Chemoselective aldimine

The aldimine of Figure 13.34 is a chiral and enantiomerically pure aldehydrazone C. This hydrazone is obtained by condensation of the aldehyde to be alkylated, and an enantiomerically pure hydrazine A, the S-proline derivative iS-aminoprolinol methyl ether (SAMP). The hydrazone C derived from aldehyde A is called the SAMP hydrazone, and the entire reaction sequence of Figure 13.34 is the Enders SAMP alkylation. The reaction of the aldehydrazone C with LDA results in the chemoselective formation of an azaenolate D, as in the case of the analogous aldimine A of Figure 13.33. The C=C double bond of the azaenolate D is fraws-configured. This selectivity is reminiscent of the -preference in the deprotonation of sterically unhindered aliphatic ketones to ketone enolates and, in fact, the origin is the same both deprotonations occur via six-membered ring transition states with chair conformations. The transition state structure with the least steric interactions is preferred in both cases. It is the one that features the C atom in the /3-position of the C,H acid in the pseudo-equatorial orientation. 

Triethylborane together with air <1999CC1745> or fty -butyUiydroperoxide <2003JOC625> also generated the THF a-radical from THF at room temperature, and promoted its addition to aldehydes to provide the threo- Aducts as the major isomers. This method was applied to the synthesis of the cytotoxin muricatacin <2003JOC7548>. As demonstrated in Equation (139), chemoselective addition of THF a-radical to an aldimine or an aldehyde could therefore be achieved in a three-component reaction system, depending on the radical initiator used <20030L1797>. 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

While selective reaction of aldehydes takes place with the typical Lewis acids TiCL, SnCl4, TMSOTf, etc., lanthanide triflates [Ln(OTf)3] are unique Lewis acids that change the reaction course dramatically aldimine reacts selectively in the coexistence of aldehydes [70]. Among a series of Ln(OTf)3 tested, Yb(OTf)3 exhibited the most prominent chemoselectivity in addition to high chemical yields. The silyl enol ethers of ketones, allyltributylstannane and Me3SiCN are all applicable as chemoselective nucleophiles (Table 2-9). Preferential formation of Yb(OTf)3-aldimine complexes was postulated by C NMR spectral analysis in the presence of PhCHO and Y-benzylideneaniline. 

Schafer found that the bulky bis(amidate) complex is an effective catalyst for intermolecular hydroamination of terminal alkyl alkynes with alkylamines, giving exclusively the anti-Markovnikov aldimine product [309]. The same titanium complexes can also be utilized in the hydroamination of substituted allenes in good yields (Scheme 14.132). Under the catalysis of an imidotitanium complex, the highly strained methylenecyclopropane can undergo hydroamination reaction with either aromatic or aliphatic amines, to give ring-opened imine products in good to excellent yields and chemoselectivities [310]. 

Interesting chemoselectivity was observed in this addition reaction. HBF4-catalyzed addition reaction selectively proceeded toward an aldimine in the presence of an aldehyde (Scheme 3.2). In general, common Lewis acids except for some lanthanide triflates or transition metals activate aldehydes rather than aldimines preferentially. The high chemoselectivity was realized because the more basic nitrogen was activated more effectively by HBF4 than the carbonyl oxygen. 

The half-unit E of salen is not accessible. Even the reaction of salicylaldehyde with a 20-fold excess of ethylenediamine at low temperatures yields only the symmetric salen. Thus, the key step in the synthesis of a triplesalen ligand C is the preparation of a half-unit, either E or G. Several methods for the preparation and isolation of derivatives of the parent salen half-unit E are described in the literature [155-159]. We applied several of these methods for the synthesis of a triplesalen ligand and obtained various new compounds [160]. However, the successful synthesis of a triplesalen ligand is based on an observation of Elias and coworkers [158]. They reported that the slightly modified diamine I (Scheme 4.4) reacts with its sterically more crowded amine function not with ketones to form ketimines, but only with aldehydes to form aldimines. On the other hand, the less crowded amine function does react with aldehydes as well with ketones to form imines. Thus, the reaction of the diamine I with the triketone H affords chemoselectively the triple ketimine J, which corresponds to the triplesalen halfunit G. In a second step, the triple ketimine J can be reacted with a simple salicylaldehyde (corresponding to F) to yield the desired triplesalen (Scheme 4.4). 

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