Multicomponent Coupling Approach to (±)-Frondosin B and a Ring-Expanded Analogue

Abstract

[reaction: see text] A recently discovered multicomponent coupling reaction is used to give direct access to a late intermediate in the synthesis of frondosin B. This intermediate can also be efficiently converted to a ring-expanded analogue of frondosin B by sustained heating of the reaction mixture. An unprecedented tandem 1,7-hydrogen shift, 8pi-electrocyclization is proposed to explain the formation of this ring-expanded species.

An efficient and practical entry to 2-amido-dienes and 3-amido-trienes from allenamides through stereoselective 1,3-hydrogen shifts

“…As shown in Scheme 5, when subjected to CSA catalyzed isomerization for protected allyl alcohol-substituted allenamides, the reactions with 37a and 37b did not stop at the intermediate 38 , but an unexpected 1,7-H-shift (for some examples of an antarafacial 1,7-H shift see [79–82]) took place at room temperature to afford 5-amido-trienes 39a and 39b stereoselectively in good yields. Furthermore, when heating the protected homo-allyl alcohol-substituted allenamide 40 , after the 1,3-hydrogen shift an unprecedented double 1,7-H-shift through intermediate 41 and 42 took place to afford the 6-amido-triene 43 in 45% yield.…”

The organocatalytic three-step total synthesis of (+)-frondosin B

“…With our modular synthesis strategy in hand, the rapid preparation of a series of frondosin B analogs for systematic structure–activity relationship studies was now possible. 12,52 To exemplify this opportunity, we prepared two representative analogs 14 and 15 based on conjugate addition of benzofuran or indole precursors (Scheme 8). Key intermediates 7b and 7c were readily prepared in high yield and enantiomeric excess from their respective trifluoroborate salts (79–90% yield, 91–97% ee, cf .…”

Five‐Membered Heterocycles: Benzofuran and Related Systems

“…One of the key intermediates (43) towards the total synthesis of frondosin B has been synthesized by a sequential reaction from phenol 40, enyne 41, and bromide 42 in a one-pot operation (Scheme 7.13) [26]. Palladium-catalyzed intramolecular CÀO bond formation between aryl halides and enolates has been employed to form 2,3-disubstituted benzo [b]furans [27].…”