A new synthesis of allyl sulfoxides via nucleophilic addition of sulfinyl carbanions to group 6 Fischer carbene complexes

[reaction: see text] A novel synthesis of allyl sulfoxides has been developed. Primary alpha-lithiosulfinyl carbanions react with group 6 Fischer carbene complexes to give allyl sulfoxides as products. The Fischer carbene complex experiments involve a 1,2-addition of two molecules of sulfinyl carbanion to give an intermediate that, after a beta-elimination, furnishes the mentioned product.     

Coupling of propargylsilanes with Fischer carbene chromium complexes: a new synthesis of conjugated dienes

The reaction of propargylsilanes with Fischer carbene complexes has been examined. If the silane-containing carbon is secondary the predominant pathway involves formation of conjugated dienes through a 1,2-silicon shift process of the initially formed vinylcarbene complex intermediate. If a primary propargylsilane is employed, the silicon does not shift and normal alkyne-Fischer carbene coupling processes are observed. The process is moderately stereoselective, resulting in the E enol ether and Z alkenylsilane.     

New methodologies for the oxidation of Fischer carbene complexes: synthesis of hydrazides

[reaction: see text] We report new, high-yield methodologies for oxidizing Fischer carbenes, particularly hydrazinocarbene complexes. The reagents traditionally used to oxidize Fischer carbenes have failed because of the stability of hydrazinocarbene complexes and the easy oxidation of formed hydrazides in the reaction conditions. The three newly developed methodologies are very mild, fast, efficient, and complementary. Differently functionalized hydrazinocarbene complexes can be oxidized to afford new hydrazides.     

Tandem annulation strategy for the convergent synthesis of benzonaphthopyranones: total synthesis of chartarin and O-methylhayumicinone

A Hauser-initiated tandem annulation has been developed for the rapid regiospecific synthesis of benzonaphthopyranones via formation of two rings in one-pot operation. This strategy has been generalized with benzonaphthopyranones 26, 29, 32, and 35. It has also been employed in a short synthesis of chartarin (3) and O-methylhayumicinone (67).     

Stereoselective [4 + 1] annulation reactions with silyl vinylketenes derived from Fischer carbene complexes

Stable silyl vinylketenes were prepared via the thermal reaction of Fischer carbene complexes with triisopropylsilyl- or tert-butyldimethylsilyl-substituted alkynes. The ability of these silyl vinylketenes to participate with carbenoid reagents in [4 + 1] annulation reactions was investigated. The best results were obtained with diazomethane and substituted diazomethane reagents, which provided cyclopentenone products in excellent yields and essentially complete stereoselectivity.     

A convergent strategy for the synthesis of beta-carba-galacto-disaccharides

[reaction in text] A convergent strategy for the synthesis of beta-carba-galacto-disaccharides is illustrated by the preparation of 1 and 4, from a central "glycone" component 22, and the corresponding "aglycone" segments, monosaccharide alcohols, 23a or 23b. The key step is the formation of the carbasugar ring via an oxocarbenium ion-enol ether cyclization.     

Intramolecular cyclohexadienone annulations of Fischer carbene complexes: model studies for the synthesis of Phomactins

The intramolecular cyclohexadienone annulation of chromium carbene complexes is examined as a method to provide general access to the Phomactin family of natural products. The importance of the stereochemistry of the carbene complex and the number of carbons in the tether connecting the carbene complex and the alkyne are probed. Additionally, the degree of the 1,4-asymmetric induction is examined.     

Facile and versatile annulation of the imidazole ring: Single and sequential cyclization reactions of Fischer carbene complexes with 1,4-diazafulvenes

We examined the reactivity of dimethylaminodiazafulvene 1 toward Fischer alkenylcarbene 2 and alkynylcarbene 3 complexes. Diazafulvene 1 reacts with alkenylcarbenes 2 through a formal [6+3] heterocyclization in a regio- and stereoselective manner to afford dihydroimidazo[1,2-a]pyridines 4. Acid-promoted dimethylamine elimination in compound 4 c gives rise to the aromatic imidazo pyridine 5. A likely mechanism for this reaction is a 1,2-nucleophilic addition/[1,2]-shift metal-promoted cyclization sequence. On the other hand, diazafulvene 1 and alkynyl carbenes 3 undergo a [6+2] cyclization to afford pyrrolo[1,2-a]imidazole carbene complex 6 that can be readily oxidized to the corresponding esters 7. When enynylcarbenes 3 e-i are treated with diazafulvene 1, consecutive and diastereoselective [6+2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 8, 9, and 12 that can be appropriately demetallated to the corresponding imidazole-based polyfused systems 10, 11, and 13 respectively. Finally, enynylcarbenes 3 d,f undergo consecutive [6+2]/[5+1] cyclization reactions with diazafulvene 1 and tBuNC, respectively, to yield tetracyclic adducts 14 and 15. All these processes result in high yields and provide a route to the preparation of imidazopyridines and pyrroloimidazoles as well as other polycyclic molecules that contain imidazole groups, which are interesting from a pharmacological and biological point of view.     

An approach to an enantioselective synthesis of crisamicin A via a novel double Hauser-Kraus annulation strategy

A double Hauser-Kraus annulation between biscyanophthalide 4 and the d-mannose derived enone 39 provides access to an advanced intermediate 54 that is an excellent scaffold to effect an enantioselective total synthesis of crisamicin A 1.     

Asymmetric synthesis of cyclopropanes from lithiated aryloxiranes and alpha,beta-unsaturated Fischer carbene complexes

A diastereo- and enantiospecific formation of tetrasubstituted cyclopropane carbene complexes and cyclopropanecarboxylates from lithiated aryloxiranes and alpha,beta-unsaturated Fischer carbene complexes is described.     

