Solid-Supported Cross-Metathesis and a Formal Alkane Metathesis for the Generation of Biologically Relevant Molecules

Abstract

Solid-phase synthetic strategies toward the generation of libraries of biologically relevant molecules were developed using olefin cross-metathesis as a key step. It is remarkably the formal alkane metathesis based on a one-pot, microwave-assisted, ruthenium-catalyzed cross-metathesis and reduction to obtain Csp3-Csp3 linkages.

Unprecedented Multifunctionality of Grubbs and Hoveyda–Grubbs Catalysts: Competitive Isomerization, Hydrogenation, Silylation and Metathesis Occurring in Solution and on Solid Phase

“…In heterogeneous phase, named solid-phase organic synthesis, we have carried out pioneering work on the application of a combination of ruthenium-catalyzed cross-metathesis and reduction to perform a formal alkane metathesis to build Csp 3 -Csp 3 linkages [31,32]. Solid-phase organic synthesis (SPOS), initially used in peptide chemistry, is now broadly applied to the preparation of a range of biologically interesting structures [33][34][35].…”

Cross‐Metathesis on Immobilized Substrates – Application to the Generation of Synthetically and Biologically Relevant Structures

“…Several investigations have led to a wide variety of examples in solution, whereas in the case of SP synthesis some pioneering work involves the tandem enyne metathesis reactions discussed above. [95] On this occasion, a one-pot CM/reduction sequence was desirable in order to gain rapid access to biologically appealingphenylpropiophenones and derivatives. [91][92][93] It is well-known that olefin reduction -a classic chemical transformation -does not have a successful and reliable correlation in SP synthesis.…”

“…[94] We came back to this transformation during our studies on the first solid-supported synthesis of chalcones through CM. [95] On this occasion, a one-pot CM/reduction sequence was desirable in order to gain rapid access to biologically appealingphenylpropiophenones and derivatives. After some unsuccessful attempts using catalyst 6, employment of complex 7 allowed the different supported olefins 120 and substituted Scheme 30.…”

Molecular Diversity by Olefin Cross-Metathesis on Solid Support. Generation of Libraries of Biologically Promising β-Lactam Derivatives

“…Particularly, solid-phase chemistry has recently aroused interest in metal-catalyzed cross-coupling reactions since undesirable soluble homodimers can be washed away during purification providing chemoselectivity, while immobilization of one of the substrates makes its homodimerization a less favorable process due to site isolation ( Scheme 1 ) [ 26 ]. In this regard, we and others have recognized the usefulness of solid-supported olefin cross-metathesis for generation of biologically relevant molecules [ 27 , 28 , 29 , 30 , 31 ], including a comprehensive study to understand the process [ 32 , 33 ]. From the viewpoint of green chemistry, using solid-phase synthetic sequences allows a significant reduction in solvent waste, since purification is performed by phase separation, avoiding chromatographic isolation of products which requires a large consumption of organic solvents [ 34 ].…”