Carbene demetallation

The use of a stereogenic carbon centre allowed an efficient asymmetric induction in the benzannulation reaction towards axial-chiral intermediates in the synthesis of configurationally stable ring-C-functionalised derivatives of al-locolchicinoids [51]. The benzannulation of carbene complex 52 with 1-pen-tyne followed by oxidative demetalation afforded a single diastereomer 53 (Scheme 33). 

Merlic developed a new variation of the thermally induced benzannulation reaction. The dienylcarbene complex 132 was reacted with isonitrile to give an orf/zo-alkoxyaniline derivative 135 [76] (Scheme 56). This annulation product is regiocomplementary to those reported from photochemical reaction of chromium dienyl(amino)carbene complexes. The metathesis of the isocyanide with the dienylcarbene complex 132 generates a chromium-complexed di-enylketenimine intermediate 133 which undergoes electrocyclisation. Final tau-tomerisation and demetalation afford the orf/zo-alkoxyaniline 135. 

A mechanistic picture which reconciles the experimental results is given in Scheme 24. It is assumed that both the heteroatom and the double bond of the allyl halide compete for an electrophilic metal carbene. Heteroatom attack yields a metalated ylide 129, which may go on to ylide 131 by demetalation and/or to allylmetal complex 130. Symmetry-allowed [2,3] rearrangement of 131 accounts for product 132, and metal elimination from 130 gives rise to products 132 and 133, corresponding to [2,3] and [1,2] rearrangement, respectively, as well as haloacetate (if R3 = CHc ). 

Heteroatom-substituted carbene complexes are normally rather stable compounds. Some reaction conditions, however, lead to seleetive demetallation of these complexes. The organic fragment can thereby be converted into different types of product (Figure 2.18). 

Elimination to yield alkenes can be induced thermally or by treatment with acids or bases (for one possible mechanism, see Figure 3.39) [138,206]. Less common thermal demetallations include the thermolysis of arylmethyloxy(phenyl)carbene complexes, which can lead to the formation of aryl-substituted acetophenones [276]. Further, (difluoroboroxy)carbene complexes of molybdenum, which can be prepared by treating molybdenum hexacarbonyl with an organolithium compound and then with boron trifluoride etherate at -60 °C, decompose at room temperature to yield acyl radicals [277]. 

Treatment of Fischer-type carbene complexes with different oxidants can lead to the formation of carbonyl compounds [150,253]. Treatment with sulfur leads to the formation of complexed thiocarbonyl compounds [141]. Conversion of the carbene carbon atom into a methylene or acetal group can be achieved by treatment with reducing agents. Treatment of vinylcarbene complexes with diborane can also lead to demetallation and formation of diols [278]. The conversion of heteroatom-substituted carbene complexes to non-heteroatom-substituted carbene complexes... 

Table 2.12. Demetallation of heteroatom-substituted carbene complexes with simultaneous C-H, C-N, and C-O bond formation.

Aminothiophenol 37 and 277 formed an isolable adduct 278 (X = S) that on heating was transformed to a mixture of complex 283 (10%) and the demetallated benzothiazepinone 284 (51%) (Scheme 50) <2003CEJ4943>. Similarly, monocyclic 1,4-oxazepinone derivatives of tungsten and chromium have been prepared by a domino [4+2]/[2+2] cycloaddition reaction of 1-alkynyl Fischer carbenes with oxazolines <20050M302>. 

Based on these reactivities various derivatives of carbenes, such as the aminocarbene 238, are prepared by displacement of the OR group in 237 with amine via addition elimination, analogous to transesterification [74,75], As an example the carbanion 240, generated by deprotonation of 239, attacks ethylene oxide to give the lactone equivalent 241, which is further alkylated by chloromethyl methyl ether, again at the -position. Finally the oc-methylene-y-lactone 242 is obtained by oxidative demetallation with a Ce(TV) salt [76],... 

A model compound from a second group of alkaloids related to colchicine (allocolchici-noid 137) has been synthesized by benzannulation of racemic benzocycloheptenyl carbene complex 135 with 1-pentyne the annulation product 136 was obtained in 48 % yield after oxidative demetalation (Scheme 47) [97]. 

Addition of carbenes to peripheral porphyrin double bonds has been studied. OEP (11) fails to react with ethyl diazoacetate, even in the presence of copper(I) iodide. The Cu-OEP, however, gave two isomeric Cu-iso-bacteriochlorins, which were demetallated to 92. Small amounts of a meso product 93 were also observed. A photochemical isomerization of 92 resulted... 

