In 2005, the ACS Green Chemistry Institute (GCI) and the global pharmaceutical corporations developed the ACS GCI Pharmaceutical Roundtable to encourage the development of green chemistry and green engineering in the pharmaceutical industry. The Roundtable has established a list of key research areas including the direct nucleophilic reactions of alcohols. The substitution of activated alcohols is a frequently used approach for the preparation of active pharmaceutical ingredients. Alcohols are transformed into the reactive halides or sulfonate esters, thereby allowing their reaction with nucleophiles. Although the direct nucleophilic substitution of an alcohol should be an attractive process, as one of the byproducts from the reaction yields water, hydroxide is a poor leaving group that hinders the reaction. Recently, the direct substitution of allylic, benzylic, and tertiary alcohols has been achieved through an SN1 reaction with catalytic amounts of Brønsted or Lewis acids. In this review, the approaches leading to a greener process are examined in detail, and the advances achieved to date in this important transformation are presented.

Herein we disclose the simple, effective, and practical alkylation of nitroalkanes that takes place with benzylic, benzhydrylic, and propargylic alcohols in trifluoroethanol. A variety of different nitroalkanes bearing functional groups can be used in this SN1‐type reaction to afford the desired products in quantitative yields. Different chiral nitro derivatives were submitted to this highly diastereoselective alkylation reaction with selected benzhydrols. A new, effective, and chiral pyrrolidine organocatalyst was prepared by using this methodology.

Ironing out the details: Proline and pyrrolidine derivatives (Hayashi- Jørgensen catalysts) are considered "work horses" in organocatalysis. This report describes a new effective ferrocenyl pyrrolidine catalyst that is able to perform well in benchmark organocatalytic reactions (see figure). The ferrocene moiety controls the conformational space and a simple alkyl group effectively covers a face of the derived enamine. This new framework can find applications in organocatalysis, and in general, in new ligand design.

N,N'-bis-((8-hydroxy-7-quinolinyl)methyl)-1,10-diaza-18-crown-6 ether 1a and its analogue 1c are known as fluorescent sensors of magnesium in living cells. With the aim to investigate the effects of the substitution pattern on the photophysical properties of ligands 1 and their metal complexes, we developed an efficient microwaves enhanced one-pot Mannich reaction to double-armed diaza-crown ligands 1 carrying a variety of substituents. This new protocol is characterized by shorter reaction times, enhanced yields, and improved product purities with respect to the use of conventional conductive heating.

We herein present a general enamine-mediated α-alkylation of α-substituted aldehydes with carbenium ions for the stereoselective construction of quaternary stereogenic centers.