Synthesis of ( S )‐8 a ‐Methyl‐3,4,8,8 a ‐Tetrahydro‐1,6‐(2 H ,7 H )‐Naphthalenedione via N ‐tosyl‐( S _a )‐binam‐l‐prolinamide Organocatalysis

Abstract

( S )‐8a‐Methyl‐3,4,8,8a‐tetrahydro‐1,6(2 H ,7 H )‐naphtalenedione 2‐Methyl‐2‐(3‐oxobutyl)‐1,3‐cyclohexanedione 2‐Methyl‐1,3‐cyclohexanedione N ‐Tosyl‐( S a )‐binam‐L‐prolinamide Methyl vinyl ketone

Green Asymmetric Organocatalysis

“…If the reaction was performed in CH 2 Cl 2 , DMF, or THF, the yields of the product dramatically dropped (35, 61, and 58 %, respectively). In 2‐MeTHF, the reaction required only 1 h, whereas under solvent‐free conditions, it was 5 days . Furthermore, the catalyst loading in 2‐MeTHF was 3.5 times lower than that in DMSO .…”

The Wieland-Miescher Ketone: A Journey from Organocatalysis to Natural Product Synthesis

“…Standard hydrogenation gives only moderate selectivity, but can be improved Scheme 11 Large-scale synthesis of WMK 1 with minimal purifications70 …”

Mechanistic Study on the Asymmetric Synthesis of the Wieland‐Miescher Ketone and Analogs

“…However, this resulted in a slight erosion of the enantioselectivity, which we attribute to the additional acid interfering with the H‐bonding essential for the bifunctional reactivity of the catalyst. Further attempts to counterbalance these two opposing factors allowed us to obtain slightly higher enantioselectivities with 2 % catalyst and 0.5 % acid co‐catalyst (entry 5, Table ), although attempts to find conditions using lower loadings of the catalyst were unfruitful (entry 6, Table and entries 7–11 in the Supporting Information, Table S1) . Finally, the conditions of entry 4 were optimal in terms of reaction time, catalyst loading and enantioselectivity.…”