Ketone acceptors

The Robinson annulation is a two-step process that combines a Michael reaction with an intramolecular aldol reaction. It takes place between a nucleophilic donor, such as a /3-keto ester, an enamine, or a /3-diketone, and an a,/3-unsaturated ketone acceptor, such as 3-buten-2-one. The product is a substituted 2-cyclohexenone. 

Most recently, reductive aldol cyclization catalyzed by In(OAc)3 in the presence of PhSiH3 was reported.50 This catalytic system is applicable to both aldehyde and ketone acceptors. As demonstrated by the reductive cyclization of 65a and 68a, cycloaldol products are produced in good yields and excellent ry -diastereoselectivity (Scheme 48). 

Scheme 2.7 Aldol reactions with ketone acceptors [33-36].

The components are a nucleophilic donor, such as a p-keto ester, and an a,P-unsaturated ketone acceptor. 

Enolized ketone Acceptor carbonyl compound Reagent Yield %) Threo erythro... 

The chiral molecular receptor (35) has been used to effect enantioselective cyclization of the enone (36). The complex of (36) and (35) undergoes energy transfer from the ketonic acceptor to (36) and results in its conversion into the cyclobutanes (37) and (38) in a total yield of 21%. Bach et aV have continued their investigations of enantioselective additions mediated by the chiral lactam hosts (39). The present reactions involve intra and intermolecular additions of quinolone systems (40) at -60°C in toluene as solvent. The irradiation affords the cycloadducts (41) and (42). As can be seen, the ee of the products is high and the chemical yields are also good. An extension of the work to intermolecular reactions of the quinolone (43) was also reported. The additions of the alkenes... 

Morrison have used model systems specially synthesised to test the efficiency of different aryl antenna groups for photon harvesting and examined effectiveness of singlet-singlet energy transfer to target ketone acceptors. 

In an attempt to constmct carbohydrates using an organocatalytic approach, protected dihydroxyacetone 54 was reacted with various ketone acceptors in the presence of L-proline. Hydroxyacetone can also be used to generate an/j-selectivity with glyoxalates [165]. 

Evans and coworkers have also reported addition of enol silanes to ketone acceptors (Scheme 17.13) [18]. In this case, Cu(OTf)2/(13) gave higher diastereo-and... 

We have seen that the traditional Roskamp process and its stereoselective variants allow one to substitute a synthetically valuable unsubstituted or substituted alkoxy ethanoyl functicm in place of the formyl C-H bmid. The analogous homologation of ketone acceptors with stabilized diazo compounds promises to become a highly advantageous tool for the synthetic chemist. Unfortunately, since ketones are far less reactive than aldehydes, comparably fewer reports in this area are known that still meet the modem criteria of catalysis, high efficiency, and stereocontrol. 

In addition to ketones, aldehydes can also be used as aldol donors in pro-line-catalyzed reactions [144]. Barbas et al. found that treating acetaldehyde solutions tvith proline provided aldehyde 185, an aldol trimer of acetaldehyde, in 84% ee and 4% yield (Scheme 4.42, Eq. (1)) [145, 146]. As shotvn by Jorgensen et al., other simple a-unbranched aldehydes can also be used as donors in proline-catalyzed cross aldolization tvith activated non-enolizable ketone acceptors to give aldols 188 in high enantioselectivity and yield (Scheme 4.42, Eq. (2)) [147]. 

A pyruvate aldolase from Pseudomonas taetrolens catalyzes the aldol addition of pyru-vafe to indole-pyruvic acid (34), a ketone [85]. This is an interesting example of an aldolase fhaf cafalyzes an aldol addition to a ketone acceptor. A variant of this aldolase was used in fhe stereoselective synfhesis of a precursor (35) of monatin (36), whose 2R,4R stereoisomer is 2700-fold sweeter fhan sucrose (Scheme 10.3) [86]. 

Gong group designed chiral primary amine-amide type catalyst for the aldoliza-tion of hydroxyacetone [24] with excellent iyn-aldol selectivity (up to >20 1 dr.) and stereoselectivity (up to 98% ee) (Scheme 5.12). Recently, Zhao and Da have further explored this type of primary amine catalysts [25]. Feng developed bispidine-derived chiral primary amine catalyst 45 for the aldolization of activated ketone acceptors with excellent enantioselectivity (Scheme 5.12) [26]. 

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