The hetero Diels-Alder reaction is one of the most important methods for the synthesis of heterocycles. In this article an overview is given for the period since 1989 describing the reaction of heterobutadienes such as oxabutadienes, thiabutadienes, azabutadienes, diaazabutadienes, nitroso-alkenes and nitroalkenes as well as of heterodienophiles such as carbonyls, thiocarbonyls, imines, iminium salts, azo- and nitroso compounds. In addition, several other less common hetero Diels-Alder reactions such as cycloadditions of thiaazabutadienes, oxaazabutadienes, dioxabutadienes, dithiabutadienes, oxathiabutadienes, diazaoxabutadienes as well as the use of N-sulfinyl-phosphaalkynes and other dienophiles are mentioned. A main point of discussion is the stereoselectivity of the reactions and the preparation of enantiopure compounds either using dienes and dienophiles carrying a chiral auxiliary or employing chiral Lewis acids. A point stressed is the synthesis of natural products using hetero Diels-Alder reactions leading to carbohydrates, alkaloids, terpenes, antibiotics, mycotoxins, cytochalasans, antitumor agents and several other classes of natural products.

Hetero diels-alder reactions in organic chemistry

Strategy and methodology development for the total synthesis of polyether ionophore antibiotics.

Under the conditions of transfer hydrogenation employing an iridium catalyst generated in situ from [Ir(cod)Cl]2, chiral phosphine ligand (R)-BINAP or (R)-Cl,MeO-BIPHEP, and m-nitrobenzoic acid, allyl acetate couples to allylic alcohols 1a−c, aliphatic alcohols 1d−l, and benzylic alcohols 1m−u to furnish products of carbonyl allylation 3a−u with exceptional levels of asymmetric induction. The very same set of optically enriched carbonyl allylation products 3a−u are accessible from enals 2a−c, aliphatic aldehydes 2d−l, and aryl aldehydes 2m−u, using iridium catalysts ligated by (−)-TMBTP or (R)-Cl,MeO-BIPHEP under identical conditions, but employing isopropanol as a hydrogen donor. A catalytically active cyclometallated complex V, which arises upon ortho-C−H insertion of iridium onto m-nitrobenzoic acid, was characterized by single-crystal X-ray diffraction. The results of isotopic labeling are consistent with intervention of symmetric iridium π-allyl intermediates or rapid interconversion of σ-allyl hapto...

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Enantioselective Iridium Catalyzed Carbonyl Allylation from the Alcohol or Aldehyde Oxidation Level via Transfer Hydrogenative Coupling of Allyl Acetate: Departure from Chirally Modified Allyl Metal Reagents in Carbonyl Addition

Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.

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Structure elucidation of colibactin and its DNA cross-links

Unstable? We're able! 1,n-Glycols serve as synthetic equivalents to unstable dialdehydes in two-directional carbonyl allylation from the alcohol oxidation level under iridium-catalyzed transfer hydrogenation conditions. Iterative asymmetric allylation employing 1,3-propanediol enables the rapid assembly of protected 1,3-polyol substructures with exceptional levels of stereocontrol.

1,n‐Glycols as Dialdehyde Equivalents in Iridium‐Catalyzed Enantioselective Carbonyl Allylation and Iterative Two‐Directional Assembly of 1,3‐Polyols

The syntheses of the spiroketal II and tricyclic glycal III portions of the polyether antibiotic monensin (I) are described. The butyric acid side chain of spiroketal II is constructed through either Sharpless epoxidation of a cis-2-butenol residue or by Brown crotylation of an α-methylacetaldehyde unit. The spiroketal is then generated through a hetero-Diels-Alder addition between a tetrahydropyranoid methylene ketone and acrolein. Finally, [6.5] - spiroketal structure II is prepared by mild acid catalyzed rearrangement of [6.6]-spiroketal epoxide 23. Glycal III was made from the C/D subunit 44. This subunit was prepared by the ester enolate Claisen rearrangement that unites the tetrahydrofuranoid C and D rings 40 and 41 by Brown crotylation, Wittig condensation, and then cyclization to form the E ring. The synthesis of the two fragments set the stage for a final ester enolate Claisen rearrangement that will form the skeleton of the polyether monensin (I)

Convergent synthesis of polyether ionophore antibiotics: Synthesis of the spiroketal and tricyclic glycal segments of monensin

The protective manipulation and synthesis of the polyether antibiotic monensin is described. The hydroxyl groups and the carboxylic acid of monensin are protected, and its spiroketal is equilibrated to provide naturally derived, advanced targets for comparison to the synthetic materials. The total synthesis of these targets from spiroketal acids 3ax and 3eq and tricyclic glycal 4 by a highly convergent ester enolate Claisen rearrangement is described. Finally, the deprotection of each to monensin is described

Robert S. Meissner

Papers

Convergent synthesis of polyether ionophore antibiotics: Synthesis of the spiroketal and tricyclic glycal segments of monensin

Convergent synthesis of polyether ionophore antibiotics: protective manipulation and synthesis of monensin A

Convenient method for the titration of amide base solutions

Convenient Method for the Titration of Amide Base Solutions.

Convergent Synthesis of Polyether Ionophore Antibiotics: Synthesis of the Spiroketal and Tricyclic Glycal Segments of Monensin.