Chiral alkenes bearing

The diastereoselectivity in the ene reaction of O2 with chiral alkenes bearing a stereogenic centre at the a-position with respect to the double bond has been extensively studied. Chiral alkenes which bear a substituent on the asymmetric carbon atom other than the hydroxy or amine functionality afford predominately erythro allylic hydroperoxides. The erythro selectivity was attributed to steric and electronic repulsions between... 

A variety of precursors of biologically relevant products have also been prepared by addition of nitrile oxides to chiral alkenes bearing a nitrogen substituted allylic stereocen-ter 37, i4°. rai. i46, iso. isi.155 obeyed diastereoselection is generally rather low and... 

Efficient acetalization of alkenes bearing various EWG with an optically active 1.3-diol 72 proceeds smoothly utilizing PdCN, CuCI. and O2 in DME to give the 1,3-dioxane 73[113], Methacrylamide bearing 4-t-butyloxazolidin-2-one 74 as a chiral auxiliary reacts with MeOH in the presence of PdCE catalyst... 

Asymmetric 1,3-dipolar cycloaddition of cyclic nitrones to crotonic acid derivatives bearing chiral auxiliaries in the presence of zinc iodide gives bicyclic isoxazolidines with high stereoselectivity (Eq. 8.51). The products are good precursors of (3-amino acids such as (+)sedridine.73 Many papers concerning 1,3-dipolar cycloaddition of nitrones to chiral alkenes have been reported, and they are well documented (see Ref. 63). 

Diastereoface-differentiating reactions of a carbenoid with an alkene bearing an easily removable, chiral substituent have been used only ocassionally for the enantioselective production of a cyclopropane 216). A recent example is given by the cyclopropanation of the (—)-ephedrine-derived olefin 223 with CH2N2/Pd(OAc)2 after removal of the protecting group, (1/ , 2R )-2-phenylcyclopropane carbaldehyde was isolated with at least 90% e.e. 37). 

Although there are many reports on the enantioselective catalytic double bond isomerization of functionalized achiral alkenes, that of alkenes bearing an isolated double bond have had limited success. The use of a chiral bis(indenyl)titanium catalyst 5 containing a chiral bridging group realized the highly enantioselective isomerizations of unfunctionalized achiral alkenes with up to 80% ee (Equation (27)).90... 

The Lewis acid catalyst 53 is now referred to as the Narasaka catalyst. This catalyst can be generated in situ from the reaction of dichlorodiisopropoxy-titanium and a diol chiral ligand derived from tartaric acid. This compound can also catalyze [2+2] cycloaddition reactions with high enantioselectivity. For example, as depicted in Scheme 5-20, in the reaction of alkenes bearing al-kylthio groups (ketene dithioacetals, alkenyl sulfides, and alkynyl sulfides) with electron-deficient olefins, the corresponding cyclobutane or methylenecyclobu-tene derivatives can be obtained in high enantiomeric excess.18... 

For the photooxygenation of chiral alkenes in solution bearing a stereogenic centre at the or more remote position with respect to the double bond, low or negligible diastereoselection is expected. The photooxygenation of 2-methyl-5-phenyl-2-hexene 156, a chiral alkene that bears a stereogenic centre at the /3-position with respect to the double bond, gave in solution low diastereoselectivity ca 10% By Na-Y... 

The 1,3-dipolar cycloadditions of 1,3-dipoles with chiral alkenes has been extensively reviewed and thus only selected examples will be highlighted here. We have chosen to divide this section on the basis of the different types of alkenes rather than on the basis of the type of 1,3-dipole. For 1,3-dipolar cycloadditions, as well as for other reactions, it is important that the chiral center intended to control the stereoselectivity of the reaction is located as close as possible to the functional group of the molecule at which the reaction takes place. Hence, alkenes bearing the chiral center vicinal to the double bond are most frequently apphed in asymmetric 1,3-dipolar cycloadditions. Examples of the application of alkenes with the chiral center localized two or more bonds apart from the alkene will also be mentioned. Application of chiral auxiliaries for alkenes is very common and will be described separately in Section 12.3. 

Many intermediate dialkylboranes derived from hydroboration with IpcBH2 can be recrystallized to enantiomeric purities approaching 100%, thus giving alcohols of 98-99% ee upon oxidation. If, instead of being oxidized in situ, the dialkylbo-rane intermediate is treated with Acetaldehyde, a-pinene is displaced for recovery and a chiral boronate bearing the R group of the alkene is obtained (eq 7). 

