Cycloadditions of Oxacyclic Allenes and a Catalytic Asymmetric Entryway to Enantioenriched Cyclic Allenes

The chemistry of strained cyclic alkynes has undergone a renaissance over the past two decades. However, a related species, strained cyclic allenes, especially heterocyclic derivatives, have only recently resurfaced and represent another class of valuable intermediates. We report a mild and facile means to generate the parent 3,4‐oxacyclic allene from a readily accessible silyl triflate precursor, and then trap it in (4+2), (3+2), and (2+2) reactions to provide a variety of cycloadducts. In addition, we describe a catalytic, decarboxylative asymmetric allylic alkylation performed on an α‐silylated substrate, to ultimately permit access to an enantioenriched allene. Generation and trapping of the enantioenriched cyclic allene occurs with complete transfer of stereochemical information in a Diels–Alder cycloaddition through a point‐chirality, axial‐chirality, point‐chirality transfer process.     

Catalytic Borylative Opening of Propargyl Cyclopropane,Epoxide, Aziridine,and Oxetane Substrates: Ligand Controlled Synthesis of Allenyl Boronates and Alkenyl Diboronates

A new copper‐catalyzed reaction for the stereo‐ and regioselective synthesis of alkenyl diboronates and allenyl boronates is presented. In this process propargyl derivatives of strained three/four‐membered rings were employed as substrates and B₂pin₂ was used as the boronate source. Selective formation of the alkenyl diboronate versus the allenyl boronate products was controlled by the choice of phosphine ligand.     

Cobalt‐Catalyzed Intermolecular [2+2] Cycloaddition between Alkynes and Allenes

An intermolecular [2+2] cycloaddition reaction between an alkyne and an allene is reported. In the presence of a cobalt(I)/diphosphine catalyst, a near equimolar mixture of the alkyne and allene is converted into a 3‐alkylidenecyclobutene derivative in good yield with high regioselectivity. The reaction tolerates a variety of internal alkynes and mono‐ or disubstituted allenes bearing various functional groups. The reaction is proposed to involve regioselective oxidative cyclization of the alkyne and allene to form a 4‐alkylidenecobaltacyclopentene intermediate, with subsequent C?C reductive elimination.     

Reductive Decarboxylative Alkynylation of N‐Hydroxyphthalimide Esters with Bromoalkynes

A new method for the synthesis of terminal and internal alkynes from the nickel‐catalyzed decarboxylative coupling of N‐hydroxyphthalimide esters and bromoalkynes is presented. This reductive cross‐electrophile coupling is the first to use a C(sp)−X electrophile, and appears to proceed via an alkynylnickel intermediate. The internal alkyne products are obtained in yields of 41–95 % without the need for a photocatalyst, light, or a strong oxidant. The reaction displays a broad scope of carboxylic acid and alkyne coupling partners, and can tolerate an array of functional groups, including carbamate NH, halogen, nitrile, olefin, ketone, and ester moieties. Mechanistic studies suggest that this process does not involve an alkynylmanganese reagent and instead proceeds through nickel‐mediated bond formation.     

Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow‐Generated Diazo Compounds and Propargylated Amines

We report herein the asymmetric coupling of flow‐generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10–20 minutes with high enantioselectivity (89–98 % de/ee), moderate yields and a wide functional group tolerance.     

Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis

The aerobic Cu/ABNO catalyzed oxidative coupling of alcohols and amines is highlighted in the synthesis of amide bonds in diverse drug‐like molecules (ABNO=9‐azabicyclo[3.3.1]nonane N‐oxyl). The robust method leverages the privileged reactivity of alcohols bearing electronegative hetero‐ atoms (O, F, N, Cl) in the β‐position. The reaction tolerates over 20 unique functional groups and is demonstrated on a 15 mmol scale under air. Steric constraints of the catalyst allow for chemoselective amidation of primary amines in the presence of secondary amines. All catalyst components are commercially available, and the reaction proceeds under mild conditions with retention of stereocenters in both reaction partners, while producing only water as a by‐product.