Aldol-type coupling reaction

Six-membered chiral acetals, derived from aliphatic aldehydes, undergo aldol-type coupling reactions with a-silyl ketones, silyl enol ethers," and with silyl ketene acetals " in the presence of titanium tetrachloride with high diastereoselectivities (equation 41) significant results are reported in Table 20. This procedure, in combination with oxidative destructive elimination of the chiral auxiliary, has been applied... 

Zhang and Danishefsky reported the first total synthesis of ( )-2 [13]. Their retrosynthetic plan for ( )-2 is illustrated in Scheme 1. The first cmcial step in this contemplated scheme is envisaged to start with the stereoselective Eschenmoser-Claisen rearrangement [15] of allyl alcohol 13 to constmct the requisite transdecalm portion 11 via intermediate 12. Rearrangement precursor 13 is accessible starting fi-om ( )-5-methyl-Wieland-Miescher ketone (15) via trans-decalone 14. The second critical step is envisioned to involve the aldol-type coupling reaction of methyl ester 10 with the known aldehyde 9 [16] to assemble the requisite... 

Morken and co-workers have reported the highly enantioselective version of this reaction, albeit with low efficacy in the aldol-type coupling [8d, e]. Unfortunately, we obtain low enantioselectivity ee 2-4%) using chiral rhodium complexes under our reaction conditions. An intramolecular adaptation has led to new opportunities in cobalt-catalyzed carbocyclizations, wherein the use of PhSiHs was essential for smooth ring formation (Eq. 4) [9]. The identical products were also formed by a combination of [Rh(COD)2]OTf/(p-CE3Ph)3P and molecular hydrogen [10]. 

Leaving precise mechanistic arguments aside, it should be stressed that an a,/9-unsatu-rated carbonyl compound can behave as a latent nucleophile with the assistance of a hydrosilane and a low-valence rhodium complex. With this simplification, isocyanates 18 and aldimines 20 were used as electrophiles for a similar protocol. Both were successfully incorporated with the aid of [Rh(COD)(P(OPh)3)2]OTf to afford 19 and 21, respectively (Scheme 6.5) in a reaction that was similar to the aldol-type coupling [11]. 

Aldol and Related Condensations As an elegant extension of the PTC-alkylation reaction, quaternary ammonium catalysts have been efficiently utilized in asymmetric aldol (Scheme 11.17a)" and nitroaldol reactions (Scheme ll.lTb) for the constmction of optically active p-hydroxy-a-amino acids. In most cases, Mukaiyama-aldol-type reactions were performed, in which the coupling of sUyl enol ethers with aldehydes was catalyzed by chiral ammonium fluoride salts, thus avoiding the need of additional bases, and allowing the reaction to be performed under homogeneous conditions. " It is important to note that salts derived from cinchona alkaloids provided preferentially iyw-diastereomers, while Maruoka s catalysts afforded awh-diastereomers. 

The shikimate pathway begins with a coupling of phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate to give the seven-carbon 3-deoxy-D-arabino-heptulo-sonic acid 7-phosphate (DAHP) through an aldol-type condensation. Elimination of phosphoric acid from DAHP, followed by an intramolecular aldol reaction, generates the first carbocyclic intermediate, 3-dehydroquinic acid. Shikimic acid (394) is... 

The synthesis pathway of quinolizidine alkaloids is based on lysine conversion by enzymatic activity to cadaverine in exactly the same way as in the case of piperidine alkaloids. Certainly, in the relatively rich literature which attempts to explain quinolizidine alkaloid synthesis °, there are different experimental variants of this conversion. According to new experimental data, the conversion is achieved by coenzyme PLP (pyridoxal phosphate) activity, when the lysine is CO2 reduced. From cadeverine, via the activity of the diamine oxidase, Schiff base formation and four minor reactions (Aldol-type reaction, hydrolysis of imine to aldehyde/amine, oxidative reaction and again Schiff base formation), the pathway is divided into two directions. The subway synthesizes (—)-lupinine by two reductive steps, and the main synthesis stream goes via the Schiff base formation and coupling to the compound substrate, from which again the synthetic pathway divides to form (+)-lupanine synthesis and (—)-sparteine synthesis. From (—)-sparteine, the route by conversion to (+)-cytisine synthesis is open (Figure 51). Cytisine is an alkaloid with the pyridone nucleus. 

