Nessan J. Kerrigan

Phosphine-Catalyzed Asymmetric Synthesis of β-Lactones from Arylketoketenes and Aromatic Aldehydes

In this paper, the development of a chiral phosphine-catalyzed formal [2 + 2] cycloaddition of aldehydes and ketoketenes that provides access to a variety of highly substituted beta-lactones (14 examples) is reported. The BINAPHANE catalytic system displays excellent enantioselectivity (seven examples with ee >or=90%) and high diastereoselectivity favoring formation of the trans-diastereomer (nine examples with dr >or=90:10).

BINAPHANE-Catalyzed Asymmetric Synthesis of trans-β-Lactams from Disubstituted Ketenes and N-Tosyl Arylimines

The development of a BINAPHANE-catalyzed formal [2 + 2]-cycloaddition of disubstituted ketenes and inexpensive N-tosyl arylimines that provides access to a variety of highly substituted β-lactams (16 examples) is described. The BINAPHANE catalytic system displays moderate to excellent enantioselectivity (up to 98% ee) and high diastereoselectivity in most cases, favoring formation of the trans-diastereomer (13 examples with dr ≥ 90:10).

Josiphos-Catalyzed Asymmetric Homodimerization of Ketoketenes

In this paper the development of a chiral phosphine-catalyzed homodimerization of ketoketenes that provides access to a variety of highly substituted ketoketene dimer β-lactones (11 examples) is reported. The Josiphos catalytic system displays good to excellent enantioselectivity (up to 96% ee). Ring-opening reactions of the enantioenriched ketoketene dimers were also carried out to access 1,3-diketones, enol esters, and β-hydroxyketones with good diastereoselectivity.

Catalytic asymmetric heterodimerization of ketenes.

In this Communication we describe an unprecedented catalytic asymmetric heterodimerization of ketenes of wide substrate scope. The alkaloid-catalyzed method provides access to ketene heterodimer β-lactones and allows even two different monosubstituted ketenes to be cross-dimerized, with excellent enantioselectivity (17 examples with ≥90% ee) and excellent heterodimer regioselectivity observed in all cases.

Organocatalytic Dimerization of Ketoketenes

A general method for the catalytic dimerization of ketoketenes is described. Tri-n-butylphosphine was found to be the optimal organocatalyst for the racemic reaction. When lithium iodide was used as an additive, the reaction was rendered selective for dimer formation (dimer/trimer > or = 16:1). Ring-opening reactions of the ketoketene dimers as well as preliminary studies toward the development of an asymmetric variant are also reported.

Asymmetric alkene epoxidation with chromium oxo salen complexes. Effect of added phosphoryl ligands

Abstract In the stoichiometric asymmetric epoxidation of E -β-methylstyrene with cationic chromium–salen oxo complexes, enantioselectivity is elevated by the addition of many different types of phosphoryl compounds. Triarylphosphine oxides are the most effective, and, amongst them, tris(3,5-dimethylphenyl)phosphine oxide gave the highest ee to date (93%). There is a ceiling effect of additive, bulky additives are ineffective, there is no substituent electronic effect within the additive and there is a saturation of its effect with increasing concentration.

Alkaloid-Catalyzed Enantioselective [3 + 2] Cycloaddition of Ketenes and Azomethine Imines

A new asymmetric synthesis of bicyclic pyrazolidinones through an alkaloid-catalyzed formal [3 + 2] cycloaddition of in situ generated ketenes and azomethine imines is described. The products were formed in good to excellent yields (52-99% for 17 examples), with good to excellent diastereoselectivity (dr 5:1 to 27:1 for 11 examples), and with excellent enantioselectivity in all cases (≥96% ee). This method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.

Phosphine-Catalyzed Asymmetric Synthesis of β-Lactones from Disubstituted Ketenes and Aldehydes

In this article we describe a general catalytic procedure for the formation of β-lactones bearing two stereogenic centers, from disubstituted ketenes and achiral aldehydes. BINAPHANE was found to display excellent enantioselectivity (≥90% ee for eight examples) and good diastereoselectivity (≥90:10 for 13 examples) in catalyzing the formation of β-lactones bearing two stereogenic centers from achiral aldehydes (both aromatic and aliphatic) and alkylarylketenes or dialkylketenes. A preference for formation of the trans diastereomer was observed in these reactions. For those reactions where BINAPHANE failed as a catalyst, tri-n-butylphosphine was found to be an effective achiral nucleophilic catalyst, effecting good yield and diastereoselectivity in racemic β-lactone formation. Evidence for the involvement of phosphonium enolate intermediates in the reaction mechanism was obtained through reaction monitoring by (31)P NMR spectroscopy and by comparison with previously characterized intermediates observed in the phosphine-catalyzed ketene homodimerization reaction.

Phosphine-Catalyzed Diastereoselective Synthesis of β-Lactones from Disubstituted Ketenes and α-Chiral Oxyaldehydes

In this article we describe a catalytic procedure for the diastereoselective synthesis of β-lactones bearing two stereogenic centers, from disubstituted ketenes and α-chiral oxyaldehydes. Tri-n-butylphosphine was found to be the optimal catalyst in terms of effecting both good yield and diastereoselectivity (dr from 3:1 to 32:1 for 8 examples) in β-lactone formation. The major isomer of the β-lactone products was determined to be the anti-diastereomer, and its formation was rationalized by a polar Felkin-Anh model. Involvement of phosphonium enolate intermediates in the reaction mechanism was indicated through reaction monitoring by (31)P NMR spectroscopy. The utility of the methodology is demonstrated by a short synthesis of a (+)-peloruside A synthon.

Asymmetric Synthesis of Deoxypropionate Derivatives via Catalytic Hydrogenolysis of Enantioenriched Z-Ketene Heterodimers.

A diastereoselective approach to deoxypropionate derivatives through Pd/C-catalyzed hydrogenolysis of enantioenriched ketene heterodimers is described. Catalytic hydrogenolysis of the Z-isomer of ketene heterodimers facilitates access to anti-deoxypropionate derivatives (10 examples with dr 7:1 to >20:1). Transfer of chirality from the Z-ketene heterodimer to an acid product was good to excellent in most cases (78-99% ee for 12 examples).