Synthesis of O‐ and N‐Heterocycles by Silyl‐Prins Cyclization of Allylsilanes

Abstract

Prins cyclization has emerged as one of the most valuable methods for the construction of heterocycles. It proceeds through intramolecular addition of a π‐nucleophile to an oxocarbenium or related ion. The use of electron‐rich alkenes, such as allylsilanes (so‐called silyl‐Prins cyclization) offers the benefit of allowing more selective reactions. The regio‐ and stereochemical outcomes of these transformations are explained by well‐stablished transition states. This review presents the most important contributions involving silyl‐Prins cyclization to the stereoselective preparation of oxygen and nitrogen heterocycles. The influence of different structural variants in the selectivity of the cyclization is discussed. These reactions have frequently been used as key steps in the synthesis of a wide variety of natural products.

Solvent-Free, Mechanochemically Scalable Synthesis of 2,3-Dihydroquinazolin-4(1H)-one Using Brønsted Acid Catalyst

“…Creation of novel N -heterocyclic molecules has always been a priority domain for the synthetic organic chemists owing to their immense relevance in wide-ranging areas of medicinal chemistry, drug design, and functional materials. − 2,3-Dihydroquinazolin-4­(1H)-ones constitute one such imperative family of molecules which has extensive applications in pharmaceutical industry owing to their distinct biological behaviors such as anticancer, diuretic, anti-inflammatory, anticonvulsant, and antihypertensive activities. − Natural products incorporating the quinazoline skeleton are quite frequent and cytotoxic alkaloid Luotonin A and its derivatives are clinically proven as anticancer agents. , They are considered as the “privileged structures” for drug design, because of their capability to bind to multiple receptors with high affinity (Figure ). With such prominent physiological significance and pharmaceutical utility of the 2,3-dihydroquinazolin-4­(1H)-one skeletons, it became utmost importance to synthesize quinazolinone-incorporating heterocycles.…”

Ni(COD)2-Catalyzed ipso-Silylation of 2-Methoxynaphthalene: A Density Functional Theory Study

“…The C–OMe activation reactions provide robust as well as practical solutions for the synthesis of organic compounds, pharmaceuticals, and industrially important intermediates on a large scale . The synthesis of novel organosilanes has provided important precursors in the synthesis of aromatic sulfones, natural products, and nanomaterials. − Therefore, the synthesis of a C–Si bond through C–OMe activation has become a notable area of research. Although there have been many reports on mechanistic investigations of transition-metal-catalyzed reactions, there have been few mechanistic studies on nickel-catalyzed activation of aryl ethers. − …”

Unexpected Domino Silyl-Prins/Aryl Migration Process from Geminal Vinylsilyl Alcohols

“…Within the silylated alkenes used in silyl-Prins cyclizations, allylsilanes have frequently shown a great potential for the stereoselective synthesis of different-sized oxygen and nitrogen heterocycles. 2 The alternative use of vinylsilanes in this process has been much less developed, although it has effectively been applied to the synthesis of dihydropyrans, 3 , 4 starting from ( Z )-vinylsilyl homoallylic alcohols. However, a rather limited number of examples has been reported for the synthesis of alkylidene oxacycles from vinylsilyl homoallylic alcohols in which the silyl group and the alcohol (or the corresponding oxocarbenium ion precursor) are bonded to the same sp 2 carbon.…”

“…Within the silylated alkenes used in silyl-Prins cyclizations, allylsilanes have frequently shown a great potential for the stereoselective synthesis of different-sized oxygen and nitrogen heterocycles . The alternative use of vinylsilanes in this process has been much less developed, although it has effectively been applied to the synthesis of dihydropyrans, , starting from ( Z )-vinylsilyl homoallylic alcohols.…”