Dihydroxylation facially selective

Jones and Vogel investigated the snbstitnent effect of a 5,6-bis(methoxycarbonyl) group in bicyclo[2.2.2]octene (48i) [117]. The substituent effect of a single 5-exo substituent on the facial selectivities of bicyclo[2.2.2]octenes 48b-48h was also characterized by our group [118]. Epoxidation and dihydroxylation of the olefin moiety of 5-exo-substituted... 

This notion is also snpported by the following experimental observations. Because substitution of a cyano gronp on the cyclopropane ring lowers the energy of the Walsh orbital of the cyclopropyl group, the resultant attennation of the interaction of the olefin orbital with the Walsh orbital, if this interaction is indispensable, would reduce the facial selectivity. However, substitution of a cyano gronp on the cyclopropyl group, as in ejco-cyano 59c and endo-cymo 59d, essentially does not modify the syn-preference in dihydroxylation and epoxidation, but even increases the syn preference (59c (98 2) and 59d (>99 <1)) in the case of dihydroxylation. 

The sterically unbiased dienes, 5,5-diarylcyclopentadienes 90, wherein one of the aryl groups is substituted with NO, Cl and NCCHj), were designed and synthesized by Halterman et al. [163] Diels-Alder cycloaddition with dimethyl acetylenedicarbo-xylate at reflux (81 °C) was studied syn addition (with respect to the substituted benzene) was favored in the case of the nitro group (90a, X = NO ) (syrr.anti = 68 32), whereas anti addition (with respect to the substituted benzene) is favored in the case of dimethylamino group (90b, X = N(CH3)2) (syn anti = 38 62). The facial preference is consistent with those observed in the hydride reduction of the relevant 2,2-diaryl-cyclopentanones 8 with sodium borohydride, and in dihydroxylation of 3,3-diarylcy-clopentenes 43 with osmium trioxide. In the present system, the interaction of the diene n orbital with the o bonds at the (3 positions (at the 5 position) is symmetry-forbidden. Thus, the major product results from approach of the dienophile from the face opposite the better n electron donor at the (3 positions, in a similar manner to spiro conjugation. Unsymmetrization of the diene % orbitals is inherent in 90, and this is consistent with the observed facial selectivities (91 for 90a 92 for 90b). 

The facial selectivity of the dihydroxylation can reliably be predicted using the mnemonic device 42. The smallest substituent on the olefin (generally the hydrogen) is always placed in the south-east quadrant (H), which is the most hindered space in the asymmetric environment. The south-west quadrant (RL) is especially attractive for large aliphatic groups in the case of PYR 39 and for aromatic groups in the case of PHAL 43. Use of DHQD 40 causes dihydroxylation from the /9-side. Treatment of enol ether 9 with the common (DHQD)2PHAL-system provides only 32 % ee. 

In order to predict facial selectivity, Sharpless and co-workers invoke a mnemonic device.25 To an approaching olefin, the greatest steric constraints are presented by the NW, and to an even greater extent, the SE quadrants. The SW and NE quadrants are more open and, in addition, the SW quadrant contains what is described as an attractive area . The attractive area is particularly well suited to accommodate flat aromatic groups. The olefin positions itself according to the constraints imposed by the ligand and is dihydroxylated from above (p-facc), in the case of dihydroquinidine derivative, or from below (a-face) in the case of dihydroquinine derivatives. The commercially available AD-mix-a and AD-mix-P are chosen according to this mnemonic. 

Figure 3.3. Facial selectivity in the Sharnlese 6 J asymmetric dihydroxylation.

Figure 3.4. Facial selectivity in asymmetric dihydroxylation using AD-mix-a and AD-mix-p.

Use of the dihydroxylation procedure with the P-lactam-substituted alkenes 16 showed a matched-mismatched phenomenon (Scheme 3.15). Use of an achiral reagent showed little facial bias. With an alkyl or ester group rather than aryl as the other alkene substituent (R1), the selectivity diminished [311]. 

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