Diels-Alder Cycloadditions of Oxacyclic Allenes and α-Pyrones.

Reactions of α-pyrones with oxacyclic allenes in Diels-Alder trappings are described. We investigate regioselectivity trends and perform competition experiments to assess the influence of structural and electronic features on relative reaction rates. We also demonstrate the stereospecific trapping of an oxacyclic allene, which proceeds in high optical yield.

Total Synthesis of Lissodendoric Acid A.

We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A . These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis.

Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B.

We report an approach to the core of the manzamine alkaloid keramaphidin B that relies on the strain-promoted cycloaddition of an azacyclic allene with a pyrone trapping partner. The cycloaddition is tolerant of nitrile and primary amide functional groups and can be complemented with a subsequent retro-Diels-Alder step. These efforts demonstrate that strained cyclic allenes can be used to build significant structural complexity and should encourage further studies of these fleeting intermediates.

Reductive Arylation of Amides via a Nickel-Catalyzed Suzuki-Miyaura-Coupling and Transfer-Hydrogenation Cascade.

We report a means to achieve the addition of two disparate nucleophiles to the amide carbonyl carbon in a single operational step. Our method takes advantage of non-precious-metal catalysis and allows for the facile conversion of amides to chiral alcohols via a one-pot Suzuki-Miyaura cross-coupling/transfer-hydrogenation process. This study is anticipated to promote the development of new transformations that allow for the conversion of carboxylic acid derivatives to functional groups bearing stereogenic centers via cascade processes.

Ni-Catalyzed Suzuki-Miyaura Cross-Coupling of Aliphatic Amides on the Benchtop.

Suzuki-Miyaura cross-couplings of amides offer an approach to the synthesis of ketones that avoids the use of basic or pyrophoric nucleophiles. However, these reactions require glovebox manipulations, thus limiting their practicality. We report a benchtop protocol for Suzuki-Miyaura cross-couplings of aliphatic amides that utilizes a paraffin capsule containing a Ni(0) precatalyst and NHC ligand.

Base-Mediated Meerwein-Ponndorf-Verley Reduction of Aromatic and Heterocyclic Ketones.

An experimental protocol to achieve the Meerwein-Ponndorf-Verley (MPV) reduction of ketones under mildly basic conditions is reported. The transformation is tolerant of a range of ketone substrates, including - and -containing heterocycles, is scalable, and shows potential to be used as a platform to access enantioenriched products. These studies provide a general method for achieving the reduction of ketones under mildly basic conditions and offer an alternative protocol to more well-known Al-based MPV reduction conditions.

Cationic Co(I)-Intermediates for Hydrofunctionalization Reactions: Regio- and Enantioselective Cobalt-Catalyzed 1,2-Hydroboration of 1,3-Dienes.

Much of the recent work on catalytic hydroboration of alkenes has focused on simple alkenes and styrene derivatives with few examples of reactions of 1,3-dienes, which have been reported to undergo mostly 1,4-additions to give allylic boronates. We find that reduced cobalt catalysts generated from 1,n- bis-diphenylphosphinoalkane complexes [PhP-(CH) -PPh]CoX; n = 1-5) or from (2-oxazolinyl)phenyldiarylphosphine complexes [(G-PHOX)CoX] (G = 4-substituent on oxazoline ring) effect selective 1,2-, 1,4-, or 4,3-additions of pinacolborane (HBPin) to a variety of 1,3-dienes depending on the ligands chosen. Conditions have been found to optimize the 1,2-additions.