Regioselectivity trends

The regioselectivity of the hydroformylation of alkenes is a function of many factors. These include inherent substrate preferences, directing effects exerted by functional groups as part of the substrate, as well as catalyst effects. In order to appreciate substrate inherent regioselectivity trends, alkenes have to be classified according to the number and nature of their substitution pattern (Scheme 3) [4]. 

Scheme 3 Regioselectivity trends on hydroformylation of different alkene classes...

To explain the regioselectivity trend in the photo-oxygenation of allylic silanes, it was proposed that an interaction between the negatively charged oxygen of the perepoxide and the silicon atom controls the abstraction of allylic hydrogen atoms (Scheme 20). The formation of cis ene adducts [86] was attributed either to the intermediacy of a zwitterionic intermediate or to a nonconcerted pathway. A perepoxide intermediate was considered unlikely. 

The hydroxyl group at the allylic position has a significant effect on the syn/anti methyl stereoselectivity [67,68] and the diastereoselectivity [63,64] of the photo-oxygenation ene reaction (see Sec. II.B). To assess the effect of the hydroxyl at the more remote homoallylic position, the reaction of O with the geminal dimethyl trisubstituted homoallylic alcohols (85, 86, 89) and the cis dis-ubstituted 90 was examined in nonpolar solvents [116], The regioselectivity trend was compared with that of the structurally similar trisubstituted alkenes (87, 88, 91) [105], The results are summarized in Table 12. 

For alkenes 87, 88, and 91, the regiochemistry is solely dependent on the steric hindrance of the allylic substituent. It is obvious that the regioselectivity trend for the homoallylic alcohols 85, 86, and 89 is different from that of compounds 87, 88, and 91, respectively, although the hydroxyl group exerts approximately the same steric hindrance as a methyl group. 

Finn, K.J., Pavlyuk, O. and Hudlicky, T. (2005) Toluene dioxygenase-mediated oxidation of bromo(methylsulfanyl) benzenes. Absolute configuration of metabolites and evaluation of chemo-and regioselectivity trends. Collection of Czechoslovak Chemical Communications, 70,1709 1726. 

Further studies of regioseleclive syn hydrocyanation of various alkynes and alkynols used nickel-based catalyst systems of the type NiL4 with either L = triphenylphosphite or L2 = a,a-bis(diphenylphosphino)-2-xylene (PHMEP)26. The regioselectivities observed with the phos-phane catalyst reflect dominant steric effects, whereas results with the phosphite catalyst system show some evidence for chelation control. Similar conversions of various amino alkynes also occur exclusively in a syn fashion with comparable regioselectivity trends, as in the alkynol case28. The products are used as precursors for the synthesis of saturated and unsaturated amino acids28. 

To date (ca 1996) many potentially usefiil sucrose derivatives have been synthesized. However, the economics and complexities of sucrochemical syntheses and the avadabiLity of cheaper substitutes have limited their acceptance hence, only a few of them are in commercial use. A change in the price and availability of petroleum feedstocks could reverse this trend. Additional impetus may come from regioselective, site-specific modifications of sucrose to produce derivatives to facilitate and improve the economics of sucrochemical syntheses. For example, the microbe yigwbacterium tumifaciens selectively oxidizes sucrose to a three-keto derivative, a precursor of alkylated sucroses for detergent use (50). Similarly, enzymes have been used for selective synthesis of specific sucrose derivatives (21). 

The chemoselectivity of the other alkenes of Table 1 is more variable. It appears that bulky substituents favour bromide over methanol attack of the bromonium ion, since dibromlde increases from 39 to 70 % on going from methyl to tert-butyl in the monosubstituted series. The same trend is observed in the disubstituted series with a contraction of the chemoselectivity span (37 to 43 % on going from methyl to teH-butyl) for the trans isomers. Since the solvated bromide ion can be viewed as a nucleophile larger than methanol, the influence of steric effects, important in determining the regioselectivity, does not seem very significant as regards the chemoselectivity. This result has been interpreted in terms of a different balance between polar and steric effects of the substituents on these two selectivities. 

