Syn-face addition

An interesting example was recently reported by Sharma and Sunoj, who demonstrated that the stereoselectivity controlling transition in an aldol reaction, as shown in Scheme 17.7, should originate from enamine carboxylic acid intermediate (17) instead of from the deprotonated enamine carboxylate (21) [35]. This proposal further implies that the syn-face addition of enamine to the electrophile... 

Figure 17.7 (a) Syn-face addition in Houk-List models (b) onti-face addition in Seebach-Eschenmoser transition state models. 

The basic principle of the stereochemistry of the hydrogenation of the C=C bond is syn (cis) addition. Established already in the early 1930s, it means that both hydrogen atoms add from the same face of the double bond. One of the highest selectivities was observed in the hydrogenation of isomeric 2,3-diphenyl-2-butenes144 the mesa compound is formed from the cis isomer in 98% yield (equation 8), whereas the trans isomer gives the racemic compound in 99% yield (equation 9). 

As a Stereochemical Prohe in Nucleophilic Additions. Historically, the more synthetically available enantiomer, (4R)-2,2-dimethyl-l,3-dioxolane-4-carhoxaldehyde, has been the compound of choice to probe stereochemistry in nucleophilic additions. Nevertheless, several studies have employed the (45)-aldeh-yde as a substrate. In analogy to its enantiomer, the reagent exhibits a moderate si enantiofacial preference for the addition of nucleophiles at the carbonyl, affording anti products. This preference for addition is predicted by Felkin-Ahn transition-state analysis, and stands in contrast to that predicted by the Cram chelate model. Thus addition of the lithium (Z)-enolate shown (eq 1) to the reagent affords an 81 19 ratio of products with the 3,4-anti relationship predominating as a result of preferential si-face addition, while the 2,3-syn relationship in each of the diastere-omers is ascribed to a Zimmerman-Traxler-type chair transition state in the aldol reaction. ... 

Addition of 2-furyllithium to the reagent afforded a 2 3 anti/syn ratio on addition of various zinc halides, this very modest si facial preference was overturned, resulting in an almost exclusive re-face addition. The resulting anti-addition product was parlayed into D-ribulose in four steps (eq 3). ... 

On p. 1023, it was mentioned that electronic effects can play a part in determining which face of a carbon-carbon double bond is attacked. The same applies to additions to carbonyl groups. For example, in 5-substituted adamantanones (2) electron-withdrawing (-/) groups W cause the attack to come from the syn face, while electron-donating groups cause it to come from the anti face. In 5,6-disubstituted norborn-2-en-7-one systems, the carbonyl appears to tilt away from the 7i-bond, with reduction occurring from the more hindered face. An ab initio study of nucleophilic addition to 4-ferf-butylcyclohexanones attempted to predict 7i-facial selectivity in that system. ... 

This model is consistent with the conformation found in the structure of Fp(cyclohexenone)BF4 and the similarities can be seen in Figure 42." - 2o Notice that the assumption that Lewis acid (Li" ) coordination occurs syn to the double bond is essential for mediation of attack on the re face of the double bond. Anti coordination (if all else is retained) would result in si face addition. 

The reactions of crotylboronic esters with aldehydes is regioselective, generating two new stereochemical relationships and potentially four possible stereoisomeric products. Thus, there are two stereochemical aspects enantioselection Re- vs. 5i-face addition) and diastereoselection (syn vs. anti). 

Syn The addition or elimination of a molecule AB from the same side or face of another molecule. 

Pride of place here must go to the asymmetric Robinson annelation, discovered as long ago as 1974, but not appreciated at the time for the landmark that it undoubtedly was.17 The normal Robinson annelation (text chapter 36) is first a Michael addition to produce an achiral triketone 82 which cyclises when the enol of the methyl ketone adds, aldol fashion, to the syn face of either of the other ketones to give 83, and hence the enone 84, the north east corner of a steroid. 

On the other hand, the oxidative addition in a non-polar solvent such as benzene gives the trans product. This oxidative addition is considered to occur by prior coordination of allylic halide to Pd(0) from the syn face and the chelation by the chlorine atom and C=C bond allows syn elimination of the chloro moiety (Scheme 3.9). The addition of jt-acceptor such as electron deficient olefins in a non-polar solvent also facilitates the syn oxidative addition [14],... 

In a closely related study, Sharma and Sunoj examined the vaUdity of transition state models based on syn-face and anti-face additions under base free as well as basic conditions in a proHne-catalyzed a-amination reaction (Scheme 17.8) [36]. Mechanistic investigation using the PCM(CH2ci2)/niPWlK/6-31-l-G computational method revealed that the addition of enamine carboxylic acid to DEAD... 

To develop better stereocontrol agents, it is crucial to understand stereoselection at a fundamental mechanistic level and appreciate the subtle but crucial differences between tacticity determination in ionic and coordination versus radical processes. As previously outlined, the propagation step of Hving radical polymerization is identical to that of free-radical polymerization and so the mechanism of tacticity determination in these processes is also identical. In radical polymerization, the planar (sp hybridized) carbon radical of the polymer terminus is prochiral, and its stereochemistry is determined during subsequent monomer addition. The addition of monomer occurs exclusively to the anti-h.ce of the radical, as the syn-face is shielded by the steric bulk of the penultimate group (Scheme 2). Hence, the prochiral polymer terminus can adopt either pro-meso or pro-racemo arrangements defined by the relative orientation of the terminal and penultimate side-chains with respect to the macromolecular C—C backbone. 

A highly diastereoselective alkcnylation of c/s-4-cyclopentene-l,3>diols has been achieved with 0-protected (Z)-l-iodo-l-octen-3-ols and palladium catalyst (S. Torii, 1989). The ( )-isomers yielded 1 1 mixtures of diastcrcomcric products. The (Z)-alkenylpalladium intermediate is thought to undergo sy/i-addition to the less crowded face of the prochiral cyclopentene followed by syn-elimination of a hydropalladium intermediate. 

The term syn addition describes the stereochemistry of reactions such as this m which two atoms or groups add to the same face of a double bond When atoms or groups add to opposite faces of the double bond the process is called anti addition... 

Overall the reaction leads to addition of two hydroxyl groups to the double bond and IS referred to as hydroxylation Both oxygens of the diol come from osmium tetraox ide via the cyclic osmate ester The reaction of OSO4 with the alkene is a syn addition and the conversion of the cyclic osmate to the diol involves cleavage of the bonds between oxygen and osmium Thus both hydroxyl groups of the diol become attached to the same face of the double bond syn hydroxylation of the alkene is observed... 

---