Stereochemistry aliphatic amines

For aliphatic amines, coordination of the lone pair to a central metal ion completes the tetrahedral stereochemistry about the nitrogen atom (equation 8), and... 

Treatment of a primary aliphatic amine with nitrous acid or its equivalent produces a diazonium Ion which results in the formation of a variety of products through solvent displacement, elimination and solvolysis with 1,2-shift and concurrent elimination of nitrogen. The stereochemistry of the deamination-substitution reaction of various secondary amines was investigated as early as 1950, when an Swl-type displacement was suggested. Thus, the process can hardly be utilized for the preparation of alcohols except in cases where additional factors controlling the reaction course exist. Deamination-substitution of a-amino acids can be utilized for the preparation of chiral alcohols. 

The work on methylamine — clearly the simplest aliphatic amine — also demonstrates, however, that not only the amine, but also the deamination method must be simple. We discussed the stereochemistry of the deamination in the rearrangement of a derivative of chiral methylamine (7.30) in Section 7.3, but first, we have doubts whether Gautier s result (1980, inversion) of the pyrolysis of that N-methyl-N-nitroso-toluenesulfonamide in an aprotic solvent at 95 °C is comparable with the direct nitrosation of an amine in water, and second, the result of Gautier is contrary to that of the stereochemical investigation of a somewhat more complex amide deamination, namely that of N-(l-methylpropyl)-N-nitroso-4-toluenesulfon-amide (White et al., 1981 see Sect. 7.3). ... 

In conclusion, we propose a specific research program for deaminations in aqueous systems based on ideas mentioned in this section, namely to investigate (a) deamination kinetics and products of a series of simple aliphatic amines in water with sodium nitrite and perchloric acid at various acidities, (b) decompositions of diazenolates of the same amines in water and (c) decompositions of a standard type of N-nitroso amides, again of the same amines and all in the same aprotic solvent. The reaction conditions should be as similar as possible in the experiments of all three series. The series of amines should include methyl-, ethyl-, 1-methylethyl-, 1-methylpropyl-, and ( cr butyl)amine and [l- H]ethylamine, but not amines with longer aliphatic chains, as the very informative work of Southam and Whiting (1982) demonstrated clearly that, in deaminations of such amines, many mechanistically complex products are formed. In addition, micellar effects increase the complexity of reactions with such amines (see Sect. 7.3). It is obvious from the series of amines that we have proposed that this program is based on the work of Brosch and Kirmse (1991), Hovinen and Fishbein (1992), Hovinen et al. (1992), Finneman et al. (1993), and Ho and Fishbein (1994). Work with chiral 1-methylpropyl- and [l- H]ethyl-amine will provide information on the stereochemistry of these reactions. 

Shibasaki [89a] has reported an asymmetric synthesis of (-h) PS-5 by using the boron enolate-imine condensation reaction. The most notable features of this approach were that the correct absolute stereochemistry at C3-C4 of the p-lactam ring was produced in a highly diastereoselective fashion and imines derived from aliphatic amines could be used in this reaction in a similar way to the silyl ketene acetal approach (Scheme 32). 

Table 12. Stereochemistry of alcohols and acetates obtained from the nitrous acid deamination of aliphatic amines in acetic acid.

The anti addition of diethyl 7V,Ar-dibromophosphoramidates to acyclic and cyclic alkenes was achieved in the presence of boron trifluoride, which makes the ionic dissociation of the N —Br bond more labile94,9s. After reduction of the initial /J,lV-dibromo adducts with sodium bisulfite, the /i-bromo-A -hydrophosphoramides 3 precursor of / -bromo amine hydrochlorides 4 were obtained (Table 4). However, a mixture of diastereomers was obtained from (Z)-l-phenyl-l-propene and (E)- and (Z)-l,2-diphenylethylene. Direct assignment of stereochemistry by H NMR of the phosphoroamidates derived from 2-butenes was not possible. Detailed analysis is, however, possible for the H-NMR spectra of the /J-bromo amine hydrochlorides. As determined by 31P NMR spectroscopy all additions to unsymmetrical aliphatic alkenes were not regiospecific. The /f-bromo amine hydrochlorides were converted to 1,2-diamines95. 

More recently, the same catalyst was used to produce cyclic amines with retention of stereochemistry from a simple linear aliphatic azide [53]. Treatment of a substituted aliphatic azide by complex 66 afforded the cyclized compound 75, by insertion of the nitrene moiety in allylic, benzylic, and even in the less reactive tertiary C—H bonds. The catalyst is inhibited by coordination of the product to the metal center. However, that can be avoided by using an in situ protecting agent (Boep is preferred over Fmoc-OSuc which leads to catalyst decomposition). 

Radical methods are of central importance in organic synthesis [1], These reactions are performed under mild and neutral conditions, which usually avoids competing ionic side reactions. Carbon-centered radicals are compatible with a range of functional groups (e.g. aliphatic alcohols, amines, ketones, esters) and also show high chemoselectivity under carefully controlled reaction conditions. Furthermore, reactions involving loss of stereochemistry at the non-radical center are not problematic, and hence radical methods are emerging as a powerful synthetic tool in the field of carbohydrate chemistry. 

Pyridine has been used effectively as a catalyst in the Kno-evenagel condensation reaction. Depending upon the nature of the base employed, the product selectivity can be altered. Different stereochemistry has been observed for aromatic heterocyclic bases such as pyridine and aliphatic tertiary amines such as tri-ethylamine. Reaction of hexanal (4) with malonic acid (5) in the presence of pyridine as the base gives the Q , -unsaturated acid (6) as the major product (91 9 When bases such as triethy-... 

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