Reduction difference camphor

Another aspect of the chemical properties of mixmres of enantiomers has been reported by Wynberg and Feringa in 1976. These authors have smdied some dia-stereoselective reactions on chiral molecules (such as the LiAlH4 reduction of camphor) in the absence of chiral auxiliaries. They found that the product distribution was significantly different if the substrate was enantiopure or racemic. Similarly, it is known that reduction of enantiopure or racemic camphor by K/liquid NH3 gives rise to different isobomeol/bomeol ratios, a detailed mechanistic analysis has been done by Rautenstrauch. °... 

It has been long known that different ratios of product alcohols (2 and 3) are obtained in the reduction of (-i-)-camphor with various metals in liquid ammonia. On the other hand, reduction of ( )-camphor with Li, Na or K in liquid NH3 affords, within experimental error, the same 82 18 ratio of (2) (3). An explanation in terms of diastereomeric bimolecular reactions has been presented. 

Stereoselective reduction of terpene ketones via hydrosilylation [36] exhibited significant difference in stereochemistry from other reduction by metal hydrides. Results of the reduction of camphor and menthone via hydrosilylation are listed in Table 6. Included also in the Table are reported selectivities obtained by using conventional reducing agents. It is seen in the Table that the bulkiness of silanes exerts remarkable influence on the stereochemical course of the reduction, i.e., a bulky hydrosilane favors the production of the more stable alcohols. This trend is quite... 

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. 

Wynberg studied stereochemistry of the McMurry reductive dimerization of camphor in detail (64). In Scheme 37, A and B are homochiral dimerization products derived by the low-valence Ti-promoted reduction, while C and D are achiral heterochiral dimers. The reaction of racemic camphor prefers homochiral dimerization (total 64.9%) over the diastereomeric heterochiral coupling (total 35.1 %). Similarly, as illustrated in Scheme 38, oxidative dimerization of the chiral phenol A can afford the chiral dimers B and C (and the enantiomers) or the meso dimer D. In fact, a significant difference is seen in diastereoselectivity between the enaritiomerically pure and racemic phenol as starting materials. The enantiomerically pure S substrate produces (S,S)-B exclusively, while the dimerization of the racemic substrate is not stereoselective. In the latter case, some indirect enantiomer effect assists the production of C, which is absent in the former reaction. Thus, it appears that, even though the reagents and reaction conditions are identical, the chirality of the substrate profoundly affects the stability of the transition state. 

The authors provided some experimental support for their hypothesis by performing various diastereoselective reactions on racemic or optically active compounds. Indeed, they found some differences in stereoselectivity between the two cases. Reduction of DL-camphor or D-camphor with lithium aluminum hydride, for example, gave ratios of isobomeol to bomeol of 7.93 and 9.20, respectively. 

Graphene was prepared by four different methods, namely the reductive pyrolysis of camphor (CG), exfoliation of graphitic oxide (EG),4 conversion of nanodiamond (DG)5 and arc evaporation of SiC (SG).6 In the first method, to prepare CG, camphor was pyrolysed over nickel particles under a reducing atmosphere. The reaction was carried out in a two-stage furnace and camphor was slowly sublimed (170 °C) by heating from the first furnace to the second furnace held at 770 °C where the... 

P450cam hydroxylates Ru-Cg-Ad when supplied with electrons via the natural NADH/putidaredoxin reductase/putd reduction relay.Ru-Cg-Ad hydroxylation occurs at only 1.6% the rate of camphor hydroxylation, and only 10% of the electrons supplied by NADH go to product formation. Presumably the rest are diverted to the formation of reduced oxygen species such as superoxide or hydrogen peroxide. The remarkable ability of P450cam to hydroxylate a molecule so structurally different from camphor supports the hypothesis that the structural flexibility inherent in the P450 fold allows these enzymes to hydroxylate structurally diverse substrates. 

