Herein, we report a nickel-catalyzed reductive cross-coupling reaction of easily accessible 3-butenyl carbamoyl chloride with primary alkyl iodide to access the chiral α-alkylated pyrrolid­inone with broad substrate scope and high enantio­meric excess. The current art of synthesis still remains challenging on the enantio­selective α-mono­alkylation of pyrrolid­inones. The newly designed chiral 8-quinoline imidazoline ligand (Quinim) is crucial for maintaining the reactivity and enantio­selectivity to ensure the reductive cyclization of mono­substituted alkenes for unprecedented synthesis of chiral non-aromatic heterocycles.

We herein describe a palladium‐catalyzed three‐component coupling of internal enamides, arylboronic acids, and Selectfluor to access the chiral β‐fluoroaminated moiety with up to 99 % ee. The prefunctionalized oxazolidinone substituted alkene enables the expedient construction of two vicinal stereocenters with excellent regio‐, diastereo‐, and enantioselectivities. The synthetic application is exhibited by selective transformation of the product into various vicinal benzylic fluoride derivatives.

The total synthesis of principinol D, a rearranged kaurane diterpenoid, is reported. This grayanane natural product is constructed via a convergent fragment coupling approach, wherein the central seven-membered ring is synthesized at a late stage. The bicyclo[3.2.1]octane fragment is accessed by a Ni-catalyzed α-vinylation reaction. Strategic reductions include a diastereoselective SmI 2mediated ketone reduction with PhSH and a new protocol for selective ester reduction in the presence of ketones. The convergent strategy reported herein may be an entry point to the larger class of kaurane diterpenoids.The grayanane diterpenoids-well-known as the active components in "mad honey" due to inhibition of voltage-gated sodium ion channels 1 -have recently been identified as structurally novel allosteric inhibitors of carbonic anhydrases 2 and phosphatases. 3 Due to the ubiquity of various subtypes of these molecular targets, potential therapeutic development could span numerous different disease areas from neurological dysfunction to cancer. 4,5 Grayananes are among a broader class of rearranged kauranes that also includes gibberellanes and 6,7-seco-kauranes (Figure 1A). The tetracyclic diterpenoid grayananes are formed by rearrangement of the kaurane 6,6-A/B ring system to a 5,7-ring system. 6 The kauranes are derived from rearrangement and cyclization of pimaranes via the beyeranes. 7,8 The first total synthesis of (±)-kaurene was completed in 1962 by Ireland and co-workers, 9 and in recent years several groups have completed elegant syntheses of members of this broader class employing a diverse array of synthetic strategies. 10 Nevertheless, much of the >1000 kaurane diterpenoids that have been isolated remain inaccessible by previously reported synthetic approaches. Synthetic efforts toward the grayananes have been especially limited 11 despite their compelling biological activities.

Enantioselective transformations of olefins are among the most important strategies for the asymmetric synthesis of organic compounds. Chemo-, diastereo-, and stereoselective control of reactions with internal acyclic alkenes for the construction of functionalized acyclic alkanes still remain a persistent challenge. Here, we report a palladium-catalyzed asymmetric regiodivergent Heck-type diarylation of internal acyclic alkenes. The 1,2-diarylation of two accessible acyclic alkenes, cinnamyl carbamates and enamides with diazonium salts and aromatic boronic acids, furnishes products containing vicinal stereogenic centers via the stereospecific formation of carbonyl coordination-assisted transient palladacycles. Moreover, the asymmetric migratory diarylation of enamides enables the formation of incontiguous stereocenters by an interrupted diastereoselective 1,3-chain-walking process. This protocol streamlines access to highly functionalized multisubstituted enantioenriched carbamates and amine derivatives which are embedded in the key biologically active motifs.

The development of carbamoyl chlorides as synthons for various amide-containing molecules and heterocycles have been summarized and discussed in this review article. Carbamoyl chlorides can participate in a diverse range...