Proton sponges chiral

Recently, there has been research activity in the area of chiral proton sponges, in particular, those containing nitrogens with pairs of different substituents. The molecular asymmetry of such sponges, especially well pronounced in the cationic forms, arises as a result of the arrangement of bulkier functions at opposite sides of the naphthalene ring plane. Synthesis of these compounds, e.g. 5248, 5333 and 5449, is also achieved via alkylation of the corresponding A,A -dialkyl- or A,A,A -trialkyl-l,8-diaminonaphthalenes (Scheme 3). 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used stoichiometrically. For achiral reactions, NEt3 can serve both functions. The subsequent reaction follows the pathway known from the reverse mode reactions, with the catalyst recovered unchanged ... 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used... 

In reactions of chiral compounds requiring the use of a base, the proton sponge practically causes no racemisation and favours the retention of high optical purity. An example is the conversion of optically active alcohols into ethers under the action of trialkyloxonium tetrafluoroborates (equation 19)218-220. 

In contrast to a-fluorination, direct a-chlorination and a-bromination were developed on the basis of ketene intermediate mechanism in the presence of O-benzoylquinine (122) by Lectka and coworkers in 2001 (Scheme 6.36) [64, 65], Ketenes derived from acid chlorides 120 with either BEMP resin or proton sponge are added to 122 to form zwitterionic enolates, which are a-halogenated by perha-loquinones 123, 124. Finally, O-benzoylquinine moiety is substituted by haloaro-matic phenolate anions, generated from 123 or 124, to afford chiral a-halocarbonyl products 121 up to 99% ee. 

Alder, R.W. (2005) Design of C2-chiral diamines that are computationally predicted to be a milhon-fold more basic than the original proton sponges. Journal of the American Chemical Society, 127, 7924-7931. 

In this chapter, the synthetic utility of Proton Sponge (1) was reviewed. This superbase, although not a main player, is indispensable for various mild and selective transformations in organic synthesis. Despite the unique characteristics of superbases, their exploitation is still limited. Recently, various types of proton sponges, including chiral ones, have been developed, and are likely to have a wide range of applications in organic and asymmetric synthesis. 

The first highly enantioselective synthesis of the p-lactam ring with Cinchona alkaloids was demonstrated by Lectka and coworkers in 2000. They employed 10 mol% of benzoylquinine (O-Bz-Q) or benzoylquinidine (O-Bz-QD), to condense electron-deficient a-imino esters and ketenes (Scheme 15.12). To ensure in situ ketene formation (in fact a chiral ketene enolate is the reactive species.), proton sponge (PS) was used as a... 

The first catalytic asymmetric Staudinger reaction to be described used chiral tertiary amines 14 and 15 derived from the Cinchona alkaloids as the nucleophile to activate the ketene via zwitterion formation. The ketene was conveniently generated in situ from the acid chloride. Because the HCl generated in the elimination would consume the chiral tertiary amine catalyst, a nonnucleophilic strong base (e.g.. Proton Sponge) was included to remove the HCl formed. Yields of -lactams were on the order of 60% in 99% ee. 

Lectka et al. reported on a practical methodology for the catalytic, asymmetric synthesis of (3-lactams 203. Compound 203 results from the reaction of ketenes (or derived zwitterionic enolates) 201 and imines 202 via C—N alkylative cyclization using benzoylquinine as a chiral catalyst and a proton sponge as the stoichiometric base with moder-ate-to-good yield and excellent diastereoselectivity and enantioselectivity (Scheme 40.41). " ... 

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