Ernst-Ulrich Würthwein

cis/trans Isomerism of Hydroalumination and Hydrogallation Products—Reflections on Stability and Rearrangement Mechanism

Treatment of (silylalkynyl)benzenes with (Me(3)C)(2)Ga-H afforded stable cis-addition products, for example, (Me(3)C)(2)Ga-C(SiMe(3))=C(H)-C(6)H(5) (1), while spontaneous cis/trans rearrangement was observed for sterically less shielded gallium hydrides. The corresponding trans-di(tert-butyl)gallium compounds (13, 14) were obtained by the reaction of C(6)H(6-n)[C(H)=C(SiMe(3))GaCl(2)](n) (11, 12) with LiCMe(3). In contrast, spontaneous isomerization took place upon reaction of (Me(3)C)(2)Al-H with phenyltrimethylsilylethyne. In this case the cis isomer (17) was detected only at low temperature, while the trans product (18) formed quantitatively above 0 degrees C. Quantum-chemical calculations showed that the trans forms are thermodynamically favored, essentially caused by a better mesomeric interaction of the C==C double bonds with the phenyl groups, a smaller steric stress in the molecules, and a short bonding contact of the coordinatively unsaturated Al or Ga atoms to C-H bonds of the aromatic rings. The rotation about the C=C double bonds follows a zwitterionic mechanism, and the relatively small rotational barrier is further lowered by an interaction to a Lewis acidic lithium cation.

[2+2]- and [4+2]-Cycloaddition reactions of 1,3-diazabutadienes with diphenylketene

Abstract 1,3-Diazabutadienes react with diphenylketene in [2+2] - and [4+2] cycloaddition reactions, depending on the substitution pattern. Spectroscopic data (IR, 1H- and 13C-NMR) and results of quantummechanical model calculations (ab initio 3-21G) are presented.

Synthesis and SAR studies of chiral non-racemic dexoxadrol analogues as uncompetitive NMDA receptor antagonists.

A series of chiral non-racemic dexoxadrol analogues with various substituents in position 4 of the piperidine ring was synthesized and pharmacologically evaluated. Only the enantiomers having (S)-configuration at the 2-position of the piperidine ring and 4-position of the dioxolane ring were considered. Key steps in the synthesis were an imino-Diels-Alder reaction of enantiomerically pure imine (S)-13, which had been obtained from d-mannitol, with Danishefskys Diene 14 and the replacement of the p-methoxybenzyl protective group with a Cbz-group. It was shown that (S,S)-configuration of the ring junction (position 2 of the piperidine ring and position 4 of the dioxolane ring) and axial orientation of the C-4-substituent ((4S)-configuration) are crucial for high NMDA receptor affinity. 2-(2,2-Diphenyl-1,3-dioxolan-4-yl)piperidines with a hydroxy moiety ((S,S,S)-5, K(i)=28nM), a fluorine atom ((S,S,S)-6, WMS-2539, K(i)=7nM) and two fluorine atoms ((S,S)-7, K(i)=48nM) in position 4 represent the most potent NMDA antagonists with high selectivity against σ(1) and σ(2) receptors and the polyamine binding site of the NMDA receptor. The NMDA receptor affinities of the new ligands were correlated with their electrostatic potentials, calculated gas phase proton affinities (negative enthalpies of deprotonation) and dipole moments. According to these calculations decreasing proton affinity and increasing dipole moment are correlated with decreasing NMDA receptor affinity.

Unusual Formation of an Azaphospholene from 1,3,4,5‐Tetramethylimidazol‐2‐ylidene and Di(isopropyl)aminophosphaalkyne

Intramolecular C-H insertion into the methyl group of the amino substituent of 1 is shown by density functional theory calculations to stabilize this intermediate in the formation of the novel 1:1 carbene-phosphaalkyne adduct 2. Compound 2 is formed in near quantitative yield by reaction of 1,3,4,5-tetramethylimidazol-2-ylidene with P≡CNiPr2 .

The [4.4.4.4]Fenestranes and[2.2.2.2]paddlane. Prospects for the realization of planar tetracoordinate carbon?

Abstract Semi-empirical (MINDO/3 and UNDO) MO calculations on highly strained planar tetracoordinate carbon candidates indicate the central carbons in cis - [4.4.4.4] fenestrane ( 1 ) to have pyramidal ( 1a ) and in trans-[4.4.4.]fenestrane ( 2 ) to have distorted tetrahedral ( 2a ) geometries. In [2.2.2.2]paddlane ( 3 ), the two central carbons are pentacoordinate. Each is nearly coplanar with four carbon neighbours; additionally, the two bridgehead carbons are connected by a single bond ( 3a ).

On the planarity of tetracoordinate carbon enclosed by annulene perimeters

Abstract Proposals that planar tetracoordinate carbon might be achieved by enclosure in an annulene perimeter have been examined by means of MNDO calculations. Unfortunately, the lowest energy forms of 1–3, and 5 are indicated to distort as far away from planarity as possible, consistent with the strain demands of the carbon skeletons. Even in hypothetical stereomutation transition states, planar tetracoordination around the central carbon should be energetically difficult to achieve in these hydrocarbons, which, at best, are expected to be unstable strained polyolefins. Planar tetracoordinate carbon is more likely to be achieved when both π and σ systems provide effective stabilization through multicenter bonding. Several illustrative proposals for experimental examination are presented.

