Efficient Catalyst-Free Henry Reaction between Nitroalkanes and Aldehydes or Trifluoromethyl Ketones Promoted by Tap Water

Abstract

The first examples of highly effective Henry reactions between nitroalkanes and aldehydes or trifluoromethyl ketones that proceed under catalyst-free and additive-free conditions, in a recyclable tap-water medium, and at room temperature are reported herein. This process tolerates a broad range of aldehydes and trifluoromethyl ketones to give a series of β-nitroalcohol products in excellent yields. Such products are widely used in the syntheses of pharmaceutical intermediates and natural products. This protocol can be successfully scaled up to a 50 mmol scale without reduction in yield. Tap water from different locations in China exhibited pH values ranging from 7.5 to 8.1, but the varying pH had no effect on the yield and the processes were successfully reproduced. Finally, the tap water was effectively recovered and reused without any post-processing, even when the reaction substrates were different.

Highly asymmetric aldol reaction of isatins and ketones catalyzed by chiral bifunctional primary-amine organocatalyst on water

“…3 From the perspective of the reaction process, an efficient organic conversion on water requires a catalyst that is soluble in both organic and aqueous phases; in other words, the catalyst should have multiple functions. 4 Extensive research has led to the development of various catalyst types that include traditional monofunctional, bifunctional, and even multifunctional catalysts. 5 Bifunctional or multifunctional catalysts are mostly highly catalytically active because they can simultaneously activate at least two functional groups, thereby promoting new transformations under a variety of conditions.…”

Rationalizing and Adapting Water-Accelerated Reactions for Sustainable Flow Organic Processes

“…Since the early discoveries by Breslow and Sharpless, , the past few decades have seen significant growth in the number of on-water reactions, some of which are synthetically useful. These have been well summarized and discussed in numerous reviews. − Despite, or perhaps because of, the very wide range of classes of reactions which are known to benefit from the on-water effect, e.g., pericyclic, , multicomponent, nucleophilic ring-opening, ,, Mannich, aldol, Henry, Lewis acid-catalyzed, and organocatalytic reactions, , the mechanistic rationalization of their rate acceleration, which may guide the discovery of new on-water reactions, is still in its infancy. This is further confounded by the limited availability of reliable kinetic data − and the complex and variable phase behavior of these reactions (Figure ), which may start off as “in water” and become “on water” as the reaction progresses or vice versa …”