Ortho-functionalization

Le Bras, J. Rager, M. N. Besace, Y. Vaissermann, J. Amouri, H. Activation and regioselective ortho-functionalization of the A-ring of P-estradiol promoted by Cplr an efficient organometallic procedure for the synthesis of 2-methoxyestradiol. Organometallics 1997, 16, 1765-1771. 

The specific ortho functionalization of arylamines is obviously important in quinoline synthesis (cf. the rc-allyl procedure devised for the preparation of o-allylanilines used as indole and quinoline precursors).76 Recently acetanilides have been subjected to orthopalladation and the ensuing complexes converted into useful precursors of 2-substituted quinoline derivatives (Scheme 143).215... 

The synthesis of ferrocene 9 relied on chemistry introduced by Sammakia, Uemura, and Richards [18]. They had shown that 2-ferrocenyl oxazoline 10 derived from t-leucine could be selectively deprotonated and trapped with electrophiles to afford ortho-functionalized planar-chiral products 11 with excellent diastereoselectivities (Scheme 2.1.2.3). Following this strategy, 9 became accessible in a highly straightforward manner by trapping the lithiated intermediate derived from 10 with benzophenone [10, 11],... 

A substantial number of important syntheses that depend on the attack of ketone enolates on ortho-functionalized aryl or heteroaryl halides, and that lead to cyclized products are discussed in Section 2.2.4.2. 

The sulfoximine group has proved to be an excellent ortho-directing group in lithiation reactions.77 The use of prochiral electrophiles has afforded ortho-functionalized (g) arylsulfoximines in good yields and modest to good diastereoselectivities up to 95%. 

These are ortho functions which are symmetric with respect to Pi 2 and para functions which are antisymmetric. The ortho combinations always have the greater weight, that is, the greater number of independent nuclear spin functions. Thus we have... 

The radical nucleophilic substitution is perfectly suited for tandem reactions [180]. Recent examples have been reported by the Rossi group (Scheme 66). Dihydrobenzofuranes and dihydroindoles substituted at the 3-position were prepared from ortho-functionalized haloaromatic compounds in high yields [181]. The nucleophiles involved in the initial electron transfer and subsequent coupling are varied. In particular, starting form naphthyl derivative 210, phosphinyl anions lead to tricyclic phosphine oxide 211 (after oxidation) in 98% yield. 

Cyclodehydration of 2-hydroxy- or 2-aminobenzene-ethanal derivatives is known as a general procedure for the synthesis of benzo-fused heteroaromatic compounds [95]. Although numerous modifications of this general method have been explored, the major difficulty seems to be the lack of a general method for the synthesis of the required ortho-functionalized arene-ethanals. 

A new synthetic strategy which leads specifically to ortho-functionalization of aromatic amines was based on the initial formation of the intermediate aminosulfonium ions 205, which were converted into ylides 206 in the presence of bases291 (equation 79). The ylides 206 underwent [2,3]-sigmatropic rearrangement to the orf/zo-substituted anilines 207. 

Examples for cyclization reactions via extrusion of partial constituents of the ortho function are the well-known decompositions of phthalic acid derivatives, 85,... 

Although the belief that steric factors influence norbomene extrusion is reasonable and supported by Catellani s studies, it is entirely possible that norbomene carbopalladation and extrusion are reversible processes. If so, a species related to 4 may be trapped as the mono-o/t/to-alkylated product. Although mono-functionalization has been observed in stoichiometric studies by Catellani [31, 42], catalytic reactions generally do not afford monoalkylated products. Interestingly, Lautens has shown that in some particular systems mono-alkylation is possible, which may occur as a result of a sterically congested system (Scheme 14) [44], This does lend some evidence to the possibility that norbomene carbopalladation and extrusion are reversible steps, and may occur between ortho functionalization steps. 

While Ferraccioli, Catellani, and Lautens had success in developing ortho-functionalization/amination reactions, there are still improvements to be made in this area of research. To date, there have been no reports of an intermolecular animation reaction as part of the Catellani reaction sequence. Although challenging, this reaction would allow access to interesting polysubstituted IV-arylamines, and should be a goal of future research. 

