Homogeneous Gold-Catalyzed Glycosylations in Continuous Flow

The use of versatile alkynyl-building blocks that are activated by gold­(I)-catalysis is demonstrated to efficiently generate a variety of glycosides in continuous flow. The application of a continuous flow setting to gold­(I)-catalyzed glycosylations enables very short reaction times and excellent control of the reaction conditions

Regioselective Catalytic Hydroboration of Propargylic Species Using Cu(I)-NHC Complexes

The catalytic regioselective hydroboration of propargylic alcohols and ethers was investigated using NHC-CuCl. We observe that different NHC-CuCl complexes catalyze hydroborations of propargylic substrates with opposite regioselectivity. A 6-NHC-CuCl complex provides α-selectivity whereas β-selectivity is achieved using a 5-NHC-CuCl complex. The reaction tolerates a wide range of functional groups

Synthesis and Reactivity Profile of Ylidenemalononitrile Enamines and Their Ester Analogs Towards Electrophiles and Nucleophiles

Herein, we describe the synthesis and reactivity of enamines derived from ylidenemalononitriles and ylidenecyanoacetates. The enamine scope was expanded by (1) increasing yields of aldehyde-derived ylidenemalononitriles, (2) incorporating silyl functionalities, and (3) using other amide acetals to expand the substitution patterns of pyridines resulting from enamine cyclization. In addition, methods to produce α-pyrones and polysubstituted pyridines from both ylidenemalononitriles and ylidenecyanoacetates are described

Improved Synthesis of Mono- and Disubstituted 2‑Halonicotinonitriles from Alkylidene Malononitriles

Pyridines with 2,3,4 and/or 5 substitution remain challenging to prepare. Existing strategies to form multisubstituted 2-halonicotinonitriles via enamines suffer from dimerization of the starting alkylidene malononitriles resulting in low yields. Through alteration of reaction conditions, a new high yielding method into enamines was realized by condensing DMF–DMA and alkylidene malononitriles in the presence of substoichiometric acetic anhydride. Cyclization of the resulting enamines under Pinner conditions provided 2-halonicotinonitriles in high overall yields

Continuous Synthesis and Use of <i>N</i>‑Heterocyclic Carbene Copper(I) Complexes from Insoluble Cu₂O

It is demonstrated that homogeneous <i>N</i>-heterocyclic carbene–copper(I)-chloride complexes can be prepared continuously by flowing NHC precursors through a packed bed of solid Cu₂O suspended in molecular sieves. The method enables the synthesis of a wide range of complexes including those that are challenging to prepare using standard approaches. Our strategy enables both sustained output of complex production for long-term catalytic reactions (greater than 5 h) and for generation of gram quantities for storage (greater than 1 g of complex in ∼16 min)

Continuous Reductions and Reductive Aminations Using Solid NaBH₄

Most successful reactions carried out under continuous flow conditions mix homogeneous solutions yielding homogeneous products. Using solids is avoided to prevent pump and reactor clogging; even though solid reagents may often be the best choice for a given transformation. Here we demonstrate that by pumping aldehydes, ketones, or in situ formed imines through a specially formulated NaBH₄ column results in efficient reductions. The column design and performance characteristics, along with substrate scope, are discussed

Continuous Photochemical Cleavage of Linkers for Solid-Phase Synthesis

Photolabile linkers are an attractive alternative for solid-phase synthesis because they can be cleaved using light. However, irradiation in a classical batch photoreactor results in incomplete cleavage of the photolabile linkers. It is demonstrated that a continuous flow photoreactor is superior to a batch photoreactor for the cleavage of a linker from polystyrene resin

Ylidenemalononitrile Enamines as Fluorescent “Turn-On” Indicators for Primary Amines

Ylidenemalononitrile enamines undergo rapid amine exchange followed by a cyclization with primary amines to yield fluorescent products with emission intensities as high as 900 times greater than the starting materials. After identifying the fluorescent species by X-ray crystallography, we demonstrate that the rate of amine exchange is substrate dependent and that by simple structural variation the fluorescence can be tuned over the entire visible spectrum. We further demonstrate their potential application in biomolecule labeling

Ylidenemalononitrile Enamines as Fluorescent “Turn-On” Indicators for Primary Amines

Ylidenemalononitrile enamines undergo rapid amine exchange followed by a cyclization with primary amines to yield fluorescent products with emission intensities as high as 900 times greater than the starting materials. After identifying the fluorescent species by X-ray crystallography, we demonstrate that the rate of amine exchange is substrate dependent and that by simple structural variation the fluorescence can be tuned over the entire visible spectrum. We further demonstrate their potential application in biomolecule labeling