Lewis aldehyde complex

Stereochemical Control Through Reaction Conditions. In the early 1990s it was found that the stereochemistry of reactions of boron enolates of N-acyloxazolidinones can be altered by using a Lewis acid complex of the aldehyde or an excess of the Lewis acid. These reactions are considered to take place through an open TS, with the stereoselectivity dependent on the steric demands of the Lewis acid. With various aldehydes, TiCl4 gave a syn isomer, whereas the reaction was... 

FIGURE 5. Important conformations of Lewis acid complexed aldehydes... 

It has been shown that the lead tetraacetate-mediated 1,2-aryl shift of various meta-substituted / -cyclohexyl aryl ketones, e.g. (10), results in excellent yields of the corresponding rearranged esters (11). A unique reaction, providing 3-hydroxy-2-arylacrylic acid ethyl esters (14), has been observed between aryl aldehydes and ethyl diazoacetate in the presence of the iron Lewis acid [rj — (C5H5)Fe(CO)2(THF)BF4], It appears that the enol esters are formed by an unusual 1,2-aryl shift from a possible intermediate (13), which in turn is formed from the reaction of the iron aldehyde complex (12) with ethyl diazoacetate (see Scheme 4). 

The behavior of the aldehyde complex toward Lewis bases was examined. The acetaldehyde moiety in the acetaldehyde complex Me2A10CPhNPh MeCHO was not displaced by a large excess of Lewis base such as pyridine or tetrahydrofuran, but was replaced by a strong electron donor substance such as trimethylamine oxide to give a crystalline trimethylamine oxide complex, Me2A10CPhNPh ONMe3, which is identical to that obtained from trimethylamine oxide and [Me2AlOCPhNPh]2. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Figure 8B1.2. Proposed structure for a chiral Lewis acid-aldehyde complex.

In polar solvents, however, the tetrahedral intermediate A of Figure 14.53 decomposes faster than it is generated, with formation of an aldehyde and ROAl(tBu)2. This solvent effect is explained in Figure 14.53, using THF as an example. The tetrahedral intermediate A contains a trivalent A1 and forms a Lewis acid-Lewis base complex with the solvent. The intermediate A is thus converted into the aluminate complex B, which contains tetravalent Al. The A1 atom in A is bonded to only one O atom, which... 

A spectacular activation of the chiral zirconium-BINOL Lewis acid complex was achieved by the addition of the (achiral ) r-butyl-calix[4]arene. Less than 2% of the catalyst were sufficient in the enantioselective allylation of various aldehydes by allyltributyltin to reach enantiomeric excesses of more than 90%, see Casolari, S. Cozzi, P. G. Orioli, P. Tagliavini, E. Umani-Ronchi, A. Chem. Commun. 1997, 2123-2124. 

Mukaiyama and co-workers developed a chiral Lewis acid complex 15 consisting of tin (II) triflate and a chiral diamine. An aldol reaction of enol silyl ether 16 and octanal is promoted by 15 to give 17 in a highly diastereo-and enantioselective manner. The enantioface of the aldehyde is selectively activated by coordination with 15. This method is similar to method 3, in that an aldehyde-chiral Lewis acid complex can be regarded as a chiral electrophile. An advantage of method 4 over method 3 is the possible catalytic use of a chiral Lewis acid. In the reaction of Scheme 3.6, 20 mol% of 15 effects the aldol reaction in 76% yield with excellent selectivity.9... 

Lewis acid complexes of -substituted a, 3-unsaturated ketones and aldehydes are unreactive toward alkenes. Crotonaldehyde and 3-penten-2-one cannot be induced to undergo ene reactions like acrolein and methyl vinyl ketone. The presence of a substituent on the -carbon stabilizes the enal- or enone-Lewis acid complex and stericdly retards the approach of an alkene to the -carbon. However, Snider et al. have found that a complex of these ketones and aldehydes with 2 equiv. of EtAlCk reacts reversibly with alkenes to give a zwitterion (22). This zwitterion, which is formed in the absence of a nucleophile, reacts reversibly to give a cyclobutane (23) or undergoes two 1,2-hydride or alkyl shifts to generate irreversibly a p, -disubstituted-a,P-unsaturated carbon compound (24). 

The isolation of the initial aldol products from the condensation of the enolates of carbene complexes and carbonyl compounds is possible if the carbonyl compound is pretreated with a Lewis acid. As indicated in equation (9), the scope of the aldol reaction can also be extended to ketones and enolizable aldehydes by this procedure. The condensations with ketones were most successful when boron trifluoride etherate was employed, and for aldehydes, the Lewis acid of choice is titanium tetrachloride. The carbonyl compound is pretreated with a stoichiometric amount of the Lewis acid and to this is added a solution of the anion generated from the caibene complex. An excess of the carbonyl-Lewis acid complex (2-10 equiv.) is employed however, above 2 equiv. only small improvements in the overall yield are realized. 

They also applied this method to the intermolecular ene reactions of aliphatic and aromatic aldehydes with alkenes containing a disubstituted vinylic carbon, a potentially valuable route to homoallylic alcohols [50]. Proton-initiated rearrangements do not take place, because the alcohol-Lewis acid complex formed in the ene reaction reacts readily to give methane and a non-acidic aluminum alkoxide. Formaldehyde and excess Me2AlCl gave good yield of ene adducts with all types of alkene, as exemplified in Sch. 26. 

Additions of allyltributyltin to an a-oxygenated aldehyde are also influenced by the choice of Lewis acid (Table 7) [16]. The relative stereochemistry of the adduct is a result of the facial preference for attack on the aldehyde-Lewis acid complex by the stannane. The reaction involving BF3 OEta is subject to Felkin-Ahn/Comforth control whereas MgBr2 and TiCU in CH2CI2 proceed by chelation control. In THF the... 

The reaction of aldehydes 3 with crotyl silanes (e.g. 5) yields 3-methylated homoallylic products such as 6 and 9. Since crotyl silanes are only weak nucleophiles, the carbonyl compound 3 must be activated. This can be done by addition of a Lewis acid (LA) to form the C2ixhony -Lewis acid complex 4. After addition of 5 and aqueous workup, the homoallylic alcohol 6 is obtained. An alkyl-oxo-carbenium ion 8 is available when treating an acetal 7 with acid or when the aldehyde 3 reacts with a silyl ether 10 in the presence of a Lewis or a Brousted acid (multicomponent crotylation). Crotylation of this alkyl-oxocarbenium ion 8 yields homoallylic ethers 9. 

In conclusion, it can be noted that high valent transition metals seem perfectly capable of serving as effective Lewis acids. Many of the systems discussed here exhibit exceptional robustness, stability and a propensity to form crystalline complexes. This would facilitate the task of crystallization and structural analysis, and one can imagine that transition metal complexes can be used as structural probes of Lewis acid-carbonyl interactions. In this vein, the first glimpse of the origins of Cram selectivity in a-chiral aldehydes may have been obtained hrom the crysM structure of a ihenium aldehyde complex. Lastly, the... 

The model proposed for the reaction of simple aromatic aldehydes (54) places the Lewis acid syn to the aldehydic hydrogen, consistent with the frequent observation of this preference in crystal structures of Lewis acid-aldehyde complexes (c/. Figures 19,27 and 28). 

This homologation reaction most likely proceeds via nucleophilic addition of the diazo compound to the Lewis acid complexed carbonyl, followed by 1,2-alkyl migration with concomitant loss of N2. Application of this reaction to an aldehyde (168) gives, via 1,2-hydride shift, the corresponding P-keto ester (169 equation 70). ... 

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