Cisltrans ratio

A thorough theoretical analysis of the Criegee mechanism for the ozonolysis of cis- and trans-symmetrical alkenes Rl IG—Cl IR has been performed by semiempirical AMI calculations <1997JOC2757>. The experimentally observed stereoselectivity for bulky groups (e.g., R = Bu ) is that from the m-alkene a cisltrans ratio of 7 3 is encountered while from a trans-alkene a 3 7 ratio for the cisltrans secondary ozonides resulted. With smaller R groups (e.g., R = Me) both as- and trans-alkenes lead preferentially to the trans secondary ozonide (Scheme 1). 

Solvent was found to affect the cisjtrans ratio of the products. Thus, cis-1,2-di-p-toluenesulphonylethylene gave 90 and 80% retention with thiophenoxide ion in ether and methanol, respectively, while azide ion gave 90% retention in aqueous acetonitrile and lower degrees of retention in dimethyl sulphoxide and in aqueous methanol (Meek and Fowler, 1968). Since isomerization was found to take place in the last case, the significance of the other results is not clear, although it may be expected that in systems which are prone to racemization, a solvent effect on the cisltrans ratio will be observed. 

This synthesis requires the separation of the diastereoisomers of 92 (obtained from D-penicillamine). An attempt to control the stereochemistry was developed by the Merck group in 1974, in a total synthesis based on the [2+2] cycloaddition of the ketene derived from azidoacetyl chloride and the chiral thiazoline 94. The reaction only gives the /ra .r-pcnam derivative 95, which could be epimerized via the Schiff base 96 (cisltrans ratio = 2 1) (Scheme 51). The separated tyr-isomcr has been transformed into synthetic penicillin G <1974JOC437>. 

Initially, a solution of cinnamaldehyde and 4-chlorobenzaldehyde in tetrahydrofuran (THF) was treated with different azolium salts under basic conditions (Scheme 6). The use of thiazolium salt 4 resulted in no formation of the desired y-butyrolactone, only benzoin products were formed. In contrast, using the NHC IMes [l,3-di(2,4,6-trimethyl-phenyl)imidazol-2-ylidene generated in situ from the salt IMesHCl by deprotonation], y-butyrolactone 3a was isolated in 53% yield and a 80 20 cisltrans ratio. This different outcome might be explained by the increased steric demand of IMes compared to 4 (Scheme 7). Most likely, IMes reversibly adds to the aldehyde groups of both substrates resulting in the intermediates la and 2a. Whereas the mesityl groups shield the former aldehyde carbon in both intermediates, the conjugate position of 2a is still accessible and can add to the electrophilic aldehyde. 

Generally, MIRC reactions lead to racemic mixtures of cyclopropanes. The stereoselectivity of the reaction is determined by the cyclization step on the in situ formed intermediate Michael adduct. The cisjtrans ratio of the substituents on this newly formed bond depends on the solvent polarity, the degree of anion-cation association and steric interactions. When the reaction takes place under phase-transfer conditions the cisltrans ratio also depends on whether or not a catalyst is used. ... 

E Z Ratio of substrate 3 97 leads to epoxide cisltrans-xtiiio 97 3. 

Ratio (cisltrans) or (endojexo) Yield (%) Yield of Unsaturated Byproducts (%) Ref... 

In fact, the use of toluene as the solvent and addition of MeOH not only improved the yield but also reduced the amount of epimerization to give 27a in a ratio of cisltram = 94 6 and in 74% yield (Table 4, Entry 3). The use of acetyl chloride (AcCl) (20 equiv) in the presence of MeOH (30 equiv) as a convenient source for HC1 considerably improved the reaction to give 27a in a higher yield with the original asymmetric center virtually retained as such (86%, cisltrans — 98 2) (Table 4, Entry 4). 

Under similar conditions, by using tributylstannyl chloride as an electrophile in place of isopropanol, allyl acetates are converted to allylstannanes in good yield (Scheme As compared with protonation, tributylstannylation is much more regio- and stereoselective. The stannylation of geranyl and neryl acetates proceeds withont loss of the stereochemical integrity and selectively provides (E)- and (Z)-isomers, respectively, in good yield. On the other hand, the stannylation of cyclohexenyl derivatives accompanies the stereochemical isomerization mixtures of cis- and trani -cyclohexenylstannanes in the same ratio (cisltrans = ca. 1 2) are obtained from the mixtures of cw-rich and trans-rich cyclohexenyl acetates (Scheme 14). ... 

The authors tested InCl3 and Sc(OTf)j as Lewis acids to catalyze the domino process. Scandium(III) triflate mostly gave a 1 1 mixture of cis- and trans-64, while indium(III) chloride was able to provide mostly a 1 2.3 ratio. The yields showed to be higher with InCl3. The reaction could also be conducted without any catalyst, but the yields were considerably lower (65-70%, cisltrans= 1 1). 

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