Relative asymmetric induction

I.3.3.3.3.I.3. Relative Asymmetric Induction Reactions of Chiral Aldehydes with Achiral Allylboron Reagents... 

Effective 1,4-asymmetric induction has been observed in reactions between 2-(alkoxyethyl)-2-propenylsilanes and aldehydes. The relative configuration of the product depends on the Lewis acid used. Titanium(IV) chloride, in the presence of diethyl ether, gave 1,4-ijn-products with excellent stereoselectivity with boron trifluoride-diethyl ether complex, the amt-isomer was the major product, but the stereoselectivity was less83. 

The addition of the anion of the racemic 2-methyl-2-propenyl sulfoxides, rac-2-methyl-3-(phenyl-sulfinylpl-propene and /w-3-(rerr-butylsulfinyl)-2-methyl-l-propene to 2-cyclopentenone gives mixtures of (E)- and (Z )-y-l, 4-addition products which are a mixture of diastereomers at sulfur2. The (T )-products usually predominate, with the relative proportions of the (Z)-product increasing as the reaction temperature is increased. No asymmetric induction originating from the stereocenter at sulfur was observed when the sulfoxide substituent was phenyl however, there was a marginal improvement in the case of the (Zi)-product when the sulfoxide substituent was ferf-butyl. 

The addition of the anion of the 1,3-dimethyl-2-butenyl sulfoxides to 2-cyclopentenone was examined2. The anion of rar-2-methyl-4-(phenylsulfinyl)-2-pentene gave a 50 50 mixture of ( )- and (Z)-y-1,4-adducts which differed in the relative configuration of the new stereocenter regarding the stereocenter at sulfur. That is, for either the (Z)- or the ( )-product there is complete asymmetric induction from the stereocenter at sulfur, but in the opposite direction. When the rm-butyl analog, ruc-4-(/wt-butylsulfinyl)-2-methyl-2-pcntcne, was reacted, it gave exclusively the ( )-adduct, likewise as a single diastereomer. 

Reaction of p-nitrophenyl 2-(p-tolylsulfinyl)acetate 161 with aryl aldimines in the presence of imidazole was found to give /j-lactams 162 and amides 163206. In the cyclization, only the two 3,4-trans derivatives were formed out of a possible four diastereomeric pairs and, interestingly, the ratio of two diastereomeric pairs went up to 6.7 1. This means not only that internal asymmetric induction207 affords the trans derivative, but that also a relatively high asymmetric induction took place during the reaction. 

The asymmetric induction cannot be explained simply by steric interaction because the R group in the aldehyde is far too remote to interact with the tartrate ester. In addition, the alkyl group present in the tartrate ligand seems to have a relatively minor effect on the overall stereoselectivity. It has thus been proposed that stereoelectronic interaction may play an important role. A more likely explanation is that transition state A is favored over transition state B, in which an n n electronic repulsion involving the aldehyde oxygen atom and the /Mace ester group causes destabilization (Fig. 3-6). This description can help explain the stereo-outcome of this type of allylation reaction. 

Also, in 1890 Fischer had proven that the reduction of fructose with sodium amalgam yields a mixture of mannitol and sorbitol and pointed out that this conformed with the van t HofF-Le Bel theory (19). It seems, therefore, that the idea of asymmetric induction was clearly in a state of incubation prior to his publication of the relative configurations of the sugars in 1891. 

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... 

Rl = large, Rg = small substituent). From the data summarized in Table 39, it is apparent that the asymmetric induction observed is excellent for aldehydes, and that stereoselection generally increases as the aldehyde ligand becomes more sterically demanding. The major aldol adduct, 166, has been rationaUzed as evolving from transition state A. A priori it is difficult to evaluate the relative... 

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). 

If stoichiometric quantities of the chiral auxiliary are used (i.e., if the chiral auxiliary is covalently bonded to the molecule bearing the prochiral centres) there are in principle three possible ways of achieving stereoselection in an aldol adduct i) condensation of a chiral aldehyde with an achiral enolate ii) condensation of an achiral aldehyde with a chiral enolate, and iii) condensation of two chiral components. Whereas Evans [14] adopted the second solution, Masamune studied the "double asymmetric induction" approach [22aj. In this context, the relevant work of Heathcock on "relative stereoselective induction" and the "Cram s rule problem" must be also considered [23]. The use of catalytic amounts of an external chiral auxiliary in order to create a local chiral environment, will not be considered here. 

The above observations are quite pertinent here since they introduce us to "relative stereoselective induction" (or "double stereodifferentiation") studied by Heathcock [23]- and to "double asymmetric induction" [29] developed by Masamune [22]. 

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