Retro-aldol reaction anti aldols

The reduction of (32) with NaBH4 also induced the retro-aldol reaction which would give the syn-compound (33) and finally an epimerization reaction j ould convert (33) to the anti-compound (34)... 

Mechanistic investigations revealed the intervention of a highly stereoselective retro aldol reaction, which could be minimized by using a catalytic amount of 1% NaOH aqueous solution and ammonium chloride, leading in turn to the establishment of a general and practical chemical process for the synthesis of optically active anti-P-hydroxy-a-amino esters 78 (Table 5.13) [41b],... 

Although attempts to catalyze bimolecular aldol condensations without resorting to enamine chemistry have not yet been successful, the Schultz group92 has prepared an antibody against the phosphinate hapten 115 that catalyzes the retro aldol reaction of 116 (kcJKm = 125 M-1 s l). The equilibrium in this case strongly disfavors the condensation product, and a histidine induced in response to the phosphinate may be involved in catalysis. Interestingly and in contrast to the previous examples, the stereoselectivity of the antibody is modest. The syn diastereomer of 116 was found to be the better substrate for the antibody by 2 1 over the anti diastereomer, but no evidence of enantioselectivity was observed. 

An early reference teaches us that even trimethylaluminum can cause deprotonation of a specialized ketone to generate the aluminum enolate under rather drastic conditions (toluene, reflux) [42]. As expected, the reaction proceeded under thermodynamic control, in which aldol and retro-aldol reactions occurred reversibly, to give a high level of anti diastereoselectivity, with concomitant removal of chelation complex 46 from the solvent (Scheme 6.22). 

In this system, the chiral phase transfer catalyst (PTC) is able to recognize one aldolate selectively. There is an equilibrium between syn- and anti-aldolates via retro-aldol addition, and the formation of a stable, chelated lithium salt blocks the non-catalyzed subsequent reaction from yielding the epoxide product ... 

A complicating factor in the analysis is the observation that aldolates can undergo syn/anti equilibration by enolization or by reverse aldolization. Aldols such as 407 can be deprotonated to the dianion (408) and this undergoes alkylation with iodomethane to give the anti product (409), as shown.230 This equilibration is clearly the basis of the aldol-transfer reaction discussed in 143 to 145 in Section 9.4.A.i. If 409 forms a new enolate, equilibration can lead to a mixture of syn and anti products. The primary mechanism for syn/anti equilibration appears to be reverse aldolization.23 A retro-aldol will convert the syn diastereomer (410) into the aldehyde and enolate components, which can regenerate 410 or form the anti diastereomer 411. Syn/anti equilibration can be much slower than reverse aldolization, as with the (Z) enolate of 2,2-dimethyl-3-pentanone).227 Aldolates derived from the more basic ketone enolates are more likely to suffer reverse aldolization than aldolates derived from the less basic enolates of esters, amides, or carboxylate salts. Steric crowding in an aldolate promotes reverse aldolization. The metal is very important, and some metals form... 

This retro aldol protocol enabled an ideal catalytic kinetic resolution of racemic aldol adducts that are usually difficult to be obtained through forward processes as illustrated by the resolutions of cyclohexanone aldol adducts. An intriguing feature of this process is that one chiral primary amine (e.g. 29) could catalyze stereoselectively the resolution of both anti- and yn-configured aldol adducts, whereas the forward reactions with the same catalyst yield selectively anti-configured aldol products. In addition, the catalytic power of 29-TfOH on both aldol and retro aldol reactions has also made possible an unprecedented asymmetric transfer aldol reaction that can generate two enantioenriched aldol adducts with opposite chiral induction from a single chiral catalyst (e.g. aldol products 48 and 49 in Scheme 5.14) [27],... 

Aromatic A-TMS-ketene imines undergo efficient aldol-type reaction with O-protected a-hydroxy aldehydes, giving iy -selectivity at ambient temperature, reversing at -78 °C to anti- Transfer of the TMS group from the ketene imine prevents (g) retro-reaction. 

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