Face selectivity, investigation

Having established the chiral synthesis of levoglucosenone 1 and its functionalized analogues in both enantiomeric forms, we next investigated the exploitation of 26, the functionalized isolevoglucosenone, for the enantiocontrolled construction of natural products on the basis of its inherent convex-face selectivity and functionality, in particular, the alkoxymethyl handle for the acetal cleavage. 

While the stereochemical outcome of the reactions with chiral (Z)-vinyl sulfoxides can be simply explained in terms of a reactive conformation, the outcome of reactions with chiral (f.)-vinyl sulfoxides cannot be satisfactorily explained. The latter reactions generally proceed with poorer selectivity and with either opposite or the same 7t-face selectivity compared to their Z counterparts94 95. Investigations with chiral (E)- and (Z)-vinyl (/Ci-sulfoxides 23 and ben-zylamine show, besides a solvent effect, that both reaction types proceed with similar diastereoselectivities. The reaction products are formed irreversibly and the extent of interconversion between the ( )- and (Z)-vinyl sulfoxide isomers is small (l-2%)96. 

The Patemo-Btichi photocycloaddition reaction - of various carbonyl compounds to furans was initially investigated by Sakurai in 1963 and was found to afford only the head-to-head photoproducts with high exo relative face selectivity. An NMR study by Whipple and Evanega later confirmed the exo mode of cycloaddition. Since the time of the origin report the photoreaction has been systematically studied by several groups and the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system has been exploited in several facets of synthesis. 

Goodman, J. M., Kahn, S. D., Paterson, I. Theoretical studies of aldol stereoselectivity the development of a force field model for enol borinates and the investigation of chiral enolate -face selectivity. J. Org. Chem. 1990, 55, 3295-3303. 

A number of investigations have explored the reactions of ally lie stannanes containing a y-alkoxy substituent. A direct preparation of these substances utilizes the kinetic deprotonation of an allyl ether followed by alkylation with tri-n-butylstannyl chloride. In a typical experiment, the deprotonation of 101 with 5-butyllithium leads to internal coordination of lithium cation and provides formation of the Z-allylstannane 102. The behavior of y-alkoxyallylstannanes is similar to the corresponding Z-alkylstannanes, and as a result, the reaction provides a stereoselective route for the synthesis of complex diol derivatives. In the allylation of chiral aldehyde 80 with stannane 102, /l-chelation dictates face selectivity. The expected. yyn, anti-product 104 is obtained with high diastereoselection via the antiperi-planar 103, which accommodates the sterically demanding silyl (TBS) ether (Scheme 5.2.23).23... 

Scheme 12.22 Investigation of the origins of face selectivity the impact of right-handed helicity.

One stoichiometric method that avoids the use of an expensive chiral auxiliary and allows for the use of nonpyrophoric bases is based on diketopiperazine chemistry. The use of this system as a chiral auxiliary is associated with a method that was developed for the preparation of the sweetener aspartame. At the same time, we were looking at the alkylation reactions of amino acid derivatives and dipeptides. These studies showed that high degrees of asymmetric induction were not simple, were limited to expensive moieties as the chiral units, and required the use of large amounts of lithium [25,26]. The cyclic system of the diketopiperazine has been used successfully by other investigators [27,28], and we also chose to exploit the face selectivity of this unit. L-Aspartic acid was chosen as the auxiliary unit because it is readily available and cheap. All of the studies were performed with sodium as the counterion because it is a more cost-effective metal at scale. Finally, we concentrated in the use of aldehydes rather than alkyl halides to allow for a general approach and so as not to limit the reaction to reactive alkyl halides. 

The face selectivity in the Diels-Alder addition of the sulfoxide (310) to A -phenylmaleimide has been investigated <88JA4625>. A single cycloadduct (311) was formed in good yield (Equation (29)). This was proved to be the endo adduct resulting from addition anti to the sulfoxide oxygen. 

Several cyclodextrin ketones with a ketone attached to the secondary face of the cyclodextrin in the form of a 2,3-0-( 1,3-acetone) group (79), and some selected cyclodextrin ketones having the ketone at the primary face, were investigated for their catalysis of epoxidation of stilbenes and styrene by oxone in 1 1 acetonitrile/H20. It was found that secondary face ketones were better catalysts giving a cat uncat over 10, and more stereoselective giving up to 76% ee in (5)-styrene oxide. ... 

In cases where either addition or substitution proceeding via double bond migration is involved, one or more asymmetric carbon centers may be generated. Thus, face selective TT-complexation with chiral Pd complexes can, in principle, lead to asymmetric processes [15],[16] (Sect, V.3.1.1), although this possibility has not yet been extensively investigated. 

Asymmetric cyclopropanation was actively investigated in the last 10 years and an enormous number of reports were published. For example, proline-daived Rh2(5-DOSP)4 160 was used for asymmetric cyclopropanation. Asymmetric cyclopropanation of iV-Boc-pyrrole 161 and fitran 162 was carried out by Davies and coworkers (Scheme 1.76) [121]. Face selectivity was influenced by steric and electronic effects on the acceptor unit iV-Boc-pyrrole 161 underwent asymmetric double cyclopropanation to give chiral azatricycloheptane... 

Esters have also been investigated as chiral controlling groups on the diene partner. Trost documented the use of dienes such as 110, incorporating a mandelic acid ester as the chiral auxiliary (Equation 9) [66]. Excellent face selectivity was observed in the Diels-Alder reaction between 110 and ju-glone (109), giving the product 111 with high diastereoinduction (>97 3) and in 98 % yield. 

In a chiral aldehyde or a chiral ketone, the carbonyl faces are diastereotopic. Thus, the addition of an enolate leads to the formation of at least one stereogenic center. An effective transfer of chirality from the stereogenic center to the diastereoface is highly desirable. In most cases of diastereoface selection of this type, the chiral aldehyde or ketone was used in the racemic form, especially in early investigations. However, from the point of view of an HPC synthesis, it is indispensable to use enantiomerically pure carbonyl compounds. Therefore, this section emphasizes those aldol reactions which are performed with enantiomerically pure aldehydes. 

In the course of investigations on the synthesis of ( + )-biotin (7) the addition of isothiocyana-toacetate enolates 8 to 1,3-thiazolines 9 has been studied16 17. The diastereofacial selectivity of these reactions is controlled by attack of the enolate on the imine face opposite the 5-pentyl group and correctly establishes the relative stereochemistry at C-l and C-2 of biotin. 

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