Ring contraction in synthesis of functionalized carbocycles

Carbocycles are a key and widely present structural motif in organic compounds. The construction of structurally intriguing carbocycles, such as highly-strained fused rings, spirocycles or highly-functionalized carbocycles with congested stereocenters, remains challenging in organic chemistry. Cyclopropanes, cyclobutanes and cyclopentanes within such carbocycles can be synthesized through ring contraction. These ring contractions involve re-arrangement of and/or small molecule extrusion from a parental ring, which is either a carbocycle or a heterocycle of larger size. This review provides an overview of synthetic methods for ring contractions to form cyclopropanes, cyclobutanes and cyclopentanes en route to structurally intriguing carbocycles

Fluorination and photocatalysis: New horizons

Recently, the understanding of the importance of fluorination in organic compounds has exploded. It provides a handle for medicinal, agricultural and materials chemists to advantageously affect the properties of a molecule. Despite these enhancements, due to the absence of fluorine containing molecules in the natural world, the pool of molecules such as these from which chemists may draw to build larger and more elaborate molecules is very limited. Single fluorines can be installed into molecules, though this process is arduous, expensive, and inefficient. This problem is compounded when sequential fluorination processes are required. From a fundamentally different approach to fluorination in this way, installing fluorines everywhere, perfluorination, is straightforward and reliable. The fluorines may then be substituted one by one to give the desired molecule. It is toward this goal that the Weaver Lab has labored, developing methodology to perform new and interesting transformations on polyfluorinated molecules to not only reduce the fluorine content, but to do it selectively, and increase the complexity of the molecule as desired. Photocatalysis and SNAr can serve in this capacity. Further, photocatalysis can be used in synthesis that does not involve fluorine, but rather take advantage of some of the other novel reactivities in which the photocatalytic cycle can be engaged. Expeditions into these realms are the subjects explored herein

Photoinduced Carboborative Ring Contraction Enables Regio- and Stereoselective Synthesis of Multiply Substituted Five-Membered Carbocycles and Heterocycles

We report herein a photoinduced carboborative ring contraction of monounsaturated six-membered carbocycles and heterocycles. The reaction produces substituted five-membered ring systems stereoselectively and on preparative scales. The products feature multiple stereocenters, including contiguous quaternary carbons. We show that the reaction can serve as a synthetic platform for ring system alteration of natural products. The reaction can also be used in natural product synthesis. A concise total synthesis of artalbic acid has been enabled by a sequence of photoinduced carboborative ring contraction, Rauhut–Currier reaction, and nitrilase-catalyzed hydrolysis. The synthetic utility of the reaction has been further demonstrated by converting the intermediate organoboranes to alcohols, amines, and alkenes