Trans-disubstituted olefin

During the early development of the Jacobsen-Katsuki epoxidation reaetion, it was elear that trans-disubstituted olefins were very poor substrates (slow reaetion rates, low enantioseleetivity) eompared to cis-disubstituted olefins. The side-on approaeh model originally proposed by Groves for porphyrin epoxidation systems was used to rationalize the differenees observed in the epoxidation of the cis and trans-disubstituted elasses (Seheme 1.4.7). ... 

This synthetic sequence for an olefin synthesis has been further developed by Kocienski who has shown that eliminative desulphonylations carried out on / -acyloxysulphones are remarkably stereoselective for the synthesis of trans-disubstituted-olefins. The method has wide applicability in that a-lithio phenyl sulphones are readily generated, and are readily coupled to aldehydes or ketones, to give j8-hydroxysulphones. The hydroxyl function of these is then esterified and the synthesis is completed by the reductive elimination with sodium amalgam. Kocienski has prepared two reviews that summarize his syntheses of a range of natural products - one of which is diumycinoP obtained... 

Cis-disubstituted olefins lead to higher enantioselectivities than do the corresponding trans-disubstituted olefins (Table 5.7), even with substituents as bulky as tri-rc-butyltin. 

Once again, cis-disubstituted olefins lead to higher enantioselectivities than do trans-disubstituted olefins, but here the differences are not as great as they were with allyl diazoacetates. Both allylic and homoallylic diazoacetamides also undergo highly enantioselective intramolecular cyclopropanation (40-43) [93,94], However, with allylic a-diazopropionates enantiocontrol i s lower by 10-30% ee [95], The composite data suggest that chi ral dirhodium(II) carboxamide catalysts are superior to chiral Cu or Ru catalysts for intramolecular cyclopropanation reactions of allylic and homoallylic diazoacetates. 

TABLE 6D.3. Asymmetric Dibydroxylation of trans-Disubstituted Olefins (% ee)... 

Olefins of the /ranr-disubstituted type have given diols with excellent enantiomeric purities when dihydroxylated with the (DHQD)2-PHAL/(DHQ-PHAL pair of chiral ligands with osmium tetroxide (see Table 6D.3 [16,26,29,31,35,40,41,46-48]). All the entries but one in Column 9 for diols obtained with these ligands exceed 90% ee (or 90% de). From other entries in Table 6D.3, particularly those of Column 3 for earlier stoichiometric ADs with the DHQD-CLB ligand, good enantioselectivities are anticipated for the dihydroxylation of most trans-disubstituted olefins when the PHAL ligands are used. 

Although trans-disubstituted olefins are readily prepared by the partial reduction of acetylenes with sodium in liquid ammonia M>, this novel olefin synthesis via hydroboration has a unique advantage over the conventional method in which four consecutive stereocenters can be created in a predictable manner as shown by the following example (Eq. 71)U8). 

The results of many dihydroxylation reactions have resulted in the compilation of a mnemonic device for the prediction of the direction of attack with catalysts based on each alkaloid (Scheme 8.17). Although this model is very useful, there can be some ambiguity as to which group is the large one and which is the medium (especially with trans-disubstituted olefins) and electronic cbaracteristics cannot be ignored [63]. This is a byproduct of the lack of an unambiguous group to orient the molecule cf. the AE reaction. Scheme 8.1). 

While the oxygen-18 labeling results described here confirm the molozonide-aldehyde mechanism for the types of olefins considered, the ozonolysis reaction in general is quite complex and seems to vary widely depending especially upon the stereochemistry of the olefin. To sum up, the molozonide-aldehyde mechanism 14) considered here appears to be applicable to any important degree only to trans-disubstituted olefins, relatively unhindered cis olefins, and perhaps to unhindered terminal olefins. As pointed out, more hindered olefins seem to react by one or more different pathways, which differ most notably from the present system in the apparent absence of a molozonide intermediate (2, 8, i2,14). 

The C-chemical shifts of sp -hybridized carbons in the vicinity of double bonds can be estimated using the additivity rule outlined on p. CIO. The conformational correction factor K differs widely for y-substituents of cis vs, trans-disubstituted olefins because the conformation is fixed by the double bond. It is thus quite easy to assign the correct isomeric structure. 

Scheme 3.28 Epoxidation of trans-disubstituted olefins with ketone 39 [35]...

The enantiomeric excesses obtained to this point for the catalytic AD of monosubstituted olefins (see Table 6D.2 [16,26,29,31,40,44-46,49]) are lower than for trans-disubstituted olefins (Table 6D.3). The entries in Column 9 show enantiomeric purities ranging from 54% ee to 97% ee for dihydroxylations with the (DHQD>2-PHAL and (DHQ)2-PH AL pair of chiral ligands. Several monosubstituted olefins with tnanching at die a-position (e.g., entries 2-4 and 11) are dihy-droxylated with higher enantioselectivities when DHQD-PHN is used as the chiral ligand instead of (DHQD)2-PHAL. Recently, a new ligand for terminal olefins has been discovered [48b]. 

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