85370-72-5Relevant articles and documents
Mise au point. Reaction de metallation ortho dirigee des composes aromatiques. Nouvelles methodologies et applications en synthese organique
Snieckus, Victor
, p. 67 - 78 (2007/10/02)
In recent years, the aromatic directed metalation reaction has developed into a broadly useful protocol for the regiospecific construction of polysubstituted aromatics and has been applied in efficient total syntheses of diverse classes of natural products.In this review, both methodological and total synthesis advences using primarily the tertiary carboxamide and carbamate as metalation directors are presented.First, general aspects such as the nature of the directed metalation group (DMG) (scheme 1), the effect of two meta-related DMGs on the metalation process (scheme 2), the relative directed metalation abilities of different DMGs (scheme 3), and the scope of reaction with various electrophiles (scheme 4) are first discussed.Next, the advantage of the directed metalation tactic for the synthesis of several classes of natural products (anthramycin, scheme 7 ; angular anthracyclinones, scheme 8 ; and cannabifuran, schemes 10 and 11) are conceptualized and briefly described.Further, the significance of silicon functionality in context of directed metalation chemistry is demonstrated by its use for protection of prefferentially reactive aromatic C-H and C-methyl sites (scheme 12), ipso desilylation (scheme 13), generation of o-quinodimethanes (scheme 14), and overcoming normal Friedel-Crafts regioselectivity in carboannelation (schemes 16-18).Aspects of the tertiary carbamate as a ortho metalation director (scheme 19) are delineated : the development of an anionic ortho-Fries rearrangement (scheme 21) ; a new, also anionic, ortho-tolyl carbamate rearrangement leading to benzofuranones (scheme 22) ; its comparison with tertiary amide a methoxymethoxy as a DMG (scheme 23) ; its use for the generation of benzamide benzyne intermediates (scheme 24) ; metalation of O-pyridyl carbamates (scheme 25) and its synthetic ramifications (schemes 26-28) ; and its application in conjunction with amide metalation for the synthesis of the ochratoxin metaolites (scheme 29).Dimetalation of benzamides (scheme 32), phthalamides (scheme 33), p,p- and o,o-aryl dicarbamates (schemes 34 and 35) are supported by reactions with various electrophiles.To conclude, recent work aimed at connecting the aromatic directed metalation strategy to other modern synthetic methods is described.Coupling the directed metalation process with the radical-induced annelation provides new routes to benzofurans (scheme 36) and furopyridines (scheme 37) and is applied to the preparation of a key synthon for the mould metabolite, aflatoxin (scheme 38).Anionic aromatic and heteroaromatic ring annelation processes which depend upon ortho metalated precursors lead to naphthalene (schemes 39-41) and 4-quinolone (scheme 42) derivatives.Aryl boronic acids with ortho-DMGs, synthesized by metalation-boronation and ipso borodesilylation methods, are cross coupled with aryl bromides under palladium (O) catalysis leading to new routes for the preparation of unsymmetrical biaryls (scheme 45).
Transmetalation and Reverse Transmetalation on Ortho-Activated Aromatic Compounds: A Direct Route to o,o'-Disubstituted Benzenes
Eaton, Philip E.,Martin, Ronald M.
, p. 2728 - 2732 (2007/10/02)
Mercury Substitution ortho to appropriately activated benzenes was achieved by using the reagent lithium tetramethylpiperidide (LiTMP)/ mercuric chloride.LiTMP provides for lithiation ortho to the activating group; HgCl2 functions as an in situ trap effecting mercury-for-lithium transmetalation.Ortho, ortho'-dimercuration was also observed; this occurs by iteration of the transmetalation process.The effects of major variables on these reactions were studied by using primarily N,N-diethylbenzamide as the activated substrate.Isopropyl benzoate, 2-phenyl-4,4-dimethyloxazoline, etc. were found to behave similarly.The mercurated aromatics could be converted to the corresponding haloaromatics in excellent yield, providing, for example, a good synthesis of o,o'-diiodo-N,N-diethylbenzamide, otherwise difficultly accessible.Reverse transmetalation methodology was employed to prepare o,o'-dilithiated-N,N-diethylbenzamide, which was characterized by its reactions with electrophiles.
Directed Metalation of Tertiary Benzamides. Silicon Protection of Ortho Sites and Ortho Methyl Groups
Mills, R. J.,Snieckus, V.
, p. 1565 - 1568 (2007/10/02)
Metalation of 2-trimethylsilyl or 2-bis(trimethylsilyl)methyl benzamides occurs selectively at the 6-position, providing regiospecific routes to various trisubstituted benzenes.
