Amination reactions base selection

Abbreviations NH3/RCN molar ratio t=reaction time C=conversion of nitrile RNH2, SB and R2NH=selectivity of primary amine, Schiff-base and secondary... 

All amines are relatively weak bases, which react with C02, H2S, and COS forming bonds that can easily be broken at elevated temperatures. Primary amines are chemically stronger than secondary, which in turn are stronger than tertiary. Weaker amines have greater selectivity for H2S, which is especially high for tertiary amines where the nitrogen atom does not have a free hydrogen association to form the carbamate ion by direct reaction... 

Reactions of selected metal complexes of multidentate amines with formaldehyde and a range of carbon acids (such as nitroethane) have led to ring-closure reactions to yield a series of three-dimensional cage molecules (see Chapter 3). Condensations of this type may also be used to produce two-dimensional macrocycles (Comba et al., 1986) - see [2.20], In such cases, it appears that imine intermediates are initially produced by condensation of the amines with formaldehyde as in the Curtis reaction. This is followed by attack of the conjugate base of the carbon acid on an imine carbon. The resulting bound (new) carbon acid then reacts with a second imine in a cis site to yield chelate ring formation. 

In contrast to chiral amines, phosphorus-based chiral catalysts were less developed for asymmetric MBH transformations. As with amine-based reactions, the selectivity of the addition in phosphine-mediated reactions depends clearly on the nature of the complementary Bronsted acid co-catalysts used. 

In oxidation reactions, however, osmium is significantly more selective than catalysts derived from other transition metals. Osmium-based catalysts for the hydroxylation and amination of aUcenes are very widely used in organic synthesis. With alkaloid-derived ligands, the hydroxylation and amination reactions are highly enantioselective (see Enantioselectivity). The use of bleach, hydrogen peroxide, ferric cyanide, and oxygen have been reported as secondary oxidants for some of these reactions. 

Di-n-butylboryl Trifluoromethanesulfomte with a tertiary amine also provides the (Z)-enolates of chiral acyl oxazolidinones in >100 1 selectivity for use in subsequent aldol additions With Triethylamine, Diisopropylethylamine (Hunig s base), or 2,6-Lutidine the order of addition is of no consequence to enolization." Triethylamine has traditionally seen the greatest utilization in these reactions based upon cost considerations however, with certain sensitive aldehyde substrates, lutidine provides milder reaction conditions." ... 

Nondynamic resolution processes for the production of chiral amines are based on selective N-acylation by either lipases from Burkholderia plantarii (Scheme 4.5C) or Alcaligenes faecalis penicillin G acylases (Scheme 4.5D). The former reaction is optimal with ethylmethoxyacetate as acylating agent [30 a], whereas fhe acylase is most selective with the natural substrate phenylacetic acid [30b]. 

In 1909, 4-amino-6-methyl-l,3,5-triazin-2-ol was obtained by cyclization of (acetylcarbamimi-doyl)urca under basic conditions.443 Subsequently, several new processes based on acylated dicyanodiamides were developed.444-447,449 Thus, when acyldicyanodiamides 1 are heated to reflux in 2-ethoxyethanol, 4-amino-1,3,5-triazin-2-ols 2 are obtained in crude yields of 60 to 100%.444,445 Catalytic amounts of amine salts significantly accelerate this reaction. After selective acid hydrolysis of acyldicyanodiamides, (acylcarbamimidoyl)ureas 3 are obtained which can also be cyclized to the 1,3,5-triazines 2. These reactions are carried out in excess sodium hydroxide solution and provide the triazines in 90 to 99% yield.443,444,446 447 Cyclization of 1-acylbiurets 4, prepared by acid hydrolysis of (acylcarbamimidoyl)ureas 3, is effected by treatment with potassium hydroxide solution.444,448 While the benzoyl derivative 3 (R = Ph) yields the corresponding l,3,5-triazine-2,4-diol 5 (R = Ph) in quantitative yield, the acetyl derivative 3 (R = Me) cyclizes only partially to the corresponding triazinediol 5 (R = Me).448... 

The highly symmetric spiro cation 57 has been shown to afford only the fused dibenzazepine-dibenzazocine derivative 58 (and none of the regioisomeric amine 59) on treatment with the phosphazene base P4-t-Bu. This is the product of a [1,2]-Stevens rearrangement of the intermediate ylide, the geometry of which is important in determining reaction path selectivity. In the presence of enantiopure BINPHAT as a counterion, the rearrangement led to some enantioselectivity in the reaction <04SL1565>. 

Dialkyl phosphites react with (hydroxymethyl)amines, giving a-amino phosphonic esters the same products can often be obtained by reaction of the phosphite with aminals, Schiff bases, or an aldehyde plus an amine321 (cf. page 708). Free phosphorous acid can itself be a-aminoalkylated in an acid medium, when according to the amine selected (ammonia can also be used) up to three methylenephosphonic acid groups can be attached to one nitrogen atom 322... 

CPG material was used as support instead of silica gel for a Heck/SAPC system [6]. There, iodobenzene was coupled with different olefins. The dependencies of different substrates and different bases on the activity were examined. The system was active for several types of olefins. The reactivity of the aryl hahdes was comparable to that of the homogeneous catalysis. Iodides reacted easily, while bromobenzene was converted inefficiently. No reaction occurred using chlorobenzene. With EtjN as base, the highest conversions were achieved. However, leaching of palladium was observed and an /Z mixture of products was isolated. When the amine was replaced by KOAc, the Heck reaction gave selectively the -isomer. No leaching was observed (detection limit approx. 0.1 ppm), but the conversion dropped to 80%. The catalytic system with KOAc as base was successfully used for five consecutive rims, with an overall TON of > 1,200. In all cases, conversion ranged from 70 to 80% and 100% selectivity of the -isomer was achieved. 

After realizing that our hypotheses about oxidative cross-coupling reactions were not as unique as assumed, we quickly turned our attentirai to intermolecular oxidative amination reactions. In the carbazole example, regioselectivity was coti-trolled by the presence of a Lewis base that was attached near the C—H bmid that would be cleaved, resulting in a metallacyle intermediate. For die development of an intramolecular reaction, we chose to take advantage of the selectivity that is often observed in the selective metalation of electron-rich heteroarenes. At the time, the palladation of indoles was presumed to operate by an electrophilic aromatic substitution mechanism. (This has since been demonstrated to be incorrect, vide infra.) We hypothesized that regioselective palladation of an indole substrate could be followed by a subsequent C—N bond reductive elimination. At the time, the exact mechanism by which the intermediate containing Pd—C and Pd—N bonds could be formed was not clear, nor was the order of the two metalation steps, but the overall process seemed plausible. 

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