Catalytic Enantioselective Quick Route to Aldol‐Tethered 1,6‐ and 1,7‐Enynes from ω‐Unsaturated Aldehydes

Abstract

An effective asymmetric route to functionalized 1,6- and 1,7-enynes has been developed based on a direct cross-aldol reaction between ω-unsaturated aldehydes and propargylic aldehydes (α,β-ynals) promoted by combined α,α-dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio- and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,β-ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols. The utility of these adducts, which are difficult to prepare through standard methodology, is demonstrated by their transformation into trisubstituted bicyclic enones using standard Pauson-Khand conditions.

Conjugated Ynones in Organic Synthesis

“…When the aldehyde has a C C bond in the chain [R = CH 2 CH(CH 2 ) 2 ], a Pauson-Khand reaction gave the expected cyclopentenone derivatives in an enantiomerically almost pure products. 525 The Pauson-Khan cyclization was the key step in the formation of a tetracyclic system from the reaction of ynone 713 with cyclobutene acyloin 714. The process starts with conversion of the ynone into cyclopentadione 715 by reaction with 714 promoted by boron trifluoride (Scheme 316).…”

“…By using chiral ligand 711 and benzoic acid in substoichiometric amounts, the corresponding products ( 712 ) were isolated after acetalization (Scheme ). When the aldehyde has a CC bond in the chain [R = CH 2 CH­(CH 2 ) 2 ], a Pauson-Khand reaction gave the expected cyclopentenone derivatives in an enantiomerically almost pure products …”