Bicyclic Cyclopentenones via the Combination of an Iridium‐ Catalyzed Allylic Substitution with a Diastereoselective Intramolecular Pauson–Khand Reaction

Abstract

Enantioselective syntheses of bicyclic cyclopentenones are described. Key steps are an iridium-catalyzed allylic substitution and an intramolecular diastereoselective Pauson-Khand reaction. The diastereoselectivity of the Pauson-Khand reaction was found to be crucially dependent on the unit connecting the propargylic and the olefinic parts of the precursor. Very high degrees of diastereoselection were obtained with an NBoc unit as connector. This methodology has been illustrated by application within an enantioselective formal total synthesis of (À)-a-kainic acid.

Enantio-, Diastereo-, and Regioselective Iridium-Catalyzed Asymmetric Allylic Alkylation of Acyclic β-Ketoesters

“…To the best of our knowledge, substrate 1q represents the first example of nucleophile bearing propargyl substitution to undergo Ir-catalyzed allylic substitutions. 20 Nitrile-containing substituents were tolerated in the reaction as well (substrate 1t ), and α- quaternary β-ketoester 3t was furnished in excellent yield, ee and regioselectivity, albeit with diminished dr (3:1). We were pleased to learn that use of α-halogenated nucleophiles (substrates 1u and 1v ) also resulted in an efficient and selective reaction as α-fluoro and α-chloro β-ketoesters 3u and 3v were obtained in excellent yields, dr, ee and regioselectivity.…”

“…Pauson–Khand cyclization of progaryl-substituted β-ketoester 3q smoothly delivered bicycle 6 . 20b Finally, ring closing metathesis of diallyl β-ketoester 3p cleanly furnished cyclohexene 7 .…”

An Improved Class of Phosphite-Oxazoline Ligands for Pd-Catalyzed Allylic Substitution Reactions

“…In this respect, a broad range of malonates, containing allyl, butenyl, pentenyl, and propargyl groups, alkylated S1 to give compounds 22 – 28 in excellent yields and enantioselectivities (ee’s ≥99%). These results are relevant since the resulting products ( 22 – 28 ) are crucial intermediates for preparing more complex chiral compounds (for some of their applications see synthetic applications section, vide infra) . The use of malononitrile (compound 29 ) and acetylacetone (compound 31 ) also gave the desired alkylated products in excellent enantioselectivities (>99% ee).…”

Application of Pauson–Khand reaction in the total synthesis of terpenes

“…After several steps, the latter was transformed into enyne 140 as a sole isomer. Then, the latter was subjected to PKR conditions which upon treatment with Co 2 (CO) 8 in the presence of Celite 138 in refluxing toluene afforded cyclopentenone subunit 141 bearing an all-carbon quaternary chiral centers. After several steps, the latter was converted to a mixture of 148, 149 and 150/151.…”