Chromium from benzannulations

Benzo[ifc,/]xanthenes result from the chromium-mediated benzannulation of the carbene complex (20) <96CC895>, whilst the photooxidative cyclisation of ( )-2-styrylchromones (21) leads to benzo[a]xanthones <96HCM251>. 

Structural analogues of the /]4-vinylketene E were isolated by Wulff, Rudler and Moser [15]. The enaminoketene complex 11 was obtained from an intramolecular reaction of the chromium pentacarbonyl carbene complex 10. The silyl vinylketene 13 was isolated from the reaction of the methoxy(phenyl)-carbene chromium complex 1 and a silyl-substituted phenylacetylene 12, and -in contrast to alkene carbene complex 7 - gave the benzannulation product 14 after heating to 165 °C in acetonitrile (Scheme 6). The last step of the benzannulation reaction is the tautomerisation of the /]4-cyclohexadienone F to afford the phenol product G. The existence of such an intermediate and its capacity to undergo a subsequent step was validated by Wulff, who synthesised an... 

A similar tandem Dotz-Mitsunobu reaction has been reported starting from a l,6-methano[10]annulene carbene complex, but no conclusion could be reached on the influence of the chiral information regarding the stereoselective course of the reaction since the chromium fragment could not be kept coordinated to the benzannulation product [47]. 

The fact that pentacarbonyl carbene complexes react with enynes in a chemo-selective and regiospecific way at the alkyne functionality was successfully applied in the total synthesis of vitamins of the Kj and K2 series [58]. Oxidation of the intermediate tricarbonyl(dihydrovitamin K) chromium complexes with silver oxide afforded the desired naphthoquinone-based vitamin K compounds 65. Compared to customary strategies, the benzannulation reaction proved to be superior as it avoids conditions favouring (E)/(Z)-isomerisation within the allylic side chain. The basic representative vitamin K3 (menadione) 66 was synthesised in a straightforward manner from pentacarbonyl carbene complex 1 and propyne (Scheme 38). 

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. 

Among the synthetically useful reactions of Fischer carbenes, the benzannulations are certainly the most prominent. In particular, the so-called Dotz reaction, first reported by Dotz in 1975 [3], is an efficient synthetic method that starting from aryl- or alkenyl-substituted alkoxycarbene complexes of chromium affords p-alkoxyphcnol derivatives by successive insertion of the alkyne and one CO ligand in an a,/Tunsaturated carbene, and subsequent electrocyclic ring closure (see Figure 1). 

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 affords arene-Cr(CO)3 complexes possessing a plane of chirality resulting from the unsymmetrical arene substitution pattern. This aspect is relevant to stereoselective synthesis, in which enantiopure arene tricarbonyl chromium complexes play a major role [56]. The benzannulation reaction avoids both harsh conditions incompatible with the retention of chiral information and the cumbersome separation of enantiomers, and is thus attractive for the diastereo- and enantioselective synthesis of arene complexes [17b, 57]. 

To date, reports of linear benzannulation are very limited [55b, 79]. One example referred to the annulation of a 2-naphthohydroquinoid chromium carbene, which was employed in the synthesis of anthracycline (see Section 8.6.2) [79]. Later, a complementary approach in this area started from 2-naphthylcyclopropenes which, in the presence of hexacarbonyl-molybdenum, served as precursors for the vinyl ketenes required for linear annulation [55b],... 

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. 

Benzoindole 114 has been synthesized by a remarkable sequence, in which the benzannulation precursor 113 is pre-assembled starting from two different chromium carbenes. It is formed in a [3+2] cycloaddition, in which the acylamino carbene complex 111 acts as the dipolar component and the alkynylcarbene complex 112 serves as the dipolarophile. The resulting 3-pyrrolylcarbene complex 113 undergoes a photoinduced intramolecular benzannu-lation to give the benzoindole 114 [84a]. This strategy complements an approach towards carbazoles [84b], Isoindolines and 1,2,3,4-tetrahydroisoquinolines are accessible from the reaction of pentacarbonyl (a-methoxyethylidene) chromium with 7r,co-dialkynes bearing a nitrogen atom in the carbon ether [84c]. 

