). It is noteworthy that the selectivity of this new route is depended on both substrates and ligands.

Palladium-Catalyzed Methylation of Alkynyl C(sp)–H Bonds with Dimethyl Sulfonium Ylides

A novel palladium-catalyzed methylation protocol for the synthesis of methyl-functionalized internal alkynes has been established. This methylation method is achieved through a C(sp)-C(sp(3)) bond formation process and represents a new synthetic application of sulfonium ylides.

Dehydrogenative [2 + 2 + 1] Heteroannulation Using a Methyl Group as a One-Carbon Unit: Access to Pyrazolo[3,4-c]quinolines

A practical and straightforward access to pyrazolo[3,4-c]quinolines by molecular sieve mediated dehydrogenative [2 + 2 + 1] heteroannulation of N-(o-alkenylaryl)imines with aryldiazonium salts is described using a sp(3)-hybrid carbon atom as a one-carbon unit. The reaction enables the formation of three new chemical bonds, a C-C bond and two C-N bonds, in a single reaction and features simple operation and excellent functional group tolerance.

Metal-Free Oxidative Decarbonylative [3+2] Annulation of Terminal Alkynes with Tertiary Alkyl Aldehydes toward Cyclopentenes

A new metal-free oxidative decarbonylative [3+2] annulation of terminal alkynes with tertiary alkyl aldehydes is presented, which features broad substrate scope and excellent selectivity. The selectivity of this reaction toward cyclopentenes and indenes relies on the nature of the aldehyde substrates. While treatment of tertiary γ,δ-unsaturated aldehydes with common terminal alkynes assembles cyclopentenes, 2-methyl-2-arylpropanals succeed in accessing indenes.