Clauson-Kaas reaction

Two approaches, based on furan, have found wide application in carbohydrate synthesis. Cycloaddition reactions of furan with 2-substituted acrylonitrile or acrolein lead to oxabicycloheptanes which, in tnm, can be transformed to monosaccharides. On the other hand, furfuryl alcohols can be converted—either by the Clauson-Kaas reaction or by mild oxidation—into 5,6-dihydro-4-pyrones, suitable for easy functionalization to sugars. 

Another general approach to sugars starts from (2-furyl)methanols (furfuryl alcohols, 22). Bromination at low temperature in methanol (Clauson-Kaas reaction) and subsequent mild acidic hydrolysis of 2,5-dimethoxy-2,5-dihydrofurans 23 obtained, leads to 6-hydroxy-2,3-dihydro-6//-pyran-3-ones 24 (Scheme 8) [40], The same dihydropyranones can be... 

The Clauson-Kaas reaction between 2,5-dimethoxytetrahydrofuran 19 and phenylsulfonamide performed in the presence of triflic acid (TfOH) led to either pyrrole 20, indole 21, or carbazole 22 depending on the amount of triflic acid used <07TL4047>. The latter two compounds were formed by the annulation of pyrrole or indole by butanedial (generated by the acid-mediated hydrolysis of 19). A double Clauson-Kaas sequence starting with hydrazine allowed for the preparation of 1,1 -bipyrrole <07JOC93 95>. 

Claisen reanangement, 228, 236, 251 Clauson-Kaas reaction, 621 Clindamycin, 107,108 Compactin, 570 Cryptoqtorin, 570 Corey lactone, 549 Cyclic, 55... 

Furan is, as a 7r-electron rich compound, easily oxidized electrolytically. In acetonitrile the oxidation potential of furan is comparable to that of anisole [35]. In methanol the oxidation is an ECEC mechanism in which 2,5-dihydro-2,5-dimethoxyfuran is formed [166] in the Clauson-Kaas reaction ... 

Anodic oxidation of chromone in aqueous methanol containing a halide gives 3-halo-2-methoxychromanone in a reaction that is a variant of the Clauson-Kaas reaction [186]. 

Benzothiophene and its alkylated derivatives afford the corresponding 2,3-dimethoxy-2,3-dihydrobenzothiophenes in the Clauson-Kaas reaction, whereas others, such as the methyl 3-methylbenzothiophene-2-carboxylates, do not [196]. 

This reaction is related to the Clauson-Kaas Reaction. 

Other experimental details for the Clauson-Kaas reaction are available,and additional references related to the Clauson-Kaas reaction are cited in the literature. 

Sulfonamides have also seen great success as partners in the Clauson-Kaas reaction. Similar to amides the pyrroles generated are protected by the starting sulfonamides. Karousis and co-workers reported a successful example of this procedure with 3-formyl-2,5-dimethoxytetrahydrofuran 7 to generate tosyl-protected pyrrole carbaldehyde 8. The tosyl-protecting group was later removed under mildly basic conditions (K2CO3, MeOH at room temperature). 

A variety of catalysts has been used to promote the Clauson-Kaas reaction. The most common are Bronsted acids but a variety of other Lewis acids have also seen some use. An interesting report by Fang used phosphorus pentoxide in toluene to shorten reaction times.Others have commented that care must be taken to rigorously remove water from this reaction with amides to avoid the generation of nitriles. ... 

The quite versatile Lewis acid, scandium triflate has a been reported to act as a mild catalyst for Clauson-Kaas reactions. Zuo and co-workers investigated a battery of Lewis acids and found the greatest success with Sc(OTf)3. In their report they used these conditions to generate a variety of aryl and heteroaryl pyrroles. In this case, deactivated nitrogen nucleophiles (15) worked well under these reaction conditions to yield heteroaryl substituted pyrroles similar to (16). 

The Clauson-Kaas reaction has also seen some utility in the synthesis of complex heterocycles where the pyrrole is generally installed early and then further functionalized. Plasencia and co-workers have a fine example of this strategy in their reported synthesis of quinoxalinhydrazides (27), which showed some anticancer activity. 

An impressive example of the functional group compatibility of the Clauson-Kaas reaction was reported by Frontata-Uribe and co-workers in the... 

Clauson-Kaas reaction 9, 461 Cleavage (s. a. Fragmentation, Lysis)... 

The key stage in the synthesis of pyrrolo[l,2-a]quinoxalines 183 (Scheme 3.54) by type PA3 (Campiani et al. 1991, 1997) involves intramolecular substitution of a fluorine atom in the aromatic ring by the carboxamide group formed in sim in the l-aryl-2-cyanopyrroles 182 by the action of KOH. The formation of compounds 182 is a multistage process synthesis of the 1-arylpyrroles by the Clauson-Kaas reaction (Clauson-Kaas and Tyle 1952) and introduction of the CN group at position 2 of the pyrrole ring according to the Scheme 3.54. 

---