Allylic derivatives stereoselectivity

Some applications of the thio-Claisen rearrangement to the syntheses of thiocarbonyl compounds, particularly unsaturated dithiocstcrs and thionesters, and of its stereocontrol aspects are reviewed in [120]. A particularly high stereoselectivity was observed with S-allyl derivatives of P-hydroxydithioesters syn products were obtained exclusively, according to the accompanying scheme [495,496]. 

Stereoselective Diels-Alder reactions have been reported in several cases. Enantioselective Diels-Alder reactions of l-phenoxycarbonyl-l,2-dihydropyridine with 1-alkylated acryloyl-pyrazolidin-3-ones using a chiral cationic palla-dium-phophinooxazolidine catalyst afforded chiral isoquinuclidines with excellent enantioselectivity <2005TL5677>. Bismuth(lll) chloride-mediated diasteroselective intramolecular [4-f2] cycloaddition reactions of A-allyl derivatives of pyrazole aldehydes led to fused sulfur-containing pyrazole heterocycles <2003SC3063>. A highly diastereoselective intramolecular hetero-Diels-Alder approach toward tetracyclic pyrazoles from 5-(3-methyl-2-butenylthio)-3-methyl-l-phenyl-4-pyrazolecarboxaldehyde has been reported <1997SL1155>. 

It is well known that silylation of allyl derivatives with vinylsilane catalyzed by a ruthenium hydride complex is accompanied by isomerization ofpropen-l-yl to propen-2-yl derivatives as well as homo-coupling of vinylsilane when equimolar amounts of the initial substances are used. If catalyst I was used in the SC of allyl amide and allyl amine with vinylsilanes, a S-fold excess of olefin to vinylsilane was used to stop homocoupling of vinylsilane, but simultaneously no more than 5% of isomerization of allyl compound was observed [19, 26]. When allyl boronate is used instead of allylamine under mild conditions (20 - 40 °C), the two reactions catalyzed by I and IV yield stereoselectively -product (see Scheme 4) [26]. 

Ti complexes have been extensively used for the stereoselective introduction of side chains in steroidal molecules, e.g. pregnenolone acetate and the steroidal C-22 aldehyde (73 equation 29). In these cases satisfactory results are only obtained by using Ti reagents, like methyl, ds-methyl and allyl derivatives, due to the strong steric hindrance that affects the position to be attacked. 1,3-Anti dia-stereoselecdon in the addition of alkyltitanium reagents to chirally -substituted aldehydes having a dithioacetal group at the a-position (75) was also observed (equation 30). ... 

Savage, I., Thomas, E. J., Wilson, P. D. Stereoselective synthesis of allylic amines by rearrangement of allylic trifluoroacetimidates stereoselective synthesis of polyoxamic acid and derivatives of other a-amino acids. J. Chem. Soc., Perkin Trans. 11999, 3291-3303. 

Allyl derivatives 11 with identical substituents at Cl and C3 are an important class of substrates for enantioselective allylic substitution (Scheme 10). Starting from either enantiomer (11 or ent-ll) the same allyl-palladium complex 12 is formed. Therefore, the first part of the catalytic cycle leading to this intermediate usually is irrelevant for the stereoselectivity of the overall reaction [31]. The two termini of the free allyl system are enantiotopic. If the catalyst is chiral, they become diasterotopic in the allyl-metal complex and, therefore, may exhibit different reactivities toward nucleophiles. Under the influence of a suitable chiral ligand attached to palladium, nucleophilic attack can be rendered regioselective leading preferentially either to product 13 or its enantiomer ent-l3. 

The regio- and stereoselectivity of many catalytic reactions that involve nucleophilic attack on T-allyl palladium intermediates are determined by the structure and conformation of these complexes in the reaction medium. For this reason, much effort has been devoted to the determination of the structures of 77 -allylic palladium complexes not only in the solid state but also in solution. X-ray, theoretical, and NMR tools have been developed and used together, so it is now possible to completely characterize a palladium 7 -allylic derivative and explain the factors that control the stability of the preferred structure. ... 

