Anionic ortho-Fries rearrangement

An anionic ortho-Fri s rearrangement has been used to make BINOL derivatives . ... 

The achievement of anionic ortho-Fries type rearrangements (320 324 and 325—>326) may open further DoM-based routes for the synthesis of oxygenated pyridines (Scheme 98) (85JOC5436). 

Attempts to use alkyllithium conditions to generate synthetically useful anions from the A,A/-dimethyl 5-, 6-, and 7-0-carabamates 366, 368, and 370 were unsuccessful, leading mainly to anionic ortho-Fries products. Under LDA conditions, the rearrangement (376->377) proceeded regio-specifically in modest yields at specific temperatures for each isomer to give products (temperature of rearrangement) 378 (-70°C), 379 (-70°C), 380 (-40°C), and 381 (20°C) (Scheme 115) [87JOM(336)l]. 

Aside from its summit position as a DMG (10, Scheme 3) the OCONEt2 provides versatile anionic aromatic chemistry anionic ortho-Fries rearrangement (9, Scheme 3) [11], a useful synthetic step by itself but also one that provides a path, after incipient phenol protection, to further DoM, resulting in a 1,2,3-sub-stituted aromatic derivative (9 —> 12, see also Scheme 13) [12] homo-ortho-Fries rearrangement to aryl acetamides (10 —> 11) providing a route to benzofura-nones which are difficult to prepare by Friedel-Crafts-based strategies [9] intra-... 

This chemistry can be very powerful, since the amide product itself offers further possibilities for functionalisation by lithiation. The synthesis of the natural product ochratoxin A (section 9.1) illustrates this point. Two successive ortholithiations of carbamate 210 are used first to introduce one amide group and then a second, by anionic ortho-Fries rearrangement. The symmetrical diamide 211 can be allylated and then cyclised in acid, with concomitant hydrolysis of the second amide and deprotection of the phenol to yield a known intermediate... 

Amides cyclise directly to ketones such as 80 the carbamates on the other hand pass through a cyclic transition state which collapses to an amide 82 (an anionic ortho-Fries rearrangement - section 2.3.2.1.4) which lactonises to 83. 

The starting point for the metallation sequence was /7-chlorophenol, whose directing power was first maximised by conversion to the carbamate 3. Ortholithiation and reaction with N,N-diethylcarbamoyl chloride gave the amide 4. The second ortho carbonyl substituent was then introduced simply by allowing the lithiated carbamate 5 to undergo an anionic ortho-Fries rearrangement to the bis-amide 6. The phenol was protected as its methyl ether 7. 

The similarly and equally accessible biaryl O-carbamate 142 (Scheme 38) requires ortho substitution (PG = OMe) or protection (PG = SiEts) to avoid anionic ortho Fries rearrangement (141) and to launch a DreM pathway leading to 144 using LDA under vigorous conditions [65]. For PG = TMS, carbamoyl migration to the incipient a-silylmethyl anion occurs... 

FRIES-, PHOTO-FRIES, AND ANIONIC ORTHO-FRIES REARRANGEMENT... 

Related reactions Fries-, Photo-Fries and Anionic Ortho-Fries rearrangement, Houben-Hoesch reaction, Minisci reaction ... 

Middel, O., Greff, Z., Taylor, N. J., Verboom, W., Reinhoudt, D. N., Snieckus, V. The First Lateral Functionalization of Calix[4]arenes by a Homologous Anionic Ortho-Fries Rearrangement. J. Org. Chem. 2000, 65, 667-675. 

Related reactiens Friedel-Cratts acylation, Fries-, photo-Fries and anionic ortho-Fries rearrangement, Minisci reaction ... 

Anionic ortho-Fries rearrangement is performed by freafment of variously subsfifufed aryl carbamates with sec-butyllithium at -78°C in tetramethylethylenediamine-tetrahydrofuran solution for 8-12 h. i The reaction involves the selective ortho-metalation of fhe aryl groups. The meta-cooperafive mefalafion effect is responsible for fhe producfion of some extremely hindered aromatic compounds (Table 5.13). 

The original Fries procedure has been modified extensively to occur under either UV irradiation (Photo-Fries Rearrangement) or anionic lithiation or lithium-bromo exchange (anionic ortho-Fries rearrangement). Other modifications include the application of microwaves,electron beam, BF3-H20, Y zeolite,zinc powder, Bi(OTf)3, and solid acid catalyst as the promoters. 

Scheme 14.34 Anionic ortho-fries rearrangement-Negishi cross-coupling strategy. Synthesis of the A/B/C/D fragment of 20-S-camptothecin 175 [150).

Combined DoM - Anionic ortho- Fries Rearrangement vs de novo Aromatic Ring Construction in Totai Synthesis... 

The total synthesis of the potent protein kinase C inhibitor (-)-balanol was accomplished by J.W. Lampe and co-workers. They took advantage of the anionic homo-Fries rearrangement to prepare the sterically congested benzophenone subunit. To this end, 2-bromo-3-benzyloxy benzyl alcohol was first acylated with a 1,3,5-trisubstituted benzoyl chloride to obtain the ester precursor in 84% yield. Next, the ester was treated with n-BuLi at -78 °C to perform a metal-halogen exchange. The resulting aryllithium rapidly underwent the anionic homo-Fries rearrangement to afford the desired tetra ortho-substituted benzophenone in 51% yield. 

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