In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

Molecular Clusters of π-Systems: Theoretical Studies of Structures, Spectra, and Origin of Interaction Energies

Wenn man die Entwicklung der organischen Chemie betrachtet, kommt man schnell zu dem Schluss, dass kein Reaktionstyp dieses Gebiet in vergleichbarer Weise gepragt hat wie die Kohlenstoff-Kohlenstoff-Kupplungen. Grignard-, Diels-Alder- und Wittig-Reaktionen sind nur drei herausragende Beispiele fur solche Prozesse, die im vergangenen Jahrhundert zweifellos entscheidend am Aufstieg der chemischen Synthese beteiligt waren. Im letzten Viertel des 20. Jahrhunderts bereicherte eine neue Familie von leistungsfahigen Reaktionen zur Knupfung von Kohlenstoff-Kohlenstoff-Bindungen das Repertoire der Synthesechemie: die ubergangsmetallkatalysierten Reaktionen, allen voran die palladiumkatalysierten Kreuzkupplungen. In diesem Aufsatz werden Auszuge aus einer Reihe von ausgewahlten Synthesen diskutiert. Die Beispiele sollen die enorme Leistungsfahigkeit dieser Prozesse in der Kunst der Totalsynthese aufzeigen und ihr Potenzial fur zukunftige chemische Synthesen unterstreichen.

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Palladiumkatalysierte Kreuzkupplungen in der Totalsynthese

Structures of Van der Waals complexes are predicted by a simple model based on electrostatic interaction between the monomers. Point multipoles are assigned to the atoms and embedded in hard sphere...

A model for the geometries of Van der Waals complexes

Synthesis of piperidines

Matrix infrared spectrum of the ammonia-hydrogen fluoride hydrogen-bonded complex

The hydrogen‐bonded complexes OC–HX (X=F, Cl, Br) has been prepared by condensing Ar/HX and Ar/CO reagent mixtures at 12 K. FTIR spectra of the complexes are characterized by strong H–X absorptions (νs) displaced below the isolated HX fundamental, strong C–O absorptions displaced above the isolated CO fundamental, and sharp degenerate librational modes (νl) in the far infrared. Observation of a single degenerate νl mode indicates linear structures for the complexes. The displacements Δνs and ΔνCO for the complexes decrease in magnitude in the series HF≳HCl≳HBr in direct relationship with the trend in hydrogen bonding strength for the hydrohalic acids.

Infrared spectra of OC–HX hydrogen‐bonded complexes in solid argon

Infrared spectra of hydrogen-bonded .pi. complexes between hydrogen halides and acetylene

Codeposition of argon diluted samples of CO2 and HF at 12 K produced new absorptions at 3871, 2354, 656, and 313 cm−1 which are assigned to the CO2⋅⋅⋅HF complex. The 3871 and 313 cm−1 absorptions are due to the H–F stretching and librational motions of the HF submolecule in the complex, as verified by DF substitution, and the 2354 and 656 cm−1 bands are due to CO2 submolecule modes. The N2O⋅⋅⋅HF complex spectrum contained bands at 3851, 2250, 1306, 583, 328, and 325 cm−1. The greater observed displacement in the HF submolecule modes suggests slightly stronger hydrogen bonding in the N2O complex. The lack of splitting in the degenerate librational mode for CO2⋅⋅⋅HF shows that this complex is linear, whereas the 3 cm−1 splitting in this mode for N2O⋅⋅⋅HF is consistent with a nonlinear complex, in agreement with microwave spectra.

Infrared spectra of the CO2⋅⋅⋅HF and N2O⋅⋅⋅HF complexes in solid argon at 12 K

The tetracyclic amine 9 was converted through several steps into secondary amine 13 and acetylated with (phenylthio)acetic acid activated by bis(2-oxo-3-oxazolidinyl)phosphinic acid to give amide 15. Treatment of 15 with sodium hydride in tetrahydrofuran at 25 o C resulted in rapid conversion into a single diastereomer, 16. This same conjugate addition has been conducted at the sulfoxide oxidation level and also with a chiral sulfoxide to provide optically active compounds (Scheme VI). Conversion of sulfoxide 19 into dione 27 followed by ketalization and reduction gave tertiary amine 34. Deprotection and oxidation with mercuric acetate gave the core strychnine skeleton 36. The β-aminoacrylate double bond in 36 was reduced to give 39 followed by epimerization to give 40. Ester 40 was protected as the sulfonamide derivative 44, and the ester was reduced to give 45. Alcohol 45 undergoes normal acid hydrolysis to give hemiketal 47. The Wieland-Gumlich aldehyde 48 was converted into the relay compound by the route shown in scheme XI, thus providing a convenient correlation and short route to 47. Hemiketal 47 was converted into ketone 52 and treated with (EtO) 2 P(O)CH 2 CN/ KN(SiMe 3 ) 2 /THF at 25°C to give the two geometrical isomers 53 (E) and 54 (Z) in a ratio 3:2. The incorrect stereoisomer could be recycled by irradiation in benzene to give a mixture of 53 and 54. Reduction of 53 gave the required allylic alcohol 55. Desilylation of 55 gave diol 56. The synthesis of strychnine and the Wieland-Gumlich aldehyde was completed by selective silylation of the allylic hydroxyl group in 56 and oxidation to give the unstable aldehyde 58. Desilylation of 58 gave the protected Wieland-Gumlich aldehyde 49, which was deprotected by treatment with sodium anthracenide to give 48

Gary L. Johnson

Papers

Matrix infrared spectrum of the ammonia-hydrogen fluoride hydrogen-bonded complex

Infrared spectra of OC–HX hydrogen‐bonded complexes in solid argon

Infrared spectra of hydrogen-bonded .pi. complexes between hydrogen halides and acetylene

Infrared spectra of the CO2⋅⋅⋅HF and N2O⋅⋅⋅HF complexes in solid argon at 12 K

Synthesis of strychnine and the Wieland-Gumlich aldehyde