https://chemistry.mdma.ch/hiveboard/rhodium/pdf/archive/merbst/quinoline1999.pdf

Quinoline, quinazoline and acridone alkaloids

Asymmetric 1,3-Dipolar Cycloaddition Reactions

The Diels-Alder reaction has both enabled and shaped the art and science of total synthesis over the last few decades to an extent which, arguably, has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Diels-Alder cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.

https://www.ch.ic.ac.uk/local/organic/pericyclic/DA.pdf

The Diels--Alder reaction in total synthesis.

Introduction Cationic domino reactions Anionic domino reactions Radical domino reactions Pericyclic domino reactions Photochemically induced domino processes Transition metal catalysis Domino reactions initiated by oxidation or reduction Enzymes in domino reactions Multicomponent reactions Special techniques in domino reactions

Domino Reactions in Organic Synthesis

Asymmetric fluorination, trifluoromethylation, and perfluoroalkylation reactions.

Both enantiomers of the menthyl half-esters (10) and (23) of ethylmalonic acid were converted into(+)-(4S,5R)-4-(2-benzyloxyethyl)-5-ethyl-3,4,5,6-tetrahydro-2-pyrone (18). A mixture of the trans-(18) and cis-lactones (19) in a ratio of ca. 4 : 1 was prepared by way of radical cyclisation of the (E)-α,β-unsaturated esters (16), while the former (18) was synthesised with high stereoselection by the cyclisation of the (Z)-esters (26). The lactone (18) was enantioselectively transformed into (–)-protoemetimol (5) and (–)-protoemetine (4), correlated to (–)-emetine (1) and (–)-tubulosine (3).

Asymmetric total synthesis of(–)-protoemetinol,(–)-protoemetine,(–)-emetine, and (–)-tubulosine by highly stereocontrolled radical cyclisations

A Novel Domino Route to Chiral Cyclobutanones and its Function as Cornerstone in the Synthesis of Versatile Natural Products

A Rapid Access to Both Enantiomers of 1,2,3,4-Tetranor B-Trienic 18,18,18-Trifluorosteroids. The First Enantiocontrolled Total Synthesis of 18,18,18-Trifluorosteroids

Stereocontrolled one-step syntheses of octahydroquinolizine and octahydroindolizine derivatives from α,β-unsaturated enamide esters was achieved under two different conditions; heating in the presence of chlorotrimethylsilane, triethylamine, and zinc chloride at 180–185 °C, and treatment with dimethyl-t-butylsilyl trifluoromethanesulphonate in the presence of triethylamine at –78 to 20 °C. A simple synthesis of an alkaloid, (±)-epilupinine, was accomplished. Hexahydrobenzo[a]-quinolizin-4-ones and an octahydroindolo[2,3-a]quinolizin-4-one were also constructed by the same method.

Stereocontrolled construction of octahydroquinolizines, octahydroindolizines, hexahydrobenzo[a]quinolizines, and an octahydroindolo[2,3-a]quinolizine by an intramolecular double Michael reaction: synthesis of (±)epilupinine

Fluorination of methyl (1R,3R,4S)-8-phenylmenthyl methylmalonates 2 using lithium hexamethyl-disilazide and 1-fluoro-2,4,6-trimethylpyridinium triflate (trifluoromethanesulfonate), gave the (R)-3 and (S)-4 isomers in a 3.8 : 1 ratio, while fluorination of ethyl-, propyl- and benzyl-malonates 10, 11 and 12 provided the (R)-13, 15 and 17 and (S)-14, 16 and 18 isomers in a 1 : 1.6–2.0 ratio. On the other hand, alkylation of (1R,3R,4S)-8-phenylmenthyl hydrogen fluoromalonates 26 in the presence of lithium hexamethyldisilazide, followed by esterification with diazomethane, produced the (R)-3,13,15,17- and 27 and (S)-4,14,16,18 and 28 isomers in a 1 : 5.7–35 ratio.

Keiichiro Fukumoto

Papers

Asymmetric total synthesis of(–)-protoemetinol,(–)-protoemetine,(–)-emetine, and (–)-tubulosine by highly stereocontrolled radical cyclisations

A Novel Domino Route to Chiral Cyclobutanones and its Function as Cornerstone in the Synthesis of Versatile Natural Products

A Rapid Access to Both Enantiomers of 1,2,3,4-Tetranor B-Trienic 18,18,18-Trifluorosteroids. The First Enantiocontrolled Total Synthesis of 18,18,18-Trifluorosteroids

Stereocontrolled construction of octahydroquinolizines, octahydroindolizines, hexahydrobenzo[a]quinolizines, and an octahydroindolo[2,3-a]quinolizine by an intramolecular double Michael reaction: synthesis of (±)epilupinine

Enantioselective construction of quaternary stereogenic centres possessing a fluorine atom