Camphor reduction

Camphor reduction, a-bromo ketone to ketone, 127 Carbenium ions ... 

Steric Effects.—The consequences upon chemical reaction of non-bonded interactions between enantiomeric pairs of molecules have been discussed an antipodal interaction effect was observed in a reductive camphor dimerization and in a camphor reduction. The full paper on the correlation of the rates of chromic acid oxidation of secondary alcohols to ketones with the strain change in going from the alcohol to the carbonyl product has now appeared. It is concluded that the properties of the product are reflected in the transition state for the oxidation. High yields of hindered carbonyls are available from the corresponding alcohols by reaction with DMSO and trifluoroacetic anhydride (TFAA) indeed, the more hindered the alcohol, the higher the yield of carbonyl compound reported Since the DMSO-TFAA reaction occurs instantaneously at low temperatures (<—50°C), it is possible to oxidize alcohols that form stable sulphonium salts only at low temperature. Thus, ( )-isoborneol reacts at room temperature to give camphene, the product of solvolysis of the sulphonium salt the oxidation product, ( + )-camphor, was obtained by the addition of base at low temperature. 

Guette and Horeau were able to derive a mathematical expression that relates the molar fraction of each product to the observed enantiomeric purities. The expression shown in Equation 6.1 is based on a more recent version developed by Kagan [7, 9] that apphes to the case where a racemic substance is partially converted into two distinct products (corresponding to diastereomers 12 and 13 in the camphor reduction). The molar fractions Xj (unreacted starting material),... 

An example of this type of reduction is that of benzaldehyde to 1-d-benzyl alcohol by a copper-aluminum alloy in the presence of deuterium oxide and sodium carbonate.Huffman et al observed that the stereoselectivity of camphor reduction is the same either sonochemically in THF or silently in liquid ammonia with the usual three alkali metals (Eq. 13),106... 

Borneol and isoboineol are respectively the endo and exo forms of the alcohol. Borneol can be prepared by reduction of camphor inactive borneol is also obtained by the acid hydration of pinene or camphene. Borneol has a smell like camphor. The m.p. of the optically active forms is 208-5 C but the racemic form has m.p. 210-5 C. Oxidized to camphor, dehydrated to camphene. 

Me2C = CHCOCH= CMca- Yellow liquid having a camphor-like odour m.p. 28 C, b.p. 198-5°C. It is formed when propanone is saturated with HCl and allowed to stand. Resembles camphor in many of its properties and is a solvent for cellulose nitrate. Used to prepare diisobutyl ketone (reduction). 

Diketimines can be prepared by condensation of 1,2-diketones with 2 equiv of an amine, or 1 equiv of a 1,2-diamine, by azeotropic removal of water. Either a chiral diketone or a chiral amine/diamine can be used in order to obtain a chiral diimine. In both cases, the use of 1,2-diamines is expected to provide better stereocontrol, because of the rigidity of the derived cyclic diimines. For example, the reaction of camphor 1,2-diketone 275 and racemic 1,2-diphenylethylenediamine (d,l)-26 gave the diimine 276 as a mixture of two diastereomers (Scheme 45) [138]. Reduction of 276 with sodium borohydride followed by hydrogenolysis of the N substituents afforded the camphordiamine, which was isolated as the dihydrochloride... 

Scheme 9.8 Ir-catalysed reduction of acetophenone with camphor-derived amino sulfide ligands.

Fry and Newberg 1,2> examined the electrochemical reduction of nor-camphor oxime (109) and camphor oxime (110) to the corresponding amines. The results of this study are shown in Table 3. It is clear from a comparison of these data with those in Table 2 that the electrochemical reduction of oximes 109 and 110 takes a very different stereochemical course from reduction of the corresponding anils 103 and 104. Reduction of oximes apparently proceeds under kinetic control, affords products corresponding to protonation at carbon from the less hindered side of the carbon-nitrogen double bond, and affords the less stable epimeric amine in each case. It is not evident why the stereochemistry of reduction of anils and oximes should differ, however. 

