Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition/Kinetic Resolution Sequence for the Enantioselective Synthesis of Spiro‐Dihydropyranone from Benzylidene Meldrum's Acid

Abstract

A catalytic enantioselective vinylogous domino reaction has been achieved from ketone-derived benzylidene Meldrum's acid and α-ketolactones to provide spirolactone dihydropyranones with more than 99% ee. An Auto Tandem Catalysis (ATC) process resulting from dual and complementary role of (DHQ)2PHAL organocatalyst resulted in a sequence involving an asymmetric vinylogous formal (4+2) cycloaddition of benzylidene and the subsequent kinetic resolution operating through a 1,3prototropic shift leading to good yields (> 50%) and the high selectivity.

An Organocatalytic and Stereoselective Vinylogous Domino Process towards Thiochromans

“…First, the VMAC sequence was achieved with aldehydes, contrariwise to the previous vinylogous addition of KAMA , which only occurred with activated ketones (see Scheme 1B). Next, the 5,6‐dihydropyran‐2‐one 5 aa with a conjugated C−C double bond was obtained from 1 a without a decarboxylative event, in sharp contrast with our previous report [6,7] . Geometric constraint within tricyclic structure 5 aa might retard the C−C double bond shift (see Supporting Information).…”

“…We recently discovered a unique vinylogous reactivity of ketone‐derived alkylidene Meldrum's acid ( KAMA ) under organocatalytic asymmetric conditions (Scheme 1B) [6,7] . Subsequent to the deprotonation of KAMA with a tertiary amine, the resulting transient vinylogous enolate species A led to a formal stepwise (4+2) cycloaddition to activated ketones, giving rise to formation of 3,6‐dihydropyran‐2‐ones as the kinetic product [6,7] .…”

“…[2,3b,5] We recently discovered a unique vinylogous reactivity of ketone-derived alkylidene Meldrum's acid (KAMA) under organocatalytic asymmetric conditions (Scheme 1B). [6,7] Subsequent to the deprotonation of KAMA with a tertiary amine, the resulting transient vinylogous enolate species A led to a formal stepwise (4 + 2) cycloaddition to activated ketones, giving rise to formation of 3,6-dihydropyran-2-ones as the kinetic product. [6,7] Aiming at exploring further this original organocatalytic reactivity, we reasoned that a suited bifunctional nucleophile, like 2-carboxaldehyde thiophenol 2, may lead to a selective 1,6-sulfa-Michael process generating enolate B which could trigger a diastereoselective formal (4 + 2) cycloaddition towards novel and valuable tricyclic thiochromans 3 (Scheme 1C).…”

Stereoselective Domino Reactions in the Synthesis of Spiro Compounds

“…The reaction passes through a 1,3-prototropic shift between ketone-derived benzylidene Meldrum’s acid 536 and α-ketolactone 537 to provide enantioenriched spirolactone-dihydropyranones 538 and 538′ (Scheme 108 ). 116 This process results from the dual and complementary role of (DHQ) 2 PHAL organocatalyst 539 .…”

Hydrogenation of BHMF with controllable selectivity to tetrahydropyranone and 1-hydroxy-2,5-hexanedione under atmospheric H2pressure

“…The production of pyranone derivatives has attracted wide attention and a great many pathways to pyranone derivatives have been reported. [59][60][61][62][63] However, most of the methods suffered from the problem of the availability of starting materials. So, the production of tetrahydropyran derivatives from readily available biomass-derived furans is a worthy topic.…”