Thomas Labahn

New Efficient Multicomponent Reactions with C−C Coupling for Combinatorial Application in Liquid and on Solid Phase

Up to nine C-C bonds are formed selectively from up to seven components starting from an alkene, a haloarene, and a dienophile [Eq. (1)]. A comparison of liquid- and solid-phase reactions reveals a surprising superiority of the solid-phase reaction.

A New Strategy for the Stereoselective Synthesis of 1,2,3-Trisubstituted Cyclopropanes

The stereoselective synthesis of highly functionalized 1,2,3-trisubstituted cyclopropanes 1 and 2, starting from readily available furans 3 or N-protected pyrrole 4, is described. Furthermore, exceptionally high diastereocontrol in agreement with the Felkin-Anh model was observed for the addition of nucleophiles to the title compounds.

A New and Efficient Access to Thiazoline‐4‐carboxylates and Cysteine Derivatives Incorporating Cyclopropyl Groups

Under basic conditions (NaHCO3, MeCN), thiocarboxamides 2, including N,N-thioureas, cleanly undergo Michael addition onto 2-chloro-2-cyclopropylideneacetates 1, attacking through the sulfur, and this is followed by an intramolecular substitution to afford 5-spirocyclopropane-annelated thiazoline-4-carboxylates 4 in 37−92% yields. The thiazolines 4 are cysteine derivatives that possess a cyclopropyl or substituted cyclopropyl group in place of the gem-dimethyl-substituted β-carbon atom of penicillamine; they can be hydrolyzed to the hydrochloride salt of the amino acid 5 by heating in acid. Under acidic conditions (CH2Cl2, HCl), the Michael adducts 7 of thioamides 2 onto 1 are formed in high to virtually quantitative yields. When treated with NaHCO3 in MeCN, the adducts 7 cyclize to thiazolinecarboxylates 4 (51−82%), but in the presence of Ti(OiPr)4 they form spirocyclopropane-annelated thiazinones 8 (19−88%).

Synthesis and investigation of the stability of Ti(III) β-diketiminato complexes. Structure of the tetrameric non-metallocene titanium fluoride complex (L2)4Ti4F6O2·2toluene supported by the β-diketiminato ligand

Abstract The titanium β-diketiminato complexes (L1)TiCl2 (1), (L1)TiCl(N2,6-iPr2C6H3) (2), and (L2)2TiCl (3) [L1=(2,6-iPr2C6H3)NC(Me)CHC(Me)N(2,6-iPr2C6H3), L2=iPrNC(Me)CHC(Me)NiPr] have been prepared by the reaction of the lithium salt of the ligand, L, with titanium trichloride. Complex 2 was isolated from supernatant solutions of 1 containing excess of the (L1)Li salt. The monochloride complex [(L2)TiCl(NiPr)]2 (4) was prepared by reduction of (L2)2TiCl2 with the excess of Na/K alloy. Fluorination of the monochloride complex 3 with Me3SnF affords polymeric [(L2)TiF2]n (5). Oxidation of 5 gives the tetrameric complex, (L2)4Ti4F6O2·2toluene (6). Compounds 1–6 were characterized by single crystal X-ray structural analyses, elemental analyses, NMR and mass spectra. The bulky ligand (L1) stabilizes the Ti(III) complex 1 with an unusual distorted square-planar pyramidal geometry around the titanium atom, by sigma bonding to the metal. The less bulky ligand (L2) in complexes 3, 4 and 6 has mixed σ and π coordination to the titanium center. Investigation of the CC, NC distances in the NCCCN unit of the coordinated β-diketiminato ligands (L1) and (L2) demonstrated the localization of the double bonds in the ligand in complexes 1–3 and 6. The stability of the complexes in solution was studied by means of NMR spectroscopy. Complexes 2 and 4 are stable in solution, the polymeric and the tetrameric nature of complexes 5 and 6 is not evident in C6D6 solution. The (L2)2TiCl stoichiometry of the complex is unstable.

Construction of bi- and tricyclic skeletons by domino-Heck-Diels-Alder reactions

Palladium-catalyzed intramolecular reactions of 2-bromo 1,6-dienes followed by intermolecular [4+2] cycloaddition with suitable dienophiles in one-pot operations gave hexahydroindenes 8 and 9 in yields of 40–78%, an hexahydro-s-indacene derivative 13 could be obtained in up to 25% yield with cyclopent-2-en-1-one (10) as a dienophile in the presence of different Lewis acids, and a spirocyclopentane-hexahydroindenone 18 could be isolated in 72% yield. When in-situ-formed iminium salts were used as heterodienophiles, hexahydro-1H-[2]pyrindinols 31 could be obtained in a one-pot two-step operation in 29–46% yield.

