Erythro/threo-Selective syntheses

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... 

FDP A was employed in a study of pancratistatin analogs to catalyze the formation of the D-threo stereochemistry (Scheme 5.24). When rhamnulose 1-phosphate aldolase (Rha 1-PA) was used the L-threo stereoisomer was obtained with excellent selectivity. Thus these two enzymes allow the stereoselective synthesis of the two threo-stereoisomers [44]. They were also utilised successfully for the synthesis of different diastereoisomers of sialyl Lewis X mimetics as se-lectin inhibitors. Not only the two threo-selective aldolases RAMA and Rha 1-PA, but also the D-erythro-selective Fuc 1-PA was employed. In this way it was possible to synthesise three of the four diastereoisomers enantioselectively (Scheme 5.25). The L-erythro stereochemistry as the only remaining diastereo-isomer was not prepared [45]. This is because the aldolase that might catalyze its formation, TDP A, is not very stereoselective and therefore often yields mixtures of diastereoisomers. 

In the synthesis shown in Scheme 13.15, racemates of both erythro- and threo-juvabione were synthesized by parallel routes. The isomeric intermediates were obtained in greater than 10 1 selectivity by choice of the E- or Z-silanes used for conjugate addition to cyclohexenone (Michael-Mukaiyama reaction). Further optimization of the stereoselectivity was achieved by the choice of the silyl substituents. The observed stereoselectivity is consistent with synclinal TSs for the addition of the crotyl silane reagents. 

The diastereoselectivity of the reduction of a-substiluted ketones has been the subject of much investigation. The reagent combination of trifluoroacetic acid and dimethylphenylsilane is an effective method for the synthesis of erythro isomers of 2-amino alcohols, 1,2-diols, and 3-hydroxyalkanoic acid derivatives.86,87,276,375 Quite often the selectivity for formation of the erythro isomer over the threo isomer of a given pair is >99 1. Examples where high erythro preference is found in the products are shown below (Eqs. 218-220).276 Similar but complementary results are obtained with R3SiH/TBAF, where the threo isomer product... 

Warren has also studied dibenzophosphole oxides. The ketophosphine oxide (230) substrate can be formed and selective reduction to either the erythro (233) or the threo (231) adducts carried out. The normal NaBH4 conditions were used for reduction to the threo isomer and CeCb was added to obtain the erythro adduct. This methodology was applied to the synthesis of ( )- and (Z)-isosafroles (232) and... 

The use of Ru catalysts for selective epoxidations has also been explored. The Ru(2,6-Cl2TPP)CO catalyst with dichloropyridine A-oxide as the stoichiometric oxidant provides good levels of stereocontrol for the synthesis of threo-dimm epoxides, 4 <05MI29>. The use of the manganese system, Mn(2,6-Cl2TPP)Cl, on amine 3 provides a 1.4 1 mixture of the 4-erythro 4-threo isomers in 88% yield after 1 hour <05JOC4226>. 

Epoxide 303 has been used an an enantioselective synthesis of the methylenecyclopropa-neacetic acid (514a) portion of (methylenecyclopropyl)acetyl-CoA (514b), a mammalian metabolite of hypoglycines A and B. Addition of the anion derived from phenyl 2-(tri-methylsilyl)ethyl sulfone to 303 produces a 3 1 mixture of threo and erythro diastereomers 509. Either diastereomer cyclizes to the same cyclopropane 511 upon treatment with LDA, which suggests that epimerization at C-5 must be occurring prior to cyclization. Selective removal of the TBPS group followed by oxidation of the alcohol to an acid and elimination affords the desired product 514a (Scheme 73) [126,127]. 

The bis(tetrahydrofuranyl) Annonaceous acetogenin ( + )-(15,16,19,20,23,24)-hexepiuva-ricin (74), has been synthesized utilizing a polyepoxide cascade reaction. The diiodide 70 is transformed into the bis-allylic alcohol 72, which is subsequently converted to a C2-sym-metric diepoxide utilizing the Sharpless asymmetric epoxidation reaction. Selective mono-tosylation of the primary hydroxyl groups served to desymmetrize the system. An acid-catalyzed deketalization followed by simultaneous epoxide opening affords the erythro trans threo trans erythro-conf gmdXion present in the tosylate 73. Transformation of 73 to the desired 74 completes the synthesis [32] (Scheme 17). 

In an inventive approach to higher-sugar lactones (Scheme 2), Marshall and Beaudoin treated the tartrate-derived enal 9 with the chiral allyl stannane shown to give the threo-adivtct 10, after funher silylation of the initially fwmed alcohol. This bis-allylic ether was hydroxylated with high erythro-selectivity to 11, convertible to the octonolactone 12. A similar sequence was used to extend di-O-isopropylidene-a/dehydo-D-arabinose to the Cn-lactone 13, an intermediate previously used in a synthesis of hikizimycin. ... 

Some interesting developments have been reported in the area of stereoselective a-substituted jS-hydroxy-ester synthesis (see also ref. 30). Masamune s group has described an alternative preparation of the E-vinyloxyborane (102) which condenses with aldehydes to give erythro-esters (103) of 97% stereochemical purity. By contrast, the Z-dicyclopentylboron analogue of (102) leads exclusively to threo-(103). The -enol ether (104) also reacts with aldehydes in the presence of TiCU to give threo-isomcrs of (103) unfortunately the Z-isomer of (104) reacts with little stereoselectivity, An alternative, completely selective, route to threo-(103) is by mono-alkylation of dianions derived from j8-hydroxy-esters. This latter method appears to have considerable potential in general synthesis. 

This method has also been extended to the synthesis of mono(benzaimulated) spiroacetals [139, 140] (Scheme 66). For both the threo and erythro glycal-deiived epoxides, the retention spiroacetals 265a and 266b could be obtained selectively using the Ti(Oi-Pr)4 protocol. The inversion spiroacetals 265b and 266a could be accessed upon addition of MeOH or AcOH to the reaction mixture however, the selectivity was much lower. 

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