Apart from the role of substituents in determining regioselectivity, several other structural features affect the reactivity of dipolarophiles. Strain increases reactivity norbornene, for example, is consistently more reactive than cyclohexene in 1,3-DCA reactions. Conjugated functional groups usually increase reactivity. This increased reactivity has most often been demonstrated with electron-attracting substituents, but for some 1,3-dipoles, enol ethers, enamines, and other alkenes with donor substituents are also quite reactive. Some reactivity data for a series of alkenes with several 1,3-dipoles are given in Table 10.6 of Part A. Additional discussion of these reactivity trends can be found in Section 10.3.1 of Part A. 

The ligands synthesized were also apphed to the isomerizing hydroformylation of more reactive 2-pentene. At 120 °C/ 20 bar quantitative conversion of olefin to aldehydes was achieved within 40 min. Trends similar to those described for internal octene hydroformylation were found. The regioselectivity obtained for the individual ligands tends to be 5% higher compared to that for the octenes. Thus, in the presence of 10 75% of n-hexanal were determined, compare Table 3. Obviously, 2-pentene is able to react more smoothly to the terminal isomer compared to olefins having the double bond in an more internal position. Illustrative for this effect are also literature results obtained for 2- and 4-octene.4,5... 

Albeit nitrile oxides are more regioselective than nitrones towards MCP, in cycloadditions with alkylidenecyclopropanes they show a lower regiocontrol than nitrones. The same trend, however, on passing from electron-donating to electron-withdrawing substituents is observed. Benzylidenecyclopropane (156) gives (entry 1, Table 28) only a 1 4 mixture (compared with 1 19 with nitrone... 

A summary of the research activities of the last four years reveals three different important trends (a) The design of new ionic ligands for excellent catalyst immobilisation in ionic liquids and high regioselectivity (b) the successful application of cheap, halogen-free ionic liquids in the biphasic Rh-catalysed hydroformylation (c) the successful development of unusual multiphasic reaction concepts for Rh-catalysed hydroformylation, namely catalysis in ionic liquid/supercritical C02 and SILP-catalysts. 

Aryl- and alkylsulfonyl radicals have been generated from the corresponding iodides and added to, e.g., propadiene (la), enantiomerically enriched (P)-(+)-propa-2,3-diene [(P)-(lc)] and (P)-(-)-cyclonona-l,2-diene [(P)-(lk)] [47]. Diaddition of sulfo-nyl radicals may compete considerably with the monoaddition [48,49]. Also, products of diiodination have been purified from likewise obtained reaction mixtures, which points to a more complex reactivity pattern of these substrates towards cumulated Jt-bonds. An analysis of regioselectivities of arylsulfonyl radical addition to allenes is in agreement with the familiar trend that a-addition occurs in propadiene (la), whereas alkyl-substitution at the cumulated Jt-bond is associated with a marked increase in formation of /3-addition products (Scheme 11.7). 

As already commented in the introduction of this chapter, regardless of its substitution pattern, the main trends of allenylidene reactivity are governed by the electron deficient character of the C and Cy carbon atoms of the cumulenic chain, the Cp being a nucleophilic center [9-15]. Thus, as occurs with their allcarbon substituted counterparts, electrophilic additions on 7i-donor-substituted allenylidene complexes are expected to take place selectively at Cp, while nucleophiles can add to both C and Cy atoms. However, the extensive 71-conjugation present in these molecules results in a reduced reactivity of the cumulenic chain and, in some cases, in marked differences in the regioselectivity of the nucleophilic additions when compared to the all-carbon substituted allenylidenes. In the following subsections updated reactivity studies on 7i-donor-substituted allenylidene complexes are presented by Periodic Group. 

---