Syn-diastereoisomer

Figure U. Anti and syn diastereoisomers of the benzo diol-epoxide (BDE). For the 7,8-diol-9,10-epoxide of benzo[a]pyrene (BPDE), these would be the (+)-anti or l(+) and (+)-syn or Il(+) isomers as indicated. Atom numbers for BDE are those for the diol epoxide of benzo[a]pyrene.

Sterically bulky OR groups (trityloxy or Bu/Ph2SiO) gave the syn-diastereoisomer (119) either exclusively or predominantly. The. vyw-sclcctivity was rationalized by a modified Felkin-Ahn model (121).94... 

Asymmetric Mukaiyama aldol reactions in aqueous media [EtOH-H20 (9 1)] were reported with FeCl2 and PYBOX ligands 27a [36] and 27b [37]. The latter provides product 28 with higher yield and diastereo- and enantioselectivity (Scheme 8.9). The ee values given are for the syn-diastereoisomer. Whereas ligand 27a is a derivative ofL-serine, compound 27b has four stereogenic centers, since it was prepared from... 

How can the Z selectivity in Wittig reactions of unstabilized ylids be explained We have a more complex situation in this reaction than we had for the other eliminations we considered, because we have two separate processes to consider formation of the oxaphosphetane and decomposition of the oxaphosphetane to the alkene. The elimination step is the easier one to explain—it is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state (as in the base-catalysed Peterson reaction). Addition of the ylid to the aldehyde can, in principle, produce two diastere-omers of the intermediate oxaphosphetane. Provided that this step is irreversible, then the stereospecificity of the elimination step means that the ratio of the final alkene geometrical isomers will reflect the stereoselectivity of this addition step. This is almost certainly the case when R is not conjugating or anion-stabilizing the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z-alkene that results reflects this. The Z selective Wittig reaction therefore consists of a kinetically controlled stereoselective first step followed by a stereospecific elimination from this intermediate. 

There is three times as much of one of the two diaslereoisomeric products as there is of the other, and the major (anti) diastereoisomer is the one in which the nucleophile has added to the front face of the carbonyl group as drawn here. We can make these same two diastereo isomers by addition of an organometallic to an aldehyde. For example, this Grignard reagent gives three times as much of the syn diastereoisomer as the anli diastereoisomer. The major product has changed, but the product still arises from attack on the front face of the carbonyl as shown. 

Only one new stereo genic centre is created, so there is no question of diastereoselectivity. But with substituted enolates, two new stereogenic centres are created, and we need to be able to predict which diastereoisomer will be formed. Here is an example from p. 699. We did not consider stereochemistry at that stage, but we can now reveal that the syn diastereoisomer is the major product of the reaction. 

Hydrocyanation of a-trifluoromethyl-P-sulfinylenamines proceeds mainly to give the syn diastereoisomer in high yield but modest stereoselectivity (30% de).12 Enantiomerically pure (E)-2-halo- (10) and (Z)-2-halovinyl sulfoxides (12) react with anions derived from diethyl malonate through an addition/elimination sequence to give enantiopure 2-malonyl sulfoxides 11 and 13 with retention of stereochemistry of the double bond (Scheme 2).13... 

Separation of the syn and anti diastereoisomers by crystallisation of the HC1 salt revealed that it was the syn diastereoisomer that was active and the reductive animation of 44 could be controlled to give 70%. vvn-45. The diastereoisomers of 45 were separated before the resolution. There is no point in resolving any earlier compound in the synthesis as even more material would be wasted in the reductive amination step. Natural ()-(/ )-mandelic acid 46 was a good resolving agent for 45 and 50% of the material derived from 44 could be isolated as the active (I )-vyn-(TS, 4S )-45. 

Heating the mixture of isomers of 109 with TsOH equilibrates the diastereoisomers so that the required more stable syn (H and Et syn) diastereoisomer of 109 crystallises out. Treating this with (+) malic acid leads to crystals of the natural enantiomer (+)-sy -109. Both the unwanted anti-diastereoisomer and the unwanted enantiomer can be equilibrated again with TsOH. This cannot be enolisation as there are no a-hydrogens and is presumably equilibration by reversible Mannich reaction as 110 lacks either stereogenic centre and so epimerises both ... 

Allyl dialkyl boranes do this reaction, transferring only the allyl group as the mechanism 67 requires, so asymmetry can be introduced by replacing BR2 with Ipc B to give 71. In this specific instance, the reaction with acetaldehyde gives predominantly just one enantiomer (2R,3S) of the a til i-diastercoi som cr of 72 accompanied by some of the other anti enantiomer and traces of the syn-diastereoisomer.3 The diastereoselectivity is therefore 99 1 and the ee 90%. 

Direct alkylation of the enolate of 77a R = cyclopentyl with the alkyl halide 78 was not very diastereoselective so an alternative route was used to allow equilibration to the more stable isomer.11 Carboxylation of the enolate gave 79a and alkylation of this malonate gave a good yield of 80. The benzyl esters were cleaved by hydrogenation and the malonate decarboxylated to give the required anti isomer of 81 in a 4 1 ratio with its syn diastereoisomer. Conversion into Trocade is straightforward. 

The experimental observation is that hydride reduction (Felkin-Anh control) of the ketone 7.153 gives the anti-alcohol anti-7.154 as the major product, but electron-transfer reduction gives its syn diastereoisomer syn-7.154.1067 This is in contrast to the reduction on p. 423, which differs in having a silyl group on the oxygen atom in a neutral radical. 

The fluorescence quenching dynamics of excited state electron donors by various pyrimidine and 5,6-dihydropyrimidine substrates have been examined and found to obey the Rehm-Weller relationship." In addition, an unexpected difference was observed between the reduction potentials for the trans-syn and cis-syn diastereoisomers of dimethylthymine cyclobutane dimers, and this has been ascribed to a stereoelectronic effect in the cis-syn dimer anion radical resulting from an unfavourable charge-dipole interaction between the added electron and the O carbonyl group of the pyrimidine ring... 

The syn diastereoisomer has no plane of symmetry but you should be able to spot a C2 axis of symmetry running straight through the middle of the ring. The axis is compatible with chirality of course. In this compound both chiral centres are S and it has an enantiomer where both are R. 

When R is not conjugating or anion-stabilizing, the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z alkene that results reflects this. The Z-selective Wittig reaction therefore consists of a stereoselective first step, to form the syn oxaphosphetane, followed by a stereospecific elimination from this intermediate to give a Z alkene. 

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