Stereoselectivity Inversion, Retention

Base-induced ring opening may also lead to stereospecific ester formation. Stereoselectivity with retention of configuration suggests that the carbanion formed upon cleavage does not undergo inversion prior... 

Stereoselectivity. See Asymmetric induction Axial/equatorial-, Cis/trans-, Enantio-, Endo/exo- or Erythro/threo-Selectivity Inversion Retention definition (e.e.), 107 footnote Steric hindrance, overcoming of in acylations, 145 in aldol type reactions, 55-56 in corrin synthesis, 261-262 in Diels-Alder cyclizations, 86 in Michael type additions, 90 in oiefinations Barton olefination, 34-35 McMurry olefination, 41 Peterson olefination, 33 in syntheses of ce-hydrdoxy ketones, 52 Steric strain, due to bridges (Bredt s rule) effect on enolization, 276, 277, 296, 299 effect on f3-lactam stability, 311-315 —, due to crowding, release of in chlorophyll synthesis, 258-259 in metc-cyclophane rearrangement, 38, 338 in dodecahedrane synthesis, 336-337 in prismane synthesis, 330 in tetrahedrane synthesis, 330 —, due to small angles, release of, 79-80, 330-333, 337... 

Carboxylate anions are better nucleophiles for allylation. The monoepoxide of cyclopentadiene 343 is attacked by AcOH regio- and stereoselectively via tt-aliylpalladium complex formation to give the m-3,5-disubstituted cyclopen-tene 344[212]. The attacks of both the Pd and the acetoxy anion proceed by inversion (overall retention) to give the cis product. 

When this prior stereoi merization is accounted for, the rearrangonent is found to have resulted fixtm a mixture of all possible suprafacial, antarafacial, inversion, and retention combinations in reughly equal amounts, indicating that no stereochemical pathway is strongly preferred. Substituted systems, however, show higher stereoselectivity. Theoretical modeling of the reaction finds no intermediate, but tire titumtinn state is diradical in character. ... 

An enantioconvergent transformation leads to a single enantiomeric product from a racemate [51]. Each enantiomer is transformed via independent pathways by the same catalyst or by two different catalysts (Figure 6.6). For example, the hydrolysis of epoxides may proceed with high regio- and stereoselectivity vdth inversion or retention of configuration. Several enantioconvergent transformations of epoxides are reported in the last section of this chapter. 

There was still some room for uncertainty on this retention-retention mechanism. The argument was, if the unobserved tt-allyl Mo complex (such as 77 or B in Scheme 2.18) was more highly reactive towards sodium malonate than experimentally observed tt-allyl Mo complexes (such as 71, 74, and 80), the reaction should proceed through inversion (since there is an equilibrium between the two tt-allyl Mo complexes via the o-allyl complex.) If so, when the isolated Mo-complex 71 was subjected to the reaction, 71 must be equilibrated to the enantiomer of 71 via the o-allyl complex prior to reaction with a nucleophile. Therefore, reaction from the Mo complex 71 should proceed with less stereoselectivity than that from a mismatched branched carbonate. This hypothesis was examined, as shown in Scheme 2.26. 

Cathodic reduction of bicyclic gem-dibromocyclopropane in the presence of chlorotrimethylsilane provides the exo-silylated isomer selectively. With a sacrificial Mg anode the current efficiency can be increased by sonication as the anode acts additionally as a chemical reducing agent [358]. The 2e reduction of (5 )-(+)-l-bromo-l-carboxy-2,2-diphenylcyclopropane showed that the stereoselectivity at a Hg cathode was strongly determined by the supporting electrolyte cation. With NH4+, a preferential retention of configuration was observed, which increased with a more negative reduction potential. By contrast, a R4N+ cation gives rise to a major inversion, which increases with the bulkiness... 

Epoxides are extremely useful intermediates in organic synthesis since they react with a variety of nucleophiles suffering opening of the epoxide ring with retention or inversion of configuration at the carbon undergoing attack. Thus, the development of highly stereoselective methods for the synthesis of certain chiral epoxides, such as the methods under discussion, has enabled the asymmetric synthesis of a wide variety of 1,2-bifunctional compounds. 

In summary (Scheme 15), 2-lithiopiperidines and 2-lithiopyrrolidines appear to be very versatile nucleophiles for the elaboration of these heterocyclic systems, affording a variety of 2-substituted heterocycles in excellent yields. The stereoselectivity of the reaction is near 100% in the piperidine series with most carbonyl electrophiles (retention of configuration) and alkyl halides (inversion of configuration). In the pyrrolidine series, the selectivity is also near 100% with carbonyl electrophiles (retention), but less selective (inversion predominates) with alkyl halides (less problematic with Af-aUylpyrrolidines). 

To the best of our knowle( e, there is no example of a Sn2 reaction with retention of configuration if the reaction center is a saturated carbon atom However, if the reaction center is a silicon atom, it is possible, by changing the substrate or the nucleophilic reagent, to obtain highly stereoselective reactions with either predominant retention or inversion of configuration. For example, when la and 1 b are... 

Stereoselective deoxygenation of epoxides. The ate complex [Bu3SnAl-(CH3)3] Li+ (1) formed from Bu3SnLi and A1(CH3)3 converts epoxides to alkenes with overall retention of stereochemistry. The results can be explained by inversion in the epoxide cleavage and antf-elimination of the Bu3Sn and O A1(CH3)3 groups. Example ... 

On submitting D-isomannide 2,5-dinitrate (15) to flash vacuum thermolysis, 1,4 3,6-dianhydro-D-mannopyranose (145) was obtained as the main product (75 - 80% yield), accompanied by 5 -10% of the monoketone 8a. In contrast, when D-isosorbide 2,5-dinitrate (14) was treated under the same conditions, a 6 3 1 mixture consisting217 of 8a, 145, and its D-gluco epimer 146 resulted (see Scheme 40). These results could be explained by a restricted number of rearrangements of intermediate radicals, with inversion or retention of configuration, respectively. By reduction with sodium borohydride, 8a was stereoselectively converted into D-isomannide (4). 

The stereoselectivity in reactions of P-alkylthio-a,(3-enones with organocuprates is dependent upon both the solvent and bulk of the ligand in the cuprate. Ether solutions favor inversion, while THF solutions favor retention (Scheme 19). It was proposed that in coordinating solvents such as THF, a more reactive enolate is formed, which eliminates before rotation occurs, thereby giving retention of configuration.108... 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

Nucleophilic alkylation with Grignard reagents (mediated by Et2AlCl) on chiral perhydropyrido(2.1 A]pyrrolo[l,2-ii][l,3,4]oxadiazinc (25) proceeds via an 5 2 mechanism below — 80 °C, forming the inversion product (26) with high stereoselectivity.22 At higher temperatures the stereoselectivity shifts in favour of retention. 

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