Simple asymmetric induction

Enantioselective aldol condensations Chiral enolates. "Simple asymmetric induction"... 

The 1-amino-l,3-diene 1, which is readily prepared using literature procedures, undergoes regio- and stereoselective hetero-Diels- Alder cycloaddition with acylnitroso derivatives to give the 3,6-dihydro-2/f-2,3-oxazines 2. The yields are generally good and diastereomeric ratios vary as a function of both the dienophile s substituent and the temperature. The simple asymmetric induction is moderate112. 

Asymmetric hydrosiiyiation of a-ketoacylamino esters catalyzed by DIOP-Rh complexes and RhCl(PPh3)3 followed by methanolysis gave a-hydroxyacylamino esters which are depsipeptide building blocks . Asymmetric induction by the chiral catalysts predominates over that by the chiral center in the substrate. A relatively large simple asymmetric induction was observed on using achiral catalyst, RhCl(PPh3)3. 

The big difference between the extent of asymmetric induction on the addition to a prostereogenic carbonyl group of simple carbanions a to a chiral sulfoxide on the one hand and enolates of sulfinyl esters on the other, can be attributed to the capacity of the ester function to chelate magnesium in the transition states and intermediates. The results already described for the addition of chiral thioacetal monosulfoxide to aldehydes (see Section 1.3.6.5.) underscore the importance of other functions, e.g., sulfide, for the extent of asymmetric induction. 

I.5.2.2.3.2.3. Asymmetric Induction from the Stereocenter at Sulfur Combined with Simple... 

In this chapter the addition of carbon nucleophiles to simple a,j8-unsaturated sulfoxides, a-sulfinyl-a,/ -unsaturated ketones and a-sulfmyl-a,/ -unsaturated lactones will be discussed separately, in most cases the asymmetric induction arises from the chirality at sulfur. 

Much higher asymmetric induction was observed in the two-phase oxidation of simple alkyl aryl and diaryl sulphides296, substituted alkyl aryl sulphides297 and dithioacetals of formaldehyde298 by sodium metaperiodate in the presence of proteins such as bovine serum y-globulin and egg albumin. Optical purities of the sulphoxides so formed ranged between 20 and 85%. 

A heterobimetallic BINOL-Ga/Li complex 53 has been developed for the enantioselective ARO of meso-cpoxides (BINOL = l,T-bi(2-naphthol)).278 Using />-methoxyphenol as the nucleophile, this etherification reaction was observed to take place with a high level of asymmetric induction. An improved catalyst 54 has also been reported that exhibits greater stability under the reaction conditions and delivers higher yields and ee s (Equation (78)).279 A simple catalyst derived from Sc(OTf)3 and the chiral bipyridine ligand 52 has been shown to be effective for the ARO of aryl-substituted /// -epoxides with aliphatic alcohols to give high ee s (Equation (79)).280... 

When quinine (or any of its diastereomers) is used as a catalyst in reactions involving relatively simple substrates such as (i) thiophenol and 5,5-dimethylcyclohexenone (19) (eq. [1]), (ii) ketene and chloral (eq. [2]) (21), (iii) o-nitrobenzaldehyde and di-fert-butyl phosphite (22,23) (eq. [3]) or (iv) ben-zaldehyde and hydrogen cyanide (16) (eq. [4]), the determining factor in establishing a reasonable mechanism to explain the high degree of asymmetric induction... 

The asymmetric induction by catalyst 379 was extensively studied in the cycloadditions of simple dienes with substituted a,/)-unsaturated aldehydes. It proved that a-substitution on the dienophile increased the enantioselectivity, whereas -substitution dramatically decreased it. In the case of substrates having both a- and -substituents, high enantiose-lectivities were observed240. 

According to this correlation model, in which the principles of steric control of asymmetric induction at carbon (40) are applied, the stereoselectivity of oxidation should depend on the balance between one transition state [Scheme 1(a)] and a more hindered transition state [Scheme 1(6)] in which the groups and R at sulfur face the moderately and least hindered regions of the peroxy acid, respectively. Based on this model and on the known absolute configuration of (+)-percamphoric acid and (+)-l-phenylperpropionic acid, the correct chirality at sulfur (+)-/ and (-)-5 was predicted for alkyl aryl sulfoxides, provided asymmetric oxidation is performed in chloroform or carbon tetrachloride solution. Although the correlation model for asymmetric oxidation of sulfides to sulfoxides is oversimplified and has been questioned by Mislow (41), it may be used in a tentative way for predicting the chirality at sulfur in simple sulfoxides. 

Discussing the stereochemical outcome of the Claisen rearrangements, two aspects had to be considered. On the one hand, the relative configuration of the new stereogenic centers was found to be exclusively syn in 201 and 202, pointing out the passing of a chair-like transition state c-a and c-jS, respectively, including a Z-acylammonium enolate structure (complete simple diastereo-selectivity/internal asymmetric induction). 

Subsequently, List reported that although the method described above was not applicable to the reduction of a,P-unsaturated ketones, use of a chiral amine in conjunction with a chiral anion provided an efficient and effective procedure for the reduction of these challenging substrates [210]. Transfer hydrogenation of a series of cyclic and acyclic a,P-unsaturated ketones with Hantzsch ester 119 could be achieved in the presence of 5 mol% of valine tert-butyl ester phosphonate salt 155 with outstanding levels of enantiomeric control (Scheme 64). A simple mechanistic model explains the sense of asymmetric induction within these transformations aUowing for reliable prediction of the reaction outcome. It should also be noted that matched chirality in the anion and amine is necessary to achieve high levels of asymmetric induction. 

In the above asymmetric aldol reaction, the introduction and the removal of the chiral auxiliary are carried out by simple procedures, and high asymmetric induction is achieved even at ice—bath temperature. However, at least a stoichiometric amount of a chiral auxiliary is required in such a stereo-differentiating reaction (chiral auxiliary is attached to the reactant.). 

A simple method for asymmetric synthesis of 2//-azirine-2-phophonates 540 was described, using various alkaloids as bases (equation 241). Moderate to good asymmetric induction was observed (69-94% yield, 33-72% ee) when quinidine was used as the base (the S isomer was obtained). A solid-phase asymmetric synthesis was also performed (541 and 542 used as bases) and good yields were usually obtained (43-88%) but only low enantioselectivity was achieved (3-11%). 

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