Expeditious Metal-Free Access to Functionalized Polycyclic Acetals under Mild Aqueous Conditions

Abstract

A facile approach for the synthesis of furopyrans and bicyclic bisacetals under mild aqueous conditions is described. This potentially green, diversity oriented approach involves cascade Michael addition and cycloacetalization of pyranones and 1,3-dicarbonyls. An interesting switch in the product class was observed depending on the type of pyranone employed. Products of type I and II obtained herein are an integral part of several bioactive natural products and medicinally interesting compounds.

Synthesis of O,S‐Containing Polycycles via One‐Pot Michael Addition–Cycloacetalisation Cascade

“…In order to optimise the reaction conditions, initially for the one‐pot synthesis of pyran‐1,4‐dioxinones (when X=Y=Z=O in B ), the reaction of acetoxypyranone 1a 7c and catechol 2a was considered as the model. It was envisioned that, under acid activation, 1a could initially undergo an oxa‐Michael reaction followed by concomitant cycloacetalisation facilitated by the in situ generated oxonium ion.…”

“…Predictably, in the absence of any acid, reactants remained as such even after extended periods (Table 1, entry 19).With the optimised reaction conditions in hand, we proceeded to validate the generality of the strategy (Table 2). Accordingly, a variety of achiral and chiral acetoxypyranones 1a–1h 7c and diols 2c–2f, 2j , and 2l were synthesized according to literature methods 9. Other diols and thiols ( 2a , 2b , 2g – 2i , 2k ) were procured from commercial sources.…”

“…In order to gain mechanistic insights, chiral acetates 1g and 1h were prepared as in literature methods, Scheme 7c. Reaction of (−)‐ 1g (>65% ee ) with the diols 2a or 2d under the optimised conditions furnished, respectively, the 1,4‐dioxinones (+)‐ 3a and (+)‐ 3f as almost racemic mixtures indicating most likely that the reaction involves an initial non‐stereoselective oxa‐Michael reaction followed by cycloacetalisation via an S N 1 pathway [Scheme , Eq.…”

Advances in the Asymmetric Synthesis of Bridged and Fused Bicyclic Acetals

“…Ramasastry and his group [10] developed an expeditious approach towards the exploration of the synthetic pathway for the functionalized fused [5,6] acetals and bicyclic bisacetals involving cascade Michael addition and cycloacetalization of pyranones and 1,3-dicarbonyl compounds. They envisaged that using a mild base under aqueous conditions, 1,3-dicarbonyl compounds could possibly undergo Michael addition to pyranones followed by concomitant cycloacetalization via the in-situ formation of oxonium ions.…”

One‐pot Three‐component Synthesis of Furan‐based Heterocycles from Benzyl Halides

“…Furans were found in medicinal applications because they can bind with various receptors . Furan analogs are well‐known structural components in natural products such as erysenegalensein J , isocoumestan , mycorrhizin A , coniofurol A , plicadin , phellifuropyranone A , and neotanshinlactone (Fig. ).…”