Alkyl-aryl aldol reaction

Alkylative aldol reactions with aryl- or vinylboron reagents are also catalyzed by rhodium complexes.404 4043 4041 Equations (54) and (55) show examples of enantioselective reactions. 

Other studies have provided additional data on the relative stabilities of the lithium aldolates 14 and 15 derived from the condensation of dilithium enediolates 13 (Rj = alkyl, aryl) with representative aldehydes (eq. [ 10]) (16). Kinetic aldol ratios were also obtained for comparison in this and related studies (16,17). As summarized in Table 4, the diastereomeric aldol chelates 14a and ISa, derived from the enolate of phenylacetic acid 13 (R = Ph), reach equilibrium after 3 days at 25° C (entries A-D). The percentage of threo diastere-omer 15 increases with the increasing steric bulk of the aldehyde ligand R3 as expected. It is noteworthy that the diastereomeric aldol chelates 14a and 15a (Rj = CH3, C2HS, i-C3H7) do not equilibrate at room temperature over the 3 day period (16). In a related study directed at delineating the stereochemical control elements of the Reformatsky reaction, Kurtev examined the equilibration of both... 

In 2007, Scheldt and co-workers reported the intramolecular desynunetrization of 1,3-diketones utilizing triazolinm pre-catalyst 249 (Scheme 39) [129], Generation of a homoenolate is followed by P-protonation and aldol reaction. In accordance with the proposed mechanism by Nair (Scheme 37), acylation occurs followed by loss of carbon dioxide. Cyclopentenes are formed in enantioselectivities up to 94% ee. The scope of this reaction is limited to aryl substitution of the diketone and alkyl substitution of R. 

This procedure demonstrates a particularly effective method for controlling the relative and absolute stereochemistry of the aldol reaction. It is quite general in scope. Alkyl-, aryl, and a,6-unsaturated aldehydes all give good results. In addition to chiral propionates, a range of related aldol reactions may be carried out. For example, the analogous aldol reactions of thioalkyl, benzyloxy, or haloacetate, as well as succinate- and crotonate-derived carboximides, have been reported. 

Pyridine-/V-oxidc is an efficient Lewis-base catalyst for aldol reactions of trimethyl-silyl enolate with both aryl and alkyl aldehydes in DMF at room temperature, tolerating a wide variety of sensitive substituents in the substrate.160... 

If the ketone is blocked on one side so that it cannot enolize—in other words it has no a protons on that side—only one aldol reaction is possible. Ketones of this type migitt bear a tertiary alkyl or an aryl substituent, f- Butyl methyl ketone (3,3-dimethylbutan-2-one), for example, gives aldol reactions with various bases in 60-70% yield. Enolization cannot occur towards the t- butyl group and must occur towards the methyl group instead. 

The precise nature of the carbonyl groups determines what happens next. If R is a leaving group (OR, Cl, etc.), the tetrahedral intermediate collapses to form a ketone and the product is a 1,3-di-ketone. The synthesis of dimedone (later in this chapter) is an example of this process where an alkoxy group is the leaving group. Alternatively, if R is an alkyl or aryl group, loss of R is not an option and the cyclization is an intramolecular aldol reaction, Dehydration produces an a,P-unsaturated ketone, which is a stable final product. 

The alkyllithium reagents to be used in tandem reactions can be prepared by direct alkylation or by an aldol reaction involving nucleophilic addition of the alkyllithium as the first step. Several complex heteroaromatic compounds, which can serve as pivotal intermediates in synthetic strategy of biologically active species, could be synthesized by this procedure. The preparation of polysubstituted pyridines has been an active research area for many years181. The synthesis of 2-alkyl- or 2-aryl-5-hydrazinopyridines 327 has never been performed directly from pyridine. The reported methods involve several steps... 

Introduction. Ti-TADDOLates are a,a,a, a -tetraaryl-2,2-disubstituted l,3-dioxolane-4,5-dimethanolatotitanium derivatives. The most common substituents are R, R = Me/Me and Ph/Me, Ar=Ph and 2-naphthyl, X, Y = C1/C1, t-PrO/Cl, Cp/Cl, and i-PrO/i-PtO. The corresponding TADDOLs (2) are available in both enantiomeric forms from tartrate esters which are acetalized (R R CO) and allowed to react with aryl Grignard reagents. The reactions performed in the presence of Ti-TADDOLates or with Ti-TADDOLate derivatives include nucleophilic additions to aldehydes - - and nitroalkenes of alkyl, aryl, and allylic - groups aldol additions hydrophosphonylations and cyanohydrin reactions of aldehydes inter- and intramolecular Diels-Alder additions ... 

Mg enolates generated from Mg bisamides can be used in aldol addition reactions with alkyl, aryl, and cyclic ketones. As shown in Scheme 3.40, these reactions are significant in that the self-coupling of ketones in aldol reactions to give tertiary yS-hydroxyketones are also possible. More specifically, these transformations are achieved principally by the use of relatively high reaction temperatures between 25 °C and 60 °C. Such conditions are a notable departure from the widely used lithium-mediated aldol additions, where increasing the reaction temperature results in retro-aldol processes and also elimination of LiOH to give enone products [30]. 

The reaction of triarylsulfonium halides with sodium alkoxides at high temperatures afforded mixtures of alkyl aryl ethers (24), diarylsulfides, hydrocarbons and aldol resins or a ketone if the alkoxide is derived from a secondary alcohol.25,36,38-41... 

P-Hydroxy tosylhydrazones, which are the products of a conventional aldol reaction between a dilithi-ated tosylhydrazone reagent and an aldehyde, can also be prepared by alternative routes. For example, Stork and Ponaras have described a procedure whereby an epoxy ketone is converted into an epoxy hydrazone. Subsequent addition of an alkyl- or aryl-magnesium bromide followed by hydrolysis yields either an a-alkyiated- or a-arylated-p-hydroxy ketone or an a,p-unsaturated ketone. Since the attack of the Grignard reagent on the epoxide occurs with inversion at the a-carbon, this reaction can be used to... 

In addition to the preceding methods that involve functionalization of an enone or enoate p-carbon with an alkyl or aryl functionality, methods for the nickel-catalyzed reductive aldol functionalization of enoates have also been developed (Scheme 3-81). Using triethylborane as the terminal reductant with Ni(cod)2 as catalyst, reductive aldol reactions proceed to give syn aldol adducts. An unusual role of phenyl iodide as a promoter for the process was found in this study. Intramolecular reductive aldol additions utilizing Ni(acac)2 as catalyst and diethylzinc as the terminal reduetant were also described. ... 

The first highly enantioselective cross-aldol-Tishchenko reaction of alkyl aryl ketones 28 and aldehydes was developed by the group of Shibasaki et al. [15]. With a chiral heterobimetallic lanthanide-based catalyst, this reaction was shown to proceed in typically very good enantioselectivity to furnish, after saponification of... 

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