Amino esters, aliphatic

Carbenoid N-H insertion of amines with diazoacetates provides a useful means for the synthesis of ot-amino esters. Fe(III) porphyrins [64] and Fe(III/IV) corroles [65] are efficient catalysts for N-H carbenoid insertion of various aromatic and aliphatic amines using EDA as a carbene source (Scheme 16). The insertion reactions occur at room temperature and can be completed in short reaction times and with high product yields. It is performed in a one-pot fashion without the need for slow... 

In 2007, AntiUa and coworkers disclosed the first asymmetric organocatalytic reduction of acyclic a-imino esters (Scheme 23) [39], Chiral VAPOL phosphate (5)-16 (5 mol%) served as a catalyst for the transfer hydrogenation of the latter (62) employing commercially available dihydropyridine 44a to give both aromatic and aliphatic a-amino esters 63 in very high yields (85-98%) and enantioselectivities (94-99% ee). 

In 2008, Gong and coworkers introduced a new chiral bisphosphoric acid 19 (Fig. 4) that consists of two BINOL phosphates linked by an oxygen atom for a three-component 1,3-dipolar cycloaddition (Scheme 42) [66]. Aldehydes 40 reacted with a-amino esters 105 and maleates 106 in the presence of Brpnsted acid 19 (10 mol%) to afford pyrrolidines 107 as endo-diastereomers in high yields (67-97%) and enantioselectivities (76-99% ee). This protocol tolerated aromatic, a,P-unsaturated, and aliphatic aldehydes. Aminomalonates as well as phenylglycine esters could be employed as dipolarophiles. 

Generally, good yields of p-amino ester were obtained with aromatic aldehydes as well with an a,p-unsaturated aldehyde (Table 13, entries 12-16). Interestingly, we noted that the reaction was sterically sensitive because ortho substitution led to a decreased conversion (Table 13, compare entries 13 and 14). Aliphatic aldehydes... 

The commercially available oxime linker 1.15 (72) has been used in peptide synthesis and for the SPS of small organic molecules such as indoles. Cleavage is carried out with either hydrazine (0.5 M hydrazine in CHCb-MeOH 2/1 for 10 min at rt) or with aliphatic amines or amino esters (DCM at rt for 12 h) to produce hydrazides and amides, respectively. 

Yamamoto and co-workers found that 27 is an excellent chiral promoter not only for the aza Diels-Alder reaction of aldimines [40] but also for the stereoselective aldol-type reaction of aldimines with ketene silyl acetals [55]. The reaction of (5)-benzyli-dene a-methylbenzylamine with trimethylsilyl ketene acetal derived from terf-butyl acetate in the presence of (R)-27 produces the (R) adduct in > 92 % diastereomeric excess (de), whereas reaction with (5)-27 gives the adduct in 74 % de. In a similar way, (5)-butylidene a-methylbenzylamine, an aliphatic imine, can be converted to the (R)-)3-amino ester in 94 % de by use of (R)-27 (Eq. 73). 

Mannich-type reactions of aldehydes, amines, and vinyl ethers proceeded smoothly in the presence of a catalytic amount of Sc(OTf)3 in aqueous media (Eq. 20) [69]. Commercially available aqueous solutions of formaldehyde and chloroacetaldehyde were used directly and the corresponding /3-amino ketones were obtained in good yields. Phenylglyoxal monohydrate, methyl glyoxylate, an aliphatic aldehyde, and an a,/3-unsaturated aldehyde also worked well to give the corresponding /3-amino esters in high yields. 

Esters. Aliphatic acids including a-amino acids and citric acid form methyl esters selectively (in the presence of aromatic acids) and in excellent yields when treated with... 

A marked improvement of the enantioselectivity was achieved by Corey and coworkers by using a bifluoride catalyst 4 [5]. Bi fluoride derivatives such as 4 are usually less hygroscopic than monofluorides such as 1 and thus easier to handle. Using catalyst 4 (10 mol%), the silyl enol ethers S reacted with various aliphatic aldehydes smoothly at —70 °C via the aldol coupling reaction to afford the chiral 5-hydroxy-a-amino esters 6 with moderate to good enantioselectivily for the syn adduct (72-89% ee) (Scheme 8.2). However, the diastereoselectiviy varied from 1 1 to 13 1 (syn anti). 

Many a-amino acid esters or related short-chained aliphatic amino esters show satisfying hydrolysis kinetics in plasma, but exhibit poor stability in aqueous solution. This poor stability is predominantly due to electron withdrawal by the positively charged amino group, but may also involve intramolecular catalysis or assistance of the ester hydrolysis by the neighboring amino group. The replacement of the glycine unit by its benzologue, as shown for... 

P-lactams P-amino acids, aliphatic and ester, aminocarbonyl, [58]... 

In the preceding section prodrugs of peptides were considered. They should not be confused with peptide esters of drugs. In the latter case, one forms a-amino acid or related short-chained aliphatic amino esters, for example, as a useful means of increasing the aqueous solubility of drugs containing a hydroxyl group... 

Dimethoxytetrahydrofuran will react with aliphatic and aromatic amines, amino esters, aryl-sulfonamides, trimethylsilylethoxycarbonylhydrazine or primary amides to give the corresponding A-substituted- C-unsubstituted-pyrroles. ... 

Aliphatic aldehydes reacted with amines and silyl enolates to give the corresponding b-amino esters in high yields. In some reactions of imines, it is known that aliphatic enolizable imines prepared from aliphatic aldehydes gave poor results. 

The key intermediate 59 required for the synthesis of sulfobacin A (59) is achieved successfully via a coupling reaction of aliphatic acid 57 and amino ester 58 using DEPC.23 Sulfobacin A is biologically active sulfonolipids isolated from the culture broth of Chryseobacterium sp. NR 2993 in a soil sample collected from Japan. 

Aliphatic amino esters can be prepared by boiling the amino acid with alcohol and an excess of hydrogen chloride. 

The best synthon for unstable succindialdehyde, for the ring synthesis of C-unsubstituted pyrroles, is 2,5-dimethoxytetrahydrofuran (section 15.1.4), or 1,4-dichloro-1,4-dimethoxybutane obtainable from it. 2,5-Dimethoxytetrahydrofuran will react with aliphatic and aromatic amines, amino esters, arylsulfonamides, trimethylsilylethoxycarbonylhydrazine, or primary amides to give the corresponding A-substituted pyrroles. 

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