Carbonyl compounds alkylation, stereochemistry

Addition of Bu3SnLi or McsSnI.i to 4-t-butylcyclohexanone affords mixtures of trans and cis adducts in ratios that depend on reaction conditions (Table ll)68. In THF, a 93 7 mixture is obtained with both reagents. This ratio is thought to represent the thermodynamic distribution—the axial stannane being favored. In ether, the cis isomer predominates, suggesting a kinetic preference for equatorial addition. Each of the two isomers can be lithiated with BuLi. Subsequent treatment with alkyl halides or carbonyl compounds affords the substituted alkoxy cyclohexanes with retention of stereochemistry. 

A closely related synthetic method involves the addition of [C6H5(CH3)2Si]2CuLi to a-unsubsti-tuted a,/j-unsaturated carbonyl compounds to give anions 4 (R2 = h), followed by alkylation with haloalkanes18 I9. The stereochemistry of the alkylation is generally the same as that of the protonation (i.e occurs via 5 and 6) so that, in its overall effect, this method is complementary to the silylmetalation-protonation. 

Asymmetric Alkylation. 7Y-[4-(Trifluoromethyl)benzyl]-cinchoninium bromide (1) has been used as chiral phase-transfer catalyst in the alkylation of indanones (eq 1). For the alkylation of a-aryl-substituted carbonyl compounds the diastere-omeric 7Y-[4-(trifluoromethyl)benzyl]cinchonidinium bromide (2) was used to obtain the opposite stereochemistry (eqs 2 and 3). The asymmetric alkylation of oxindoles was used as the key step in an asymmetric synthesis of (—)-physostigmine (eq 4). ... 

J.l Regiochemistry and Stereochemistry of Alkylations of Nitrogen Derivatives of Carbonyl Compounds... 

The addition of ozone (O3) to alkenes to give a primary ozonide (molozonide), which rearranges to an ozonide and eventually leads, on reduction, to carbonyl compounds (aldehydes and/or ketones), has already been mentioned and the reaction itself is shown in Scheme 6.11. However, it is important to recognize that this is only one example of a 4th- 2n electrocyclic addition and that orbital overlap for many sets of these reactions dictates their courses as well. Thus, to show the similarity of some of these dipolar 3 -f 2 addition reactions Equations 6.53-6.56 are provided. Although any alkene might be used as an example, (Z)-2-butene is used in each to emphasize that aU of them occur with retention of stereochemistry and, in the first (Equation 6.53), the reaction with ozone to form the primary ozonide (molozonide) is presented again (i.e., see Scheme 6.11). In a similar way, with a suitable azide, R-N3, readily prepared from an alkyl halide (Chapter 7), the same alkene forms a triazoline (Equation 6.54) and with nitrous oxide (N2O) the heterocycle (Chapter 13) cis -4,5-dimethyl-A -l,2,3-oxadiazoline (ds-4,5-dihydro-4,5-dimethyl-l,2,3-oxadiazole) (Equation 6.55). Finally, with a nitrile oxide, such as the oxide derived from ethanenitrile (acetonitrile [CH3ON]), the same alkene yields a different heterocycle, the dihydroisoxazole, 3,4,5-trimethyl-4,5-dihydroisoxazole (Equation 6.56). 

Titanium compounds are frequently investigated as Lewis acids in radical reactions [677-680]. When addition of an alkyl radical to a chiral vinylsulfoxide was conducted in the absence or presence of Ti(0-/-Pr)2Cl2, the stereochemistry of the product was reversed, very high diastereoselectivity being observed in the presence of the titanium salt (Eq. 302) [681,682]. The stereochemistry and high selectivity in the presence of the titanium salt were readily rationalized on the basis of a chelation intermediate between the titanium metal and the carbonyl and sulfoxide oxygens, as shown in Eq. (302). 

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