Catalytic Asymmetric Synthesis of <i>anti-</i>1,2-Diols

Catalytic Asymmetric Synthesis of anti-1,2-Diol

De Novo Synthesis of a Methylene-Bridged Neu5Ac-α-(2,3)-Gal <i>C</i>-Disaccharide

A general strategy toward the synthesis of C-ketosides of N-acetylneuraminic acid (Neu5Ac) has been developed and successfully applied to the synthesis of methylene-bridged Neu5Ac-α-(2,3)-Gal C-disaccharide 2. The key strategic element of this novel approach is a stereoselective, 6-exo-trig selective, electrophilic cyclization of the appropriate open chain precursor 4 by means of phenylselenyl triflate. The open chain precursor was formed by the addition of lithiated iodide 18 accessible from d-galactose to open chain aldehyde 5a obtained from d-glucono-δ-lactone by chain elongation. Subsequent C1-incorporation using Tebbe-reagent, formation of a cyclic carbonate, and deprotection of the two isopropylidene ketals afforded tetrol 4 which, upon treatment with phenylselenyl triflate, was stereoselectively cyclized in a 6-exo-trig selective manner. A selena-Pummerer rearrangement, oxidation, and esterification readily led to methyl ester 37 which, after deacetylation, could be regioselectively tetrabenzoylated with benzoyl cyanide. Triflate activation of the axial hydroxyl group in 40 and nucleophilic displacement by azide ion with inversion of configuration afforded azide 41, which was reduced with hydrogen and Pearlman's catalyst. Concomitant removal of the benzyl ethers and subsequent saponification of all ester moieties successfully completed the de novo synthesis of the desired methylene bridged Neu5Ac-α-(2,3)-Gal C-disaccharide 2

A Highly Enantioselective Amino Acid-Catalyzed Route to Functionalized α-Amino Acids

The development of syntheses providing enantiomerically pure α-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized α-amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected α-imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized α-amino acids in high yields with excellent regio-, diastereo-, and enantioselectivities. Study of seven examples yielded six with product ee values of ≥99%. In reactions involving ketone donors where diastereoisomeric products could be formed, two adjacent stereogenic centers were created simultaneously upon carbon−carbon bond formation with complete syn-stereocontrol. Significantly, this methodology utilizes readily available and rather inexpensive starting materials, does not require any preactivation of substrates or metal ion assistance, and can be carried out on a gram scale under operationally simple reaction conditions. The keto-functionality present in the products provides a particularly attractive site for versatile modifications. This study compliments and extends our bioorganic approach to asymmetric synthesis to a versatile synthon class. Given that we have shown that a variety of optically active amino acids can be synthesized with proline catalysis, where an l-amino acid begets other l-amino acids, our results may stimulate thoughts concerning prebiotic syntheses of optically active amino acids based on this route

A Highly Enantioselective Route to Either Enantiomer of Both α- and β-Amino Acid Derivatives

This report describes the unprecedented use of unmodified aldehydes as donors in a catalytic asymmetric Mannich-type reaction. The proline-catalyzed reaction of N-PMP-protected α-imino ethyl glyoxylate with unmodified aliphatic aldehydes provided a general and very mild entry to either enantiomer of β-amino and α-amino acids and derivatives in high yield and stereoselectivity. Six of the seven aldehydes studied yielded products with ee values of 99% or greater. The diastereoselectivity of the reaction increased with the bulkiness of the substituents of the aldehyde donor in the order R = Me i-Pr n-Pent. In five of the cases studied, excellent syn stereoselectivities were achieved. In addition, the corresponding chiral β-amino aldehyde adducts can be readily converted to the corresponding amino acid derivatives. Most significantly, this approach provides facile access to substituted β-lactams

The Direct Organocatalytic Asymmetric Mannich Reaction: Unmodified Aldehydes as Nucleophiles

The unprecedented application of unmodified aldehydes as nucleophilic donors in direct catalytic asymmetric Mannich-type reactions is disclosed in a full account. Our efforts in broadening the applicability of chiral pyrrolidine-based catalysts in direct asymmetric Mannich-type reactions led to the highly diastereo- and enantioselective and concise synthesis of functionalized α- and β-amino acids, β-lactams, and amino alcohols