Hoye and Richardson have published an ingeneous synthesis of the tricyclic iridoid sarracenin (170) which relied on the Paterno-Buchi cycloaddition between acetaldehyde and cyclopentadiene as the intial step (Scheme 38)79. This reaction provided a 5 1 mixture of adducts 166a and 166b. The major adduct was opened with camphor-10-sulfonic acid (CSA) in methanol and the alcohol was tosylated to give 167. Displacement with malonate 168 and decarboalkoxylation/demethylation steps gave 169. Ozonolysis, reductive workup and acid-catalyzed acetalization then furnished 170. 

In 1965, Denney et al. (98) reported the reaction of a number of alkenes with ferf-butyl hydroperoxide (TBHP) and cupric salts of chiral acids. The use of ethyl camphorate copper complex 144 in the allylic oxidation of cyclopentene provides, upon reduction of the camphorate ester, the allylic alcohol in low yield and low selectivity, Eq. 82. The initial publication only provided the observed rotation of cyclopentenol, but comparison to subsequent literature values (99) reveals that this reaction proceeds in 12% ee and 43% yield (based on the metal complex). 

Thomas and co-workers have examined camphor-derived chiral stannanes recently [52], However, poor selectivity (< 5% ee) was obtained for the reduction of bromoketones in the absence of any Lewis acid. 

Scheme 4.41 Stereoselective synthesis of camphor-based allenes byAIH3 reduction.

Crown ethers have also been found to lower the rate of reduction by metal hydrides. Wiegers and Smith (1978) reported that the rate of reduction of camphor by LiAlH4 in tetrahydrofuran was depressed by a factor of 6 on addition of one equivalent of crown ether [201]. They also concluded that, although the free cation shows a catalytic effect in metal hydride reduction, it is not indispensable. Dibenzo-18-crown-6 [11] was also found to lower the rate of... 

It was recognized (32) that not all species 4 (R = sec-alkyl) undergo disproportionation readily, since the reagent formed from camphor and LAH was more stereoselective than LAH in the reduction of 5. This was attributed to the bulky isobomyloxy complex formed in the reaction of camphor with LAH, which is analogous to the tri-r-butoxy complex. Disproportionation to the tetraalkoxy-aluminum species in these cases is disfavored by steric hindrance. 

LiAlH(OBu )3 does not undergo disproportionation to the tetraalkoxy species. Reduction of the aromatic ketones studied involved either monomeric LAH or both this species and the monoalkoxy species, depending on the steric hindrance of the substrate. In a similar study of the reduction of camphor in THF (39), the kinetic results were also consistent with disproportionation of r-butoxy species (eqs. [6] and [7]), active reducing species being LAH and LiAl(OBu )H3. In the reduction of camphor with a series of reagents prepared by the reaction of LAH... 

Johnson and Klein (72) prepared the chiral diol (+)-1,2,2-trimethyl-1,3-bis(hydroxymethyl)cyclopentane (50) by the LAH reduction of (+ )-camphoric acid. Consideration of models of the complex of 50 with LAH suggested that... 

A 1,2-amino alcohol, ( + )-(lR,4S)-3-exo-anilino-2-exo-hydroxybornane (103), was synthesized from (-I-)-camphor and converted to its LAH complex (eq. [26]). Reduction of acetophenone, propiophenone, and butyrophenone at low... 

Reduction of (+ )-camphor with LAH gives a mixture of (—)-isobomeol (90%) and ( + )-bomeol (10%) (129). The complex with bomeol reacts much slower with ketones. 

Similarly, aliphatic thiones are also readily reduced at microcathodes in DMF. Thus, thiocamphor exhibits a one-electron reversible step at —1.88 V versus SCE, which is about 0.9 V more positive than the potential of the reduction of camphor under the same experimental conditions. q , 8-unsaturated thiones such as (18) were also investigated polarographically in pro-tic media. Similarly [179-182], reduction of Q , 8-ethylenic ketones and aldehydes in acidic media yielded dimers. 

Electrochemical reduction of camphor-and norcamphoroxime at a Hg cathode proceeds with a high degree of stereoselectivity to give products of opposite stereochemistry to those formed in the dissolving metal (Na-alcohol) reduction of the oximes. The electrolyses are proposed to proceed by a kinetically controlled attack by the electrode on each oxime from the less hindered side (Fig. 62) [348]. In contrast, the corresponding N-phenyl imines yield products of the same stereochemistry as those isolated from a dissolving metal reduction. Cyclic voltammetry and polarographic data point to RH and intermediates in this case that are proto-nated from the least hindered side [349]. 

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