Double benzannulation

Scheme 24 Diastereoselective biaryl synthesis via double benzannulation...

Having sufficient amounts of these novel dienes in hand opens the field for further study. Cycloaddition of acetylenedicarboxylic acid dimethyl ester (ADDE) to [3]dendralene 7 in toluene first afforded the l l-adduct 43, which by a second addition of ADDE provided the expected 2 l-adduct 44. After this had been aromatized by treatment with DDQ to the naphthalene derivative 45, a double benzannulation could be carried out as described in Scheme 8 [13]. 

The binaphthohydroquinone skeleton is accessible by a double benzannulation of a bi-phenylbis(carbene) complex using two equivalents of alkyne. Application of one alkyne equivalent affords the mono-benzannulated product the second benzannulation step proceeds with distinctly lower yield [68a]. A complementary approach to biaryls is based on 1,3-dialkynes (for example, 64) which undergo a stepwise benzannulation sequence (for example, yielding 65 and 66) (Scheme 26) [68c]. A one-step protocol starting from the ethylene-bridged bis-carbene complex 67 affords the conformationally less flexible biaryl 68, albeit in only moderate yield. 

Obviously, CuCla exhibits dual roles as an alkynophilic Lewis acid and as a chlorinating agent in this reaction. With conjugated diyne 25, double benzannulation occurred and 2,2 -binaphthyls 26 were obtained exclusively in a highly stereoselective manner (Scheme 15.9). 

Double benzannulation can be applied to the diastereoselective synthesis of biaryls. Upon reaction with diphenylbutadiyne the biscarbene complex 96 bearing a Cj-symmetric (2J ,3R)-butane-2,3-diol bridge affords a single R,R,S-diastereomer of the tethered 2,2 -binaphthol 97 in moderate yield (Scheme 11.28) [53],... 

The three different benzoxepins are simply assigned by the position of the oxygen 1 -benzoxepin, 2-benzoxepin, 3-benzoxepin. Among the four possible dibenzoxepins only dibenz[6,d]oxepin and dibenz[6,/]oxepin are of importance whereas the two other isomers are only of theoretical interest because they contain unfavorable o-quinoid structures. Benzannulation across all of the C-C double bonds leads to tribenz[6,rf,/]oxepin. 

According to the Hantzsch-Widman system, the seven-membered unsaturated hcterocyclc with one sulfur atom is named thiepin (1). The three different benzothiepins are assigned by the position of sulfur 1-benzothiepin (2), 2-benzothiepin (3) and 3-benzothiepin (4). Of the four possible dibenzothiepins only dibenzo[6,r/]thiepin (5) and dibenzo[A,/]thiepin (6) are of importance for synthesis, while the other two isomers, which contain unfavorable o-quinoid structures, exist mainly as the stable dihydro compounds, i.c. 5,7-dihydrodibenzo[c,t ]thiepin (7) and 6,1 l-dihydrodibenzo[6,c ]thiepin (8). Benzannulation over all double bonds results in tri-benzo[6,(7,/]thiepin (9). 

Chemoselectivity plays an important role in the benzannulation reaction as five-membered rings such as indene or furan derivatives are potential side products. The branching point is again the rf-vinylcarbene complex D intermediate which maybe formed either as a (Z)- or an ( )-metallatriene the (E)-configuration is required for the cyclisation with the terminal double bond. (Z)-Metallatriene D, however, leads to the formation of furan derivatives H (Scheme 8). Studies on the formation of (E)- and (Z)-isomers discussing stereoelectronic effects have been undertaken by Wulff [17]. 

A double linear annulation was observed in the benzannulation reaction of the helical biscarbene complex 27 with 3-hexyne along with a product bearing... 

The second option involves the incorporation of either chiral amines or chiral alcohols into the heteroatom-carbene side chain (R ), which represents the most versatile approach to diastereoselective benzannulation. The optically pure (2R,3R)-butane-2,3-diol was used to tether the biscarbene complex 37. The double intramolecular benzannulation reaction with diphenylbutadiyne allowed introduction of an additional stereogenic element in terms of an axis... 

The thermal benzannulation of Group 6 carbene complexes with alkynes (the Dotz reaction) is highly developed and has been used extensively in synthesis [90,91]. It is thought to proceed through a chromium vinylketene intermediate generated by sequential insertion of the alkyne followed by carbon monoxide into the chromium-carbene-carbon double bond [92]. The realization that photodriven CO insertion into Z-dienylcarbene complexes should generate the same vinylketene intermediate led to the development of a photochemical variant of the Dotz reaction (Table 14). 

A bidirectional benzannulation strategy allows the extension of an existing biaryl skeleton. The BINOL-derived bis-carbene complex 69, accessible through a sequence of regioselective double ortfio-lithiation/Fischer carbene complex synthesis, undergoes bidirectional benzannulation to give the dinuclear biphenanthrene complex 70. The optical induction exerted by the binaphthyl core is, however, only moderate a mixture of C2- and Cj-symmetrical bis(phenanthrohydroquinone) bis-chromium complexes is formed, in which the C2-... 

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. 

Pyrazolyl- [85], dihydropyridyl- [86], and pyrrolizinylcarbene complexes [87] have also been subjected to the benzannulation to give the respective oxygenated benzo-N-heterocycles. Finally, a,/ ,y,dienyl carbene complexes containing a heterocyde at the internal double bond have been utilized to prepare 2,3-dihydro-l,2-benzisoxazoles and indazoles by intramolecular benzannulation [60h]. 

Divinylbenzene-hydrophilic methacrylate copolymer 944 DNOC 1350 Domesticine 1064 DOtz benzannulation 454-459 Double Fourier transform filtering 984, 985 DRD 953 Drinking water,... 

Analogously to the all-carbon cyclophanes, ether exomethylene paracyclophanes can easily be prepared via the Pd-catalyzed benzannulation of bis-enynes (Scheme 14.29a) [21b]. Additionally, introduction of an ester tether between two enynes allowed for the synthesis of methacyclophanes containing an endocyclic double bond [21c] (Scheme 14.29b). In agreement with the general reactivity profile of enynes toward Pd-catalyzed homo-benzannulation, ester-containing substrates provided better yields of desired cyclophanes under milder reaction conditions than those of all-carbon or ether tethered bis-enynes. 

The synthesis of a series of 6,6-bisbenzannulated spiroketals has been achieved by a novel microwave-assisted double intramolecular hetero-Michael addition approach, with good yield (Choi et al, 2009). In this synthesis, coupling of an aryl acetylene and an aryl aldehyde led to an alky mol via acetylide anion addition, which was followed by oxidation to give the desired ynone. Spirocyclization afforded bis-benzannulated spiroketals. 

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