Bridgehead amines

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. 

These results show that bridgehead amines are not a requisite and secondly that bidentate ligands can also be used successfully. Molecular modelling is... 

The bridgehead-amine-derived electrophilic fluorinating reagents l-alkyl-4-fluoro-l,4-di-azoniabicyclo[2.2.2]octane ditriflate 5 a or bis(tetrafluoroborates) 5b and 6 can be prepared from l-alkyl-4-aza-l-azoniabicyclo[2.2.2]octane salts and elemental fluorine. For example, treatment of l-methyl-4-aza-l-azoniabicyclo[2.2.2]octane triflate (4a) and lithium triflate in acetonitrile at — 35CC with neat fluorine over three hours gives l-fluoro-4-methyl-l,4-dia-zoniabicyclo[2.2.2]octane ditriflate (5a).81 The reagents 5b, 6, 7, and 8 can be synthesized in a similar manner.76 83... 

Oxyaminatkm.1 The ratio of amino alcohol to diol formed by reaction of alkenes with the reagent is considerably improved by the presence of tertiary alkyl bridgehead amines. Of these ligands, quinuclidine (I, 976 4, 417) is the most efficient. In this case DME is used in place of pyridine as solvent. 

Some bridgehead amines [l,4-diazabicyclo-[2,2,2]octane (102), quinuclidine (103) and quinuclidine-3-ol] form 1 1 molecular complexes with quinones 104. Formation of 2 1 (amine/quinone) complexes was observed in solutions of DABCO (102) and chloranil (104, R = Cl). These tertiary amines are able to form complexes, while non-bridgehead amines (triethylamine, piperidine) cannot because of steric hindrance or nitrogen inversion183. Stable complexes may be predicted (by CNDO/2 calculations) for... 

In both the chloride and bromide structures, the halide was also found to be encapsulated, but was positioned more centrally within the cavity, as explained by a better size match between the ligand and halide (Figure 7B) [48], In both cases the cryptand is hexaprotonated and all six of the protonated amines exhibit hydrogen bonding with the internal halide, with average NH—X distances of 3.30 A for chloride and 3.39 A for bromide. The distance between the bridgehead amines is 7.40 A and 7.50 A for the chloride and bromide complexes, respectively. 

Distances between the bridgehead amines vary according to the topicity of the receptors. For monotopic complexes, the bridgehead distances are between 6.5 and 7.9 A. In terms of incorporating multiple species, however, the azacryptands appear to be the most flexible, as seen additionally in the dinitrate structure with 5 [30]. When... 

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. 

Here, the two arms are separated by the bridgehead amine, and the pendant group designation follows. Hence, the N-methylated analog is [2.2]NCH3. The macrocycles with the pendant hydroxyethyl and methoxyethyl groups are... 

For the nonquaternized 28b and 29, the bridgehead amines are protonated upon complexation with oxo anions such as sulfate, probably due to the presence of extra protons from the H2SO4 or [nBu4N][HS04] reagents used... 

Figure 14 View down the bridgehead amines of the structure of the fluoride complexes of (a) 28a and (b) 28b.

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