Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

Abstract

Nucleophilic substitutions (S N) are typically promoted by acid chlorides as sacrificial reagents to improve the thermodynamic driving force and lower kinetic barriers. However, the cheapest acid chloride phosgene (COCl 2) is a highly toxic gas. Against this background, phenyl chloroformate (PCF) was discovered as inherently safer phosgene substitute for the S N-type formation of CÀ Cl and CÀ Br bonds using alcohols. Thereby, application of the Lewis bases 1-formylpyrroldine (FPyr) and diethylcyclopropenone (DEC) as catalysts turned out to be pivotal to shift the chemoselectivity in favor of halo alkane generation. Primary, secondary and tertiary, benzylic, allylic and aliphatic alcohols are appropriate starting materials. A variety of functional groups are tolerated, which includes even acid labile moieties such as tert-butyl esters and acetals. Since the by-product phenol can be isolated, a recycling to PCF with inexpensive phosgene would be feasible on a technical scale. Eventually, a thorough competitive study demonstrated that PCF is indeed superior to phosgene and other substitutes.

Copper-Catalyzed Oxidative Coupling of Quinazoline-3-Oxides: Synthesis of O-Quinazolinic Carbamates

“…In recent years, organic carbamates have attracted much attention from the synthetic community due to their diverse interesting properties. − In addition to being an important class of privileged structures in pharmaceuticals in the forms of drugs and prodrugs, the carbamate motif is also broadly existed in agrochemicals and polymers. − The most common methods to organic carbamates rely on the nucleophilic addition of alcohols to isocyanates or isocyanate intermediates generated in situ form acyl azides via Curtius rearrangement (Scheme ). − In addition, the utilization of CO 2 , ,,− CO, ,− or COCl 2 − as C1 synthon to combine with amines and alcohols provides an alternative convenient access to organic carbamates. − Very recently, some supplementary strategies have also been developed through transition metal-catalyzed or novel rearrangement process. − …”

Tropolonate Salts as Acyl-Transfer Catalysts under Thermal and Photochemical Conditions: Reaction Scope and Mechanistic Insights

“…We had previously developed several methods to use tropone as a stoichiometric or catalytic system in esterification and amidation reactions of carboxylic acids . Presumably, tropone possesses these types of reactivities because of its ability to partially aromatize , to the tropylium oxide form (Figure ), which displays Lewis base characteristics . Its 2-hydroxy derivative, tropolone, has been frequently used as a model system to study intramolecular proton transfer and tunneling processes .…”

Extended Single-Electron Transfer Model and Dynamically Associated Energy Transfer Event in a Dual-Functional Catalyst System

“…Organocatalysis has vastly expanded over 20 years and is gradually developing into one of the three pillars besides the counterparts of metal catalysis and biocatalysis in the area of catalysis. − Dating back to 1859, Liebig showed the first example of organocatalysis, in which the pure organic molecule of acetaldehyde was used to achieve a catalytic organic transformation from cyanogen to oxamide. , However, the chemical synthesis community overlooked the research field of organocatalysis in the following one-and-a-half centuries. − This situation was altered significantly until 2000 by the exploration of a new type of reaction of organic enamine and iminium catalysis, leading to the frequent utilization of the conception of “organocatalysis”. Moreover, the pioneer works of List and MacMillan demonstrated that small organic molecules could catalyze the same chemical reactions as much larger organic molecules following a similar mechanism. − The rapid expansion of organocatalysis can be attributed to many advantages of organic small-molecule catalysts in comparison to metal catalysts, including relative nontoxicity, availability from natural biological sources, as well as air and water stability. , These further promote organocatalysis to serve as an effective platform to meet operational requirements of industrial applications on the merits of the concise experimental procedure, atom economy, and reduction in time and energy cost. , However, this synthesis method is merely applicable to a limited amount of reactions since it generally requires prefunctionalization of substrates, introduction of sacrificial agents, − or suffers from harsh reaction conditions such as high temperature , and high pressure , in most cases.…”