Arenes Chromium carbene complexes

The chemistry outlined on the next page was used to produce a cyclic arene-chromium carbene complex.100... 

Chromium carbene complexes having electron-rich arenes tethered to the car-bene oxygen or carbon underwent photodriven intramolecular Friedel-Crafts acylation in the presence of zinc chloride (Eqs. 32 and 33) [118]. The process was highly regioselective, undergoing acylation exclusively para to the activating group. 

Trimethylsilyldiazomethane, 327 Silyl substituted arenes Bis(trimethylsilyl)acetylene, 97 Chromium carbene complexes, 82 Titanium(IV) chloride-Diethylalu-minum chloride, 309 Other organosilanes Osmium tetroxide-Trimethylamine N-oxide-Pyridine, 223 Tributyltin chloride, 315 Di- x-carbonylhexacarbonyldicobalt, 99 Trimethylsilyl trifluoromethanesul-fonate, 329... 

The present overview deals with the application of Fischer chromium carbene complexes in the benzannulation reaction for the preparation of highly substituted aromatic compounds. Before focussing on specific arenes (Section 8.5), details of the mechanism are given (Section 8.2), and the scope and limitations of the reaction are defined (Section 8.3). A short description of the experimental procedure is given thereafter (Section 8.4). Finally, the contribution deals with the application of the chromium carbene benzannulation to natural compounds and molecules with biological activity (Section 8.6). 

The chromium carbonyl linkers 1.40 (98) and 1.41 (99) were prepared from commercial triphenylphospine resin and respectively from pre-formed p-arene chromium carbenes and Fischer chromium amino carbenes. Their SP elaboration is followed by cleavage with pyridine at reflux for 2 h (1.40) and with iodine in DCM for 1 h at rt (1.41) both linkers produce the desired compounds in good yields. A similar cobalt carbonyl linker 1.42 (100) was prepared as a mixmre of mono- (1.42a) and bis- (1.42b) phosphine complex, either from pre-formed alkyne complexes on triphenylphosphine resin or by direct alkyne loading on the bisphosphine cobalt complex traceless cleavage was obtained after SP transformations by aerial oxidation (DCM, O2, hp, 72 h, rt) and modified alkynes were released with good yields and... 

Generally, arene(alkoxy)carbene chromium complexes react with aryl-, alkyl-, terminal or internal alkynes in ethers or acetonitrile to yield 4-alkoxy-l-naphthols, with the more hindered substituent ortho to the hydroxyl group . Upon treatment with alkynes, aryl(dialkylamino)carbene chromium complexes do not yield aminonaphthols, but they form indene derivatives . Vinyl(dialkylamino)carbene complexes, however, react with alkynes to yield aminophenols as the main products The solvent is one of the many factors that affects this type of reaction, for which the most important is the polarity and/or coordinating ability of the solvent. The Dotz benzannulation reaction yields either arene chromium tricarbonyl complexes or the decomplexed phenols, depending on the work-up conditions. Oxidative work-up yields either decomplexed phenols or the corresponding quinones. 

The Dotz benzannulation reaction (DBR) is the reaction of an a,P unsaturated Fischer carbene with an alkyne to produce a highly substituted phenol. Alternatively, the DBR can be considered a metal templated 3 + 1 + 2 cycloaddition of an allylic carbine (3 carbon unit), carbon monoxide (1 carbon unit), and an alkyne (2 carbon unit). The initial product of the reaction is the arene chromium tricarbonyl complex of the phenol as in 4. These complexes are typically unstable in air such that workup and purification of the product lead to the complete loss of the metal. Chromium is the most often used metal for the benzannulation. Molybdinum, tungsten, and manganese have been used but usually give mixtures of products and require harsh reaction conditions. 

Due to the inherent unsymmetric arene substitution pattern the benzannulation reaction creates a plane of chirality in the resulting tricarbonyl chromium complex, and - under achiral conditions - produces a racemic mixture of arene Cr(CO)3 complexes. Since the resolution of planar chiral arene chromium complexes can be rather tedious, diastereoselective benzannulation approaches towards optically pure planar chiral products appear highly attractive. This strategy requires the incorporation of chiral information into the starting materials which may be based on one of three options a stereogenic element can be introduced in the alkyne side chain, in the carbene carbon side chain or - most general and most attractive - in the heteroatom carbene side chain (Scheme 20). 

Arasabenzene, with chromium, 5, 339 Arcyriacyanin A, via Heck couplings, 11, 320 Arduengo-type carbenes with titanium(IV), 4, 366 with vanadium, 5, 10 (Arene(chromium carbonyls analytical applications, 5, 261 benzyl cation stabilization, 5, 245 biomedical applications, 5, 260 chiral, as asymmetric catalysis ligands, 5, 241 chromatographic separation, 5, 239 cine and tele nucleophilic substitutions, 5, 236 kinetic and mechanistic studies, 5, 257 liquid crystalline behaviour, 5, 262 lithiations and electrophile reactions, 5, 236 as main polymer chain unit, 5, 251 mass spectroscopic studies, 5, 256 miscellaneous compounds, 5, 258 NMR studies, 5, 255 palladium coupling, 5, 239 polymer-bound complexes, 5, 250 spectroscopic studies, 5, 256 X-ray data analysis, 5, 257... 

