Highly Enantioselective Synthesis Using Prolinol as a Chiral Auxiliary: Silver-Mediated Synthesis of Axially Chiral Vinylallenes and Subsequent (Hetero)-Diels–Alder Reactions

Abstract

Using (S)-prolinol as a chiral auxiliary, axially chiral vinylallenes with excellent enantiopurity (up to >99% enantiomeric excess (ee)) were readily prepared from optically pure propargylamines in the presence of AgNO 3 under microwave irradiation. Subsequent (hetero)-Diels−Alder reaction of these axially chiral vinylallenes with azodicarboxylates or maleimides on water demonstrates excellent axial-to-point chirality transfer (up to 99% ee).

Rhodium(I)‐Catalyzed Three‐Component [4+2+1] Cycloaddition of Two Vinylallenes and CO

“…Many important skeletons or potentially useful compounds in drug discovery have been synthesized by these methods [5] . Especially, intermolecular or intramolecular cycloaddition reactions using vinylallenes, such as [4+1], [1a–f] [4+2], [1g–m] [4+4], [1n] [4+4+1], [1o] and [3+2]/[2+3] [1p] cycloadditions, developed, respectively by Siegel et al., Murakami et al., and Lee and co‐workers, have become powerful methods to synthesize various ring compounds (Scheme 1 a). It is interesting to note that all these ring formation reactions (except one in Scheme 1 b, see below) using vinylallenes cannot be used to synthesize seven‐membered rings.…”

Impact of Microwaves on Organic Synthesis and Strategies toward Flow Processes and Scaling Up

“…As depicted in Scheme 20 A, vinylallenes can be obtained enantioselectively from the alkyne in the presence of a chiral auxiliary under MW irradiation. 102 Optically active propargylammine, in which ( S )-prolinol was the stereogenic group, reacted in the presence of AgNO 3 in acetonitrile at 70 °C under MW irradiation (50 W) in 20 min. The reaction proceeded to generate the desired allene derivatives in 70% average yield, exemplified by a series of 11 cases with high stereoselectivity (79 → 99% ee).…”

One-Pot Access to 1,7a-Dihydro-1,3a-ethano-indene and 1,8a-Dihydro-1,3a-ethano-azulene Skeletons by a Sequential Gold(I)-Catalyzed Propargyl Claisen Rearrangement/Nazarov Cyclization/[4+2] Cycloaddition Reaction

“…The rest of the solution was diluted with MeOH and treated with NaBH 4 to reduce the aldehyde to alcohol 7 , to avoid isomerization of the double bond during chromatography . Although vinyl allenes are known to readily react with dienophiles, in fact, no traces of products deriving from the reaction of the maleimide with the vinyl allene from I (Scheme ) were detected, consistent with the fast ring closure step of the latter to give diene 2a (R = Me, n = 1). While allene intermediates can be isolated in the tandem Claisen rearrangement/hydroarylation reaction of 3-aryl-substituted vinyl allenes, with substrates of type 1 , only the Nazarov product intermediate 2 can be observed while monitoring the reaction by 1 H NMR.…”