Helvetica Chimica Acta

doi: 10.1002/hlca.19890720801pmid: N/A

Brade, Walter; Vasella, Andrea

doi: 10.1002/hlca.19890720802pmid: N/A

A new method for the synthesis of naphtho[2,3‐b]pyrandiones from sulfonyllactones and 1‐nitroglycals is presented. Thus, the sulfonyllactone 6 reacted with the 1‐nitroglycal 7 in the presence of LDA at room temperature to give the naphthopyrandione 9 in high yields (Scheme 1). Reaction at a lower temperature led to the (intermediate) Michael‐addition products 8. The sulfonyllactone 4 and the 1‐nitroglycal 5 were prepared for the synthesis of the naphthopyrandione 18 (Scheme 2). The base‐promoted condensation of 4 and 5 gave 17, which was deprotected to give 18, the enantiomer of the fungal metabolite (+)‐cryptosporin 1.

Adams, Christoph M.; Hafner, Andreas; Koller, Markus; Marcuzzi, Alessandro; Prewo, Roland; Solana, Isabel; Vincent, Beverly; von Philipsborn, Wolfgang

doi: 10.1002/hlca.19890720803pmid: N/A

The synthesis of 36 [Fe(CO)2L1(η4‐diene)], three [Fe(CO)2L1(η4‐encne)], and five [Ru(CO)2L1(η4‐diene)] complexes (L1 = Ph3P, Et3P, (EtO)3P, (MeO)3p, C6H11NC) by thermal, selective CO ligand displacement in the corresponding tricarbonyl precursor complexes is described. In a second step, photochemical CO displacement by another phosphorus ligand L2 leads to a new type of η4‐diene complexes with a centre of chirality at the metal atom (Fe, Ru). 23 Fe and three Ru complexes of this type have been prepared and characterized. In the case of complexes with unsymmetrical dienes, racemic diastereoisomers are formed which can be separated by chromatographic methods. The molecular structures of [Fe(CO)(Ph3P)((MeO)3P)(buta‐1,3‐diene)] (52), [Fe(CO)(Ph3P)((MeO)3P)(isoprene)] (58) and [Fe(CO)(Et3P)(EtO)3P(hexa‐2,4‐dienal)] (62a) were determined by X‐ray diffraction. All complexes were investigated by 13C‐, 31P‐ and, in part, 1H‐NMR spectroscopy. At low temperatures, conformational isomers (rotamers) can be differentiated which probably arise from ψ rotation at the coordinated metal centre.

Sontag, Christoph; Berke, Heinz; Sarter, Christian; Erker, Gerhard

doi: 10.1002/hlca.19890720804pmid: N/A

Reaction of (η3‐allyl)(cyclopentadienyl)zirconium(4+) chloride with (2,3‐dimethylbutadiene)magnesium or (2‐phenylbutadiene)magnesium gave the (η3‐allyl)(η4‐conjugated diene)(cyclopcntadienyl)zirconium complexes 3c and 3d, respectively. The analogous reaction between (η/3‐allyl)(cyclopentadienyl)hafnium(4+) chloride with (buta‐diene)magnesium afforded (η3‐allyl)(η4‐butadiene)(η5‐cyclopentadienyl)hafnium 3e. Photolysis of the complexes 3 produced their stereoisomers 4. The open‐chain π ligands in 3 open themselves towards the apical Cp ligand, in 4 they both are turned around by 180°. The Gibbs activation energy of the 4→3 rearrangement of the Hf complex does not deviate significantly from those of the Zr‐containing systems (4c→3e: ΔG≠ rearr. (−10°) = 81.3 ± 1.3 kJ/mol; 4d→3d: ΔG≠ (‐10°) = 85.7 ± 1.3 kJ/mol; 4e→3e: ΔG≠ (‐5°) = 84.4 ± 1.3 kJ/mol). A modified ex‐tended‐Hückel theory (MEHT) was used in order to simulate the thermally induced rearrangement of the diene ligand in 3/4. The calculations indicate that there should be a combinational interconversion of both the diene and allyl ligand. A diene inversion becomes energetically favoured, if a simultanous allyl rotation occurs. The transition state 9 lies ca. 90 kJ/mol above the optimized geometry of 4a and 115kJ/mol above 3a. Orbital considerations show that a spatially different ‘valence’ orbital of the [Zr(allyl)Cp] fragment 6 in comparison with [ZrCp2]7 causes the conformational preference of the diene ligand in 3a with a higher rearrangement barrier.

Boyé, Olivier; Itoh, Yoshikuni; Brossi, Arnold

doi: 10.1002/hlca.19890720805pmid: N/A

Synthesis of deaminocolchinyl methyl ether 9 was achieved from tetramethoxy‐substituted biphenyl‐2‐carb‐aldehyde 12 via tricyclic ketone 20 and 5,6‐didehydro congener 11. Compound 9 was identical in every respect with material prepared from colchicine via 6,7‐didehydro congener 10. Measuring inhibition of tubulin polymerization in vitro showed compounds 4, 5, and 9–11 of the alloseries of colchicinoids to be particularly potent inhibitors.

