An efficient and direct Cu-assisted nitrating approach to create synthetically valuable and challenging tertiary α-nitro-α-substituted moieties has been developed using ceric ammonium nitrate as a nitrating reagent, oxidant, and Lewis acid. Notably, the commonly used clinical drug ketamine was smoothly synthesized in four steps.

Abstractα-Halogenated ketones are both unique structure moieties existing in biologically natural products and valuable synthetic intermediates for the preparation of functional molecules. An efficient and scalable method for the preparation of α-halogenated ketone using iron (III) chloride and iron (III) bromide as halogen sources with phenyliodonium diacetate as oxidant has been developed, featuring mild reaction conditions, environmentally friendly reagents, and wide substrate scope. Notably, the three-step synthesis of drug prasugrel was achieved using this developed method as a key step with 30% yield on gram-scale. Additionally, the reaction mechanism involving chloride cation was proposed based on some preliminary control experiments.

A novel α-arylation of deoxybenzoins with non-prefunctionalized arenes is developed through an iron-catalyzed oxidative dehydrogenative approach. The reaction shows broad substrate scope and functional group tolerance and thus provides efficient access to synthetically useful 1,2,2-triarylethanones. A reasonable mechanism is also proposed.

The direct and efficient construction of α-aryl-β-substituted cyclic ketone scaffolds has been achieved using a Cu-mediated one-pot Michael addition/α-arylation strategy. The reaction features easily available materials, broad substrate scope, moderate to good yield, and an excellent diastereoselectivity.

A novel carbon electrophile induced intermolecular oxa-Diels–Alder/semipinacol rearrangement/aldol cascade reaction of allylic silyl ether with β,γ-unsaturated α-ketoester has been developed under the promotion of SnCl4. This highly efficient transformation enables the quick construction of polycyclic architectures with up to five contiguous stereogenic centers in a single operation with moderate to good yields as well as high diastereoselectivity and would provide versatile short approaches to frameworks and/or analogues of numerous biologically important polycyclic natural products.

Two isomers (3 and 4) with a configuration at C-21 opposite to that proposed for didemnaketal A were synthesized through a process in which the longest linear sequence involved 29 steps. Comparative NMR analysis of these isomers and natural didemnaketal A suggests the possibility of misassignments at other stereocenters in the proposed structure of didemnaketal A.

NH4HF2 has been used for the first time to selectively remove the TBS protecting groups from diol ketone precursors in the synthesis of highly functionalized spiroketals. This method allows the synthesis of [5,6], [6,6], and [6,7] spiroketal skeletons, as well as benzannulated spiroketal with retention of acid-sensitive groups. In this way, spiroketals can be synthesized with diverse substituent groups in the skeleton or on side chains. To demonstrate the utility of this methodology, the diverse transformations of highly functionalized spiroketal 3f were also investigated.

The total synthesis of isomer of didemnaketal A was achieved in 26 steps. The position of esters is switched at C7 and C8 with respect to their proposed position in natural didemnaketal A, which shows potent anti-HIV activity but so far has not been synthesized in the laboratory. Structural analysis of synthetic isomer of didemnaketal A indicates that the esters at C7 and C8 are correctly assigned, suggesting that the problems for the structural reassignment of natural didemnaketal A lie elsewhere.

A Lewis acid promoted tandem semipinacol-type 1,2-carbon migration/aldol reaction of trimethylsilane-protected vinylogous α-ketols with aldehyde or dimethyl acetals is reported. This reaction provides a direct and rapid way for the construction of 6-substituted spiro[4.5]decanes which extensively exist in Daphniphyllum alkaloids. By the use of this method, further construction of a [5–6–7] all-carbon tricyclic core of Calyciphylline A-type alkaloids was also completed.

An efficient strategy for the total synthesis of (+)-przewalskin B is reported. The key steps feature an intermolecular SN2′ substitution of iodoallylic phosphate with organocupper reagent, a diastereoselective organocatalytic aldol cyclization, as well as a Rh2(OAc)4-mediated intramolecular carbene insertion to the tertiary C–H bond.

A full account of the total synthesis of (±)-maistemonine, (±)-stemonamide, and (±)-isomaistemonine is presented. Two approaches have been developed to construct the basic pyrrolo[1,2-a]azepine core of the Stemona alkaloids, featuring a tandem semipinacol/Schmidt rearrangement of a secondary azide and a highly stereoselectively desymmetrizing intramolecular Schmidt reaction, respectively. To build the common spiro-γ-butyrolactone, a new protocol was carried out by utilizing an intramolecular ketone-ester condensation as the key transformation. The vicinal butyrolactone moiety of (±)-maistemonine was stereoselectively introduced via a one-pot procedure involving the epimerization at C-3 and carbonyl allylation/lactonization. Moreover, (±)-stemonamide was divergently synthesized from a common intermediate, and (±)-isomaistemonine was obtained via the epimerization of (±)-maistemonine at C-12.

The FeCl3-catalyzed aerobic oxidation process for the synthesis of benzoxazoles, benzothiazole and benzimidazole has been discovered. This method has proved to be effective to a wide range of substrates, and it has been applied for the synthesis of JTP-426467.

A short and efficient approach to aza-quaternary pyrrolo[1,2-a]azepine 8 and aza-quaternary indolizine 23, as the crucial intermediates for syntheses of stemonamine (1a) and cephalotaxine (1b), has been developed on the basis of the key intramolecular Schmidt reaction of symmetric azido-diones 5 and 18, respectively.

The direct and efficient construction of α-aryl-β-substituted cyclic ketone scaffolds has been achieved using a Cu-mediated one-pot Michael addition/α-arylation strategy. The reaction features easily available materials, broad substrate scope, moderate to good yield, and an excellent diastereoselectivity.

A novel and tunable α-hydroxylation/α-chlorination of benzyl ketone derivatives has been developed for the construction of hetero-quaternary carbon centers by iron(III) chloride hexahydrate mediated selective transformations through the application of different oxidants, especially the crystal water in the catalyst as an OH source is firstly reported in this hydroxylation.