3- Methylcyclohexene, enantiomers

To add another complication recently, (R)-(—)-10-methyl-A1(-9)-octalin (7) has been prepared and its hydrogenation studied over Pt, Pd, and Rh catalysts.91 Like the apopinenes and the (R)-(—)-4-methylcyclohexene, this R enantiomer may undergo double bond migration to its 5 enantiomer, which... 

Figure 3.32 showed the reaction of our enantiomerically pure chiral cyclic dialkylborane with (Vi )-3-ethyl- l-methylcyclohexene. ft took place relatively slowly with the rate constant k6 The reaction of the same dialkylborane with the isomeric. S -alkene was shown in Figure 3.33. ft took place considerably faster with the rate constant ky The combination of the two reactions is shown in Figure 3.34. There the same enantiomerically pure borane is reacted simultaneously with both alkene enantiomers (i.e., the racemate). What is happening In the first moment of the reaction the R- and the 5-alkene react in the ratio k6 (small )/ 5 (big). The matched pair thus reacts faster than the mismatched pair. This means that at low conversions (< 50%) the trialkylborane produced is essentially derived from the 5-alkene only, ft has the stereostructure E. Therefore, relative to the main by-product F, compound E is produced...

In the structure shown in Figure 3.24 the top side attack of this borane on the C=C double bond of 1-methylcyclohexene prevails kinetically over the bottom side attack. This is because only the top side attack of the boranes avoids steric interactions between the methyl substituents on the borane and the six-membered ring. In other words, the reagent determines the face to which it adds. We thus have reagent control of stereoselectivity. As a result, the mixture of the diastereomeric trialkylboranes C and D, both of which are pure enantiomers, is produced with ds = 97.8 2.2. After the normal Na0H/H202 treatment, they give a 97.8 2.2 mixture of the enantiomeric trans-2-... 

The S,S enantiomer of this alcohol is obtained with the same ee value of 95.6% when the enantiomer of the borane shown in Figure 3.24 is used for the hydroboration of 1-methylcyclohexene. The first problem we ran into in the introduction to Section 3.4 is thereby solved ... 

Strategy Notice the relationship of the hydroxyl groups in the two diols. In diol (a), the two hydroxyls are cis, and in (b) they are trans. Since ring-opening of epoxides forms trans -1,2-diols, only diol (b) can be formed by this route. The cw-I,2-diol in (a), results from treatment of 1-methylcyclohexene with OsO The enantiomers of the diols are also formed. 

Because 3-methylcyclohexene has one tetrahedral stereogenic center it is a chiral compound and exists as a pair of enantiomers. 

LEH displays relatively narrow substrate specificity and accepts only few substrates. These include both enantiomers of 1-methylcyclohexene oxide (1 and 2, Scheme 2) and all four stereoisomers of the natural substrate limonene-1,2-epoxide (3-6, Scheme 2). The substrates are converted with different enantioselec-tivities and regioselectivities. The four stereoisomers of limonene-1,2-epoxide are hydrolyzed in an enantioconvergent fashion. Conversion of the diastereomeric mixture of 3 and 4 leads to enantioconvergent formation of (li ,2i ,4i)-limonene-l,2-diol, whereas conversion of 5 and 6 leads to enantioconvergent... 

Scheme 2 Conversion of the two enantiomers of 1 -methylcyclohexene oxide and the four stereoisomers of limonene-1,2-epoxide by LEH. Adapted from K. H. Hopmann B. M. Hallberg F. Himo, J. Am. Chem. Soc. 2005, 127, 14339-14347.

The regioselectivity of LEH has been studied experimentally with different substrates. Studies with the enantiomers of 1-methylcyclohexene oxide (1 and 2, Scheme 2) revealed preferred attack at the methyl-substituted oxirane carbon, Cl, with a regioselectivity of 85(C1) 15(C2). This indicated an acid-catalyzed mechanism, which would result in preferred attack at the more substituted carbon. However, conversion of limonene-1,2-epoxide did not support this conclusion and showed somewhat intriguing results. Exclusive attack at the more substituted carbon (Cl) is seen for the stereoisomers 4 and 5, while exclusive attack at the less substituted carbon (C2) is observed for stereoisomers 3 and 6 (Scheme 2). Interestingly, the two limonene-1,2-epoxide stereoisomers with the same stereochemistry at the oxirane ring, (IR,2S) for 3 and 5 and IS,2R) for 4 and 6, exhibit attack at opposite carbons (Scheme 2). A suggested explanation for the differences was differential binding of the substrates in the active site, which would lead to attack at different carbons. ... 

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