Base-induced rearrangement esters

This reaction was initially reported by Favorskii in 1894. It is a base-induced rearrangement of a-halo ketones to the corresponding carboxylic acid derivatives (e.g., acids, esters, and amides) with the same number of carbon atoms in the skeletons and the bases can be hydroxide, alkoxide, or amines. Therefore, it is generally known as the Favorskii rearrangement. Occasionally, it is also referred to as the Favorskii reaction. ... 

A fourth approach to the oxatricyclo-[5.3.1.0 ]-undecane ring system of furanether B (18.8) was published recently by de Groot et al. 159) who relied upon a stereoselective base-induced rearrangement reaction of 1,4-diol monosulfonate esters to establish the bridged ether core of 18.8 (26.103 26.105, Scheme 35). The starting material of the synthesis was the known ketone 26.99 which was converted to the required methanesulfonate 26.103 by standard procedures. 

The advantage of using the prepared 2,3-epoxylactones for the study of the base-induced rearrangements discussed above is now clear. Direct treatment of the 2-bromolactones with aqueous base will cause rapid epimerisation at that center, and thus in aqueous base the bromodeoxylactone 17 will give both the 2,3-cis- as well as the 2,3-fra s-epoxide of the open aldonates. In the lactone form of course only cis-epoxides can be formed. The procedure for preparation of L-gluconic acid is thus performed by stirring 17 in acetone with excess of solid anhydrous potassium carbonate for about 30 min, followed by filtration, concentration, addition of water, and 3 molar equivalents of potassium hydroxide. After 3 days at room temperature the mixture is acidified and the product isolated as the ethyl ester [27]. 

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

Under the same conditions of NaH/THF, the ester 3 gave ltf-2-benzopyran derivative 5 in 60% yield, apparently by 6-endo-dig ring closure. Closer study of this latter transformation, however, revealed that the initial product of base-induced cyclisation was in fact the isobenzofuran 4, which was extremely labile, and that 5 was formed from 4 by acid-catalysed rearrangement during work-up of the reaction mixture. 

An alternate route to substituted tetrahydrobenzazepines (Scheme 33) commenced with the Michael addition of the ester 351 to acrylonitrile in the presence of Triton B, and the intermediate cyanoester was converted to 352 by reduction of the ester function with lithium borohydride and O-benzylation (168). Base-induced hydrolysis of the nitrile group of 352 delivered the corresponding acid, which was transformed to 353 via a Curtius rearrangement. Subjection of 353 to a modified two-step Tschemiac-Einhom reaction involving AMiydroxymethyla-tion and subsequent acid-catalyzed cyclization gave 354. 

Lopez, J C, Gomez, A M, Valverde, S, Fraser-Reid, B, Ferrier rearrangement under nonacidic conditions based on iodonium-induced rearrangements of allylic n-pentenyl esters, n-pentenyl glycosides, and phenyl thioglycosides, J. Org. Chem., 60, 3851-3858, 1995. 

Schreiber et al. have been able to apply their enediyne intramolecular Diels-Alder approach to the synthesis of dynemicin model systems [268-270], culminating in the total synthesis of di- and tri-O-methyl dynemicin A methyl esters 388 and 389 (Scheme 7-78) [271], derivatives of the natural product itself. Highlights of this synthetic approach include (a) intramolecular lactonization and concomitant Diels-Alder cyclization (380- 381) (b) allylic hydroxylation followed by an allylic diazene rearrangement in order to regiospecifically isomerize a double bond (381 - 382) (c) a-hydroxylation of the lactone 381 and subsequent conversion to the P-ketoester 383 (d) annelation of the anthraquinone unit (383- 384- 385- 386) (e) mild base-induced P-elimination of the N-protecting group of 386 to give the free amine 387 and (f) a final oxidation to complete the anthraquinone (387 - 388). 

The first total synthesis of the epoxyisonitrile natural product (64) involves a base-induced fragmentation reaction to provide the unsaturated ester fragment (Scheme 49).The stereospecific rearrangement of 2,2-dimethylcyclobutanol into optically active 1,2-c/s-disubstituted cyclopropanes has been reported (Scheme 50). 

Diphenylphosphinic mixed anhydrides have been utilized to form peptide bonds. Peptides are easier to isolate by this method than by employing 1,3-Dicyclohexylcarbodiimide. These anhydrides are the method of choice for the formation of amides of 2-alkenoic acids (eq 1 ). Carbodiimide and acyl carbonate methods proved to be inferior. Primary amines result in better yields than secondary amines. This activation protocol can be employed to form thiol esters (eq 2) p-Amino acids are readily converted to p-lactams with chlorodiphenylphosphine oxide (eq 3). Secondary amines work best. This activation protocol has been utilized to convert acids to amines via a Curtius rearrangement. Phenols have been generated from diene acids, presumably via base-induced elimination of diphenylphosphinic acid from the mixed anhydrides to form ketenes which spontaneously cyclize. Acids have been converted to ketones via activation followed by reaction with organometallic reagents (eq 4)."... 

The acidity of the propargylic proton of the starting compound 18 allows the equilibration with the allene 19 induced by bases such as tertiary amines or alcoholates (Scheme 7.4). Such prototropic rearrangements furnish the title compounds 19 with at least one proton at the terminal carbon atom, often in good yields. The EWG group involves carboxylic acids [33], esters [34], ketones [35, 36], isonitriles [37], sul-fones [38], sulfoxides [39, 40] and phosphonates [41], The oxidation of easily accessi-... 

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