Bicyclo octanes aromatization

Despite the Tbt stabilization, the silabenzene and germabenzene are highly reactive towards water or alcohols (the RO residue adds to the heteroatom, and a hydrogen adds to a 2- or 4-carbon atom, destroying the aromaticity) benzophenone, styrene, and phenylacetylene afford bicyclo[2.2.2]octane-derivatives. In all these products, the heteroatom (Y = Si or Ge) has. sp3-hybridization. 

A major initial limitation of the benzocyclobutene approach to o-quinodimethanes was the lack of efficient, large-scale syntheses for many specifically substituted derivatives. Fortunately, recent developments have lemov much of this impediment. Q>nceptually, the synthesis of benzocyclobutenes from aromatic precursors can be envisaged in only a limited number of ways. These include [2 -i- 2] cycloadditions involving benzynes and alkenes, intramolecular cyclization on to a benzyne, cyclizations involving arene anions, and electrocyclic closure of o-quinodimethanes. Benzocyclobutene derivatives can also be prepared by aromatization of bicyclo[4.2.0]octanes. Detailed discussion of variations to these approaches can be found in the cited reviews. The cobalt catalyzed co-oligomerization of 1,5-hexadiynes with al-kynes, especially bis(trimethylsilyl)acetylene, has also been employed for the preparation of specifically substituted benzocyclobutenes. In the latter case the cyclobutenes are often not isolated but converted directly to o-quinodimethanes and subsequent products. ... 

Similar procedures are also successful in the construction of cyclobutane rings in other stereochemical environments, including the formation of bicyclo[3.1.1]heptane (67)and bridged tricyclic systems such as (68), (69) ° and (70). ° A variety of annelated cyclobutanes have been prepared by the photochemical procedure as above, yields are sometimes poor or only moderate. Examples include bicy-clo[2.1.0]pentanes (71), °° bicyclo[2.2.0]hexanes (72)"° and cyclobuteno aromatics (e.g, 73), " o-nor-steroids e.g. 74)," A-bisnorsteroids" and triterpenes" as well as the highly strained tricyclo[4.2.0.0 ]octane system (75)," and the [4.4.4.5]fenestrane (76)." ... 

However, the stereoselective reductions of the 5-substituted adamantanones 3.50 [CT2, G5, KA4, LL5], and bicyclo-[2.2.2]-octan-2-one 3.51 [MK5] have been interpreted in terms of Cieplak s model [C6, CT3]. Unfortunately, the observed stereoselectivities are low (de <40%), so that it is difficult to dissect the various parameters involved in such reductions [CHS, N2], The electronic contribution to the stereoselectivity of the reduction of substituted 9-benzonorbomenones 3.52 is very important [G5, OTl, OT2] (Figure 3.20). Halogen substituents on the aromatic ring favor syn attack by all hydrides on those very rigid systems. Electrostatic effects have been invoked to interpret these results [PW2, WTl]. 

Pyridines and pyrimidines were patented separately, to complete an impressive array of protection for the heterocyclic triketones [35]. Nevertheless, after the first patent appeared regarding this novel substance class, most of the major companies started programs in the field. There were basically two strategies Some companies searched for novel diones that were at the time outside the scope of the Zeneca published patents, while other companies searched for novel aromatic acids. For example, Sandoz (now Syngenta) concentrated on the search for novel diones, and several compounds containing bicyclo[3.2.1]octane-2.4-dione, such as 29 [36, 37] and 30 [38], as well as the oxazinedione types (31) [39, 40], were important compounds for use in corn (Fig. 4.3.5). A collaboration between Sandoz and SDS Biotech has also led to the identification of proform triketones containing bicyclo[3.2.1]octane-2.4-diones for use in rice, such as benzobicyclon (9) [41]. 

LCs. Among them are carboranes D and E and other 12- and 10-vertex doi o-boranes, which uniquely combine some aspects of the electronic strnctnre of conventional aromatics with steric features of bicyclo[2.2.2]octane. ° Therefore, they are attractive for designing new materials with unusual combination of properties and for addressing questions in the area of fundamental and applied liquid crystal research and technology. 

Like cyclohexyl systems, the bicyclo-[2.2.2]octanes are usually only prepared with an alkyl terminal group and the principal route to the central intermediate (l-alkylbicyclo[2.2.2]octane with a 4-hy-droxy-,4-methoxy- or 4-bromo-substituent) is shown in Scheme 3 [45, 46]. All three intermediates can provide the 4-alkylbi-cyclo[2.2.2]octane-l-carboxylic acids (although the hydroxy or methoxy route is more direct) and the bromo compound can be used in Friedel-Crafts alkylation of aromatic compounds. The main examples of bicyclo[2.2.2]octane systems are cyano-aryl esters (3.2, X = CN [47-49], alkyl- and alkoxy-aryl esters (3.2, X = R, OR) [48,... 

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