Bridgehead-type amines

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

A parallel library of optically active bicyclic tertiary amines 127 bearing N-chiral bridgehead nitrogen atoms was readily prepared by condensation of primary amines, cyclic amino acids 126, and aldehydes. This method gives access to a large variety of substituted hexahydro-l/7-pyrrolo[l,2-/ ]imidazol-l-ones of type 127 (Scheme 16). These... 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

Some bridgehead amines such as 4-iodo-l-cubylamine (58%) and 1-adamantyl-amine (85%) were also obtained in this way [47]. The direct formation of alkylammonium tosylates is advantageous because of the instability of some amines of this type. No special precautions, as with BTI, were needed with HTI which, however, did not work with some cyclic carboxamides also, malonamide did not undergo degradation but tosyloxylation, affording a-tosyloxymalonamide (81%) [48]. The reaction involved the intermediacy of TV-phenyliodonium salts (RCONHI + Ph TsO-), which were actually isolated from carboxamides and [methoxy(tosyloxy)iodo]benzene [49]. 

Bowman-James and co-workers have designed polyamide cryptand-type systems based on triamines, such as tren (e.g. 14) and trpn (e.g. 15), and shown that they bind anions [23]. The crystal structure of the hydrochloric acid and fluoride complexes of 14 reveal that the anions are encapsulated within the cavity of the amidocryptand and boxmd to the six-amide NH groups. In contrast the hydrochloric acid structure of the expanded trpn-based amidocryptand 15 shows the encapsulation of two chloride anions within the cryptand, bridged by a water molecule. Each chloride is boimd to the water molecule as well as a protonated bridgehead amine and two hydrogen bonds from the amides groups. 

Consideration of the chemical properties of quinuclidine derivatives led to the conclusion that this type of compound was characterized both by the presence of unshielded free lone pair electrons attached to the bridgehead nitrogen atom and by the specific conformation of the molecule. In contrast to aliphatic tertiary amines and iV-substituted piperidines quinuclidine has a rigidly fixed structure, each of the two rings in the structure having a bath form. 

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