Cryptands ketones

Bicozamycin benzoate, registered for use in aquaculture in Japan, 3 221t Bicyclic cryptands, 14 161 Bicyclic ketones, trans-fused, 13 655 Bicyclic monoterpenes, aroma chemicals,... 

Pierre and Handel (1974) observed that cyclohexanone was cleanly reduced to cyclohexanol by LiAlH4 in diglyme solution. On addition of one equivalent (based on Li+) of the strong Li+-complexing agent [2.1.1]-cryptand, all the LiAlH4 was solubilized, but the reduction was completely inhibited. In the presence of additional amounts of either Lil or Nal, the ketone was reduced in the normal way. On the basis of these results, the authors concluded that the... 

The effect of cryptands on the reduction of ketones and aldehydes by metal hydrides has also been studied by Loupy et al. (1976). Their results showed that, whereas cryptating the lithium cation in LiAlH4 completely inhibited the reduction of isobutyraldehyde, it merely reduced the rate of reduction of aromatic aldehydes and ketones. The authors rationalized the difference between the results obtained with aliphatic and aromatic compounds in terms of frontier orbital theory, which gave the following reactivity sequence Li+-co-ordinated aliphatic C=0 x Li+-co-ordinated aromatic C=0 > non-co-ordinated aromatic C=0 > non-co-ordinated aliphatic C=0. By increasing the reaction time, Loupy and Seyden-Penne (1978) showed that cyclohexenone [197] was reduced by LiAlH4 and LiBH4, even in the presence of [2.1.1]-cryptand, albeit much more slowly. In diethyl ether in the absence of... 

Polymer-supported onium ions are relatively unstable under severe conditions, especially concentrated alkali154). Polymer-supported crown ethers and cryptands are stable under such conditions. In practice, they could be reused without loss of catalytic activity for the alkylation of ketones under basic conditions, whereas the activity of polymer-supported ammonium ion 7 decreased by a factor of 3 after two recycles of the catalyst147). 

In non-hydroxylic solvents, the effects of the cation co-ordination become important, particularly if the cation is Li+ or Zn + 2. Lithium borohydride reductions of cyclohexanone, in THF, for example, are strongly inhibited by addition of the stoichiometric amount of the lithium specific [2.1.1]cryptand (Handel and Pierre, 1975). In the reduction of a,P-unsaturated ketones, lithium borohydride shows a strong selectivity for 1,2-addition (D Incan et al., 1982a,b) but in the presence of the cryptand, conjugate addition is favoured indeed, the selectivity is then indistinguishable from tetrabutyl-ammonium borohydride (D lncan and Loupy, 1981 Loupy and Seyden-Penne, 1979, 1980). 

Perfluorinations of many ethers [155], cryptands [156], polyethers [119, 157], including the largest perfluoro-macrocycle [158], perfluoro [60]-crown-20 [123, 159], and the first perfluorinated sugar [160], orthocarbonates [161, 162], ketones [163, 164], esters [124, 165], phosphanes [166] and alkyl halides [167, 168] have been successfully accomplished by the LaMar or aerosol processes (Table 2.4). 

Because of their electrophilic nature, Li" cations accelerate the reduction of carbonyl compounds by LiAlH4 or NaBH4. Li -complexing agents, such as cryptands, crown ethers or polyamines decrease the rate of reduction. In the case of a,p-unsaturated ketones, this slow down is associated with altered regioselectivity. For example, L1A1H4 reduction of cyclohexenones in the absence of the cryptand proceeds predominantly with 1,2-reduction. In the presence of the cryptand, 1,4-attack is favored. This selectivity is more pronounced with LiAlHa than with NaBHa (Scheme 36) and is also dependent on solvent. For example, with diethyl ether the 1,2-attack prevails, whereas when the cation is complexed, 1,4-addition predominates. 

Another successful alkylation of a cyclopropyl ketone was reported by Handel and CO workers when they reacted cyclopropyl phenyl ketone (211) with excess potassium hydride (5 M equivalents) in the presence of [2.2.2]cryptand methylation with methyl iodide gave 212 in 90% yield. The conditions are crucial without the cryptand, 211 is reduced to the corresponding secondary alcohol in 82 % yield. 

Crown ethers and cryptands can also be used for such reactions . In this regard is should be mentioned that, in homogeneous organic phase, the complexation of LiAlH4 and NaBH4 by specific cryptands ([2.1.1] and [2.2.1] for Li and Na , respectively) inhibits or greatly slows down the reduction of ketones, due to the absence of the electrophilic activation by the inorganic cation 263 -266)... 

Diethylmagnesium, in the presence of either 2,1,1-cryptand or EtLi, provides significant amounts of 1,4-addition products with pyridine. 2 new method for assessing s.e.t. in Grignard/ketone... 

A series of papers on the metal hydride reduction of aldehydes and ketones, - and some other functional groups, has demonstrated the importance of the metal ion for example, y " is indispensable in the lithium aluminium hydride reduction of many ketones in aprotic solvents, through transition state (46), and reaction is prevented by the specific lithium complexing cryptand (47). 

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