Current Organic Chemistry - Volume 7, Issue 4, 2003

In this era of heightened environmental awareness and ever-increasing demand for higher efficiency from chemical processes, one of the major challenges facing organic synthesis is the utilization of abundantly available carbon sources as precursors for more advanced intermediates. The dual problems of activation of thermodynamically stable precursors and their stereoselective incorporation pose new challenges, solutions of which may have broader implications in asymmetric catalysis. This review summarizes our recent efforts to discover broadly applicable control elements in key enantioselective carbon-carbon and carbon-hydrogen bondforming reactions. Transition metal complexes of 1,2-diol phosphinites derived from readily available monosaccharides catalyze a variety of asymmetric reactions of prochiral olefins including Markovnikov addition of HCN to vinyl arenes and hydrogenation of dehydroamino acids. Enantioselectivities of these reactions can be optimized through steric and electronic tuning of the bis-phosphinite ligand system. Both R and S enantiomers of the precursors of protoptypical 2-arylpropionic acids and of various α-amino acids can be prepared by these routes. We have also discovered new protocols for a nearly quantitative and highly selective codimerization of ethylene or propylene, and various functionalized vinylarenes and strained olefins. Various strategies for stereochemical control in an enantioselective version of this reaction will be discussed. These include design and synthesis of new ligands and applications of the ‘hemi-labile ligand concept’. During these investigations important synergistic relationships between such ligands and coordinating properties of various counter ions were also uncovered. These discoveries may contribute to the discovery of more selective homogeneous catalysts.

Palladium catalyzed allylic alkylations are important reactions in organic synthesis. In general stabilized carbanions are used as soft C-nucleophiles. Nonstabilized enolates from ketones and esters often cause problems, and the developments and improvements made with these interesting nucleophiles are summarized in this review.With respect to ketone enolates, best results are obtained with the corresponding tin derivatives, but enoxy-borates also can be used. With ketone enolates α-allylated products are obtained. In the presence of suitable chiral ligands, the optically active substitution products are obtained with high stereoselectivity. In contrast, sterically hindered ester enolates do not provide allylation products, but give rise to cyclopropane deriva-tives. This can be explained by an attack of the enolate at the central carbon atom of the intermediatly formed π-allyl complex. In contrast, if silylketene acetals are used as nucleophiles, or vinylepoxides as ally-lic substrates, the α-allylated products are obtained. This is also true with more or less stabilized enolates derived from pyrazinones or azlactones, giving rise to α-alkylated amino acid derivates. “Normal” unsatu-rated amino acids can be obtained by using chelated amino acid ester enolates as nucleophiles. This enolates show a high reactivity and therefore these reactions can be carried out under very mild conditions, condi-tions under which the π-σ-π-isomerization of the π-allyl intermediates can be suppressed. This opens up totally new synthetic posibilities. In the presence of chiral ligands optically active amino acids are obtaine

The author's work in the use of cyclopropylcarbene-transition metal complexes is summarized in this manuscript. Reactions leading to the formation of cyclopentenones, cycloheptadienones, and highly functionalized vinylic iodides have been developed based on various processes that result in opening of the cyclopropane ring.

The rhodium-catalyzed intramolecular hydroacylation of unsaturated aldehydes leads to the formation of cyclopentanone derivatives. The cyclization catalyzed by Wilkinson's complex is highly diastereoselective, and via this reaction, 3,4-disubstituted 4-pentenals were used to prepare the four stereoisomers of 3,4-disubstituted cyclopentanones. Several biologically active molecules, including 8- isoprostanoic acid, prostanoic acid, (-)-brefeldin A, 11-deoxyprostaglandin, and the nepetalactones,, have been synthesized in enantiomerically pure form from these cyclopentanones. In this review, the asymmetric synthesis of cyclopentanones via the enantioselective cyclization catalyzed by rhodium complex incorporating optically active ligands will be discussed.

The objective of this review is to survey the current state of the Wacker and related alkene oxidation reactions focusing on the reactions of higher alkenes and emphasizing the mechanistic pictures that have evolved, the current understanding regarding issues of selectivity, recent applications of the chemistry in synthesis, and the use of other transition metal catalysts to effect related oxidation reactions.