1 -Naphthaldehyde imines

Figure 4.24. (a) Addition to 1-naphthyloxazolines [142] (b) Addition to 2-naphthyloxazolines [142] (c) addition to 1-naphthyloxazolines lacking a chelating group [144] (d) addition to 1-naphthaldehyde imines [145] (e) addition to crotyl amino acid imines [146,147] (f) addition to cyclohexene and cyclopentene aldehyde amino acids imines [148]. 

The methodology was extended to an asymmetric introduction of snbstitnents to a naphthalene ring. When chiral naphthyloxazolines 13 were used as substrates, di- or trisubstituted dihydronaphthalenes 15 were obtained in high diastereomeric ratio (dr) after the treatment of intermediate azaenolate 14 with an electrophile (equation 7) °. Analogous reactions with a chiral naphthaldehyde imine were also reported . 

This type of catalytic strategy has recently been extended to enantio-selective addition of alkyllithiums to certain prochiral imines (Scheme 18) (35). Relevantly, in the presence of a small amount of a chiral ether ligand, 1-naphthyllithium reacts with a sterically hindered imine of l-fluoro-2-naphthaldehyde (conjugate addition/elimination) to afford a binaphthyl compound in greater than 80% ee. 

Neyroz et al. [97] have covalently linked 2NpOH to phos-phatidylethanolamine moiety by the Schiff-base formation between the NH2 of the phospholipid and the aldehyde moiety of 2-hydroxy-1-naphthaldehyde, followed by selective reduction of the imine to obtain a stable secondary amine. This fluorescent phospholipid easily incorporates into DML vesicle membrane and exhibits the typical behavior of ESPT probes. The emission spectrum of this probe inserted in the liposome is similar to that in ethanol medium and is affected by acetate used as a proton acceptor. 

Imines derived from 3-methoxy-2-naphthaldehydes react with organomagnesium compounds by a 1,4-addition mechanism. This reaction can be performed with high diastereoselectivity by using an apropriate chiral auxiliary. The method was applied for the synthesis of optically pure /3-tetralones.243... 

A typical experimental procedure is illustrated in Fig. 2. Mixing the 2-naphthaldehyde-derived A-Boc imine with isovaleraldehyde in the presence of (S)-proline (20 mol%) in acetonitrile at 0 °C resulted in an initially homogenous reaction mixture (Fig. 2a). After complete consumption of the starting material (10 h), a large amount of the de-... 

The transition metal catalyzed asymmetric addition of aryl organometallic reagents to aldehydes, ketones, and imines has provided efficient access to chiral aryl alcohols or aryl amines [89]. Arylboronic acids are less toxic, stable toward air and moisture, and tolerant towards a variety of functional groups, and are ideal reagents for the addition to aldehydes. However, when Sakai et al. [90] attempted the enantioselective Rh-catalyzed addition of phenylboronic acid to naphthaldehyde, only 41% ee was obtained. Chiral spiro phosphite complex (S)-18c was found to be an efficient catalyst for asymmetric addition reactions of arylboronic acids to aldehydes, providing diarylmethanols in excellent yields (88-98%) with up to 87% ee (Scheme 30) [20c]. 

The reaction of methyllithium with the 4-methoxyphenylimine of 1-naphthaldehyde in the presence of a chiral ligand derived from a catechol dialkyl ether as an asymmetric controller (A) afforded the corresponding 1,2-addition product as an optically active amine in 70% ee (ref.93). A solution of methyllithium (R Li) (2.0 mmol) in diethyl ether was added at -tOO C to a solution of the imine (R = 1-Naph 1.0 mmol) and ligand A (2.6 mmol) in toluene and the reaction mixture was then stirred for 1 hour at the same temperarture and finally quenched with water. 

LAG of an equimolar mixture of 2-hydroxy-1-naphthaldehyde and 5-aminoisophthalic acid in Retsch MM200 grinder mill afforded imine product, 5-[(2-oxo-2H-naphthalen-l-ylidenemethyl)-amino]-bezene-l,3-dicarboxylic acid (Scheme 3.11). Kaimer et al. noted the dependence of the solvent used for LAG on the reaction time needed for full conversion milling with methanol, pyridine, and DMF took 50, 40, and 20min, respectively [11]. Solution-phase synthesis in methanol at room temperature was complete in 30 min. PXRD and X-ray diffraction analysis revealed that variation of solvents used for LAG led to imine product (methanol), or its solvates (pyridine and DMF). 

The nuclear magnetic resonance spectra of SchifF bases formed from primary amines and ortAo-hydroxy aldehydes and ketones show that the Schiff bases derived from l-hydroxy-2-acetonaphthone and from 2-hydroxy-1-naphthaldehyde exist as keto amines (7a) although their formation involves loss of most of the resonance energy of one of the aromatic rings When R is a phenyl group, the phenol-imine tautomer (7b) predominates Schiff bases derived from ortho-hydroxy aldehydes and ketones have the phenol-imine structure (8) . Evidently, in such compounds the keto-amine tautomer... 

Table 6 Catalytic, enantioselective additions of silyl ketene imines to 2-naphthaldehyde...

The relative stabifization of the E or K tautomers in 2-4 depends mostly on the position of benzoannelation (Figure 10.3). In contrast to 2 and 3, imines of 3-hydroxy-2-naphthaldehyde 4 exist exclusively as the enolimine tautomers [50 - 54]. Loss of aromaticity in 2 and 3 is restricted to one ring of the naphthalene moiety, whereas in 4 both rings are involved, which leads to destabilization of the... 

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