Stereoselective synthesis shifts

A highly stereoselective synthesis of ( )-deplancheine has been developed (121), utilizing a photocyclization process for the preparation of enelactam 181, which was reduced by zinc in acetic acid to lactam 182. In the latter, the double bond was shifted to the 19,20 position stereoselectively with an E geometry by the use of nonacarbonyldiiron catalyst to supply 159, previously synthesized and transformed to ( )-7 by Winterfeldt et al. (112). 

For preparative applications, the expensive and configurationally unstable donor 128 can be simply prepared in situ by the action of ribose 5-phosphate isomerase (EC 5.3.1.6) on D-ribose 5-phosphate (39). This technique was applied to the stereoselective synthesis of d-[1-13C] fructose 6-phosphate 38 from [13C] formaldehyde [376,377] which also included a second enzymatic isomerization of the D-arafrino-3-hexulose 6-phosphate intermediate 129 into the more stable 2-hexulose derivative 38. Notable are the conflicting demands for high substrate levels (necessary to shift the fully reversible multi-component equilibrium) versus the notorious enzyme inactivation that occurs at higher formaldehyde concentrations. 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

An electrocyclization of the 1,3,5-triene 12 was employed in the stereoselective synthesis of ( )-pallescensin (ll)95. Thermolysis of furan 12 in xylene (200°C) presumably forms the intermediate 13 via 1.6-ECRC, how ever 13 is not observed, rather it undergoes a suprafacial [1,5] hydrogen shift to afford the cts-fused tricyclic 14. The synthesis of ( )-pallescensin (11) required the trans-fused tricycle 15 rather than the cis, and it was found that this desired stereoisomer could be obtained w hen the 1,6-ECRC was carried out in the presence of silica gel. It was reasoned that the mildly acidic silicon dioxide could reasonably effect the acid-catalyzed epimerization of 14 to 15. Reduction and protodesilylation of 15 completed the synthesis of 11. 

Stereoselective synthesis of 1-oxygenated dienes, starting from propargylic esters, has been reported with gold catalysts [168]. In this case, a 1,2-H shift on cyclic intermediate 196 allows the formation of a vinyl gold intermediate 197, which, upon protodemetalation, furnishes the (1 ,3 ) diene 198 (Scheme 80). 

Yakura, T, Muramatsu, W., and Uenishi, J. (2005) Stereoselective synthesis of Cj-C]2 dihydropyran portion of antitumor laulimalide using copper-catalyzed oxonium yhde formation-[2,3] shift. Chem. Pharm. Bull., 53,989-994. 

Enzymatic synthesis in reaction mixtures with mainly undissolved substrates and/or products is a synthetic strategy in which the compounds are present mostly as pure solids [28, 29]. It retains the main advantages of conventional enzymatic synthesis such as high regio- and stereoselectivity, absence of racemization, and reduced side-chain protection. When product precipitates, the reaction yields are improved, so that the necessity to use organic solvents to shift the thermodynamic equilibrium toward synthesis is reduced and synthesis is made favorable even in water. 

The Norrish-Yang reaction, with the spin-center-shift extension, facilitates access to a variety of cyclic compounds. This will be discussed here, with examples of the synthesis of three- to six-membered rings synthesis of macro- and bicydic compounds and the photochemistry of imides will not be covered. The examples especially demonstrate the capabilities of the reaction with regard to stereoselectivity. 

As a further stereoselective organic synthesis [40-47] using reactive sp2 carbon-centered radicals, eq. 10.23 shows the preparation of chiral 4-te/7-butylcyclohexene (49) from the optically pure o-bromophenyl sulfoxide (48) through 1,5-H shift by sp2 carbon-centered radical, followed by (3-elimination. This reaction looks like a thermal concerted intramolecular elimination reaction (Ei). 

A particularly successful synthesis of Epothilone A is based on two DERA-cata-lyzed steps. In these two of the seven stereocentres of Epothilone A were established. When a racemic aldehyde was released in situ from its acetal, DERA converted only the R-enantiomer into the stable cyclic hemiacetal. This is a combined kinetic resolution and carbon-carbon bond formation yielding a building block with two chiral centers. Since the alcohol function was oxidized, the optical information obtained from the kinetic resolution was lost. Thus, for the overall yield it would have been better if DERA had displayed no stereoselectivity towards the acceptor (Scheme 5.32). In the DERA-catalyzed synthesis of another part of Epothilone A DERA is again highly stereoselective. Fortunately its preference is for the S-enan-tiomer of the acceptor aldehyde, the enantiomer that has to be submitted to the carbon-carbon bond formation in order to obtain the desired building block, again a stable hemiacetal (Scheme 5.32). Indeed, both DERA-catalyzed reactions yield open chain products that form stable cyclic hemiacetals. This ensures that the equilibria of these aldol reactions are shifted towards the desired products. Further synthetic manipulations converted these intermediates into Epothilone A [55]. 

Pt(II) to the alkyne of the substrate likely triggers all these events. The cycloisomerization might undergo a metallacyclic intermediate that proceeds to eliminate /3-H. The formation of cyclopropanes is presumably succeeded via alkenyl platinum carbene followed by platina(IV)cyclobutane intermediates. The extension using formal metathesis of the enynes includes two transformations, the formation of 1,3-diene moieties and the stereoselective tetrasubstituted aUcene derivatives via O C allyl shift, both leading to diverse structural motifs and serving as the key step in the total synthesis of bioactive targets (Scheme 83). 

Bp3-Et20 resulted in a shift of stereoselectivity towards 3-glycoside formation in the synthesis of sordaricin [345]. 

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