An asymmetric C-C coupling, one of the most important and challenging problems in synthetic organic chemistry, seems to be most appropriate for the creation of a complete set of diastereomers because of the applicability of a convergent, combinatorial strategy [38-40]. In Nature, such reactions are facilitated by lyases which catalyze the (usually reversible) addition of carbo-nucleophiles to C=0 double bonds, in a manner mechanistically most often categorized as aldol and Claisen additions or acyloin reactions [41], The most frequent reaction type is the aldol reaction, and some 30 lyases of the aldol type ( aldolases ) have been identified so far [42], of which the majority are involved in carbohydrate, amino acid, or hydroxy acid metabolism. This review will focus on the current state of development of this type of enzyme and will outline the scope and limitations for their preparative application in asymmetric synthesis. 

As outlined in Scheme 28, the synthesis of the P-ketophosphonate 131 began with a one-pot anh -aldol/reduction step between ethyl ketone 101 and aldehyde 133, giving the 1,3-syn diol 134 (>30 ldr) [130, 132-136, 145, 146], The diol 134 was then converted into the carboxylic acid 135 in six steps. Completion of the subunit 131 required conversion into the acid chloride and reaction with the lithium anion of methyl-(di-l,l,l-trifluoroethyl)-phosphonate. The C9-C24 aldehyde 132 was prepared in two steps from 136, an intermediate from previous routes [55-58], The Still-Gennari-type coupling of 131 and 132 was readily achieved via treatment with... 

From a synthetic point of view, the above studies have stimulated the synthesis of new types of /3-diketonato complexes. Thus, reactions at position 4 of the l-metalla-2,6-diox-acyclohexane rings, usually denominated the y-position (equation 2), such as halogen-ation , thiocyanogenation, chlorosulfenylation , arylsulfenylation, acylation, nitration, formylation , chloromethylation and dimethylaminomethylation (equation 2) ° have been performed as well as Suzuki coupling reactions (equation 3) , or an aldol reaction with p-nitrobenzaldehyde under Lewis acidic conditions (equation 4f. ... 

Cross-coupling between allylic alcohol and aldehyde is efficiently catalyzed by RuCl2(PPh3)3 in water to form an aldol-type product 48 [22], This reaction has limitations in the substituents of the aldehydes, and the use of aliphatic aldehydes provides complicated mixtures. Cross-coupling of imines with allylic alcohols under similar conditions generates Mannich-type reaction products 50 as major products, together with aldol-type products 48 [22], The selectivity of the reaction was improved by using methanol as the solvent, whereupon no aldol-type product was observed (Eqs. 12.19 and 12.20). 

Aldol-type condensation of silyl enol ethers with acetals under the influence of la is rather familiar. Unlike the Mukaiyama aldol reaction, 1-5 mol % loading of la is enough to complete the coupling reaction under mild conditions [20]. This transformation is applicable to the synthesis of a wide variety of / -alkoxy carbonyl substrates and has three characteristic features ... 

Spectacular enantioselection has been observed in hydrogenation (cf. Section 2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], olefin epoxidation (cf Section 2.4.3) [5] and dihydroxylation (cf Section 3.3.2) [6], hydrovinylation (cf Section 3.3.3) [7], hydroformylation (cf Section 2.1.1) [4a, 8], carbene reactions [9] (cf Section 3.1.10), olefin isomerization (cf Section 3.2.14) [10], olefin oligomerization (cf Section 2.3.1.1) [11], organometallic addition to aldehydes [12], allylic alkylation [13], Grignard coupling reactions [14], aldol-type reactions [15], Diels-Alder reactions [12a, 16], and ene reactions [17], among others. This chapter presents several selected examples of practical significance. 

Diazo ketones also possess an electrophilic diazo group, and hence are susceptible to diazo-coupling reactions with suitable soft nucleophiles. Examples are given in equations (11) and (12). Phospha-zines such as (19) are useful synthetic intermediates in their own right. The carbon terminus of the 1,3-dipole possesses nucleophilic properties and can participate in aldol-type reactions with the particularly electrophilic carbonyl groups in 1,2-di- and 1,2,3-tri-carbonyl compounds. Intramolecular condensations occur with greater ease (equation 13). Reaction of diazo ketones of the type summarized in equations (9)-(12) have been thoroughly reviewed. ... 

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