Bis(adamantylimido) compounds, with monomeric chromium(VI) complexes, 5, 348 Bis(alkene) complexes conjugated, Rh complexes, 7, 214 mononuclear Ru and Os compounds, 6, 401 -02 in Ru and Os half-sandwich rj6-arenes, 6, 538 with tungsten carbonyls and isocyanides, 5, 685 Bis(u-alkenylcyclopentadienyl) complexes, with Ti(II), 4, 254 Bis(alkoxide) nitrogen-donor complexes, with Zr(IV), 4, 805 Bis(alkoxide) titanium alkynes, in cross-coupling, 4, 276 Bis(alkoxo) complexes, with bis-Cp Ti(IV), 4, 588 Bis[alkoxy(alkylamino)carbene]gold complexes, preparation, 2, 288... 

Heinrich Dotz, from the Kekule-Institut (a predestined name ) of the University of Bonn, is another famous chemist who has given his name to a reaction. Coming from E. O. Fischer s school, he advantageously exploited his serendipitous discovery of the very rich reactivity of Fischer-type carbene complexes in synthesizing polycydic arene derivatives. This chromium-templated carbene benzannulation approach to densely functionalized arenes (Dotz reaction) is the subject of the chapter (No. 8) that he has co-authored with J. Stendel Jr. 

The benzannulation technique is also applicable to the benzene homologation and functionalization of annulenes, as well to a quadruple arene modification of dendritic cores. The reaction of chromium carbene functionalized l,6-methano[10]annulene 82 with 3-hexyne under standard conditions afforded a fair yield of the benzannulation product 83 after protection and oxidative work-up (Scheme 32) [75]. The chromium complex 84 evidently partly survived the oxidation conditions using Feln a syn-stereochemistry with respect to the Cr(CO)3 fragment and the methano bridge was suggested on the basis of NMR data, which is in contrast to the preferred formation of anti-annulation products bearing cydophane skeletons [75b]. 

Apart from the construction of phenanthrenes, carbene complexes have also been used for the synthesis of more extended polycyclic arenes. An unusual dimerization of chromium coordinated ortbo-ethynyl aryl carbenes results in the formation of chrysenes (Scheme 37) [81]. This unusual reaction course is presumably due to the rigid C2 bridge that links the carbene and alkyne moieties, and thus prevents a subsequent intramolecular alkyne insertion into the metal-carbene bond. Instead, a double intermolecular alkyne insertion favored by the weak chromium-alkyne bond is believed to occur forming a central ten-membered ring that may then rearrange to the fused arene system. For example, under typical benzannulation conditions, carbene complex 97 affords an equimolar mixture of chrysene 98a and its monochromium complex 98b. The peri-interactions between the former alkyne substituent (in the 5- and 11-positions) and the aryl hydrogen induce helicity in the chrysene skeleton. 

The diverse chemistry of chromium carbonyl complexes has its origin in the discovery of Cr(CO)6 in 1926 by Job and Cassal. Early developments in this area included the preparation of the (jj -arene)Cr(CO)3 family of organometallics by Nicholls and Whiting in 1959, the synthesis of the first structurally characterized carbene complex by Fischer and Maasbdl (1965), and a... 

The chromium-templated coupling of alkenyl- or arylcarbene, aUcyne and carbonyl ligands generates arene tricarbonylchromium complexes as primary benzannulation products which - based on their unsymmetric substitution pattern - bear a plane of chirality. Chiral arene complexes are powerful reagents in stereoselective synthesis however, the preparation of pure enantiomers is a lengthy and often tedious procedure, and thus diastereoselective benzannulation appears to be an attractive alternative. In order to lure the chromium fragment to one or the other face of the arene formed, chiral information may be incorporated in the carbene complex or the aUcyne. 

Dotz has reviewed the use of chiral centers in either the alkyne or chromium carbene to control the facial selectivity of the chromium arene complex. Examples of these diastereoselective benzannulations exist with the controlling stereocenter in the alkyne, the chromate ester (or amide), or the unsaturated carbene. ... 

A considerable number of ehromium arene complexes have been studied, none of which have particularly large second-order responses, and the most efficient of which are matched by cumulenyl carbene complexes in whieh the pentacarbonyl-chromium unit functions as an acceptor. Nonlinearities for the (arene)ehromium... 

In a more general and attractive alternative readily available chiral alcohol auxiliaries such as (-r)- or (-)-menthol have been incorporated into the carbene ligand. Benzannulation of chromium carbene 15 afforded arene complexes 16 and 17 (d.e. 81%) that have been diastereopurified by chromatography and characterized by X-ray analysis (Scheme 11.8) [29]. 

Herndon et al. have investigated the reactions of Fischer carbene chromium complexes with conjugated enediynes that feature a pendant alkene group such as 32. The experimental results confirm that arene... 

Alternatively, the arene can be left complexed so that the chemistry of the Ti -arene complex can be exploited (see Section 10.3). " The Dotz reaction between the cyclohexenyl carbene 8.52 and the benzylic alkyne 8.53 in the presence of a silylating agent gave the ti -complex 8.54 (Scheme 8.18). Treatment of this complex with LDA resulted in formation of the anion a- to sulfur 8.55 that cyclized by nucleophilic attack onto the chromium-complexed aromatic ring. Oxidative work-up then gave the tetracycle 8.57. 

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