Erythro adduct

The bromination of /razw-stilbenes in methanol, trifluoroethanol and in acetic acid leads almost exclusively to the erythro adducts via a 100% anti addition, regardless the substituents and the solvent. In contrast, the stereochemistry of the reaction of c/s-stilbenes exhibits a considerable dependence on the substituents and on the solvents the reaction of p-methoxystilbenes is always stereo-convergent, that of p,p -bis(trifluoromethyl)stilbenes is stereo-specific in all investigated solvents, whereas unsubstituted stilbenes can produce variable stereochemical outcomes ranging from stereo-specific to stereo-convergent in going from methanol to trifluoroethanol as solvent. 

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

One possible explanation for the diastereoface selection (AAGt -78°C 3 kcal/mol) observed for these chiral enolates is illustrated in Scheme 23. In the respective aldol transition states derived from conformers A and B leading to erythro diastereomers A and B, it may be assumed that developing imide resonance (118) will lock the chiral auxiliary in one of the in-plane conformations illustrated in products A or B. Based on an examination of models, it is projected that developing CHj R, allyhc strain steric interaction (37) disfavors that transition state leading to A. These steric considerations are largely attenuated in the transition state leading to the observed erythro adduct B. ... 

Precursors of type E (erythro fragment) (Scheme 6.69) were obtained by cycloaddition of a nitrile oxide dipole to a-alkoxyalkenes. This strategy was used in the syntheses of dl- and D-hvidosamine (298) (Scheme 6.73). Fithium aluminum hydride reduction of the erythro adduct 130 produced aminoalcohols 135 in a 78 22 ratio (2,4-erythro/threo) in high yield. The mixture was subjected to HCl hydrolysis to give the hexosamine hydrochlorides 136, which after several steps, produced D-hvidosamine 137 possessing the D-ribo configuration (298). 

Aldol condensation. The aldol condensation of silyl enol ethers with an aldehyde in the presence of 1 (0.1 5 equivalents) results mainly or even exclusively in erythro-adducts (equations I and II) regardless of the stereochemistry of the cnolatc. 

Stiihmer and Hess war b1M have reported addition of aniline, ) -naphthylamine, and others to ci - and bmu-atilbene oxide to afford tkreo and erythro adducts respectively, as shown in Eq. <627), Their observations are consistent with the premise that ring-opening is accompanied by Walden inversion at the site of nucJecphiJic attack. 

The Lewis acid catalyzed conjugate addition of allylsilanes (140) to (142) and allylstannanes (154) and (155) to ot,0-enones, described by Sakurai,68a,68b is highly efficient and experimentally simple in contrast to the allylcuprate additions. Various substituents can be incorporated into the allylsilanes (allylstannanes), e.g. alkoxy, alkoxycarbonyl and halogen, some of which are incompatible with cuprate reagents 69 In addition, Heathcock and Yamamoto report that diastereoselectivity is correlated to the alkene geometry of both the allylmetals and the acceptor units for example, allylation of ( )-enones (143) and (146) affords predominantly the syn adducts (144) and (147), while (Z)-enone (149) gives predominantly the anti adduct (150 Scheme 25).680 On the other hand, with cyclohexen-2-one the (Z)-silane (141) affords predominantly the threo adduct (152), while (142) affords erythro adduct (ISS).686 The more reactive allylstannanes (154) and (155) also afford similar diastereoselectivity.68e,f... 

Pulverized tram-cinnamic acid 3 (2.0 mmol, a or / -modification) and Br2 gas (5 mmol) gave a 100% yield of the erythro-adduct 4. 

HomoaUyUc alcohols. Alkenyldimethoxyboranes add to aldehydes regioselec-tively to form homoallylic alcohols. The reaction is also diastereoselective (Z)-alkenylboranes react to form erythro-adducts, and (E)-alkenylboranes produce threo-adducts. The boranes are prepared by treatment of alkenyl potassium compounds with fluorodimethoxyborane (6, 261-262). 

Stereoselective reactions with aldehydes. The related (E)-2-pentenyltin reagent 2 also reacts with aldehydes to form predominantly erythro adducts such as 3. This reaction was used for a stereoselective synthesis of an aggregation pheromone (4) of the European elm bark beetle.1... 

Nucleophiles such as enolates or substituted allylmetal compounds are known to react with prochiral aldehydes and ketones to form mixtures of threo or erythro adducts. In case of aldehydes, high degrees of diastereoselection have been achieved 48 91,108). In the following three Sections, reactions of titanium and zirconium enolates as well as allyl derivatives are presented. 

The problem of diastereoselective aldol addition has been largely solved48,108). Under kinetic control Z enolates favor erythro adducts and E enolates the threo diastereomers, although exceptions are known. This has been explained on the basis of a six-membered chair transition state in which the faces of the reaction partners are oriented so as to minimize 1,3 axial steric interactions 481108). This means that there is no simple way to prepare erythro aldols from cyclic ketones, since the enolates are geometrically fixed in the E geometry. 

