A new one-pot approach to synthesize densely substituted racemic and enantiopure pyrroles from beta-lactams has been developed. The approach relies on the regiocontrolled cyclization of beta-allenamine intermediates derived from the ring opening of 2-azetidinone-tethered allenols. In this approach four points of diversity are introduced, one of which is the position of the allene moiety on the beta-lactam ring.

Versatile routes that lead to a variety of functionalized enantiopure tetrahydrofurans, dihydropyrans, and tetrahydrooxepines are based on chemo-, regio-, and stereocontrolled metal-catalyzed oxycyclization reactions of β,γ- and γ,δ-allendiols, which were readily prepared from (R)-2,3-O-isopropylideneglyceraldehyde. The application of Pd(II), Pt(II), Au(III), or La(III) salts as the catalysts gives controlled access to differently sized oxacycles in enantiopure form. Usually, chemoselective cyclization reactions occurred exclusively by attack of the secondary hydroxy group (except for the oxybromination of phenyl β,γ-allenic diols 3b and 3d) to an allenic carbon atom. Regio- and stereocontrol issues are mainly influenced by the nature of the metal catalysts and substituents.

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Abstract:The regioselective metal/acid co-catalyzed direct bis-oxycyclization of alkynyldioxolanes allows the efficient synthesis of optically pure biand tricyclic bridged acetal systems.

2‐Azetidinone‐tethered alkynols, readily prepared from the corresponding aldehydes or ketones, were used as starting materials for the oxycyclization reaction catalyzed by precious metals. AgOAc exclusively affords dihydrofurans, methylenetetrahydrofurans, or methylenetetrahydro‐2H‐pyrans through specific 5‐endo, 5‐exo, or 6‐exo pathways, respectively. Interestingly, in the presence of a catalytic amount of PtII or AuIII salts, cyclization reactions occurred preferentially through a tandem oxycyclization/hydroxylation of alkynols to afford a variety of nonfused, spiranic and fused oxabicyclic β‐lactams in moderate to high yields. Besides, it has been observed that the tandem gold‐catalyzed cycloetherification/hydroxylation of a methoxymethyl alkynyl ether can be accomplished.

A mild, palladium(II)-catalyzed reaction of alpha-allenols with alpha-allenic esters in a heterocyclization/cross-coupling sequence, applicable to a wide range of substitution patterns, has been developed for the preparation of 2,3,4-trifunctionalized 2,5-dihydrofurans. Our studies indicate high levels of chemo- and regiocontrol. The possibility of using optically active substrates as well as substrates of increased steric demand, such as tertiary alpha-allenols, makes this novel sequence of heterocyclization/cross-coupling an attractive method in organic synthesis. The current mechanistic hypothesis invokes a regiocontrolled palladium(II)-mediated intramolecular oxypalladation of the free allenol component, that then undergoes a cross-coupling reaction with the allenic ester partner, followed by a trans-beta-deacyloxypalladation with concomitant regeneration of the Pd(II) species.

Positive discrimination: Chemo- and regioselective palladium-catalyzed cycloetherification of allendiols, namely beta,gamma- and gamma,delta-allendiols, may occur by judicious choice of palladium-catalyzed conditions owing to their potential ability to discriminate between both nucleophilic sites (see scheme).