Electrocyclization Reactions of 1-Aza- and 1-Oxapentadienyl and -heptatrienyl Cations: Synthesis of Pyrrole and Furan Derivatives

Quantum chemical DFT calculations (B3LYP/6−31+G*) have been used to gain insight into the conformational and energy properties of the 1-aza- and 1-oxapentadienyl and -heptatrienyl cations 1, 2, 3, and 4. The calculated thermodynamic and kinetic data of the ring-closure reactions giving the cyclic products 5−14 are reported and discussed with respect to the experimental results. Experimentally, synthetic routes to the α,β-unsaturated carbonyl compounds 24 and 27, each with a leaving group in the γ-position, have been developed. These compounds have been investigated with respect to their ability to undergo 1,5-electrocyclization reactions to yield 2,5-disubstituted furans 28 upon heating in the presence of acid, presumably through the intermediate formation of the 1-oxapentadienyl cations 2. From the corresponding imine 29a the pyrrole 30d was obtained after treatment with tetrakis(triphenylphosphane)palladium. In the presence of benzylamine and the Pd0 catalyst, the corresponding pyrroles 30a−c were formed from 24 and 27. The homologous α,β,γ,δ-unsaturated carbonyl compounds 31 afforded 2-vinyl-substituted furans 32 upon heating with acid, and the 2-vinyl-substituted pyrroles 34 on treatment with benzylamine and the Pd catalyst. No seven-membered heterocyclic rings were formed. Surprisingly, the α,β-unsaturated carbonyl compounds with two phenyl substituents at the γ-position also provided pyrrole derivatives 40 through a formal dimerization. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Structure Elucidation of New Fusarins Revealing Insights in the Rearrangement Mechanisms of the Fusarium Mycotoxin Fusarin C

Fusarin C is a Fusarium mycotoxin that rearranges under reversed phase chromatographic conditions. In this study, the rearrangement of fusarin C was examined in detail, and the formation of fusarins under different conditions was optimized. All relevant fusarins including (10Z)-, (8Z)-, and (6Z)-fusarin C were isolated and identified by NMR. To confirm the involvement of the 2-pyrrolidone ring in the rearrangement of fusarin C, 15-methoxy-fusarin C was synthesized. For the first time, the structure of open-chain fusarin C was elucidated, and on the basis of these data, the rearrangement product of fusarin C was identified as epi-fusarin C. The results were confirmed by detailed NMR measurements and density functional theory calculations. Furthermore, a new fusarin C like metabolite, which was named dihydrofusarin C, was detected by analysis of the crude extract of fusarin C with high-performance liquid chromatography coupled to UV and Fourier transform mass spectrometry.

Alternativ-Liganden, XXXVII. Phosphanliganden mit Bor als Lewis-acidem Zentrum: Synthese und Koordinationseigenschaften / Alternative Ligands, XXXVII. Phosphane Ligands with Boron as Lewis-acidic Centre: Synthesis and Coordinating Properties

The complex [Rh(CO)Cl{Me2PC(Me)=C(Me)BMe2}2] (5) has been prepared again in order to prove its structure with weak bonding interactions between the basic rhodium centre and the Lewisacidic Me2B group of the donor/acceptor ligand Me2PC(Me)=C(Me)BMe2 (1). For further investigations additional ligands with P-donor and B-acceptor centres, e. g. Ph2PC(Ph)=C(Ph)BPh2 (2), B(OCH2PMe2)3 (3), and B(CH2CH2PMe2)3 (4), have been prepared and the coordinating properties have been studied by reactions of 1 and 4 with [(π-C5Me5)Rh(CO)2] and Pd(PPh3)4, respectively. Because single crystals of the products [(π-C5Me5)Rh(CO)Me2PC(Me)=C(Me)BMe2] (6), [(π-C5Me5)Rh(CO){Me2PC(Me)=C(Me)BMe2}2] (7) as well as [Pd{B(CH2CH2PMe2)3}] (8) or [(Ph3P)Pd{B(CH2CH2PMe2)3}] (9) could not be generated, quantum chemical calculations have been used to elucidate the coordination geometry expected for 5, 8 and 9. The calculations support the structure of 5 within the expected limitations of the experimental and theoretical methods and - in spite of the extremely soft coordination sphere of 8 and 9 - are in accord with spectroscopic results for the cage structures.

An Al/P-Based Frustrated Lewis Pair as an Efficient Ambiphilic Ligand: Coordination of Boron Trihalides, Rearrangement, and Formation of HBX2 Complexes (X = Br, I)

The Al/P-based frustrated Lewis pair (FLP) Mes2P-C(═CH-Ph)-Al(CMe3)2 (1) reacted with boron halides BX3 (X = F, Cl, Br, I) as an ambiphilic ligand to form complexes (2-5) in which the boron atoms were coordinated to phosphorus and one of the halogen atoms to aluminum. Nonplanar five-membered heterocycles resulted that had five different ring atoms (AlCPBX). The distance of the bridging halogen atoms to the AlCPB plane increased steadily with the radius of the halogen atoms. Only the BF3 adduct showed a dynamic behavior in solution at room temperature with equivalent tert-butyl or mesityl groups in the NMR spectra, while in other cases, the rigid conformation led to the magnetic inequivalence of the substituents at Al and P with well-resolved signals for each group. The BBr3 and BI3 complexes underwent in solution at room temperature a spontaneous stereoselective rearrangement with the concomitant release of isobutene. The obtained products, Mes2P-(μ-C═CH-Ph)(μ-HBX2)-AlX(CMe3) (6 and 7) may be viewed as unique adducts of a modified new Al/P-based FLP, Mes2P-C(═CH-Ph)-AlX(CMe3) (X = Br, I), with dihalogenboranes, HBX2. The trapped boranes are either completely unknown (X = I) or unstable in the free form. Quantum-chemical calculations suggest an ionic rearrangement mechanism via the formation of a borenium cation, β-hydride elimination, and hydride transfer. The bromine migration from boron to aluminum corresponds to a formal suprafacial 1,3-sigmatropic rearrangement.