Separate the isomers by flash column chromatography on silica gel (ethyl acetate then acetone as eluant). The first diastereomer eluted from the column is the erythro adduct, with further elution affording the corresponding threo isomer. The diastereomers are recrystallized separately from ethyl acetate to afford the erythro diastereomer (1/ S,2S/ )-2-diphenylphosphinoyl-1-phenylbutan-1-ol (1.05 g, 73%) and the threo diastereomer (1/ S,2/ S)-2-diphenylphosphinoyl-1-phenylbutan-1-ol (180 mg, 13%) as needles. 

Reactions of vinylisoxazolines have also been studied. In reactions of 1,3-butadiene (60) with nitrile oxides, the erythro adducts (62) were formed in preference to the corresponding threo isomers (63) (Scheme 38) (83T2247 85T5569), the isomer ratios ranging from 2.7 1 to 6.7 1. The... 

A f/ireo-selective siloxonium (aldol-like) pathway II was favored when BF3 OEt2 was used as catalyst (Sch. 3) [11]. The reaction of benzaldehyde by quenching after 5 min resulted in 48 % yield of the final cyclic products 3 (1 8 cisitrans ratio) and 46 % yield of the Mukaiyama-like aldol products 5 (1 2 threolerythro ratio). When either threo or erythro adduct was re-subjected to trifluoroacetic acid media, each underwent conversion to the corresponding y-pyrones 3. 

By analogy with previous results with enol silyl ethers of ketones, non-substituted silyl ketene acetals result in less stereoregulation. Propionate-derived silyl ketene acetals, on the other hand, result in a high level of asymmetric induction. Reactions with aliphatic aldehydes, however, result in slightly reduced optical yield. With phenyl ester-derived silyl ketene acetals, erythro adducts predominate, but selectivities are usually moderate compared with the reactions of ketone silyl enol ethers. Exceptions are a, 8-unsaturated aldehydes, for which diastereo- and enantioselectivity are excellent. The observed erythro selectivity and re-face attack of nucleophiles on the carbonyl carbon of aldehydes are consistent with the aforementioned aldol reactions of ketone enol silyl ethers [47]. 

Table XIV summarizes the reaction of silyl enol ether (14a) with an acetal (15a) in the presence of various acids. The reaction proceeded smoothly with the aid of acidic solids even under heterogeneous conditions (a suspension state) to afford the corresponding aldol adducts in good yield (Entries 1 - 5,7). Among the strong solid acids examined, aluminum ion-exchanged montmo-rillonite (Al-Mont) showed the highest catalytic activity (Entries 1,2) and good diastereoselectivity for the erythro adduct, especially in 1,2-dimethoxyethane (DME)(Entry 2).

The addition of the phosphine oxide anion to the carbonyl is dramatically affected by solvent, base and temperature. These conditions can be modified in order to maximize the erythro isomer formation. In nonpolar solvents the addition proceeds with virtually no selectivity. Substantial improvements are seen by Ae use of ethers, and the highest ratios of erythro adduct (225) are obtained in THF with the lithium complexing reagent TMEDA present at -78 C or lower temperatures (equation S6). 

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... 

Unlike the elimination of erythro adducts, the elimination of the threo intermediate is stereospecifle for aromatic and aliphatic substituents. A study of various methods of reduction found that NaBH4 in EtOH gave the best combination of threo selectivity and yield. ... 

The (E)- and (Z)-selectivity in HWE reactions is determined by a combination of the stereoselectivity in the initial carbon-carbon bond formation and the reversibility of the intermediate adducts. The ( )-selectivity has been explained by the formation of the thermodynamically more stable threo-a.dduct, which then decomposes via the oxaphosphetane intermediate to the ( )-olefin. The (Z)-selec-tivity has been attributed to the predominant formation of the erythro-adduct which collapses irreversibly via a transient oxaphosphetane intermediate to the (Z)-olefin. ... 

We have examined a purely logical way in which the "Cram s rule problem" can be attacked — double stereodifferentiation. For example, either reactant in an aldol condensation can be chiral and exhibit diastereoface selectivity. Suppose we have an aldehyde which reacts with achiral enolates to give the two possible erythro adducts in a 10 1 ratio ... 

Halogeno-l,2,4-thiadiazol-5-yl sulfenyl chlorides (455) react rapidly with olefins at — 40°C to yield adducts (e.g., 456 from butene). The stereospecific mechanism of the exclusive trans addition probably involves epi-sulfonium ions as intermediates. Thus, erythro adducts arise from trans-2-buteneand threo adducts from ds-2-butene terminal olefins (e.g., isobutylene, 3,3-dimethylbut-l-ene) produce single products, the assigned structures of which (Markovnikov or otherwise) are consistent with their H NMR spectra.209... 

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