Stereoselective hydroxy group effect

Similarly to peroxycarboxylic acids, DMDO is subject to cis or syn stereoselectivity by hydroxy and other hydrogen-bonding functional groups.93 However a study of several substituted cyclohexenes in CH3CN —H20 suggested a dominance by steric effects. In particular, the hydroxy groups in cyclohex-2-enol and... 

Stereoselective cyclization controlled by a substituent remote from the reaction center is often difficult to achieve. However, 1-mediated cyclization of the substrates illustrated in Eq. 9.54 proceeds in a highly stereoselective manner when the hydroxy group is converted to a magnesium alkoxide prior to cyclization [99,100]. The effect of the alkoxide group is much more favorable than that of the corresponding TBS ether. 

Hydrogen bonding also accounts for the stereoselectivity found in the cycloaddition to 4-substituted 4-hydroxy-2-cyclopentenones (175). The importance of this effect is evident by comparing the results from 26 with those of unprotected 25 as illustrated in Scheme 6.30. The acetylation of the hydroxy group causes a drop in the ratio of diastereoisomers from 85 15 to 57 43 (175). 

The effect of proximal groups on the diastereoselectivity in the addition of allylindium to a carbonyl group has been extensively surveyed.153 When a- and /3-hydroxy aldehydes are subjected to the allylation, excellent diastereocontrol is realized, syn- 1,2-Diol and anti- 1,3-diol products are formed, respectively, at accelerated rates (Tables 1 and 2). Protection of the free hydroxy group results in the alternative formation of 1,2-anti products. High stereoselectivities have been observed for indium-promoted allylations of a- and /3-hydroxy aldehydes in aqueous media, implying that a chelate control still operates even in water.72,73,154-158... 

Epoxidation of acyclic allyl alcohols with peracid and Mo/TBHP displays an opposite stereospecificity to that for the V/TBHP system. Trimethylsilyl-substituted allylic alcohols give t/zreo-epoxyalcohols with MCPBA and erythro-alcohols with VO(acac)a-TBHP, with high stereoselectivity. In the stereospecific epoxidation of cis- and trans-allyl alcohols, formation of a transition state is assumed with the development of two H bonds between the hydrogen atom of the hydroxy group of the allyl alcohol and the oxygen of the peracid, and between the hydrogen of the peracid OH and the oxygen of the ether 10. An analysis of the diastereometric transition-state interactions for stereoselective epoxidation of acyclic allylic alcohols has been published. A conformational effect may be responsible for the unexpected cis major product in Eq. 2. 

In 1978, Larcheveque and coworkers reported modest yields and diastereoselectivities in alkylations of enolates of (-)-ephedrine amides. However, two years later, Evans and Takacs and Sonnet and Heath reported simultaneously that amides derived from (S)-prolinol were much more suitable substrates for such reactions. Deprotonations of these amides with LDA in the THF gave (Z)-enolates (due to allylic strain that would be associated with ( )-enolate formation) and the stereochemical outcome of the alkylation step was rationalized by assuming that the reagent approached preferentially from the less-hindered Jt-face of a chelated species such as (133 Scheme 62). When the hydroxy group of the starting prolinol amide was protected by conversion into various ether derivatives, alkylations of the corresponding lithium enolates were re-face selective. Apparently, in these cases steric factors rather than chelation effects controlled the stereoselectivity of the alkylation. It is of interest to note that enolates such as (133) are attached primarily from the 5/-face by terminal epoxides. ... 

---