Isoborneol

Ordinary commercial camphor is (-i-)-cam phor, from the wood of the camphor tree. Cinnamonum camphora. Camphor is of great technical importance, being used in the manufacture of celluloid and explosives, and for medical purposes, /t is manufactured from pinene through bornyl chloride to camphene, which is either directly oxidized to camphor or is hydrated to isoborneol, which is then oxidized to camphor. A large number of camphor derivatives have been prepared, including halogen, nitro and hydroxy derivatives and sulphonic acids. 

The structure of the bicychc monoterpene borneol is shown in Figure 26 7 Isoborneol a stereoisomer of borneol can be prepared in the labora tory by a two step sequence In the first step borneol is oxidized to camphor by treatment with chromic acid In the second step camphor is reduced with sodium borohydride to a mixture of 85% isoborneol and 15% borneol On the basis of these transformations deduce structural formulas for isoborneol and camphor... 

Carbocation rearrangements occur in the reactions of some secondary alco hols with DAST, thus isobutyl alcohol gives a mixture of isobutyl fluoride and tert-hxAy] fluonde [95] (Table 6), and both bomeol and isoborneol rearrange to the same 3-fluoro-2 2,3-tnraethylbicyclo[2 2 IJheptane (72-74%) accompanied by camphene [95]... 

Of synthetic importance is the Wagner-Meerwein rearrangement especially in the chemistry of terpenes and related compounds." For example isoborneol 5 can be dehydrated and rearranged under acidic conditions to yield camphene 6 ... 

Isoborneol yields camphor on oxidation, but it yields camphene on dehydration much more readily than borneol does. If a solution of isoborneol in benzene be heated with chloride of zinc for an hour, an almost quantitative yield of camphene is obtained. Pure borneol under the same conditions is practically unchanged. 

The following table exhibits the principal difference between borneol and isoborneol —... 

Camphene hydrate is a tertiary alcohol, and a study of its characters and method of preparation caused Aschan to consider that it is improbable that borneol and isoborneol are stereoisomeric, but that they probably have different constitutional formulae. 

Semmler and Tobias consider that eudesmol and globulol are related in the same manner asiborneol and isoborneol. 

Camphor, Cj HjgO, occurs in the wood of the camphor tree Laurus camphora) as dextro-camphor. This is the ordinary camphor of commerce, known as Japan camphor, whilst the less common laevo-camphor is found in the oil of Matricaria parthenium. Camphor can also be obtained by the oxidation of borneol or isoborneol with nitric acid. Camphor may be prepared from turpentine in numerous ways, and there are many patents existing for its artificial preparation. Artificial camphor, however, does not appear to be able to compete commercially with the natural product. Amongst the methods may be enumerated the following —... 

Pinene hydrochloride is prepared in the usual manner from turpentine, and this is allowed to react with acetate of silver. Isobornyl acatate is formed, which is hydrolysed, and the isoborneol oxidised to camphor. Acetate of lead is also used, as is also acetate of zinc. 

Propose a mechanistic pathway for the biosynthesis of isoborneol. A carbo-cation rearrangement is needed at one point in the scheme. 

Isoborneol (Problem 27.37) is converted into camphene on treatment with dilute sulfuric acid. Propose a mechanism for the reaction, which involves a carbocation rearrangement. 

In a flame-dried Schlenk tube 0.37 g(1.88 mmol) of (-)-3-exo-(dimethylamino)isoborneol (C) and 200 mL of dry toluene are placed under an atmosphere of argon. 27 mL of 4.2 M diethylzinc (113 mmol) in toluene are added and the resulting solution is stirred at 15°C for 15 min. After cooling to — 78°C, lOg (94.2 mmol) of benzaldehyde are added and the mixture is wanned to O C. After stirring for 6 h, the reaction is quenched by the addition of sat. NH4C1 soln. Extractive workup is followed by distillation yield 12.4 g (97%) 98% ee [determined by HPLC analysis. Baseline separation of rac-1 -phenyl-1 -propanol was achieved on a Bakerbond dinitrobenzoyl phenylglycine column (eluent 2-propanol/hexanc 1 3 flow rate l.OmL/ min detection UV 254 nm)] [a] 0 —47 (c = 6.11, CHC13). 

With the stcrically constrained /(-amino alcohols N-P asymmetric amplification phenomena were observed similar to the effects found with 3-e.Y0-(dimethylamino)isoborneol (vide supra). Thus, alkylation of benzaldehyde with diethylzinc, catalyzed by a partially resolved catalyst N-P, gives 1-phenyl-1-propanol with an enantiomeric excess, which impressively exceeds the optical purity of the catalyst employed12. 

The isoborneol-10-sulfonamide unit represents a new type of chiral structure that has been successfully used in different reactions of organometallic addition to aldehydes with excellent results in some cases. In particular, this unique type of ligand has been investigated by Yus and Ramon for the enantioselective... 

Isoborneol-derived P-hydroxy-sulfide ligand for addition of ZnEt2 to benzaldehyde. 

On the other hand, several S/O ligands have been successfully applied to the enantioselective addition of ZnEt2 to aldehydes. As an example, Aral et al. have developed isoborneol-derived p-hydroxy-sulfide ligands and employed them in the enantioselective addition of ZnEt2 to benzaldehyde, providing enantio-selectivities of up to 88% ee (Scheme 3.54). These authors showed that the enantioselectivity of the reaction did not depend on the substituent of the sulfur atom. 

After finding the right combination for the diamine linkers, Yus et al. tried to determine whether it was compulsory to use two isoborneol-10-sulfonamide moieties. In this context, these authors have prepared the ligand depicted in Scheme 4.24 by reaction of the best amine linker, trani-cyclohexane-1,2-diamine, with camphorsulfonyl chloride and then with methanesulfonyl chloride, followed by reduction with AlH(i-Bu)2 and then hydrolysis.When this new ligand was involved in the enantioselective addition of ZnEt2 to acetophenone, the expected tertiary alcohol was obtained in excellent yield and enantioselectivity of 96% ee, as shown in Scheme 4.24. According to this result, the authors concluded that the second isoborneol unit seemed not to be necessary to obtain a high enantioselectivity. 

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

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