A new efficient and stereoselective synthesis of furo[2, 3 5,6]pyrano[4,3-i)]quinoline derivatives and has been achieved by intramolecular hetero Diels-Alder reactions of aldimines generated in situ from aromatic amines and the O-allyl derivative of the chiral sugar derived aldehyde in acetonitrile in the presence of a catalytic amount (10 mol%) of BiCl3. The products are formed with extremely high (>95%) trans-selectivity in good to excellent yields (Equation 20) [38a]. The authors have also carried out the diastereoselective synthesis of new hexahydropyrazolo[4, 3 5,6]thiopyrano[4,3-t>] in the similar conditions [38b]. 

Addition of NBS and pivalic add to the r,2 -unsaturated nucleoside derivative gave the product 31 stereoselectively treatment of 31 with allyl trimethylsilane and tin(IV) chlcHide led to the I -C-allyl derivative 32, and a number of other carbon nucleophiles were similarly introduced. " ... 

Hydrosilylation of I-vinyl-1-cyclohexene (77) proceeds stereoselectively to give the (Z)-l-ethylidene-2-silylcyclohexane 78, which is converted into (Z)-2-ethylidenecyclohe.xanol (79)[74]. Hydrosilylation of cyclopentadiene affords the 3-silylated 1-cyclopentene 80. which is an allylic silane and used for further transformations[75.75a]. Cyclization of the 1,3,8, lO-undecatetraene system in the di(2.4-pentadienyl)malonate 69 via hydrosilylation gives the cyclopentane derivative 81. which corresponds to 2.6-octadienylsilanc[l8,76]. 

Halogen atoms can be stereoselectively introduced by ring-opening of y-azir-idinyl-a,P-enoates (Scheme 2.39). Treatment of 149 with diethylaminosulfur tri-fluoride (DAST) results in stereospecific ring-opening to yield fluorinated derivative 150 [59]. A related stereoselective conversion of y-aziridinyl-a,P-enoates 151 into allyl halides 152 by use of lithium halide in the presence of Amberlyst 15 was also reported recently [60]. 

Allyl anion synthons A and C, bearing one or two electronegative hetero-substituents in the y-position are widely used for the combination of the homoenolate (or / -enolate) moiety B or D with carbonyl compounds by means of allylmetal reagents 1 or 4, since hydrolysis of the addition products 2 or 5 leads to 4-hydroxy-substituted aldehydes or ketones 3, or carboxylic acids, respectively. At present, 1-hetero-substituted allylmetal reagents of type 1, rather than 4, offer the widest opportunity for the variation of the substitution pattern and for the control of the different levels of stereoselectivity. The resulting aldehydes of type 3 (R1 = H) are easily oxidized to form carboxylic acids 6 (or their derivatives). 

Finally, 2-allyl-4,5-tra ,s-diphenyl-l,3-bis(4-methylphenylsulfonyl)-l,3,2-diazaborolidincs have been used74. The 2-propenyl derivative undergoes highly stereoselective reactions with achiral aldehydes (95 - 97% ee) the ( )-2-butenyl derivatives (91-95% ee) and the analogous 2-chloro- and 2-bromo-2-propenyl derivatives (84-99% ee) also give excellent results in reactions with achiral aldehydes. 

Similar stereoselectivities are achieved in the allylation of enantiomerically pure proline-derived a-oxoamides47. l-Bromo-3-methy]-2-butcne reacts with clean allylic inversion. Since pinacol-type coupling products are also produced under the reaction conditions, this was taken as evidence for a radical addition mechanism47. 

The data presented demonstrate that allylic sulfoxides can provide an easy and highly stereoselective route to allylic alcohols taking advantage of the facility of the allylic sulfoxide-sulfenate [2,3]-sigmatropic rearrangement. This is of considerable synthetic utility, since a number of stereoselective and useful transformations of allylic alcohols and their derivatives have become available in recent years107-109. 

Fused cyclic ethers can be derived from appropriately substituted sugars. An example is given with the stereoselective 5-exo radical cyclization of allylic... 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

Potential precursors to stereoselective INOC and ISOC reactions (e.g., 195 and 196, respectively) have been prepared via stereoselective conjugate additions of several allylic alcohols (e.g., 194,X = 0) and an allylic thiol (e.g., 194,X = S) to a chiral (E)-nitro alkene (e. g., 193) that was derived from (P)-2,3-isopropylidene... 

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