Figure 23.10 Integrated three-step continuous-flow system for the preparation oi ortho-functionalized phenols.

A reduction of the melting temperatures of aromatic LC polyesters can also be accomplished efficiently by the partial incorporation of kinked comonomers. Suitable monomers are meta- or ortho-functionalized benzene rings, meta- or ortho-functionalized six-member heterocycles, and 2,5-func-tionalized five-member heterocycles. A frequently used alternative is two benzene rings connected by linking groups such as... 

Reproduced from Urano M, Wada S, Suzuki H. A novel dry route to ortho-functionalized triarylbismuthanes that are difficult to access by conventional wet routes. Chem Commun 2003 1202-03, with permission from the Royal Society of Chemistry. 

Another heteroannulation is combination of aryl and alkenyl halides with ortho-functionalized phenylalkynes 95 to give heterocycles 97 such as benzofurans and indoles (Scheme 3.11). In this reaction, trans addition of Ar-Pd to a triple bond and endo cyclization, as shown by 96, occur. 

H. Wang, T.-S. Chung, D.R. Paul, Physical aging and plasticization of thick and thin films of the thermally rearranged ortho-functional polyimide 6FDA-HAB, Journal of Membrane Science 458 (2014) 27-35. 

A series of arylations of olefins by C-H bond cleavage without direction by an ortho functional group has also been reported, and these reactions can be divided into two sets. In one case, the C-H bond of an arene adds across an olefin to form an alkylarene product. This reaction has been called hydroarylation. In a second case, oxidative coupling of an arene with an olefin has been reported. This reaction forms an aryl-substituted olefin as product, and has been called an oxidative arylation of olefins. The first reaction forms the same t)q)es of products that are formed from Friedel-Crafts reactions, but with selectivity controlled by the irietal catalyst. For example, the metal-catalyzed process can form products enriched in the isomer resulting from anti-Markovnikov addition, or it could form the products from Markovnikov addition with control of absolute stereochemistry. Examples of hydroarylation and oxidative arylation of olefins are shown in Equations 18.63 - and 18.64. ... 

The ready availability of ortAo-functionalized arylboronic acids by a metallation-boronation sequence provides a s)mthetic link to the crosscoupling protocol, which allows syntheses of various polycyclic heteroaromatics via cyclization between two ortho functionalities. The synthesis of arylboronic acids having an CONl 2 OCONEt2, NH Boc, or and their coupling with various... 

H. Wang, D.R. Paul, T.S. Chung, The effect of purge environment on thermal rearrangement of ortho-functional polyamide and polyimide. Polymer 54 (23) (2013) 2324-2334. 

More recently, a palladium-catalyzed tandem protocol for the synthesis of cyclopentene fused heterocycles from diazabicyclic alkenes and ortho-functionalized atyl iodides was elaborated. A number of cyclopentene fused dihydrobenzofurans and indolines were prepared by this procedure (Scheme 2.50). The reaction can he tuned toward the formation of either... 

Phenolic oxidations are pivotal steps frequently involved in the biosynthesis of natural products, which possess a variety of important biological activities. Therefore, a continuing interest exists in such transformations, in particular in asymmetric oxidative protocols. Kita et al. performed asymmetric dearomatization of naphthols 43 mediated by chiral hypervalent iodine(III) reagents, 33 and 45 having a rigid spirobiindane backbone (Scheme 20) [66, 67]. A series of other ortho-functionalized spirobiindane reagents of type 46 were synthesized. Intramolecular oxidative substitution of 43 afforded five-membered spirolactone 44 with good levels of enantioselectivity (up to 92% ee). Conformationally flexible iodoarenes employed in this study produced almost racemic products. Catalytic use of these chiral catalysts with wCPBA as cooxidant afforded the chiral spirolactones without detrimental effects on the ee values. 

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