Anti-face addition

The important aspect of their study relates to the stereochemical mode of addition in the most preferred transition state in (a) and (b). In model-(a). Re-face addition of enamine carboxylic acid on the Re-face of the aldehyde is the lowest energy addition leading to an enantiomeric excess of about 99% in favor of (2S,3S) stereoisomer and anti-diastereomer as the major product In model-(b), on the other hand, anti-face addition involving the Si-Re mode respectively between enamine carboxylate and aldehyde is of the lowest energy. This approach predicts... 

In a closely related study, Sharma and Sunoj examined the validity of transition state models based on sy -face and anti-face additions under base free as well as basic conditions in a proline-catalyzed a-amination reaction (Scheme 17.8) [36]. Mechanistic investigation using the PCM(CH2cu)/mPWlK/6-31-i-G computational method revealed that the addition of enamine carboxyUc add to DEAD... 

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

In 1993, ten challenges faced the catalysis research community. One of these was the anti-Markovnikov addition of water or ammonia to olefins to directly synthesize primary alcohols or amines [323]. Despite some progress, the direct addition of N-H bonds across unsaturated C-C bonds, an apparently simple reaction, stiU remains a challenging fundamental and economic task for the coming century. 

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. ... 

Fumarate hydratase. The most studied enzyme of this group is probably the porcine mitochondrial fumarate hydratase (fumarase see also Chapter 9), a tetramer of 48.5-kDa subunits with a turnover number of 2 x 10 s T It accelerates the hydration reaction more than lO -fold. A similar enzyme, the 467-residue fumarase C whose three-dimensional structure is known, is foxmd in cells of E. coli when grown aerobically. The product of the fumarate hydratase reaction is L-malate (S-malate). The stereospecificity is extremely high. If the reaction is carried out in HjO an atom of H is incorporated into the pro-R position, i.e., the proton is added strictly from the re face of the trigonal carbon (Eq. 13-12). To obtain L-malate the hydroxyl must have been added from the opposite side of the double bond. Such anti (trans) addition is much more common in both nonenzymatic and enzymatic reactions than is addition of both H and OH (or -Y) from the same side (syn, cis, or adjacent addition). For concerted addition it is a natural result of stereoelectronic control. Almost all enzymatic addition and elimination reactions involving free carboxylic acids are anti with the proton entering from the re face. 

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). 

The tr-route predicts syn selectivity for 10 by consideration of 7t —> tt c=o interaction. The n > jr ( =0 barrier must be disrupted by the nucleophile to enter from the anti face [43, 44]. Additionally, the electrostatic repulsion between the olefin and the nucleophile, both being electron-rich, also favors syn addition [45]. However, there exists a good possibility for olefin-cation coordination to guide the... 

Zimmerman-Traxler transition structure, as shown on the lower left [79], however the open structure shown in the lower right, which does not require coordination of the bulky silyloxy group to titanium, should also be considered. The aldehyde may be oriented to avoid the large tert-butyldimethylsilyl (TBS) group as shown, with the R group away from the TBS. Both of these models have the aldehyde approaching the enol ether from the front face, opposite the side that is shielded by the sulfonamide. Note also that the siloxy group is oriented downward, to avoid the sulfonamide. An anti-selective addition (92% ds) was also reported for the reaction of the E(0)-eno ether of this auxiliary with isobutyraldehyde [79]. 

It is important to recognize that this reaction gives products corresponding to anti-Markovnikov addition of water to the carbon-carbon double bond. This behavior evidently results because carbonium ions are not intermediates - rearrangement does not occur in hydroboration. The stereochemistry of this reaction involves syn addition, that is, addition to the double bond is on the same face of the alkene. 

Anti stereoselectivity Addition of atoms or groups of atoms from opposite sides or faces of a carbon-carbon double bond. 

We discuss the addition stereochemistry of CI2 and Br2 to alkenes in more detail in Section 6.7. For now, it is sufficient to point out that these reactions proceed with anti (from the opposite side or face) addition of halogen atoms that is, they occur with anti stereoselectivity. 

Addition of acetic acid to ions A and B of Figure 21.38 must give the anti acetate, because the opening is an Sn2 reaction. Attack on ion C is more problematic, because it is difficult to explain the stereospecificity of the reaction. StUl, it must be admitted that the syn and anti faces of the ion are different, and in principle, this difference could lead to a stereospecific reaction (Fig. 21.39). 

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... 

The reaction of chlorine and bromine with cycloalkenes illustrates an important stereo chemical feature of halogen addition Anti addition is observed the two bromine atoms of Br2 or the two chlorines of CI2 add to opposite faces of the double bond... 

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