Mono‐, Di‐, and Trimetallic Complexes of the Nonalternating Polycondensed π‐Perimeter Decacyclene, C36H18: Synthesis, Structure, and Spectroelectrochemistry of [{(η5‐Me4EtC5)Co}2(μ‐η5:η4‐C36H18)]

Reaction of the half-sandwich complexes [(eta5-Me4RC5)M(eta2:O-acac)] (M = Co, Ni; R = Me or Et) with di- and trianions of the polycondensed pi-hydrocarbon decacyclene results in formation of the first Co and Ni triple-decker complexes of this hydrocarbon. For the title compound NMR spectra as well as a crystal structure analysis reveal an antarafacial coordination of two (eta5-Me4EtC5)Co fragments at the central six-membered ring and one of the neighboring five-membered rings of decacyclene. The bridging pi-perimeter decacyclene displays a bowl-shaped topology. In the case of Ni, coordination of two (eta5-Me5C5)Ni fragments at the central six-membered ring of decacyclene is observed, based on the results of 1H and 13C NMR studies. This coordination mode is without precedent for nickel organometallic compounds reported so far. The cobalt complex shows a rich spectroelectrochemistry. Results of cyclic voltammetry and coupled ESR experiments reveal a strong interaction of both metal centers in the mixed-valent monocation of [(eta5-Me4EtC5)Co2(mu-eta5:eta4-C36H18)]. This categorizes the title compound into Robin Day class III.

Highly Substituted Spiro[4.4]nonatrienes from a -Amino-Substituted ,-Unsaturated Fischer Carbene Complex and Three Molecules of an Arylalkyne

A novel mode of reaction towards arylethynes is shown by the β-trimethylsilyl-substituted α,β-unsaturated Fischer carbene complexes 1. A mixture of the isomeric, highly substituted spiro[4.4]nonatrienes 2 and 3 is formed by the formal insertion of three alkyne molecules and subsequent cyclization (see scheme). Such selective triple insertions of alkynes into ethenylcarbene complexes have not been previously observed.

Cyclopropyl building blocks in organic synthesis. Part 81: Striving for unusually strained oxiranes: epoxidation of spirocyclopropanated methylenecyclopropanes

1-Oxa[3]triangulane 13, the epoxide of methylenespiropentane, is thermally stable up to 300°C, but immediately rearranges to spiro[2.3]hexan-4-one (7) in the presence of lithium iodide at ambient temperature. The permethylated bicyclopropylidene 10 is simply less reactive than the parent bicyclopropylidene (6a) towards dimethyldioxirane, but yields the isolable epoxide 11 (94%) with mCPBA. In contrast, the partially or fully spirocyclopropanated bicyclopropylidenes 18, 20, and 22, upon treatment with mCPBA or dimethyldioxirane, did not furnish the corresponding epoxides, but underwent oxidation with rearrangement to the corresponding cyclobutanones 19, 21 and 23 in yields of 59, 100 and 97%, respectively.

Convenient Syntheses of Novel α‐ and β‐Amino Acids with Spiropentyl Groups

Racemic spiropentylglycine (8) has been synthesized by sodium borohydride reduction of benzyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Bn), nucleophilic substitution of the chlorine in the product 6 with azide and hydrogenolytic deprotection of the resulting 7 (overall yield 15%). An alternative approach to 8 consisted of the coupling of the higher-order cuprate 10, generated by halogen-metal exchange from bromospiropentane (9), with the electrophilic glycine equivalent 11 followed by deprotection (overall yield 47%). Enantiomerically pure (1′-aminospiropentyl)acetic acid [(R)-16] (overall yield 16% from 5-Me) and 1-aminospiropentanecarboxylic acid [(R)-23] (29% from 5-Me) were obtained from the Michael adduct 14-Me of (4R,5S)-4,5-diphenyloxazolidin-2-one (13) and methyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Me). Racemic 1-aminospiropentanecarboxylic acid (R/S-23) was prepared by rhodium-catalyzed addition of dimethyl diazomalonate to methylenecyclopropane and subsequent Curtius degradation of the halfester 28 via the azide 29 (overall yield 14%). Upon standing in aqueous solution, 23 underwent complete rearrangement to the new 1-amino-2-methylenecyclobutanecarboxylic acid (24). The interesting derivative of azabicyclo[3.1.0]hexane-1-carboxylate 34 with an annelated spiropentane moiety and a β-amino acid fragment was incidentally obtained in a one-step intermolecular domino reaction starting with the addition of lithium benzylamide to methyl 2-chloro-2-cyclopropylideneacetate (32, 41% yield).

Preparation and structural features of new dialkylamino-substituted cyclopropenylidenepentacarbonylchromium complexes

Abstract The (2-ethoxy-3-dimethylaminocyclopropenylidene)pentacarbonylchromium complex 2 was prepared from dimethylaminoacetylene in 78% yield. It reacted with dimethylamine and diethylamine at room temperature to give quantitative yields of the bis(dialkylamino)cyclopropenylidene complexes 3a , b . The structural data and 13 C-NMR chemical shifts of 2 and 3b show interesting differences relating to the different donor abilities of alkoxy and dialkylamino groups.