Tietze’s total synthesis

Scheme 14.20 Tietze s total synthesis of (+)-(R)-pinnatolide (134) via multicomponent domino allylation reaction.

Scheme 14.42 Tietze s total synthesis of linoxepin (275) (DME, dimethoxyethane).

The key step in Biichi s total synthesis of loganin (5i)23 made use of the expansion of a four-membered ring to an oxygen-containing heterocycle by retro-aldol reaction. This strategy was later exploited by Tietze in his total synthesis of hydroxyloganin (54) as well as hydroxyloganic acid (55) 24). 

The domino Knoevenagel condensation hetero-Diels-Alder reaction was used for the enantioselective total synthesis of the active anti-influenza A virus indole alkaloid hirsutine and related compounds by L.F. Tietze and co-workers. The Knoevenagel condensation was carried out between an enantiopure aldehyde and Meldrum s acid in the presence of ethyienediamine diacetate. The resulting highly reactive 1-oxa-1,3-butadiene underwent a hetero-Diels-Alder reaction with 4-methoxybenzyi butenyl ether ElZ = 1 1) in situ. The product exhibited a 1,3-asymmetric induction greater than 20 1. 

Beifuss, U., Tietze, M., Baumer, S., Deppenmeier, U. Methanophenazine structure, total synthesis, and function of a new cofactor from methanogenic Archaea. Angew. Chem., Int. Ed. Engl. 2000, 39, 2470-2472. 

L. F. Tietze, S. Biller, T. Wolfram, Synlett 2010, 2130-2132. First enantioselective total synthesis of the reported structure of (R)-(+)-orizaterpenyl benzoate using an asymmetric allylation of a prochiral ketone in a domino process. 

Estrone is an estrogenic hormone. Tietze s group reported a very elegant method for the enantioseletive total synthesis of estrone (Scheme 7.2) [6]. The best part of the strategy is the generation of the steroid ring B through consecutive inter- and intramolecular Heck reactions. They discovered that the treatment of functionalized aromatic compound 5 and the enantiopure hydrindene derivative 6 with Pd(OAc)2 and PPhj in the presence of -Bu NOAc in a mixed DMF/MeCN/H O... 

An interesting entry to functionalized dihydropyrans has been intensively studied by Tietze in the 1990s using a three-component domino-Knoevenagel Hetero-Diels-Alder sequence. The overall transformation involves the transient formation of an activated heterodienophile by condensation of simple aldehydes with 1,3-dicarbonyls such as barbituric acids [127], Meldrum s acid [128], or activated carbonyls. In situ cycloaddition with electron-rich alkenes furnished the expected functionalized dihydropyrans. Two recent examples concern the reactivity of 1,4-benzoquinones and pyrazolones as 1,3-dicarbonyl equivalents under microwave irradiation. In the first case, a new three-component catalyst-free efficient one-pot transformation was proposed for the synthesis of pyrano-1,4-benzoquinone scaffolds [129]. In this synthetic method, 2,5-dihydroxy-3-undecyl-1,4-benzoquinone, paraformaldehyde, and alkenes were suspended in ethanol and placed under microwave irradiations to lead regioselectively the corresponding pyrano-l,4-benzoquinone derivatives (Scheme 38). The total regioselectivity was... 

Deoxyloganin (24) has previously been synthesized by Tietze and coworkers, utilizing an intramolecular hetero-Diels-Alder reaction to construct the iridoid core (Scheme 10). The synthesis commenced with conversion of (5)-citronellal (47) to enol ether 48 in seven steps. Knoevenagel condensation of the aldehyde with Meldrum s acid, followed by in situ intramolecular hetero-Diels-Alder reaction afforded pyran 49, with all the carbons required for the natural product core installed. Conversion of 49a, via methanolysis and a reduction/elimination sequence, to lactol acetate 50, was achieved in four steps. Finally, glycosylation and deprotection provided the natural product in a total of 14 steps. 

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