Aromatic and aliphatic aldehydes

This condensation finds considerable generality, enol silyl ethers of a variety of ketones and both aromatic and aliphatic aldehydes are usable For enol silyl ethers of substituted cyclohexanones the reaction is regio- and stereospecific [id]. 

The best procedure reported to date for the asymmetric allylation of aldehydes using tributyl(2-propenyl)stannane involves the catalyzed addition with the BINOL-TiCl2 complex as catalyst. Good yields and ee s were obtained for both aromatic and aliphatic aldehydes using 20 mol% of the catalyst127. 

In the presence of a catalytic amount of tetrabutylammonium fluoride, either freshly dried over molecular sieves22 or as the trihydrate16, silylnitronates 2 derived from primary nitroalkanes react readily at — 78 C or below, via their in situ generated nitronates. with aromatic and aliphatic aldehydes to give the silyl-protected (/J, S )-nitroaldol adducts 3 in excellent yield4,22-24-26,27. Silylnitronates, derived from secondary nitroalkanes. afford the adducts in 30 40% overall yield24. In contrast to the classical Henry reaction (vide supra), the addition of silylnitronates to aldehydes is irreversible. Ketones are unreaetive under such conditions. 

In the author s laboratory, ligand 51 (Fig. 3) was investigated and gratifyingly very high ee s were obtained in the diethylzinc addition to both aromatic and aliphatic aldehydes (Scheme 39) [51]. 

A polymer-supported version of our optimal ligand was also developed [52]. Its preparation involves attachment of aziridine carbinols to polymer-bound triphenylchloromethane (Scheme 40). This polymer-bound ligand 53 was almost equally effective in the enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes with ee s ranging from 77-97% for the latter type of substrate [52]. It is of practical interest that this polymer-supported ligand could be reused without losing much of its efficiency. 

Ketones such as acetone, hydroxyacetone, and methoxyacetone can be condensed with both aromatic and aliphatic aldehydes.198... 

Organic-Base Catalyzed. Asymmetric direct aldol reactions have received considerable attention recently (Eq. 8.98).251 Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with chiral cyclic secondary amines as catalysts.252 L-proline and 5,5-dimethylthiazolidinium-4-carboxylate (DMTC) were found to be the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding... 

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

Eleven aromatic and aliphatic aldehydes have been alkylated with Et2Zn in the presence of homoannularyl bridged hydroxyamino ferrocene (—>123. The resulting carbinols have ee values varying from 66% to 97%. This new ferro-cenyl catalyst has been used successfully to alkylate aromatic and linear or branched chain aliphatic aldehydes to secondary alcohols with up to 97% ee. This ligand is effective even for -branched aliphatic substrate. 

TABLE 2-14. Asymmetric Alkylation of Aromatic and Aliphatic Aldehydes... 

More recently, Kobayashi and co-workers reported on Zr-catalyzed additions of ketene and thioketene acetals to a range of aromatic and aliphatic aldehydes (Scheme 6.25) [83], As in the Erker study, the presence of protic additives proved critical here as well. As the example in Scheme 6.25 illustrates, the addition of larger amounts of iPrOH improved the yield and ee it was reported that in the absence of the alcohol additive much lower yield and enantioselectivities" were attained. The proposed catalytic cycle, depicted in Scheme 6.25, provides a plausible rationale for the role of the additive Si transfer is facilitated by iPrOH to regenerate the chiral catalyst. Finally, it is worthy of mention... 

As with the aldehyde reductases, ketone reductases are specific for NADPH as reductant. Also, some isoenzymes of ketone reductase have not been purified to homogeneity and therefore not fully characterized. It is clear, however, that the ketone reductases catalyze reduction of aromatic, aliphatic, cyclic, and unsaturated ketones to the corresponding alcohols. The ketone reductases also catalyze reduction of aromatic and aliphatic aldehydes to primary alcohols. The distribution and specificity of ketone reductases has been reviewed (103). 

The use of polymer-supported quaternary ammonium salts to catalyse the Wadsworth-Emmons reaction produces acceptable yields from both aromatic and aliphatic aldehydes and ketones [16]. 

