TRANS-ANTI - ERYTHRO

One way to determine what stereoisomers are obtained from many reactions that create a product with two asymmetric carbons is the mnemonic CIS-SYN-ERYTHRO, which is easy to remember because all three terms mean on the same side. You can change any two of the terms but you can t change just one. (For example, TRANS-ANTI-ERYTHRO, TRANS-SYN-ERYTHREO, and CIS-ANTI-THREO are allowed, but TRANS-SYN-ERYTHRO is not allowed.) So if you have a trans reactant that undergoes addition of Br2 (which is anti), the erythro products are obtained. This mnemonic will work for all reactions that have a product with a structure that can be described by erythro or threo. 

You can change any two of the three terms but you caimot change just one. For example, TRANS-ANTI-(ERYTHRO or CIS), and CIS-ANTI-(THREO or TRANS) are allowed because in each case two terms were changed. In other words, anti addition to a trans aUcene forms the erythro (or cis) enantiomers, and anti addition to a cis alkene forms the threo (or trans) enantiomers. TRANS-SYN-(ERYTHRO or CIS) is not allowed, because only one term was changed. Thus, syn addition to a trans alkene does not form the erythro (or cis) enantiomers. 

At the instant Pasteur recognized the existence of stereoisomers (objects), he also accepted the existence of stereoprocesses (operations). For the notion of isomer carries with it criteria of distinguishability among these is the possibility that a given isomer can be formed, separated, or altered in a way which differentiates it from other isomers. This applies equally to isomers with many properties in common, e.g. optical antipodes, or to those with essentially all different properties, e.g. cis-trans, syn-anti, gauche-anti, erythro-threo, or axial-equatorial pairs. Now, the stereo-path may be part of an overall conversion which, if described in some detail, we term a mechanism. Our present task is to attempt to understand those elementary or single-step processes by which stereochemical choices are made. 

When TiCU is used as a catalyst with substituted dienes such as (14), a predominant route is the Mu-kaiyama aldol process, " When diene (14) reacts with benzaldehyde the trans (anti) product is observed. When compound (42) is used as the aldehyde, one observes exclusive formation of the (erythro) aldol products (Table 14). These stereochemical results can be rationalized by using a Zimmerman-Traxler transition state (Scheme 18). Chelation by the metal of the aldehyde a-alkoxy group causes it to be placed in a pseudo axial position in the transition state structure. This results in a stereochemical relationship that gives syn aldol products. ... 

More recently, Cocuzza [61] prepared iV-acetyl-deazathienamycin 96 [62] following a similar strategy (Scheme 31). The hydroxyethyl side-chain was introduced via the reaction of the zirconium enolate of 93 with acetaldehyde. A 1 1 mixture of threo-trans and erythro-trans isomers 94 was obtained. Compound 96 is devoid of antibacterial activity. However the benzhydryl esters, 97 and 98, are active against gram-positive bacteria and show some anti-P-lactamase activity [61]. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

In investigating the mechanism of addition to a double bond, perhaps the most useful type of information is the stereochemistry of the reaction. The two carbons of the double bond and the four atoms immediately attached to them are all in a plane (p. 8) there are thus three possibilities. Both Y and W may enter from the same side of the plane, in which case the addition is stereospecific and syn they may enter from opposite sides for stereospecific anti addition or the reaction may be nonstereospecific. In order to determine which of these possibilities is occurring in a given reaction, the following type of experiment is often done YW is added to the cis and trans isomers of an alkene of the form ABC=CBA. We may use the cis alkene as an example. If the addition is syn, the product will be the erythro dl pair, because each carbon has a 50% chance of being attacked by Y ... 

Of course, the trans isomer will give the opposite results the threo pair if the addition is syn and the erythro pair if it is anti. The threo and erythro isomers have different physical properties. In the special case where Y=W (as in the addition of Br2), the erythro pair is a meso compound. In addition to triple-bond compounds of the type ACsCA, syn addition results in a cis alkene and anti addition in a trans alkene. By the definition given on page 166 addition to triple bonds cannot be stereospecific, though it can be, and often is, stereoselective. 

The erythro compound shows little or no kinetic isotope effect, but the threo compound has a moderate one, H/fcD 2-3-3-3, for both syn and anti processes. This suggests that an E2 process is involved. Eliminations from the cyclic bromides may produce trans alkenes by syn eliminations or by anti eliminations, if n 8 in(189). 

For example, f/zreo-5-trimethylsilyloctan-4-ol (4.69) under acidic conditions (H2SO4 or BF3) undergoes anti-elimination to give ds-oct-4-ene (4.71) and under basic conditions (NaH or KH) undergoes syn-elimination to give trans-oct-4-ene (4.72). The erythro-5-trimethylsilyl octan-4-ol (4.70) gives opposite result (Scheme 4.40). 

Hydroxylation, the addition of two hydroxyl groups across double bonds, converts alkenes and cycloalkenes into vicinal dials. Stereochem-ically. the addition may occur in the syn or the anti mode. In open-chain alkenes (with the exception of terminal alkenes for which stereochemistry is irrelevant), syn hydroxylation transforms cis alkenes into erythro (or meso) diols and trans alkenes into threo (or dl) diols. anti Hydroxylation of cis alkenes gives threo (or dl) diols, whereas anti hydroxylation of trans alkenes yields erythro (or meso) diols. syn Hydroxylation of cycloalkenes gives cis diols, whereas anti hydroxylation furnishes trans diols (Table I). 

The addition of a symmetrical molecule to an unsymmetrical substrate via an anti-addition route, results in a threo d,l pair from a cis starting material, and a meso isomer from a trans starting material. If an unsymmetrical molecule were added to a trans starting material, then an erythro dj pair results. Thus, this reaction is stereoselective, because preferentially one set of products is in each case produced but, further, it is stereospecific, because a given isomer leads to one product pair while the other isomer leads to the other product pair. 

Therefore, erythro and threo-2-deuterio-1,2-diphenylethyl-Ar-carbomethoxy sulfamates, upon decomposition, give a-deuterio /rarar-stilbene (7) and protio trans-stilbene (9), respectively. This is consistent with syn elimination and an El mechanism. It is important to note that elimination can be accomplished in an anti fashion. However, it is still considered somewhat rare. The conversion of 10 to 11 is rationalized to be driven to a r/-elimination by conformational effects.3... 

Addition of Br2 anti cis > threo enantiomers trans > erythro enantiomers ... 

Two asymmetric carbons have been created in the product. Because the reactant is trans and addition of Br2 is anti, the erythro enantiomers are formed. 

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