Diazafulvene 424 reacts with alkenylcarbenes 425 through a formal [64-3] heterocyclization in a regio- and stereoselective manner to afford dihydroimidazo[l,2- ]pyridines 426. When enyne carbenes are treated with diazafulvene 424, consecutive and diastereoselective [64-2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 429 that can be appropriately demetallated to the corresponding imidazole-based fused systems. Finally, enyne carbenes undergo consecutive [64-2]/[54-l] cyclization reactions with diazafulvene 424 and rt-butyl-NC to yield tetracyclic adducts 432 (Scheme 102) <2006CEJ3201>. 

Fischer carbene complexes undergo demetallative hydrosilylation. It can be adapted to a synthesis of allylsilanes. ... 

In alkenyl- and alkynylcarbene complexes the addition of nucleophiles to the carbene carbon competes with the addition to the 3-carbon of the conjugated C-C multiple bond. [17] The regioselectivity of the addition of amines to alkynylcarbene complexes is temperature dependent 1,2-addition is favoured by lower temperatures. [17c] Enolates turned out to be efficient C-nucleophiles for Michael addition reactions to unsaturated metal carbenes. The product distribution may depend on steric factors as shown in Scheme 7 for the addition of different enolates to alkenylcarbene complex 10. The less bulky acetone enolate 11 adds to the carbene carbon protonation of the primary addition product results in demetalation and in the formation of a mixture of isomeric enones 12. In contrast, the more bulky cyclopentanone enolate 13 adds to the less shielded vinylic position. 

Organometallic reagents were used for the synthesis of bicyclic aromatic compounds via Moore-type cyclization. Rahm and Wulff described the new synthesis of 5-hydroxyindolines with the use of a chromium carbene complex bearing alkynyl substituent 22." The amino-tethered bis-alkynyl carbene complex 22 was transformed into indoline 23 by thermolysis in the presence of a hydrogen source. The low yield of product 23 was improved when the reaction was carried out in the presence of the electrophile, added to protect the phenol function. This process involves the insertion of one carbon monoxide group from the chromium complex into the skeleton of an eneyne compound 24. The resulting enyne-ketene 25 undergoes a cycloaromatization reaction to afford the 1,4-diradical intermediate 26. Subsequent demetalation yields product 23."... 

Related pathways can operate in the endo-moAt, yielding the same functionality, but in a different carbon skeleton (Scheme 6.100). Other reactions may also occur, such as demetallation of the carbene to give an alkene 6.248. 

Alternatively, demetallation to give enol ethers 839 can be achieved by treatment with pyridine (Scheme 8.14). Under these conditions, as pyridine is a weak base, an equilibrium is established between the carbene 8.35 and its anion 837. The anion, however, can also reprotonate on chromium to give a chromium hydride 838. This is followed by reductive elimination. The enol ether 839 is obtained as its Z-isomer, a consequence of the carbene anion having S-geometry to keep the alkyl group away from the bulky Cr(CO)s moiety the chromium is converted into a pyridine complex. 

The single electron transfer (SET) reduction of Fischer alkynyl carbene complexes 95 with potassium graphite (CgK) results in the formation of cyclopentadienes 100 (Scheme 5.20) [31], The radical anion intermediates 96, generated by the SET reduction of Fischer alkynyl carbene complexes 95, undergo tail-to-tail dimerization to form bis-carbene anions 97. The intermediates 97 are protonated with a strong acid to produce the intermediates 98, which convert in situ into chromium cyclopentadienylcarbene 99. After the demetallation of the cyclopentadienylcarbene 99, cyclopentadienes 100 are obtained. 

Similar to aminolysis, the alcoholysis reaction can be applied to the synthesis of higher nuclearity metal carbenes as well. Low-temperature addition of 0.4 equivalents of pentaerythritol in DMF to a solution of chromium acetoxycarbene generated in situ from benzoyl chromates 133 (or 134) affords moderate yields of tetra-kischromium carbene 135 (or 136) which undergoes complete benzannulation with 3-hexyne to give an 80% yield of the spherical tetrakishydroquinone 137 after in situ protection of the naphthol intermediate with TBDMSCl and subsequent oxidative demetallation (Scheme 11.32) [57]. 

O-Glycosidic styrylcarbene complexes 298-302 prepared from chromium methyl-carbenes 239-243 and ben2aldehyde in a trans-selective aldol condensation undergo a chromium-templated benzarmulation upon reaction with per-benzyl-protected ethynyl glucopyranose 303. Oxidative demetallation results in the formation of hydroquinoid C- and O-biphenyl disacdiarides 304-308 (Scheme 11.62) [117]. 

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