Chiral proton catalysts

When the alkylation was performed with ethyl allyl carbonate as the precursor of the it-allyl intermediate, only 32% ee was obtained, indicative of a subtle proton-transfer process involved in the catalytic process such as in Scheme 8E.39. The chiral rhodium catalyst was shown to be the primary source of the asymmetric induction because the same reaction in the absence of the rhodium catalyst generated a racemic product in 91% yield. It is interesting that the use of only half an equivalent of the chiral ligand together with half an equivalent of achiral ligand (dppb) with respect to [Pd + Rh] was sufficient to give a high enantioselectivity (93% ee). 

The same group subsequently discovered that the loading of the chiral diamine catalyst can be reduced substantially if triethylamine is added in stoichiometric amounts as an achiral proton acceptor [37b]. As shown at the top of Scheme 13.23, as little as 0.5 mol% catalyst 45 was sufficient to achieve yields and ee comparable with the stoichiometric variant (application of the Oriyama catalysts 44 and 45 in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). Oriyama et al. have also reported that 1,3-diols can efficiently be desymme-trized by use of catalysts 44 or 45. For best performance n-butyronitrile was used as solvent and 4-tert-butylbenzoyl chloride as acylating agent (Scheme 13.23, bottom) [38]. 

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... 

The Chen group also demonstrated a successful conjugate addition/ asymmetric protonation of a-prochiral imide 4 using thiophenol in the presence of 10 mol% 3 (Scheme 6.1) [43]. It was hypothesized that the ammonium group of the catalyst serves as a chiral proton source for the catalyst-stabilized enone intermediate formed after initial 1,4-addition of the thiol (Fig. 6.4). 

The chemistry of asymmetric protonation of enols or enolates has further developed since the original review in Comprehensive Asymmetric Catalysis [1], Numbers of literature reports of new chiral proton sources have emerged and several reviews [2-6] cover the topics up to early 2001. This chapter concentrates on new examples of catalytic enantioselective protonation of prochiral metal enolates (Scheme 1). Compounds 1-41 [7-45] shown in Fig. 1 are the chiral proton sources or chiral catalysts reported since 1998 which have been employed for the asymmetric protonation of metal enolates. Some of these have been successfully utilized in the catalytic version. 

Other chiral organic catalysts of major success are the protonated phenylalanine-derived imidazohnones 28 developed by MacMillan [48], that have found widespread use in a number of relevant processes [5, 6]. Immobihzed versions of these catalysts have been developed both on soluble (PEG-supported catalyst 29 [49]), and insoluble supports (catalysts 30 and 31 [50]), and employed in enantioselechve Diels-Alder cycloadditions of dienes with unsaturated aldehydes (Scheme 8.16). 

Nakai and a coworker achieved a conceptually different protonation of silyl enol ethers using a chiral cationic palladium complex 40 developed by Shibasaki and his colleagues [61] as a chiral catalyst and water as an achiral proton source [62]. This reaction was hypothesized to progress via a chiral palladium enolate which was diastereoselectively protonated by water to provide the optically active ketone and the chiral Pd catalyst regenerated. A small amount of diisopropylamine was indispensable to accomplish a high level of asymmetric induction and the best enantioselectivity (79% ee) was observed for trimethylsilyl enol ether of 2-methyl-l-tetralone 52 (Scheme 11). 

Levacher and co-workers have reported the deracemization of alkyl diarylmelhanes with (-)-sparteine or a chiral proton source (25 26) <01TL4515>. Spivey has also applied ortho metallation techniques to synthesize pyridine analogs for use as phase transfer catalysts <01JCS(P1)1785>. 

In a full paper we described detailed studies of our various approaches to chiral induction in the amino acid products of transaminations. In that paper we also pointed out the odd fact that the Tabushi laboratory had reported the use of large concentrations of buffer in their reaction, which would have been expected to interfere with the selective proton transfer by an internal catalytic group if the buffer itself could start playing the role of protonating catalyst. 

The first example of asymmetric synthesis of allenic esters by a samarium(ii)-mediated reduction of propargylic compounds through dynamic kinetic protonation performed in the presence of a palladium catalyst was reported by Mikami and colleagues. Various chiral proton sources were involved and furnished enantio-enriched allenic esters, as shown in Scheme 2.47. 

The greater scope of this reaction was attributed to the dual cyclic Bronsted acid/H-Bond donar cocatalysis mechanism. The catalytic cycle initially involves imine protonation by the chiral thiourea catalyst 170 associated via H-bonding to the conjugate base (X ) of a weak Bronsted acid (H-X, benzoic acid in this case) additive. Intramolecular cyclization of the protonated iminium ion 146, followed by rearomatization regenerates the Bronsted acid cocatlayst (benzoic acid). Note for brevity, the plausible rearrangement (RR) step of the inital CCij-spiroalkylated adduct to the final tetrahydrohydroisoquinoline scaffold 147 is not shown. 

A plausible reaction mechanism is hypothesized by the authors. The electron-rich styrene substrate 44 would be protonated by phosphoric acid catalysts 45 to generate the tertiary carbocation intermediate A. The neutral resonance structure B, activated by B -H would receive the subsequent hydride addition giving the observed products 46 and regenerating the chiral acid catalyst 45 (Scheme 18). 

Boronic acids and their derivatives are very popular as components of chiral Lewis acids and promoters for various reaction processes [481]. Indeed, the chiral acyloxyb-oranes and the oxazaborolidines (Section 1.2.3.5) described in Chapter 11 made a mark in organic synthesis. Recently, Ryu and Corey extended the apphcation of chiral oxaborolidinium catalysts to the cyanosilylation of aldehydes [482]. Chiral diaz-aborohdine salts were evaluated in the enantioselective protonation of enol ethers [145]. Likewise, a tartramide-derived dioxaborolane is key as a chiral promoter in the asymmetric cyclopropanation of allyhc alcohols [483]. More examples and details on the applications of boronic add derivatives as reaction promoters and catalysts are provided in Chapter 10. 

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