Asymmetric induction, intramolecular

These and other examples of intramolecular asymmetric induction by the sulfinyl group have been discussed by Montanari in his review paper (9). 

It is interesting that anodic methoxylation and subsequent chemical alkylation of optically active V-protected a-amino acids with one more chiral center affords the final products in high optical purity, although the diastereomeric purity of the intermediate methoxylated products does not seem to be so high [405,406]. Intramolecular asymmetric induction may occur in the chemical alkylation step. 

Intramolecular asymmetric induction has also been used in electrochemistry as in the reduction of optically active alcohol esters or amides of a-keto [469,470] and unsaturated [471] acids and oximes [472] and in the oxidation of olefins [473]. A maximum asymmetric yield of 81% was obtained in the reduction of (5 )-4-isopropyl-2-oxazolidinone phenyl-glyoxylate [470]. Nonaka and coworkers [474,475] found that amino acid A-carboxy anhydrides were polymerized with various electrogenerated bases as catalyst to give the poly(amino acids) with high chirality in high yields. Conductive chiral poly(thiophenes) prepared by electropolymerization can be used for chiral anion recognition [476]. 

Electrochemical diasteroselective substitutions based on intramolecular asymmetric induction are highly useful for asymmetric synthesis. Recently, many studies focused on this subject have been done. 

The BINAP-Ru-catalyzed hydrogenation of the allylic alcohol 94 results in the diastereoselective formation of 95, an intermediate for 1/9-methylcarbapenems (96) possessing an improved stability toward dehydropeptidase (Scheme 28). The combined effects of tbe intermolecular asymmetric induction caused by the (/ )-Tol-BINAP-Ru catalyst (Tol-BINAP = p-tolyl analog of BINAP) and the intramolecular asymmetric induction originating from the pre-existing chiral moiety in the substrate 94 cooperate in the generation of the extremely high diastereos-electivity, /5 a = 99.9 0.1, to form the y8-methylated isomer 96 [87]. 

Diastereoselective hydrogenation with BINAP-Ru combines chirality transfer from the catalyst and intramolecular asymmetric induction, providing an efficient entry to statine analogues ... 

Bottom Intramolecular asymmetric induction in [2,3]-Wittig rearrangements. 

An effect of this type is obviously intermolccular, but it will be shown below that phenomena are also known which exemplify what may be considered as intramolecular asymmetric inductions. 

High levels of asymmetric induction have been achieved in the hydroboration of 1,3-, 1,4-, and 1,5-dienes with thexylborane (482,483,489,490). The first chiral center is formed by an intermolecular reaction. In the second step, the organoborane intermediate undergoes an intramolecular hydroboration, creating the second chiral center with high diastereoselectivity. 

This section describes Michael-analogous processes in which, mostly under electrophilic conditions, ally - or alkynylsilanes undergo addition to enones or dienones (Sakurai reactions). The intramolecular addition of allylsilanes is an extremely useful reaction especially for the construction of carbocyclic ring systems, which occurs in a diastereoselective manner, in many cases with complete asymmetric induction. 

The 1,6-intramolecular addition of unsymmetrical allylsilanes to conjugated dienones proceeded to give a trans relation between the angular substituents and the vinyl groups (complete 1,3-asymmetric induction). Ethylaluminum dichloride has been most successfully used in all reactions described35-53. 

Addition of such a-lithiosulfinyl carbanions to aldehydes could proceed with asymmetric induction at the newly formed carbinol functionality. One study of this process, including variation of solvent, reaction temperature, base used for deprotonation, structure of aldehyde, and various metal salts additives (e.g., MgBrj, AlMej, ZnClj, Cul), has shown only about 20-25% asymmetric induction (equation 22) . Another study, however, has been much more successful Solladie and Moine obtain the highly diastereocontrolled aldol-type condensation as shown in equation 23, in which dias-tereomer 24 is the only observed product, isolated in 75% yield This intermediate is then transformed stereospecifically via a sulfoxide-assisted intramolecular 8, 2 process into formylchromene 25, which is a valuable chiron precursor to enantiomerically pure a-Tocopherol (Vitamin E, 26). 

In contrast to the intramolecular carbenoid C-H insertion, the inter-molecular version has not been greatly developed and has been for a long time regarded as a rather inefficient and unselective process. In this context, Davies and Hansen have developed asymmetric intermolecular carbenoid C H insertions catalysed by rhodium(II) (5 )-A-(p-dodecylphenyl)sulfonylprolinate. " Therefore, these catalysts were found to induce asymmetric induction in the decomposition of aryldiazoacetates performed in the presence of cycloalkanes,... 

As described hitherto, diastereoselectivity is controlled by the stereogenic center present in the starting material (intramolecular chiral induction). If these chiral substrates are hydrogenated with a chiral catalyst, which exerts chiral induction intermolecularly, then the hydrogenation stereoselectivity will be controlled both by the substrate (substrate-controlled) and by the chiral catalyst (catalyst-controlled). On occasion, this will amplify the stereoselectivity, or suppress the selectivity, and is termed double stereo-differentiation or double asymmetric induction [68]. If the directions of substrate-control and catalyst-control are the same this is a matched pair, but if the directions of the two types of control are opposite then it is a mismatched pair. 

Intermolecular cycloadditions or Diels-Alder reactions have proved to be a successful route to several valuable intermediates for natural product syntheses. In creating new chiral centers, most of these reactions apply single asymmetric induction. As mentioned in Chapter 3, in the asymmetric synthesis of the octa-hydronaphthalene fragment, the Roush reaction is used twice. Subsequent intramolecular cyclization leads to the key intermediate, the aglycones, of several natural antitumor antibiotics. On the other hand, the Diels-Alder reaction of a dienophile-bearing chiral auxiliary can also be used intramolecularly to build... 

Overman s group [71,72] enlisted an intramolecular Heck reaction to form a quaternary center in their efforts toward ( )-gelsemine. When the cyclization precursor 70 was submitted to the ligandless conditions [Pd2(dba)3, Et3N] in the weakly coordinating solvent toluene, the quaternary center was formed as a 9 1 ratio of diastereomers (72 71 = 89 11). Addition of a silver salt in polar solvent THF completely reversed the sense of asymmetric induction in the cyclization reaction (72 71 = 3 97). 

Dauben et al. (15) applied the Aratani catalyst to intramolecular cyclopropanation reactions. Diazoketoesters were poor substrates for this catalyst, conferring little asymmetric induction to the product, Eq. 10. Better results were found using diazo ketones (34). The product cyclopropane was formed in selectivities as high as 77% ee (35a, n = 1). A reversal in the absolute sense of induction was noted upon cyclopropanation of the homologous substrate 34b (n = 2) using this catalyst, Eq. 11. Dauben notes that the reaction does not proceed at low temperature, as expected for a Cu(II) precatalyst, but that thermal activation of the catalyst results in lower selectivities (44% ee, 80°C, PhH, 35a, n = 1). Complex ent-11 may be activated at ambient temperature by reduction with 0.25 equiv (to catalyst) DIBAL-H, affording the optimized selectivities in this reaction. The active species in these reactions is presumably the aluminum alkoxide (33). Dauben cautions that this catalyst slowly decomposes under these conditions. 

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