5-Acceptor-substituted 2-amino

The C-H insertion a to nitrogen can be extended to acyclic systems. The reaction with jY-benzyl-iV-methylamine is an excellent example of the interplay between steric and electronic effects. The benzylic position would be electronically the most activated, but due to the steric crowding, the C-H insertion occurred exclusively at the iV-methyl site (Equation (27)).86 This is a general method for generating a-aryl-/5-amino acid derivatives. The N,N-dimethylamino group undergoes a very favorable C-H insertion by the donor/acceptor-substituted carbenoids. Indeed, the reaction is so favorable that double C-H insertion was readily achieved to form the elaborated -symmetric amine 10 (Equation (28)).87... 

Additional routes to a-allenic-a-amino acids were described more recently and utilize radical [136] or transition metal-catalyzed [137] allenylations, in addition to copper-promoted Michael additions [15b]. Thus, sterically demanding amino acid derivatives (e.g. 151) are accessible via a 1,6-addition reaction of lithium di-tert-butyl-cyanocuprate with acceptor-substituted enynes of type 150 (Scheme 18.48). 

Nucleophilic 1,4- and 1,6-additions of cuprates and other organometallic reagents to acceptor-substituted dienes have been utilized extensively in target-oriented stereoselective synthesis52-61. Schollkopf and coworkers55 reported the diastereoselective 1,6-addition of a bislactim ether-derived cuprate to 3,5-heptadien-2-one (90% ds equation 17). The corresponding reactions of dienoates were conducted with the lithiated bislactim ether and proceeded with diastereoselectivities of >99% ds (equation 18)56 the adducts could be converted easily into diastereo- and enantiomerically pure amino acid derivatives. 

Isonitrile complexes, having a similar electronic structure to carbonyl complexes, can also react with nucleophiles. Amino-substituted carbene complexes can be prepared in this way (Figure 2.6) [109-112]. Complexes of acceptor-substituted isonitriles can undergo 1,3-dipolar cycloaddition reactions with aldehydes, electron-poor olefins [113], isocyanates [114,115], carbon disulfide [115], etc., to yield heterocycloalkylidene complexes (Figure 2.6). 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

In order to assess the generality of this procedure for the preparation of acceptor-substituted anthranilic acids it was applied to 2-amino-3-chlorobenzoic acid, which was obtained with excellent overall yield of 53% (lit. 16%). 

The optical properties of chromophores can be varied by means of substituents. Electron donors (e g., alkyl, alkoxy, or substituted amino groups) and electron acceptors (e g., cyano, alkylsulfonyl, or carbalkoxy groups) can intensify fluorescence depending on their position on the chromophore. 

The prototype molecule for donor/acceptor substitution is 4-dimethyl-amino-4 -nitroazobenzene. Here, the n- n band is shifted far to the red due to the charge transfer character of the transition. The band has few vibrational features, and its energy is influenced by the polarity of the solvent. The weak n Tt band cannot be seen under the intense it —> it band (Figure 1.13). Most commercial azo dyes are pseudo-stilbenes rather than azobenzene-type molecules. 

Table 3. Selected Examples of Elimination/Addition Reactions of l-Amino-1-acceptor-Substituted Cyclopropanes...

The palladium-catalyzed hydrogenolysis of 1-aminocyclopropanecarboxylic acid (18, R = H) and its methyl ester led to the cleavage of two different cyclopropyl bonds, depending on the reaction conditions.In water or methanol, fission of the proximal bond was favored, whereas in acetic acid the C2 —C3 bond was preferentially cleaved. This result was unexpected because protonation of the amino group should make this system similar to acceptor-substituted cyclo-... 

S-T h i ocy a n a to v i n y 1 aide h y des 119 were also versatile C3S building blocks in the synthesis of acceptor substituted 2-amino-isothiazolium salts 131 and 132 by intramolecular cyclocondensation of thiocyanatovinylaldehyde hydrazones 129 (93TL1909). The alternative cyclization route to 1,2,3-thiadiazines was not observed. Alicyclic aldehydes 119 reacted with benzhydrazides (R = ArCO) to unstable benzhydrazones 129 (R = ArCO) that cyclized spontaneously to 130 (R = ArCO). The imines 130... 

Antibodies to the donor-acceptor-substituted stilbene trans-4-N,N-dimethyl-amino-4 -cyanostilbene (DCS) and other donor-acceptor-substituted stilbenes were... 

Three of the amino acids that occur in proteins, lysine, arginine and histidine, contain an amino or substituted amino group in their side chains which gives them basic properties, i.e. enables them to act as proton acceptors. 

Since most often the selective formation of just one stereoisomer is desired, it is of great importance to develop highly selective methods. For example the second step, the aldol reaction, can be carried out in the presence of a chiral auxiliary—e.g. a chiral base—to yield a product with high enantiomeric excess. This has been demonstrated for example for the reaction of 2-methylcyclopenta-1,3-dione with methyl vinyl ketone in the presence of a chiral amine or a-amino acid. By using either enantiomer of the amino acid proline—i.e. (S)-(-)-proline or (/ )-(+)-proline—as chiral auxiliary, either enantiomer of the annulation product 7a-methyl-5,6,7,7a-tetrahydroindan-l,5-dione could be obtained with high enantiomeric excess. a-Substituted ketones, e.g. 2-methylcyclohexanone 9, usually add with the higher substituted a-carbon to the Michael acceptor ... 

In contrast to the dihalogens, there are only a few spectral studies of complex formation of halocarbon acceptors in solution. Indeed, the appearance of new absorption bands is observed in the tetrabromomethane solutions with diazabicyclooctene [49,50] and with halide anions [5]. The formation of tetrachloromethane complexes with aromatic donors has been suggested without definitive spectral characterization [51,52]. Moreover, recent spectral measurements of the intermolecular interactions of CBr4 or CHBr3 with alkyl-, amino- and methoxy-substituted benzenes and polycyclic aromatic donors reveal the appearance of new absorption bands only in the case of the strongest donors, viz. Act = 380 nm with tetramethyl-p-phenylendiamine (TMPD) and Act = 300 nm with 9,10-dimethoxy-l,4 5,8-... 

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