Three‐Component Sequential Aza[4+2] Cycloaddition/Allylboration/Retro‐Sulfinyl‐Ene Reaction: A New Stereocontrolled Entry to Palustrine Alkaloids and Other 2,6‐Disubstituted Piperidines

Abstract

Multicomponent reactions [1] that generate complex, functionalized structures from simple substrates are very attractive step-economical strategies in target-oriented synthesis.[2] We have recently reported on the three-component hetero [4+2] cycloaddition/allylboration reaction [3] for the preparation of a-hydroxyalkylated piperidines [4] and furans [5a] (Scheme 1). In the case of piperidines, this one-pot process is initiated by a hetero-Diels-Alder reaction between boronate-substituted hydrozonobutadienes (1) and electron-poor dienophiles. The formation of the resulting cycloadduct unmasks an allylboronate that adds in situ onto aldehydes to provide polysubstituted piperidine products in a highly stereoselective fashion.We were interested in the challenge of adapting this process to access 2,6-disubstituted piperidine units [6] such as those featured in the palustrine class of alkaloids exemplified

OC165: Crux of the heart in fetuses: echo-histological correlations

“…Besides the cross‐coupling reactions, alkenyl and dienyl boronic acids participate in Diels–Alder reactions leading to boron containing adducts, which can be easily transformed into highly functionalized systems. Dialkoxyboryl 1,3‐butadiene derivatives, with the borate ester at C22 and C1,3 have been reported to react with typical dienophiles and heterodienophiles,4 whereas 3‐boronoacrolein derivatives5 and their imino analogues6 behave as heterodienes. Alkenyl boranes7 and boronates8 reacted as dienophiles9 leading to highly regio‐ and endo ‐selective cycloaddition products.…”

Cycloadditions with StereoselectiveCNBond Formation in Total Syntheses

“…62 This strategy has allowed for the synthesis of (-)-methyl dihydropalustramate 148 (Scheme 41.31), a degradation product of the toxic alkaloid palustrine of marsh horse tail Equisetum palustre. 63 The reaction of 4-borono-1-hydrazonodiene 142, Waldner sulfinimide dienophile 143, 64 and propanal 141 at 80 C during 70 hours allowed for the isolation of only one diastereoisomer of the 2,6-disubstituted piperidine derivative 147. The hetero Diels-Alder proceeded via an endo approach 144 of the dienophile to the azadiene from the face opposite of the SÀO bond.…”

Synthesis of Benzo‐ and Naphthoquinonyl Boronic Acids: Exploring the Diels–Alder Reactivity

“…4 The C‐2‐boron‐substituted 1,3‐butadienyl derivatives5 afforded alkenyl boron cycloadducts that have been also used in subsequent palladium cross‐coupling reactions 6. β‐Boronoacrolein pinacolates7 and their imino analogues8 behave as oxa‐ and azadienes to afford to dihydropyran or piperidine heterocycles, respectively. Alkenyl boranes9 and boronates10 are reactive dienophiles giving highly regio‐ and endo‐selective cycloadditions 11.…”