Camphor stereoselective reactions

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. °... 

In recent years, several modifications of the Darzens condensation have been reported. Similar to the aldol reaction, the majority of the work reported has been directed toward diastereo- and enantioselective processes. In fact, when the aldol reaction is highly stereoselective, or when the aldol product can be isolated, useful quantities of the required glycidic ester can be obtained. Recent reports have demonstrated that diastereomeric enolate components can provide stereoselectivity in the reaction examples include the camphor-derived substrate 26, in situ generated a-bromo-A -... 

Camphor derived acetates 1 (Helmchen-type65) and 3 (Oppolzer-lype66) add to aldehydes in a stereoselective manner when the Mukaiyama variation via the corresponding silylketene acetals is undertaken. Careful optimization of the reaction conditions provides predominantly... 

For acrylates, or type I reagents, applied in asymmetric Diels-Alder reactions, several chiral auxiliaries such as menthol derivatives, camphor derivatives,16,3 and oxazolidinones4 are available. Carbohydrate compounds have also been reported as chiral auxiliaries in a recent publication, although the stereoselectivity was not good.5 Here are examples in which asymmetric Diels-... 

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. 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

Ashby and coworkers reported in 1974 stereochemical studies on addition of lithium trimethyhnagnesate to several ketones . The reactions of 4-ferf-butylcyclohexanone with methyllithium, with dimethylmagnesium and with lithium trimethyhnagnesate in ether afforded mixtures of the corresponding axial and equatorial alcohols in ratios of 65 35, 70 30 and 69 31, respectively (equation 11). Reaction of 3,3,5-trimethylcyclohexanone with lithium trimethylmagnesate yielded exclusively the axial alcohol (equation 12). Reaction of norcamphor provided 95% of the endo alcohol and 5% of the exo alcohol (equation 13). In contrast, reaction of camphor yielded the exo alcohol with high stereoselectivity (equation 14). Among the methylmetals examined, no difference in the stereoselectivity was virtually observed. 

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. 

As with most camphor-based chiral auxiliaries, the size and steric congestion at the C-8 position of the camphor moiety can determine its efficiency. Through the formation of a connection between C-8 and C-2, a novel camphor-based oxazinone auxiliary 29, which can be prepared from camphor in 3 steps,52 becomes highly effective in directing stereoselective aldol reactions (Scheme 5.11).53... 

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. 

A stereoselective synthesis of 3-( 1,2,4-triazolo[4,3-A ]azin-3-yl)-bicyclo[2.2.1 ]heptanones 58 starting from (l/ )-(+)camphor 56 has been described. The reaction comprises oxidative cyclization of the intermediate hydrazones 57 with methanolic bromine <02TA821>. 

The first stereoselective selenenylation reactions were reported using the binaphthyl-based diselenide 16 as the reagent precursor.71-76 After that, several other diselenides have been prepared initial attempts used quite long syntheses to obtain these compounds, for example, the C2 symmetrical diselenides 1777-79 and 2380 and the mannose-derived diselenide 18.81-84 The ferrocenyl-based diselenide 1985-89 is using expensive starting materials and in 1995 more simple and easy accessible diselenides like 20 and 21 have been described in literature.90-93 Camphor-based diselenides such as 2294-98 have been prepared and, based on the success of diselenides 20 and 21, structural variants 2499,100 and diselenides with different coordinating heteroatoms such as sulfur and selenium 25101-108 and 26109 have been described recently. 

Stereoselective formation of carbocycles has been carried out through [RhCl(cod)]2 (cod = cyclooctadiene) catalyzed reaction of alkenylzirconocene chloride to co-carbonyl carboxymide <07TL6471>. When the camphor sultam auxiliary is incorporated into amide 206, the Rh(I)-catalyzed reaction of alkenylzirconocene chloride 207 forms the cyclization product 211 with high diastereoselectivity. The tt-facial differentiation of the double bond in 206 for the initial attack of vinyl group can be explained by taking into consideration either of the reactive conformers A or B. No matter which reactive conformer is involved, the attack of the vinyl group to the less crowded C p si-face would account for the observed chirality. 

Also for stereoselective radical reactions such as radical additions or radical cyclizations, the camphor sultam 2 is suitable as an auxiliary (Scheme 7). The acyl radical which was gener-... 

Among terpenoid substrates bearing the alkyl ketone moiety, 4-caranone" and 2-pincne-4-one," in addition to camphor, are worth mentioning. The stereoselectivity of aminomethylation" is remarkably affected by the reaction conditions moreover, the tendency of 2-pinene-4-one, like steroid substrates, to give the vinylogous Mannich base (Table 8, Chap. I, C. 1) is important. 

The use of the corresponding thiourea in this reaction leads to equal amounts of both diastereomers, that is, no stereoselectivity is observed48. Chiral carbamates, derived from (-)-menthol and (+ )-camphor, give, in a similar reaction, a-aminoalkanephosphonic acids with optical purity up to 42 %71. 

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