Novel helicene-like quinones 222 were prepared from silylene-tethered binaphthols based on the newly developed chromium-templated [3+2+1] benzannulation reaction (Figure 7) <2005EJ01541>. 

P. Quayle and co-workers utilized the Dotz benzannulation reaction for the synthesis of diterpenoid quinones." The authors developed a novel synthetic approach to 12-O-methyl royleanone using a simple vinyl chromium carbene complex along with a disubstituted oxygenated acetylene. The bicyclic hydrazone was converted to the corresponding vinyllithium derivative by the Shapiro reaction and then functionalized to give the desired crude Fischer chromium carbene complex. The benzannulation took place in refluxing THF with excellent regioselectivity, and the natural product was obtained in 37% overall yield from the hydrazone. 

A comprehensive treatment of the benzannulation of Fischer carbene complexes with alkynes is not possible in this review, and thus instead the material presented here will hopefully serve to give the reader an overview of its scope and limitations. The first report of this reaction was in 1975 by Dotz in which he describes the formation of the naphthol chromium tricarbonyl complex (236) from the reaction of the phenyl chromium complex (la) with diphenylacetylene. In the intervening years over 100 papers have been published describing various aspects of this reaction.The reaction of the generic cartene complex (233 Scheme 34) with alkynes will serve to focus the organization of the scope and limitations of the benzaimulation reaction. The issues to be considered are (i) the regioselectivity with unsymmetri-cal alkynes (ii) possible mechanisms (iii) applications in natural product syntheses (iv) the effect of substitution on the aryl or alkenyl substituent of the carbene carbon (v) functionality on the alkyne (vi) effects of the solvent and the concentration of the alkyne (vii) tandem applications with other reactions of carbene complexes (viii) reactions where aromatization is blocked (cyclohexadienone annulation) (ix) annulation of aryl versus alkenyl carbene complexes (x) the effect of the ligands L on the metal (xi) the effect of the ancilliary substituent RX and (xii) reactions with —C X functionality. 

C. A. Merlic made use of this procedure in a benzannulation reaction leading to ortho-substituted phenols. Note that the photochemical method perfectly complements the Dotz-reaction which gives p-alkoxyphenols from chromium carbene complexes and alkynes. 

Synthesis of Five-Membered Carbocycles An annulation of chromium arylcarbenes by alkynes without CO-insertion leads to five-membered rings. It has been observed as a side reaction along the benzannulation which may become predominant depending on the nature of the carbene heteroatom substitution pattern, [72] the metal [40] and its coligands [73] and the solvent [43] used. In this respect, indene derivatives have been obtained from arylcarbene complexes of chromium and tungsten. [73,74]... 

Also known as the Dotz benzannulation, the Dotz reaction is the Cr(CO)3-coordinated hydroquinone from vinyhc alkoxy pentacaiboityl chromium caibene (Fischer carbene) complex and alkynes. 

A recent synthesis of this building block has been published by Eastham et al. in 2006 (48). Their key step is a Dotz benzannulation reaction and is shown in Scheme 2.10. The bromohydrin 66 was formed from dihydrofuran (50). Cobalt-mediated cyclization, followed by ozonolysis with reductive work-up yielded 68 after hydrazine formation. Reductive removal of the hydrazine function, followed by chromium-carbonyl formation gave the Dotz reaction precursor 69. This reacted with an alkyne in the Dotz reaction, and was then oxidized and hydrogenated 70). Pyrolysis gave the protected alcohol and the remaining free alcohol was protected as a triflate (—> 71). Reductive removal of the triflate and deprotection of the silyl ether yielded the desired 33 in 1.2% overall yield. 

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]. 

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