Stereoselective hydrosiiyiation of terpene ketones such as camphor and menthone catalyzed by Rh(PPh3)3Cl followed by hydrolysis produces different stereochemistry from reductions using metal hydrides . Bulky hydrosilanes favor the production of the more stable alcohols ... 

The reduction of alkyl aryl ketones with camphor derived reagents generally yields a relatively high asymmetric induction. The reduction results obtained using different reagents are compared in Tabic 8, entries 10 65. 

Scheme 3.15 illustrates a different auxiliary derived from camphor, and which has similar design features, but which affords higher diastereoselectivity [75]. Additionally, Scheme 3.15 illustrates the selective formation of either an E(0)- or Z(0)-enoIate based on the presence or absence of HMPA in the reaction mixture. Thus, deprotonation of the ester with LICA is 98% selective for the fO>enolate and deprotonation in the presence of HMPA is 96% selective for the ZfO]-enolate. Alkylation with benzyl bromide is more selective for the E(0)-enolate than for the Z(0), but after diastereomer separation, reduction gives enantiomerically pure R-or S-2-methyl-3-phenylpropanol, opposite enantiomers from the same auxiliary... 

In an original publication which describes the addition of diphenylmethyl chloride to the enolate of ( + )-camphor [( + )-2] and subsequent reduction, it was claimed that the endo, tWoalcohol 24 was formed in such a reaction sequence23. However, other authors found the exo.e.xo-alcoho]24 using the same procedure, and attributed this to possible differences in the reaction and/or work-up methods which were not described precisely in the original article. The alcohols 24 thus obtained were used for the formation of chiral enol ethers and esters used as dienophiles in Diels - Alder reactions (Section D. 1.6.1.1.1.2.2.1.). 

Reduction of cyt P-450(m) by pyridinyl radicals is faster without camphor as substrate than with, despite an increase in the reduction potential from — 340 mV to —170 mV. This trend suggests that redox is dependent on the accessibility of the haem pocket to the radical. The order is reversed with 1-methyl-3-carbamidopyridinium radical, which is thought to react by a different mechanism. 

Not only stereospecificity but also reactivity differs widely from one substrate to another. For example, the relative rate for the reductions of cyclohexanone, 53, and camphor is 100 26 V/O (Irwin and Jones 1976). After accumulation of knowledge on HLADH-mediated reactions, it was recognized that the diamond-lattice theory proposed by Prelog and illustrated in Fig. 2 was unsatisfactory in predicting the steric course and reactivity for a variety of substrate structures. Jones and Jakovac (1982), therefore, proposed a new concept (cubic-space model) as a substitute for the diamond-lattice theory. According to their proposal, the active site of HLADH is... 

This huge difference in reactivity is certainly not owing to electronic factors only, since it cannot be large in these two ketones. Moreover, camphor is reduced more slowly, by a factor of 6, over that of norbornanone by 9-BBN, whereas the factor is more than 900 in case of sodium borohydride reduction (Chart 25.4). 

In 2003, Rawal reported the use of TADDOLs 177 as chiral H-bonding catalysts to facilitate highly enantioselec-tive hetero-Diels-Alder reactions between dienes 181 and different aldehydes 86 (Scheme 6.29A) [82], and also BINOL-based catalysts 178 were found to facilitate this reaction with excellent selectivities [83]. TADDOLs were also successfully used as organocatalysts for other asymmetric transformations like Mukaiyama aldol reactions, nitroso aldol reactions, or Strecker reactions to mention a few examples only [84]. In addition, also BINOL derivatives have been employed as efficient chiral H-bonding activators as exemplified in the Morita-Baylis-Hilhnan reaction of enone 184 with different carbaldehydes 86 [85]. The use of chiral squaramides for asymmetric reactions dates back to 2005 when Xie et al. first used camphor-derived squaric amino alcohols as ligands in borane reductions [86]. The first truly organocatalytic application was described by Rawal et al. in 2008 who found that minute amounts of the bifunctional cinchona alkaloid-based squaramide 180 are... 

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