Bircher, Hansruedi; Neuenschwander, Markus

doi: 10.1002/hlca.19890720806pmid: N/A

Substituent Effects on NMR Spectra of Pentafulvenes. 13C, 13C‐NMR Coupling Constants (1J(C, C))

Seebach, Dieter; Brändli, Urs; Müller, Hans‐Martin; Dobler, Max; Egli, Martin; Przybylski, Michael; Schneider, Klaus

doi: 10.1002/hlca.19890720807pmid: N/A

The temperature and concentration dependence of the previously reported formation of oligolides from (R)‐ or (S)‐3‐hydroxybutanoic acid under Yamaguchi's macrolactonization conditions (2,4,6‐trichlorobenzoyl chloride/base) was studied. While the content of hexolide 2 in the product mixture is almost invariably ca. 35%, the amounts of pentolide 1 and of the larger rings strongly depend upon the temperature employed (Fig.1). Cyclic oligomers (5,6) are also obtained from 3‐hydroxypentanoic acid. Enantiomerically pure β‐butyrolactone can be used for the preparation of pento‐, hexo‐, and heptolide under Shanzer's macrolactonization conditions (tetra‐oxadistannacyclodecane ‘template’). The X‐ray crystal structures of the pentolide 1 and of two modifications (space groups C 2 and P 21) of the hexolide 2 were determined (Figs. 2–6 and Tables 1 and 5). No close contacts between substituent atoms and atoms in the rings or between ring atoms are observed in these structures. The hexolide C 2 modification is ‘just a large ring’, while the crystals of the P 21 modification contain folded rings the backbones of which resemble the seam of a tennis ball. A comparison of the torsion angles in the folded hexolide ring of the P 21 modification with those in the helical poly‐(R)‐3‐hydroxybutanoate (PHB) suggests (Table 2) that the same interactions might be responsible for folding in the first and helix formation in the second case. Molecular modeling with force‐field energy minimization of the tetrolide from four homochiral β‐hydroxybutanoic acid units was undertaken, in order to find possible reasons for the fact that we failed to detect the tetrolide in the reaction mixtures. The calculated conformational energies (per monomer) for some of the tetrolide models (Figs. 7–9 and Tables 3 and 4) are not significantly higher than for the pentolide and hexolide crystal structures. We conclude that thermodynamic instability is an unlikely reason for the lack of tetrolide isolation. This result and failure to observe equilibration of pentolide 1 to a mixture of oligomers under the reaction conditions suggest that product distribution is governed by kinetic control.

Bennett, Grace A.; Mullen, George B.; Georgiev, Vassil St.

doi: 10.1002/hlca.19890720808pmid: N/A

A new synthetic approach towards the indole ring system is described. When dimethyl 1‐methyl‐2‐oxa‐1‐aza‐spiro[4.5]dec‐3‐ene‐3,4‐dicarboxylate (6) was refluxed in toluene, the previously known dimethyl 4,5,6,7‐tetra‐hydro‐1‐methyl‐1H‐indole‐2,3‐dicarboxylate (7) was obtained in 71% yield, via a 2,3‐dihydroisoxazole‐pyrrole rearrangement. After treatment with DDQ, the tetrahydro analogue 7 was converted to the corresponding dimethyl 1‐methyl‐1H‐indole‐2,3‐dicarboxylate (8).

Burger, Ulrich; Mentha, Yves G.; Millasson, Patricia; Lottaz, Pierre‐André; Mareda, Jiri

doi: 10.1002/hlca.19890720809pmid: N/A

Starting from dibenzo[a, c]cyclooctene (4) and 4‐methyl‐3H‐1,2,4‐triazol‐3,5(4H)‐dione (MTAD), the strained skeleton of the title azo compound 1 is assembled in a tandem photo‐Diels‐Alder addition/di‐π‐methane rearrangement sequence. The synthesis is completed by a stepwise hydrolytic oxidation of the ensuing triazolidine‐dione 2 with nickel peroxide. Thermolysis of 1 in benzene solution is shown to be governed by an initial 1,3‐dipolar cycloreversion which leads, via an intermediate diazo compound 11, to cyclobuta[1]phenanthrene 8 and two further carbene‐derived C16H12 products. Photolysis of 1 at 350 nm leads in modest yield (12%), via a diazenyl diradical, to an unstable bridged bicyclobutane 10 (dibenzooctavalene). MNDO calculations suggest the latter to have a rapidly inverting, twisted structure of C2 symmetry.

Herdewijn, Piet; Charubala, Ramamurthy; Pfleiderer, Wolfgang

doi: 10.1002/hlca.19890720810pmid: N/A

A series of new 2′–5′ oligonucleotides carrying the 9‐(3′‐azido‐3′deoxy‐β‐D‐xylofuranosyl)adenine moiety as a building block has been synthesized via the phosphotriester method. The use of the 2‐(4‐nitrophenyl)ethyl (npe) and 2‐(4‐nitrophenyl)ethoxycarbonyl (npeoc) blocking groups for phosphate, amino, and hydroxy protection guaranteed straightforward syntheses in high yields and easy deblocking lo form the 2′–5′ trimers 21, 22, and 25 and the tetramer 23. Catalytic reduction of the azido groups in [9‐(3′‐azido‐3′‐deoxy‐β‐D‐xylofuranosyl)adenine]2′‐yl‐[2′‐(Op‐ammonio)→ 5′]‐[9‐(3′‐azido‐3′‐deoxy‐β‐D‐xylofuranosyl)adenin]‐2′‐yl‐[2′‐(Op‐ammonio)→ 5′]‐9‐(3′‐azido‐3′‐deoxy‐β‐D‐xylofuranosyl)adenine (21) led to the corresponding 9‐(3′‐amino‐3′‐deoxy‐β‐D‐xylofuranosyl)‐adenine 2′–5′ trimer 26 in which the two internucleotidic linkages are formally neutralized by intramolecular betaine formation.