Opposite regioselectivity

With titanated 2-alkenyl carbamates, the opposite regioselectivity can also be observed. Lithiated l-(4-methylphenylsulfonyl)-2-alkenyl diisopropylcarbamates, after metal exchange with chlorotriisopropoxytitanium, add to aldehydes y-selectivelylls. The less reactive titanat-ing reagent tetraisopropoxytitanium does not apparently react with these stabilized lithium carbanions, because in its presence a-selectivity is retained (Section 1.3.3.3.1.3.2.). 

Hydrometallation and carbometallation of alkynylsilanes proceeds regio-and stereospecifically, the metal becoming attached to the silicon-bearing carbon atom in what is normally a co-addition process (hydrostannylation, however, shows the opposite regioselectivity). Electrophilic cleavage, with retention, of the carbon-metal bond then leads to vinylsilanes of various types. 

The formation of the tricarbonylchromium-complexed fulvene 81 from the 3-dimethylamino-3-(2 -trimethylsilyloxy-2 -propyl)propenylidene complex 80 and 1-pentyne also constitutes a formal [3+2] cycloaddition, although the mechanism is still obscure (Scheme 17) [76]. The rf-complex 81 must arise after an initial alkyne insertion, followed by cyclization, 1,2-shift of the dimethylamino group, and subsequent elimination of the trimethylsilyloxy moiety. Particularly conspicuous here are the alkyne insertion with opposite regioselectivity as compared to that in the Dotz reaction, and the migration of the dimethylamino functionality, which must occur by an intra- or intermo-lecular process. The mode of formation of the cyclopenta[Z ]pyran by-product 82 will be discussed in the next section. 

As outlined above, enantioconvergent processes require two separate reaction pathways in order to transform a racemic substrate into a single product enantiomer. This is accomplished by employing a catalyst, which transforms one of the substrate enantiomers to the product with retention of configuration. Concurrently, another catalyst, with opposite enantioselectivity and opposite regioselectivity, transforms the other substrate enantiomer with inversion of configuration (Figure 5.24). 

Scheme 11 Opposite regioselectivities of the electrophilic additions to enam-ines and their onium ions...

The opposite regioselectivity is reported due to misprint a private communication from Meroia. 

The opposite regioselectivity is observed in intermolecular alkylative coupling of terminal alkynes and aldehydes with diethylzinc and with alkenylzirconium/ZnCl2 (Scheme 88). 

Vinyl Fischer carbenes can be used as three-carbon components in Ni(0)-mediated and Rh(l)-catalyzed [3 + 2 + 21-reactions with alkynes (Schemes 48 and 49)142 and with allenes (Schemes 50 and 51).143 All three of the proposed mechanisms for the [3 + 2 + 2]-cycloadditions involve an initial carbene transfer from chromium to nickel or rhodium (Schemes 49, 52, and 53). As is seen from the products of the two [3 + 2 + 2]-reactions with 1,1-dimethylallene, although the nickel and rhodium carbenes 147G and 147K appear similar, the initial insertion of the allene occurs with opposite regioselectivity. 

The intramolecular competition of two propargylic alkoxy groups, one on each side of the alkyne, is interesting. In a series of substrates related to 94 [180], always the 1,2-disubstituted allene 95 (Scheme 1.41) and not a 1,1,3-trisubstituted allene is formed (see also [225, 226]). The opposite regioselectivity was described in one publication (deprotonation with tBuLi, then protonation), but the allenes described there proved to be labile and quickly converted to other products [227]. 

R = Me, Et, and PhCH2, respectively Fig. 8.1). In 80% human plasma at pH 7.4 and 37°, these model prodrugs were hydrolyzed with tm values of 3.5, 16, and 2.6 min, respectively [59]. Such rates of enzymatic hydrolysis are comparable to those of various carbamoylmethyl esters of benzoic acid (Table 8.2). It is important to note that the direct liberation of benzoic acid by Reaction a (Fig. 8.1) was severalfold faster than the competitive Reaction b. Reaction c was very slow in human plasma (tm > 100 h). In HO -catalyzed hydrolysis, the opposite regioselectivity was seen, with the terminal ester bridge being cleaved markedly faster than the central one. No data appears to be available on chemical hydrolysis at neutral pH. 

