Synthesis of Polyoxygenated Heterocycles by Diastereoselective Functionalization of a Bio-Based Chiral Aldehyde Exploiting the Passerini Reaction

Abstract

A chiral bio-based building block, prepared by the lipase-mediated desymmetrization of an erythritol derivative, was further functionalized and then submitted to stereoselective Passerini reactions, allowing the synthesis of a small library of new molecules. Thanks to the presence of different functional groups, further cyclizations were performed providing bicyclic polyoxygenated heterocycles.

Study and application of graphene oxide in the synthesis of 2,3-disubstituted quinolinesviaa Povarov multicomponent reaction and subsequent oxidation

“…Nevertheless, GO-assisted one-pot multistep reactions have been seldom explored, 34 at least using organo-or metal-functionalized GO composites. 35 Building on our experience in the development of new synthetic methodologies using MCRs [36][37][38][39][40][41][42][43][44] and in one-pot multistep processes, 45,46 and inspired by the potential of MCRs involving the employment of an external oxidant, 47 we decided to study the GO-promoted Povarov multicomponent reaction between anilines, aldehydes and 2,3-dihydrofuran (DHF) that acts as dienophile to give tetrahydroquinolines (THQs) 1, and their subsequent oxidation to 2,3 disubstituted quinolines 2 (Scheme 1).…”

The 100 facets of the Passerini reaction

“…Monoacetate 147, resulting from the desymmetrization of 138, was homologated to α,β-unsaturated ester 148, with the aim of converting the acetoxymethyl moiety into the aldehyde. 101 However, regardless of the reaction conditions (chemical or enzymatic), as soon as alcohol 149 was released, it immediately underwent a moderately stereoselective intramolecular Michael addition, affording 150 with the cis stereoisomer slightly prevailing. To obtain the chiral aldehyde needed for the Passerini reaction, we performed a protecting group exchange on 147 ( tert -butyldimethylsilyl ether introduction, followed by acetate hydrolysis).…”

“…Moreover, submitting 153 to acidic conditions the densely functionalized tetrahydro[3,2- b ]furan-5-one 157 was isolated, which is an analogue of naturally occurring (+)-goniofufurone. 101 …”

Total Synthesis of 4-epi-Bengamide E

“…Actually, when aldehydes different from formaldehyde or unsymmetric ketones are used, this reaction generates a new stereogenic center, generally with poor diastereoselectivity. In this context, we have developed the diversity-oriented synthesis of chiral polysubstituted Oand N-heterocycles employing erythritol as the starting material [34][35][36].…”