We describe here a convenient and mild, carbon monoxide gas‐free palladium‐catalyzed procedure to obtain N‐substituted phthalimides with molybdenum hexacarbonyl as carbon monoxide precursor. These conditions tolerate a number of functional groups on the benzene ring as well as a number of amines and give the corresponding phthalimides in good to excellent yields.
The selective copper‐catalyzed borylation of silylalkynes in the presence of a diboron reagent and methanol produced a variety of (Z)‐β‐(borylvinyl)silanes. The appropriate use of a selective ligand for copper allows the chemo‐, regio‐, and stereoselective monoborylation of silylalkynes. The β‐regioselectivity of an N‐heterocyclic carbene (NHC)‐copper catalyst was investigated by DFT calculations.
A direct enantioselective reaction of cyclopent‐2‐enone‐derived Morita–Baylis–Hillman alcohols with 4‐hydroxycoumarins has been developed under the catalysis of a chiral primary amine derived from cinchonine in combination with a Brønsted acid. The reaction provides pyranocoumarin products with three vicinal chiral carbon centers in highly regio‐, diastereo‐ and enantioselectivities through a tandem allylic alkylation/intramolecular oxa‐Michael addition.
Readily available cyclobutanols having a butyne‐1,4‐diol moiety underwent a sequential regioselective Meyer–Schuster rearrangement and 1,2‐shift, furnishing α‐hydroxy‐α‐vinylcyclopentanones. The reaction mechanism is consistent with the formation of an allenol intermediate that racemizes under the reaction conditions. Subsequent activation of the allenol leads to an enantio‐ and diastereoselective route to this scaffold.
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(I)‐catalyzed cycloisomerization of enynes with tethered (S)‐2‐methyl‐2‐propanesulfinyl imine affords 5‐ or 6‐membered cyclic compounds containing exocyclic 1,3‐diene moieties in a stereoselective manner. The reaction proceeds through β‐hydride elimination of a 7‐membered azarhodacycle intermediate, which is generated from three unsaturated bonds (i.e., alkene, alkyne, and CN bonds) and an Rh(I) complex. The resultant cyclic compounds could be reacted with various dienophiles to afford spiroamides as single isomers through the Diels–Alder reaction.
In the presence of 1,1,1,3,3,3‐hexafluoro‐2‐propanol (1,1,1,3,3,3‐hexafluoroisopropyl alcohol, HFIP), isoquinolines react with acylzirconocene chlorides to give N‐acyl adducts with incorporation of a proton at the C‐1 position. The present procedure could be applied to the reaction of quinolines. These reactions provide us with an alternative method for the Reissert‐type reduction reactions of azaaromatics with N‐acylating reagents and reducing reagents.
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.
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.
A straightforward, tandem, copper‐catalyzed N‐arylation–condensation has been developed using chiral cyclic 1,2‐diamines and ortho‐haloaryl aldehydes or ketones. The corresponding chiral tricyclic 1,4‐benzodiazepines were synthesized in high yields. Subsequently, the 1,4‐diazepines have been converted to a new class of tetracyclic N‐fused imidazobenzodiazepines (ImBDs) using the van Leusen reaction. A one‐pot sequential strategy has also been demonstrated for the synthesis of ImBDs. The synthetic utility of 1,4‐benzodiazepines and ImBDs is described.