The 1,3-dipolar cycloaddition reaction [57] between alkene and nitrone [58] is an effective procedure for generating new chiral centers attached to heteroatoms. J0r-gensen et al. [59a] found that remarkably high endo selectivity was induced in the 1,3-dipolar reaction by use of a phenanthroline-coordinated Mg(II) catalyst prepared in the presence of I2 as a co-catalyst (Sch. 32). By reaction of 74, an alkene bearing a chiral oxazolidinone, with benzylidenephenylamine A -oxide 73 in the presence of the Mg(II)-phenanthroline catalyst (10 mol %), one of the four possible diastereomers of the isoxazolines 75 was formed exclusively in an almost quantitative yield. 

Asymmetric methylalumination of alkenes bears fruit because chiral zirconium 136 was discovered to be an effective catalyst (Scheme 6.120) [152]. In initial attempts, the reaction proceeded in higli yield but with moderate to high ee (65-85%). More promising results were obtained by re-examining conditions that involved a proper choice of solvent CH3CHCI2. 

Reactions with Alkenes Bearing Chiral Residues... 

The Simmons-Smith reaction takes place via an intermediate organozinc species, which can be generated in the presence of chiral ligands for zinc. Alternatively, standard (achiral) zinc reagents can be used to cyclopropanate an alkene bearing a chiral residue. The reactions of allylic alcohols are rapid, and the forma-... 

Better diastereoselectivities were achieved with dipolarophiles such as unsaturated esters that bear a chiral auxiliary297-298. For instance, cycloaddition of the EVE-azomethine ylide, generated from the following imine by metalation, with the chiral alkene (27 )-2-(2-methoxycar-bonylethenyl)-3-phenyl-l,3-diazabicyclo[3.3.0]octane affords the pyrrolidine derivative as a single regio- and stereoisomer297. 

As one of the fundamental bond constructions, the carbonyl-ene reaction - between an aldehyde and an alkene bearing an allylic hydrogen - attracts considerable attention [1] from the synthetic community. Given the versatile chemistry of the product homoallylic alcohols, both the intra- and intermolecular versions of asymmetric carbonyl-ene reactions are valuable processes. [2] Within the catalytic field, [3] the continuing development of chiral Lewis acids further advances the utility and scope of carbonyl-ene chemistry. We wish to highlight a number of these developments. 

The dihydroxylation reaction is very general, giving high yields of diol products from electron-rich or electron-poor alkenes. High levels of stereocontrol can often be obtained on dihydroxylation of alkenes bearing one or more chiral centre. The large steric requirements of the reagent normally dictates that dihydroxylation with osmium tetroxide takes place predominantly from the less-hindered side of the double bond. 

By stereoselective additions of carbenes or carbene equivalents to alkenes optically pure cyclopropanes are obtained. " In concerted [2+1] cycloadditions the stereochemistry of the alkene is conserved in the products. (Z)-configurated alkenes lead stereospecifically to cis-cyclopropanes. So far, compared to [2+1] cycloadditions involving alkenes bearing the chiral auxiliary, asymmetric reactions involving chiral carbene precursors proved to be less efficient. 

Asymmetric ylide cyclopropanations have been studied since 1960 and have been intensively discussed and documented in the literature. Besides chiral aminosulfoxonium ylides, chiral sulfonium as well as chiral sulfoxonium ylides have been examined in reagent-controlled asymmetric cyclopropanations. However, asymmetric ylide cyclopropanations with alkenes bearing the chiral inductor proved to be more efficient. 

Reactions of ketenes, e.g. dihaloketenes, with electron-rich alkenes bearing the chiral auxiliary, for example enolethers, carbohydrate-derived anomeric enolethers or ketene acetals, lead to cyclobutanones with moderate stereoselectivities. 

Chiral Auxiliary-hased Epoxidation of Substituted Alkenes. High diastereoselectivities were found for the m-CPBA or dimethyldioxirane epoxidation of chiral oxazolidine-substituted alkenes bearing a strongly basic urea group (eq 29). However, in most cases, the diastereoselectivities were superior with dimethyldioxirane. 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

Jacobsen and Watson reported a nickel-catalysed intramolecular addition of arylnitriles across an alkeneic double bond (arylcyanation), giving access to chiral indanes bearing a quaternary stereocentre (78, Scheme 8.30). 

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