New strategy for convergent steroid synthesis

We published recently our results on a new and convergent synthesis of natural steroids. The strategy was based on a cycloaddition reaction of Nazarov reagents 2 and 5 with cyclohexenones 1 and 4. In this paper we report results that deal with the synthesis of two new bicyclic Nazarov reagents (13 and 19) and their cycloaddition with two cyclohexenones (1 and 4). These new results constitute an important improvement concerning the versatility of the strategy since tetracycles having the stereochemistry found in natural steroids are now available.     

The first synthesis of cyclopropanone acetals from the reaction of Fischer carbene complexes with ketene acetals

The reaction of iso-propoxy stabilized Fischer carbene complexes with ketene acetals gives moderate to excellent yields of cyclopropanone acetals when carried out under a carbon monoxide atmosphere. This is in contrast to the known reaction of methoxy substituted complexes which give cyclic ortho esters under the same conditions. A mechanism is proposed which involves a branch point between the two products as the zwitterionic intermediate resulting from nucleophilic addition of the ketene acetal to the carbene carbon. A 1,3-migration of the methoxyl group to the cationic center leads to the ortho ester and a ring closure by backside attack leads to the cyclopropanone acetal. A double-labeling experiment shows that the 1,3-migration occurs by an intramolecular process that is proposed to involve a bridging oxonium ion. The effect of the isopropoxy group is thus interpreted to be to sterically hinder the formation of a bridged oxonium ion.     

Diastereoselective cyclopropanation of ketone enols with Fischer carbene complexes

Treatment of aryl/heteroaryl methoxycarbene complexes of chromium with -substituted ketone lithium enolates between -78 degrees C and room temperature resulted in the diastereoselective synthesis of 1,2,2,3-tetrasubstituted cyclopropanols. An exception has been observed in the reaction with cyclohexanone lithium enolate that yielded a bicyclic 2-buten-4-olide. 1,2-Dimethoxycyclopropanes and 1-methoxy-2-trimethylsilyloxycyclopropanes were isolated by quenching the reactions with MeOTf or Me3SiCl, respectively. This novel cyclopropanation process involves formation of lithium (3-oxoalkyl)pentacarbonylchromate intermediates which on warming undergo intramolecular addition to the carbonyl group. This cyclization is equivalent to the cyclopropanation in smooth conditions of electron-rich alkenes with Fischer carbene complexes.     

Synthesis of nitrogen-containing compounds using chromium Fischer carbene complexes

Synthetic utility of the Fischer-type carbene complexes of chromium for the preparation of nitrogen-containing compounds is demonstrated. Alkoxy carbene complexes reacted with imines to give (optically active) 3-pyrrolines and beta-methoxy allylic amine derivatives in good yields. The amino carbene complexes reacted with alpha,beta-unsaturated aldehydes to give substituted pyrroles in good yields.     

Easy and regioselective synthesis of highly functionalized o-quinodimethide precursors from Fischer carbene complexes and isocyanides

Highly functionalized cis- and trans-1,2-bis(trialkylsilyloxy)benzocyclobutene derivatives have been synthesized in a completely regioselective fashion from easily available Fischer alkenylcyclobutenyl(alkoxy)carbene complexes and isocyanides. This methodology can be viewed as an alternative to existing methods of synthesis of this kind of compounds and overcomes the main problem of introducing functionality in the aromatic ring. Both cis and trans derivatives underwent the expected fragmentation to generate o-quinodimethide intermediates upon thermal treatment, affording complex polycyclic structures in a stereoselective manner when heating was carried out in the presence of a range of electron deficient dienophiles.     

Study of the ESI-mass spectrometry ionization mechanism of Fischer carbene complexes

By means of deuterium-labeling experiments, we have carried out a systematic ESI-MS study to determine the mechanism of ESI ionization of alkenyl and alkynyl group 6 Fischer carbene complexes. These compounds can be ionized under ESI conditions only in the presence of additives such as hydroquinone (HQ) or tetrathiafulvalene (TTF). Our results demonstrate that in the ESI source an anion-radical is formed after the initial HQ- or TTF-mediated electron transfer to the metallic carbene complex. For alkenyl carbene complexes, this species evolves by extrusion of a hydrogen radical to form an allenylchromium anion that is detected as the [M - H](-) ion in the mass spectrum. The preference for this mechanistic pathway could be rationalized by DFT calculations. In the case of alkynyl carbene complexes, experiments combining deuterated substrate, additive, and solvent demonstrate that the previously proposed allene-anion carbene complex is not formed. Instead, the H transfer from the ethoxy group in the anion radical, followed by extrusion of a hydrogen radical, leads to an allenyl anion that is detected in the ESI-MS as [M - H - CO](-).     

Novel [1,5] sigmatropic rearrangements of cyclohexadienones generated from Fischer carbene complexes. A new strategy for installing the C-20 angular ethyl group in Aspidospermidine alkaloids

[formula: see text] We report here the first examples of a [1,5] sigmatropic rearrangement in a 4a-alkyl-4a-hydrocarbazol-4-one to yield a 3-alkylcarbazol-4-one with a re-aromatized indole nucleus. The reaction of 1-methyl-3-substituted-indole-2-carbene complexes 1 with terminal alkynes yields 3,4a-dialkyl-1-methoxy-9-methylcarbazol-4-ones 2. These 4a-substituted carbazolones thermally rearrange to cleanly give the more highly aromatic 3,3-dialkyl-1-methoxy-9-methylcarbazol-4-ones 3. This reaction provides a convenient entry to the Aspidosperma family of alkaloids, which contain a 3,3-disubstituted carbazole nucleus.