Considering that the described reaction is feasible for both aromatic and aliphatic aldehydes, that the experimental procedure is very easy, that the yields, in spite of moderate, are not far from the theoretical, the described method is certainly a useful contribution for the synthesis of symmetrical divinyl tellurides. 

Good yields of secondary amines are achieved using both the methods in the reactions of aromatic and aliphatic aldehydes as well as of diaUcyl ketones and cycloalkanones with aliphatic and alicyclic amines (and ammonia). Anilines give low yields, but when 2 equiv is used in the sodium hydrogen telluride method, the yields are improved. In the reaction of ammonia with aldehydes, symmetrical secondary amines are obtained, whereas glu-taraldehyde and amines lead to N-substituted piperidines. 

Moderate to good yields of a,j8-unsaturated epoxides are obtained, allowing aromatic and aliphatic aldehydes to react with dialkyltelluronium allylide (the dusobutyl derivatives are the reagents of choice). ... 

The moderate c/x-selectivity, observed for aromatic and aliphatic aldehydes, decreases if an NOj group or ort/to-substituents are linked to the aromatic ring. 

Stetter expanded Umpolung reactivity to include the addition of acyl anion equivalents to a,P-unsaturated acceptors to afford 1,4-dicarbonyls Eq. 5a [57-60]. Utilizing cyanide or thiazolylidene carbenes as catalysts, Stetter showed that a variety of aromatic and aliphatic aldehydes act as competent nucleophilic coupling partners with a wide range of a,p-unsaturated ketones, esters, and nitriles [61]. The ability to bring two different electrophilic partners... 

Utilizing prochiral a,a-disubstituted Michael acceptors, the Stetter reaction catalyzed by 76a has proven to be both enantio- and diastereoselective, allowing control of the formation of contiguous stereocenters Eq. 8 [73]. It is noteworthy that a substantial increase in diastereoselectivity is observed, from 3 1 to 15 1, when HMDS, the conjugate acid formed upon pre-catalyst deprotonation, is removed from the reaction vessel. Reproducible results and comparable enantioselectivities are observed with free carbenes for example, free carbene 95 provides 94 in 15 1 diastereoselectivity. The reaction scope is quite general and tolerates both aromatic and aliphatic aldehydes (Table 9). 

Song et al. extended this methodology to include cyanosilylation of aldehydes and ketones (Eq. 32) [160], They propose that NHC 276 interacts with TMSCN to form complex LXXVIII followed by cyano group transfer to the aldehyde (Scheme 48). The carbene is then regenerated and the desired product is obtained when LXXIX fragments. Concurrently, Kondo, Aoyama and co-workers describe similar reaction conditions for the synthesis of cyanohydrins in high yields [161, 162], while Suzuki and co-workers reported a cyanosilylation of aromatic and aliphatic aldehydes in good yields [163]. 

Utihzing the readily accessible diastereomeric atropoisomeric thioureas (aR/ aR)-(R,R)-88 as the catalyst (10mol%) various (hetero)aromatic and aliphatic aldehydes could be cyanosilylated to the corresponding TMS-protected cyanohydrins... 

The reaction scope was further developed with a range of aromatic and aliphatic aldehydes to furnish a range of p-hydroxy-a-amino acids, which are important constituents of many natural products (62). The resultant bicyclic adducts were obtained in good to excellent yield and represent differentially and orthagonally protected p-hydroxy-a-amino acids. The template removal was easily conducted by... 

Trimethyloxazole 257 undergoes photochemically induced [2 + 2] cycloaddition with aromatic and aliphatic aldehydes to provide bicyclic oxazolines 258 with excellent regiochemical and stereochemical control. Diastereoselec-tivities from 75-99% can be achieved, which is the first reported example of a Paterno-Biichi reaction involving an oxazole. The oxetane cycloadducts can be hydrolyzed to a-amino-(3-hydroxy ketones. Other oxazoles have not been evaluated to determine if they undergo the photochemical cycloaddition (Scheme 8.71). 

Allylation of carbonyl compounds. The coupling reaction of allylic bromides with carbonyl compounds such as aromatic and aliphatic aldehydes as well as ketones leads to the corresponding allylic alcohol in good yields (54-85%) and with high regioselectivity (see, for instance, equation 16)25. 

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