N-Benzyl aldimines

In the presence of 42 (2mol% loading), aliphahc and aromafic N-allyl as well as N-benzyl aldimines were efficiently converted after 20 h at -70 °C in toluene to the respective Strecker adducts and subsequently trifluoroacetylated to obtain the products 1-10 in good to excellent yields (65-99%) and ee values J7-97%) (Scheme 6.41). It turned out that N-benzyl imines could be used as substrates without significant difference in comparison to analogous N-allyl imines (e.g., N-benzyl adduct 8 85% yield, 87% ee N-allyl adduct 9 88% yield, 86% ee Scheme 6.41). 

Scheme 6.48 Product range of the asymmetric hydrophosphonylation of N-benzylated aldimines promoted by thiourea derivative 47.

Ellman, Bergman, and coworker reported a rhodium-catalyzed procedure for the synthesis of pyridines from alkynes and a,/ -unsaturated N-benzyl aldimines and ketimines in 2008 [107]. The reaction proceeded via C-H alkenylation/electrocyclization/aromatization sequence through dihydropyridine intermediates. The C-H activated complex was isolated and determination by X-ray analysis. Good yields of highly substituted pyridines were produced in one-pot manner (Scheme 3.50). 

Experiments showed that TADDOL (2,2-dimethyl-a,a,a, a -tetraphenyl-l,3-dioxolane-4,5-dimethanol) can also be appUed to catalyze the asymmetric Strecker reaction of aromatic N-benzyl aldimines [48]. In initial experiments some asymmetric introduction (22-56% ee) was gained by moderate to high yields (68-93%). 

This tertiary amide-functionalized Schiff base thiourea was found to efficiently catalyze the asymmetric Strecker reaction [157] of N-benzyl-protected aldimines and also one ketimine in high enantioselectivities (86-99% ee) and proved superior to 42 examined under the same conditions (1 mol% loading, toluene, -78 °C, HCN) (Scheme 6.46) [198]. 

List and co-workers reported the 47-catalyzed (lmol% loading) asymmetric acetylcyanation of N-benzyl-protected aliphatic and aromatic aldimines by using commercially available liquid acetyl cyanide as the cyanide source instead of HCN [161]. Under optimized reaction parameters (toluene, -40 °C) the procedure resulted in the desired N-protected a-amino nitriles 1-5 in yields ranging from 62... 

Vallee reported another example of a BINOL-based Lewis acid catalyst for the asymmetric Strecker reaction of ketoimines. While a traditional (BINOL)Ti(IV)-based system provided poor enantioselectivity [61], Sc(BINOL)2Li proved to be highly enantioselective for the cyanation of N-benzyl acetophenonimine (95% ee at 50% conversion, 91% ee at 80% conversion) [62], Unfortunately, results were provided only for a single ketoimine and a single aromatic aldimine, leaving the generality of the methodology in question. 

Asymmetric synthesis of P-amino acid esters. The chiral diazaborolidine 1 (16,155) also effects diastereo- and enantioselective reactions of (S)-r-butyl thiopro-ponoate (2) with N-benzyl or N-allyl aldimines 3 to form j3-amino acid esters 4, precursors to chiral irons-pAactams (5) in 90-99% ee. 

In 2010, Kahn found that dimeric vanadium(v) salen complex [S,S,S,S)-5, which had previously been reported as a catalyst for the asymmetric synthesis of 0-acetyl cyanohydrins 4, was an effective catalyst for the asymmetric addition of cyanide to N-benzyl-protected aldimines to give (J )-amino nitriles 16 in 65-92% yields with up to 94% enantiomeric excess. Addition of a small amount of water and low temperature were essential to achieve both high conversion and high asymmetric induction for asymmetric catalysis. In this system, catalyst 5 could be reused approximately four times while maintaining its high activity. 

The stereochemical outcome in these additions can be understood by invoking Cram chelate [48] and Felkin-Anh-type [49] transition states for N-benzyl and N-sulfonyl aldimines, respectively (Figure 11.2 see also Chapter 2). The consequences of these results and their applications are noteworthy. Thus, selection of the appropriate N-protecting group can lead to preferential formation of either syn or anti 1,2-diamines at will [46]. 

In contrast to the epoxides, preparative routes to the aziridines are fairly evenly split between the [C=N + C] and the [C=C + N] routes. Among contributions in the former category, aziridine carboxylate derivatives 110 can be prepared through the lanthanide-catalyzed reaction of imines with diazo compounds, such as ethyl diazoacetate (EDA). In this protocol, iV-benzyl aryl aldimines and imines derived from aromatic amines and hindered aliphatic aldehydes are appropriate substrates <99T12929>. An intramolecular variant of this reaction (e.g.. Ill —> 112) has also been reported <990L667>. 

Deprotection of Fmoc-amino acid Wang resins under standard conditions yielded the polymer-bound amino acids 1. Condensation with 3,4-dichlorobenzaldehyde gave aldimines 2. Subsequent alkylation with electrophiles such as benzyl-, naphthyl- or allylbromide in the presence of 2-[(l,l-dimethylethyl)imino]- W,N-diethyl - 2,2,3,4,5,6- hexahydro-1,3-dimethyl-1,2,3-diazaphosphorin-2(lH)-amine (BEMP) gave the disubstituted aldimines 3. Transketalisation with hydroxylamine hydrochloride yielded the free amine 4 which was acylated and cleaved to give the final product 5 in good yields and purities. 

In parallel with the directed hydroarylation of olefins, a series of papers described the formation of ketones from heteroarenes, carbon monoxide, and an alkene. Moore first reported the reaction of CO and ethylene with pyridine at the position a to nitrogen to form a ketone (Equation 18.28). Related reactions at the less-hindered C-H bond in the 4-position of an A/-benzyl imidazole were also reported (Equation 18.29). - Reaction of CO and ethylene to form a ketone at the ortho C-H bond of a 2-arylpyridine or an N-Bu aromatic aldimine has also been reported (Equations 18.30 and 18.31). Reaction at an sp C-H bond of an N-2-pyridylpiperazine results in both alkylative carbonylation and dehydrogenation of the piperazine to form an a,p-unsaturated ketone (Equation 18.32). The proposed mechanism of the alkylative carbonylation reaction is shown in Scheme 18.6. This process is believed to occur by oxidative addition of the C-H bond, insertion of CO into the metal-heteroaryl linkage, insertion of olefin into the metal-acyl bond, and reductive elimination to form the new C-H bond in the product. 

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