Scheme 10 Different acid catalysts lead to opposite regioselectivity...

Of course, the cleavage reactions of both 2-aryl- and 2-alkyl aziridines are stereoselective because only the trans-diastereomers of the corresponding regioisomers 1 and 2 are formed. In other words, 2-aryl substituted aziridines showed opposite regioselectivity to 2-alkyl aziridines. With bicyclic aziridines, exclusive formation of the trans diastereomer is observed in the case of symmetric bicyclic aziridines. Unsymmetrical aziridines such as styrene, octene, and undecene aziridines produce a minor amount of the other regioisomer. 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

The magnesium ion-mediated nitrone cycloadditions of an a,y-disubstituted allyl alcohol are stereoselective, and show opposite regioselectivity to that observed when zinc-mediated reactions are examined (Scheme 11.48) (167). The exo-syn-isomer of the isoxazolidine-5-alcohol regioisomer and the exo-syn-isomer of the isoxazolidine-4-alcohol regioisomer are the exclusive cycloadducts in the magnesium- and zinc-mediated reactions, respectively. 

Additionally, some Pd-catalyzed type II zinc-ene cyclizations have been described. When the allylic acetate 181 was treated with EtiZn in the presence of a catalytic amount of Pd(PPh3)4, its slow conversion to a cyclic organozinc species by a type zinc-ene reaction was observed and iodinolysis afforded the six-membered ring 182 in relatively low yield. The regioselectivity was noteworthy as C-C bond formation occurred at the most substituted terminus of the allylmetal. By contrast, the type II palladium-ene cyclization of the allylic acetate 181, in conjunction with a /1-elimination process, proceeded with opposite regioselectivity and led to the six-membered ring 183 (equation 88)114. 

Contra-trans-diaxial cleavage of epoxides.2 The reaction of the a, p-epoxy alcohol 2 with NaSeC6H5 provides the 1,3-diol 3 in 90% yield. Use of 1 results in the opposite regioselectivity to provide 4 as the major product. 

The opposite regioselectivity observed for the addition of methylbutenyltin to similar allyl substrates (equations 241 and 242),137>139 caused by the presence of maleic anhydride in the latter case (equation 242), may be viewed as support for a change in mechanism when the electron deficient alkene ligand is present. Conversely, both reactions could proceed by metal addition, with the regiocontrol exercised by the maleic anhydride acting in the addition-reductive elimination sequence. 

Addition of MeMgl158 or PhLi160 to ir-allylpalladium complexes derived from methylenenoibomane exhibits selective C—C bond formation at die more hindered allyl terminus. Soft carbon nucleophiles with the same allyl species show the opposite regioselectivity (equation 252).158,160... 

CO2 insertion into TT-allylpalladium complexes exhibits the opposite regioselectivity, with, for example, exclusive reaction at the more substituted terminus of a butenylpalladium complex (equation... 

Although the regioselectivity for the silylformylation of 1-alkynes is excellent, that of internal alkynes is low except for 2-alkynoates (vide supra). Also, in the reactions of 1-alkynes, the silyl group is always delivered to the terminal position and the formyl to the C-2 position, thus it is impossible to synthesize 3-silyl-2-alkenals, which requires opposite regioselectivity. Intramolecular directed reactions can circumvent these limitations and expand the scope of the silylformylation of alkynes. 

Intramolecular aldo condensation.1 The opposite regioselectivity of this system (1) as compared to that of piperidinium acetate (1, 888-889) is also observed with dialdehydes of the general structure 2. 

The opposite regioselectivity is observed when peroxides are present. The product is 1 -bromo-2-methylbutane. 

Treatment of epoxides with halides under acidic reaction conditions does not always lead to attack of the halide at the most highly substituted carbon atom. The examples in Schemes 4.89 and 4.90 show that often the opposite regioselectivity is... 

Reductive cleavage of epoxides,1 Epoxides are usually reduced by hydride reagents, particularly LiAlH4, by attack at the less-substituted carbon to provide the more-substituted alcohol. However, reductions with Zn(BH4)2 adsorbed on Si02 in THF at 25° can show the opposite regioselectivity. Thus the epoxide of a 1-alkene is... 

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