Amines medium ring size

A particularly useful general method for the synthesis of saturated nitrogen- and oxygen-containing partially unsaturated heterocycles, from 5-membered to medium ring-sized, is the Grubbs olefin metathesis applied, for example, to acyclic diaUcenyl-amines, as illustrated by syntheses of a dihydropyrrole and a tetrahydropyridine. ... 

Using the phthalimide/methylthioether-pair, a variety of photochemical transformations resulting in medium- and macrocyclic sulfur containing amines, lactams, lactones, and crownether analogues, respectively, with a maximum ring-size of 38 atoms have been described [26,27]. Scheme 10 summarizes some selected examples. 

The first application of the single-step procedure to the synthesis of azacafix-arenes was laimched by Ito et al., who prepared a series of azacafix[ ]arenes 4a-f with different ring sizes (w = 3 to 8) [16,17]. As shown in Scheme 2, starting from the N-methylation of 3-bromoaniline (2) in 3 steps, the resultant 3-bromo-N-methylaniline (3) was subjected to the Buchwald-Hartwig aryl amination reaction to yield azacaUxarenes 4a-f, which were isolated by medium-pressure liquid chromatography. 

Using the decarboxylative photocyclization, the synthesis of medium- and macrocyclic amines, lactones, polyethers, lactams, as well as cycloalkynes were accessible in ring sizes up to 26 (Scheme 14) and even in multigram quantities. The regioselectivity of the radical cyclization step was studied for unsymmetrically substituted pyridinecarboximides and trimeUitic acid imides, respectively, where the site of the C-C-bond formation is controlled by the maximum spin density of the radical anion intermediates. ... 

Enoate 3-substitution and 3-disubstitution cause a decrease in the rate of the initial conjugate addition step of the reaction sequence that is directly related to the steric bulk of the substituent.103,105 Equation (24) provides a representative case in the a-alkylation of enoates by means of conjugate amination-enol-ate alkylation followed by dehydroamination.106 When 3-substitution results in stereoisomeric ( )- and (Z)-alkenoate substrates, tandem difunctionalization typically proceeds with greater facility for ( )-isomers.64103 Obviously, when the double bond of the ester is part of a medium-sized ring, an ( )-alke-noate geometry is mandated in such cases, tandem vicinal difunctionalization proceeds with uniformly excellent results (equation 25).25... 

Sometimes, aldehydes or ketones resulting from Dess-Martin oxidation are attacked intramolecularly by nitrogen atoms belonging to diverse functionalities, when such attack results in aminals inside stable medium-sized rings.82 Sometimes, these aminals suffer dehydration to enamines. 

Transannular reactions of enamines with the amino group of one side of a medium-size ring and the C=C double bond on the other side of the ring, positioned so that it can interact with the amine nitrogen, have been observed316. For example, protonation of 201 gives the transannular bonded product 202, but alkylation leads to the open product 203 (equation 23). 

A very interesting synthesis of medium-sized cyclic amines has been performed by selective ring cleavage of sulfonylated bicyclic amines.246 A Julia-type desulfonylation of an activated p-amino sulfone is the key step in this method, which takes place even in the presence of a hydroxyl leaving group in the P position (Eq. 140). 

The phthalimide functional group has absorption and ET properties which make it very attractive in terms of PET processes in which it is the oxidizing species. The application of phthalimide derivatives in carbon-carbon bond forming processes with electron-donating groups such as ethers, thioethers, amines, arenes, carboxylates, etc., has been reviewed. A PET decarboxylation-cycliz-ation sequence has been used for the synthesis of medium-sized (8-16) heterocyclic ring systems (15) from AT-phthaloylanthranilic amides coupled to ca-aminoacids (14). The same PET protocol has been used to convert di-, tri-, and tetrapeptides into cyclopeptides with a minimum of protection and activation... 

Negishi et al. [154] demonstrated the carbopalladation mode of an allene to be feasible for an intramolecular approach to medium- and large-sized rings. The new C-C bond is formed at the central carbon atom of the allene moiety to give a 7t-allylpalladium complex, which in turn can be trapped by a variety of nucleophiles (arylstannanes to give arylated products, malonates, phenols, amines, etc.) (Scheme 8.32). The yields are remarkably good without using sophisticated nucleophile delivery techniques. 

Irradiation of the tertiary N-methyl,N-phenyl amines 29 gave the corresponding cycHzation products 30 in yields of 6 to 20% (Scheme 10 Table 84.3). The regioselectivity of the mesolytic CH-activation step was pronounced, except for the case where n = 4. This observation goes parallel with the thioether case vide supra). The conversions were low for the precursors to medium-sized ring systems higher conversions and yields up to 39% were obtained for dibenzylated amines. ... 

Preparation of Phosphites. Alcohols, diols, and phenols are readily converted to phosphites. Analogous reactions are seen with thiols and amines. Diaryl phenols react to form medium-sized heterocyclic ring systems (eq 1 ). ... 

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