Isotetronic acid

Butenolide, 2-hydroxy — see Isotetronic acids Butenolide, 3-hydroxy — see Tetronic acids But-2-enolide, 4-alkylidene-synthesis, 4, 697 Butenolides H NMR, 4, 578 mass spectrometry, 4, 585 structure, 4, 551 synthesis, 1, 416 trimethylsilylation... 

In addition, the bifunctional amine-acid catalyst approach involving the (S)-(- -)-l-(2-pyrrodinylmethyl)pyrrolidine la TFA eombination was also used by Dondoni and coworkers. The homoaldol reaction of ethyl pyruvate in the presenee of diamine la TFA salt (30 mol%) produced an isotetronic acid derivative (6) after treatment with an acidic resin (Scheme 9.3). Furthermore, the proteetion of the resulting enol with TBDMSCl afford product in 59% yield and 86% ee. 

The use of ethyl pyruvate (38c), as both source of nucleophile and electrophile, in the aldol reaction catalyzed by catalyst 75a (Scheme 4.24) led to the formation of the isotetronic acid derivative 76 with good enantioselectivity. Although, initially... 

Isotetronic acids were readily assembled through an organocatalyzed domino aldol-lactonization reaction starting from a-keto carboxylic acids and aldehydes [5]. As chiral organocatalyst, the proline-derived benzimidazol pyrrolidine 8 was employed, which proved superior to proUne itself Electron-poor aldehydes were both more reactive and selective. Thus, as a typical example, pyruvate was converted into isotetronic acid 10 in 77% yield and 83% ee upon treatment with para-nitrobenzyldehyde (9) and 10mol% 8 (Scheme 8.3). 

Scheme 8.3 Domino aldol-lactonization reaction for the assembly of isotetronic acids [5].

In synthesis of isotetronic acid derivatives, aldol-type reactions of 1,2-dicarbonyl substrates including oxalyl chloride and pyruvates are used as powerful mefhodologies. For instance, Langer et al. reported systematic investigations on such reaction of oxalyl chloride 21 wifh l,3-bis(trimethylsilyloxy)-l,3-butadienes 22 or 24 as masked dianion equivalenfs (Scheme 10) [21]. By using a catalytic amoxmt of MesSiOTf, y-lactone formation smoothly occurred to yield the lactones (E)-23 or (Z)-25, respectively. This methodology is also effective for the synthesis of medium-sized bicyclic y-bufenolides such as 25c [22]. 

Over the past 12 years or so, significant progresses of the "direct" aldol reaction have been achieved. In particular, the aldol-type reactions of pyruvic acid and its derivatives are useful for the synthesis of isotetronic acid derivatives. In 2000, Jorgensen et al. [23] reported the first example of asymmetric homoaldol reaction of ethyl pyruvate 26a in this work, chiral (R)-f-Bu-bis(l,3-oxazolin-2 -yl)methane (BOX)-Cu(OTf)2 catalyst was used (Scheme 11). Organocata-lytic version of similar reactions has been investigated. For instance, Dondoni et al. examined catalyst efficiency of several prolin-based organocatalysts for homoaldol reaction of 26a and foxmd that a combination of (S)-l-(2-pyrro-lidinylmethyl)pyrrolidine 29 and trifluoroacetic acid is effective [24]. 

P. Dambruoso, A. Massi, A. Dondoni, Efficiency in isotetronic acid synthesis via a diamine-acid couple catalyzed ethyl pyruvate homoaldol reaction, Org. Lett. 7 (2005) 4657-4660. 

J.-M. Vincent, C. Margottin, M. Berlande, D. Cavagnat, T. Buffeteau, Y. Landais, A concise organocatalytic and enantioselective synthesis of isotetronic acids, Chem. Commun. (2007) 4782-4784. 

The use of nitro-olefins as starting materials for conversion into nitro-qxixides is mentioned in Ch ter 10. The preparation of 2,3-unsaturated nucleosides is covered in Chapter 20 and the synthesis of derivatives of 3-hydroxy-2(SH)-furanose (isotetronic acid) from boizylidene acetal... 

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