A novel enzyme‐initiated multicomponent reaction from readily available aldehyde, nitrostyrene, cyclohexanone and acetamide substrates was discovered, enabling the facile construction of six new C C/ N bonds and two rings in single step, one‐pot operation, for the synthesis of spirooxazino derivatives in moderate to high yields. Several methods such as isotope labelling and enzyme mutation were used to probe the possible mechanism of this complex synthesis.
A synthetic strategy has been developed for the synthesis of 2‐dialkylaminoquinolines from easily available quinoline N‐oxides, tertiary amines, diisopropyl H‐phosphonate and carbon tetrachloride (CCl4) in one pot under metal‐free conditions at room temperature.
By using N,N‐dimethylformamide (DMF) as a methylenating reagent, the copper‐catalyzed C H activation of indole was demonstrated as an efficient and facile protocol for synthesizing 3,3′‐diindolylmethane (DIM) and its derivatives. The results indicate that copper chloride was the best catalyst among the investigated transition metal salts, which affords an excellent regioselectivity and good yield when tert‐butyl hydroperoxide (TBHP) was used as an oxidant.
A regioselective synthesis of indole‐3‐carboxylic acid esters from anilines and diazo compounds has been realized by making use of the pyrimidyl group‐assisted rhodium‐catalyzed C H activation and C N bond formation. The reaction proceeds under mild conditions, exhibits good functional group tolerance and scalability. Reutilization of the pyrimidyl directing group in the resulting products provided an efficient strategy for further C‐7 functionalization of indoles. Moreover, the pyrimidyl moiety could be readily removed as a leaving group to offer various free N H indoles.
The concise synthesis of a pharmaceutical candidate is described. The chiral core of the molecule is assembled using an aza‐benzoin condensation and a dynamic kinetic resolution (DKR) as the key reactions. This enables superb control of the regio‐, diastereo‐ and enantioselectivity of the synthesis. Both biocatalysts and transition metal catalysts are remarkably effective in the key asymmetric reduction step. Similar approaches could be considered in the synthesis of other 1,2‐amino alcohols where traditional approaches based on functionalization of alkenes, epoxides or aziridines may suffer from selectivity issues.
The development of new C H functionalization protocols based on inexpensive cobalt catalysts is currently attracting significant interest. Functionalized 8‐aminoquinoline compounds are high‐potential building blocks in organic chemistry and pharmaceutical compounds and new facile routes for their preparation would be highly valuable. Recently, copper has been applied as catalyst for the functionalization of 8‐aminoquinoline compounds and found to operate through a single electron transfer (SET) mechanism, although requiring elevated reaction temperatures. Herein, we described the first example of a cobalt‐catalyzed remote C H functionalization of 8‐aminoquinoline compounds operating through a SET mechanism, exemplified using a practical and mild nitration protocol. The reaction uses inexpensive cobalt nitrate hexahydrate [Co(NO3)2⋅6 H2O] as catalyst and tert‐butyl nitrite (TBN) as nitro source. This methodology offers the basis for the facile preparation of many new functionalized 8‐aminoquinoline derivatives.
Chiral primary amine‐catalyzed asymmetric C H functionalization has been achieved. In this process, enantiotopic Csp3 H functionalization at the α‐position to the nitrogen atom of 4‐[ortho‐(dialkylamino)phenyl]but‐3‐en‐2‐one is activated by chiral 9‐amino(9‐deoxy)‐epi‐quinine to afford tetrahydroquinine derivatives with high enantioselectivities (up to 97% ee).
A facile and efficient one‐pot synthesis of isoxazol‐3(2H)‐ones has been developed starting from α‐acyl cinnamides and tosyliminophenyliodinane catalyzed by copper(II) acetate [Cu(OAc)2] under very mild conditions involving a tandem aza‐Michael addition and intramolecular cyclization sequence.
A nickel‐catalyzed facile synthesis of structurally diverse five‐membered lactams from aliphatic amides and terminal acetylenes with the assistance of an 8‐aminoquinolyl auxiliary has been achieved. A broad range of terminal acetylenes and aliphatic amides proved to be the efficient coupling partners, furnishing the corresponding lactams in moderate to good yields. The transformation is proven to undergo an oxidative alkynylation followed by the intramolecular annulation process. The methodology can be extended to aromatic amides and acrylamides, which provides an efficient and straightforward protocol for the construction of a variety of isoindolinone and pyrrolidinone derivatives.
An efficient copper‐catalyzed α‐aminoxylation of ketones with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) is presented for the synthesis of 2‐aryloxy‐1‐aryl‐2‐(2,2,6,6‐tetramethylpiperidin‐1‐yloxy)ethanones in moderate to excellent yields. It is noteworthy that the copper/iron (Cu/Fe) catalyst can be recovered and reused several times with high catalytic reactivity.
Direct functionalization of the ubiquitous C H bond is receiving much attention because complex structures can be formed from simple precursors. This paper reports a useful method for the direct hydroxylation of 2‐phenylpyridines using palladium(II) chloride and aqueous hydrogen peroxide. In this method, hydrogen peroxide, which has high atom efficiency, is employed as the oxidant and phenol derivatives are generated via C H activation.
A new palladium‐catalyzed route to 3‐hydroxy‐4‐arylcyclopentanones and 4‐arylcyclopentenones in a diastereo‐ and enantioselective manner by a Heck–Matsuda desymmetrization was achieved from the commercially available meso cis‐4‐cyclopentene‐1,3‐diol. This method is highly practical, mild, high yielding and is carried out under “open vessel” conditions. Protected and unprotected substrates provide distinct products bearing considerable value as synthetic scaffolds for the synthesis of natural and unnatural bioactive compounds containing a five‐membered ring.
The rhodium(III)‐catalyzed aromatic C H activation/intramolecular Heck‐type reaction has been studied to synthesize spirocyclic compounds, an important class of molecules in medicinal chemistry and natural product synthesis. This approach was efficient with a variety of substituted N‐methoxybenzamides tethered to different cyclic alkenes having a 5‐, 6‐ or 7‐membered ring. This practical method affords sterically hindered o‐substituted aryl spirocycles that are valuable compounds for further functionalization to access relevant building blocks.
Pyrroles, ubiquitous bioactive heterocycles in nature, are readily prepared via a palladium‐catalyzed oxidative annulation of cyclic trans‐enamines to various internal alkynes in the absence of a directing group.
Herein a practical and efficient protocol for preparing a range of aminoisoquinolines is reported. Various aminoisoquinolines were prepared in moderate to good yields from the corresponding 2‐methylbenzonitriles and benzonitriles upon treatment with potassium tert‐butoxide.
A direct cyanation of benzyl ethers and 1,3‐diarylpropenes with TMSCN was performed under solvent‐ and metal‐free conditions. This oxidative cross dehydrative coupling (CDC) reaction was promoted by 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) and provided rapid access to a broad range of nitriles in good to excellent yields.
Dynamic systems based on consecutive thia‐Michael and Henry reactions were generated and transformed using lipase‐catalyzed asymmetric transformation. Substituted thiolane structures with three contiguous stereocenters were resolved in the process in high yields and high enantiomeric excesses.
