Aldehydes Lewis acid complexes

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... 

In addition to the studies by Reetz and Denmark already described in the previous sections, several aldehyde-Lewis acid complexes have been reported. In all cases, the Lewis acid is located trans to the aldehyde residue and coordinate in a tz-fashion. 

Treatment of boracycle 13 [28] with [(MeCN)3Cr(CO)3] in THF gave air- and moisture-sensitive [( / -borabenzene-THF)Cr(CO)3] (14) that reacts with 3-(di-raethylamino)acrolein to afford [(t7 -borabenzene-(3-(dimethylamino)acrolein) Cr(CO)3] (15). The crystal structure of 15 displays the following features, each of which is typical for aldehyde-Lewis acid complexes (1) the Lewis acidic atom lies in the plane of the carbonyl group (B-04-C7-C8=-176 ) (2) the Lewis acid binds syn to the hydrogen of the aldehyde rather than anti, (3) the Lewis acid-oxygen-carbon angle is roughly 120° (B-04-C7 = 123°) (Scheme 1-4). 

Fig. 18. Kiyooka s model of the aldehyde-Lewis acid complex...

Fig.9. Conformation of anti aldehyde-Lewis acid complexes proposed anomeric effect and formyl hydrogen bond...

Up until this point we have been primarily concerned with the identity of the nucleophile which in fact adds to the aldehyde substrate. What is the structure of the aldehyde-Lewis acid complex which undergoes reaction With SnCl4 and the aldehyde which we have seen up until now, 2-methyl-3-benzyloxypropanal, we see no evidence by either or l Sn NMR spectroscopy, for any species other than the well-defined bidentate chelate formed from SnCl4 and substrate. However, there are other possibilities. 

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... 

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. 

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. 

The proposed exo transition state (for cyclopentadiene) is illustrated in Fig. 4, and shows that one of the -NCH2Ar groups blocks the lower face of the j-tran.v-coordi-nated dienophile [25]. The authors proposed s-trans geometry for the complex a-sub-stituted unsaturated aldehyde/Lewis acid, in contrast with to previous observations that this aldehyde reacts in the s-cis form [17]. 

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. 

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. 

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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