Cyclic ethers regiospecificity

Regiospecific 1-(co-hydroxyalkylation) of a,p-ethylenemercaptals with cyclic ethers G... 

The use of DAMgBr 39 in Et20/HMPA/TMSCPEt3N leads to the thermodynamic enolates or silyl enol ethers. This methodology is one of the best direct regiospecific preparations of thermodynamic silylenol ethers from unsymmetric cyclic ketones. 

Bordeau and coworkers have described an efficient and stereoselective synthesis of kinetic silylenol ethers. Less highly substituted silylenolates are regiospecifically prepared in high yield, around room temperature under kinetic conditions, from unsymmetric cyclic ketones and [(DA)2Mg] in THF/heptane (equation 68). 

Ester, ether, and cyclic acetal groups are used as blocking groups to allow regiospecific reactions to take place, ie, reaction at specific unblocked hydroxyl groups. 

The same sequence is applicable to ketones, but in this case TiCU is superior to ZnBr2 as the catalyst. The method can be used with both cyclic and acyclic ketones and is applicable to both kinetic and thermodynamic silyl enol ethers for control of regiospecificity. ... 

Silyl enol ethers, which are readily generated regiospecifically from ketones, can also be reduced to al-kenes, particularly by hydroboration. " Hydroboration of silyl enol ethers results in the addition of boron to the 3-c on of the double bond to afford fra/is-3-trimethylsilyloxy organoboranes, which in cyclic systems undergo anti elimination in the presence of acid to give the alkenic product (Scheme 42). A number of acids have been tested successfully, including carboxylic acids, BF3-Et20 and... 

Though anions of allyl ethers, the extra functionality allows regiospecific heteroatom-directed lithiation 160 in the manner of chapter 7. Hence reaction of 160 with an aldehyde goes through a six-membered cyclic transition state 161 to give the enol derivative 163 and hence the y-hydroxyaldehyde 164. 

The triethylsilyl ether 147 thus formed regiospecifically from the diol 150 [Rl=(BnO)2 (0), R2=Bn], which was optically resolved by a chiral column chromatography, was transformed to Ins(2,4,5)P3 and Ins(l,4,5)P3 (Schema 3-23). At this stage, temporary protection of OH-1 with the silyl group is not necessary, i.e. 150 can be directly phosphorylated by the phosphite-phosphonium approach as described in the section on phosphorylation (Scheme 2-6). H The diol 150 was used furthermore as a versatile synthetic intermediate for the synthesis of myo-inositol 1,2-cyclic-4,5-trisphosphate 152 (Scheme 3-23), 8 2-acyl analogues of Ins(1,4,5)P3, and inositol phospholipid. 

The preparation of silyl enol ethers from carbonyl compounds represents one of the major uses of TMSOTf. Recently, the stereochemistry and regiospecificity of such transformation has been addressed for aldehydes and -(iV-alkoxycarbonylamino) ketones, respectively. On the other hand, enantiopure silyl enol ethers can be formed by addition of TMSOTf to zinc enolates, which are obtained from the copper-catalyzed enantioselective conjugate addition of dialkylzinc reagents to cyclic (eq 36) and acyclic enones. ... 

Stork, G. Danheiser, R. L. Regiospecific Alkylation of Cyclic j3-Diketone Enol Ethers. General Synthesis of 4-Alkylcyclohexenones /. Or. Chem. 1973, 38, 1775-1776. 

For regiospecific alkylation of kinetic enolates of cyclic /3-diketone enol ethers, see G. Stork and R. L. Danheiser, J. Org. Chem., 38, 1775 (1973). 

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