Steric bias

Notably, some substrates possess enough steric bias to exert sterospecificity for the Bucherer-Bergs reaction. For instance, ketone 21, derived from enone 20 via a Corey-Chaykovsky reaction, underwent a Bucherer-Bergs reaction to fashion spirohydantoin 22 as a single isomer. 

At the other extreme of the stereoselectivity spectrum of the Bucherer-Bergs reaction, the steric bias is sometimes not powerful enough to exert any selectivity at all, as exemplified by the conversion of 37 — 38. " Amino acid 38 was produced as a 1 1 mixture of two diastereomers. 

Mehta et al. also studied the facial selectivities of exo-substituted 7-norbomenones 15a and 15b, which exhibit steric bias with respect to the anti side of the n face (with respect to the exo substituent) [76, 77]. In the reduction with sodium borohy-dride, high anti preference (more than 85%) was observed in the parent derivative 15a. Weak electron-withdrawing substituents (CH OCH, CH OAc, COONa) also showed anti preference, the magnitude being comparable to that in the case of the parent compound (15a) this is indicative of the steric bias of 15a. In the case of a strong electron-withdrawing substituent (di- or mono-CO CH, CN), the syn preference of addition was increased, becoming predominant in some cases (di-CO CHj (15b) syn. anti = 55 45 mono-CO CH synianti = 32 68 mono-CN syn anti =... 

On the other hand, the observed syn preference of 59a is consistent with a study of hydroboration of 59a with diborane by Schueler and Rhodes [127], who obtained a mixture of the monoalcohols (symanti = 74 26) upon oxidative work-up. A similar magnitude of. yyn-preference was found (syn anti = 73 27) in the hydroboration with a bulkier borane, 2,3-dimethyl-2-butylborane (thexyl borane) [127]. This lack of effect of the bulk of the reagent in the hydroboration of 59a is consistent with the idea that the n face of 59a is free from steric bias [127], and that the syn preference of 59a found in dihydroxylation and epoxidation is non-sterically determined [128]. 

The dibenzobicyclo[2.2.2]octatriene system (71) essentially involves interaction of three composite n orbitals, i.e., the olefinic n orbital as the reaction center, and two aromatic k orbitals. A simplified interaction network, i.e., two n component systems free from steric bias, is intriguing. In this context the facial selectivities of... 

Although there have been many experimental and theoretical studies on the behavior of facially perturbed dienes (see below), only a few systematic experiments have been carried out to characterize facially perturbed dienophiles. Dienophiles embedded in the norbomane or norbomene motif have been rather intensively studied [146-150]. In most cases, steric effect controls selectivity, but in some cases the reactions are considered to be free from steric bias, and the selectivity has been explained in terms of other factors, such as orbital effects [151, 152]. 

The stereoselectivity then depends on the conformation of the enone and the location of substituents that establish a steric bias for one of the two potential directions of approach. In the ketone 11, the preferred approach is from the (3-face, since this permits maintaining a chair conformation as the reaction proceeds.132... 

Scheme 10.17 illustrates allylation by reaction of radical intermediates with allyl stannanes. The first entry uses a carbohydrate-derived xanthate as the radical source. The addition in this case is highly stereoselective because the shape of the bicyclic ring system provides a steric bias. In Entry 2, a primary phenylthiocar-bonate ester is used as the radical source. In Entry 3, the allyl group is introduced at a rather congested carbon. The reaction is completely stereoselective, presumably because of steric features of the tricyclic system. In Entry 4, a primary selenide serves as the radical source. Entry 5 involves a tandem alkylation-allylation with triethylboron generating the ethyl radical that initiates the reaction. This reaction was done in the presence of a Lewis acid, but lanthanide salts also give good results. 

Rhodium( I)-catalyzed hydroformylation of cyclic enol acetals 1 leads to acetal-protected syn-3,5-dihydroxyalkanals 2 with extraordinarily high levels (>50 1) of diastereoselectivity (Scheme 5.2) [2]. The diastereoselectivity cannot be ascribed to any obvious steric bias, and serves as a powerful demonstration that the hydroformylation reaction may be subject to exquisite stereoelectronic control. Indeed, while the addition of a pseudo-axial methyl group to the acetal carbon (as in acetonide 3) has a deleterious effect on the rate of the reaction, the sy -diastereomer 4 is still produced selectively, in what is surely a contra-steric hydroformylation reaction. 

To improve these selectivities, Hashimoto studied several catalysts that had been found highly effective for enantioselective C—H insertion reactions. The new catalysts incorporated an additional benzene in the naphthyl system to increase the steric bias of the catalyst. By using the second-generation catalysts in trifluorotoluene as solvent, at 0 °C, and short reaction times gave ee ratios of 68-92%. Lowered reaction temperature generally resulted in reduced chemical yields but did not erode the ee ratio. Tether lengths one smaller or one larger also tended to erode the ee ratio (Scheme 4.73). 

Scheme 10.3 Free radical retrosynthetic disassembly of bond d in 7. Advantages it does not necessitate the construction of a functionalised medium-sized ring. It forms the bicyclooctane ring system by a favourable 5-exo-trig pathway. Conformational and steric bias will allow the stereochemistry of the methyl a to the ketone to be controlled.

Adam has found that in compounds 28 the reaction occurs with a diastereoselectivity antv.syn > 90 10, whatever the substituent, and, hence, the stereocontrol is exclusively by steric bias (Sch. 12) [10d],... 

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