Alkenes chiral, diastereoselective addition

It has already been mentioned (Section III) that the study of the diastereoselection in the electrophilic addition of singlet oxygen to the n face of chiral alkenes is of primary interest for the achievement of a selective oxyfunctionalization reaction. Zeolite confinement and cation- 7r interactions might be expected to affect significantly the diastereoselectivity in the photooxygenation of chiral alkenes. 

The stereochemical result is no longer characterized solely by the fact that the newly formed stereocenters have a uniform configuration relative to each other. This was the only type of stereocontrol possible in the reference reaction 9-BBN + 1-methylcyclohexene (Figure 3.25). In the hydroborations of the cited chiral alkenes with 9-BBN, an additional question arises. What is the relationship between the new stereocenters and the stereocenter(s) already present in the alkene When a uniform relationship between the old and the new stereocenters arises, a type of diastereoselectivity not mentioned previously is present. It is called induced or relative diastereoselectivity. It is based on the fact that the substituents on the stereocenter(s) of the chiral alkene hinder one face of the chiral alkene more than the other. This is an example of what is called substrate control of stereoselectivity. Accordingly, in the hydroborations/oxidations of Figures 3.26 and 3.27, 9-BBN does not add to the top and the bottom sides of the alkenes with the same reaction rate. The transition states of the two modes of addition are not equivalent with respect to energy. The reason for this inequality is that the associated transition states are diastereotopic. They thus have different energies—just diastereomers. 

The conclusion drawn from Section 3.4.1 for the hydroborations to be discussed here is this an addition reaction of an enantiomerically pure chiral reagent to a C=X double bond with enantiotopic faces can take place via two transition states that are diastereotopic and thus generally different from one another in energy. In agreement with this statement, there are diastereoselective additions of enantiomerically pure mono- or dialkylboranes to C=C double bonds that possess enantiotopic faces. Consequently, when one subsequently oxidizes all C— B bonds to C—OH bonds, one has realized an enantioselective hydration of the respective alkene. 

If, as in the reaction example in Figure 3.32, during the addition to enantiomerically pure chiral alkenes, substrate and reagent control of diastereoselectivity act in opposite directions, we have a so-called mismatched pair. For obvious reasons it reacts with relatively little diastereoselectivity and also relatively slowly. Side reactions and, as a consequence, reduced yields are not unusual in this type of reaction. However, there are cases in which mismatched paris still give rise to highly diastereoselective reactions, just not as high as the matched pair. 

Conversely, the addition of enantiomerically pure chiral dialkylboranes to enantiomerically pure chiral alkenes can also take place in such a way that substrate control and reagent control of diastereoselectivity act in the same direction. Then we have a matched pair. It reacts faster than the corresponding mismatched pair and with especially high diastereoselectivity. This approach to stereoselective synthesis is also referred to as double stereodifferentiation. 

There have been many studies on the use of chiral electrophilic selenium reagents for stereoselective additions to alkenes <1998JA3376, B-1999MI35, 1999T1, 2000AGE3740> with notable diastereoselectivity in some cases. 

With suitable substrates, addition of two OH groups creates one new stereo-genic center from a terminal alkene and two new stereogenic centers from internal alkenes. Addition to alkenes of the form RCH=CH2 has been made enantioselective, and addition to RCH=CHR both diastereoselective and enan-tioselective, by using chiral additives or chiral catalysts, such as 173, 174 (derivatives of the... 

Enantioselective and diastereoselective addition have also been achieved by using preformed derivatives of OSO4, already containing chiral ligands, and by the use of OSO4 on alkenes that have a chiral group elsewhere in the... 

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... 

Irradiation of 1,3-dioxolanes in the presence of a sensitizer such as benzophenone (PhjCO), leads to the abstraction of an acetal hydrogen atom (by the triplet state ketone) to generate 1,3-dioxolanyl radicals, together with the resonance-stabilized diphenyl ketyl radical (Scheme 16). These nucleophilic 1,3-diox-olanyl radicals have been shown to add to a variety of alkenes to form adduct radicals, which can then accept a hydrogen atom from the diphenyl ketyl radical to give the desired alkylated product. The diastereoselective addition of 1,3-dioxolanyl radicals to alkenes bearing chiral auxiliaries has also recently been reported, while the photochemical alkylation of diketene with 2-undecyl-l,3-dioxolane has been utilized as a key step in the synthesis of (-)-tetrahydrolipstatin (Scheme 17). ... 

Das, S., Kumar, J.S.D., Shivaramayya, K., and George, M.V., Formation of lactams via photoelectron-transfer catalyzed reactions of N-aUylamines with a,P-unsaturated esters. Tetrahedron, 52,3425,1996. (a) Bertrand, S., Glapski, C, Hoffmann, N., and Pete, J-P., Highly efficient photochemical addition of tertiary amines to electron deficient alkenes. Diastereoselective addition to (5R)-5-menthyloxy-2(5ff]-furanone. Tetrahedron Lett., 40, 3169, 1999 (b) Bertrand, S., Hoflfrnann, N., and Pete, J-P., Stereoselective radical addition of tertiary amines to (5R)-5-menthyloxy-2[5H]-furanone application to the enantioselective synthesis of (-)-isoretronecanol and (-l-)-labumine. Tetrahedron Lett., 40,3173,1999 (c) Farrant, E. and Mann, J., Novel synthesis of the indoUzidine alkaloid skeleton with appropriate functionality and stereochemistry for use as a chiral scaffold, /. Chem. Soc., Perkin Trans. 1,1083,1997. 

Dipolar addition is closely related to the Diels-Alder reaction, but allows the formation of five-membered adducts, including cyclopentane derivatives. Like Diels-Alder reactions, 1,3-dipolar cycloaddition involves [4+2] concerted reaction of a 1,3-dipolar species (the An component and a dipolar In component). Very often, condensation of chiral acrylates with nitrile oxides or nitrones gives only modest diastereoselectivity.82 1,3-Dipolar cycloaddition between nitrones and alkenes is most useful and convenient for the preparation of iso-xazolidine derivatives, which can then be readily converted to 1,3-amino alcohol equivalents under mild conditions.83 The low selectivity of the 1,3-dipolar reaction can be overcome to some extent by introducing a chiral auxiliary to the substrate. As shown in Scheme 5-51, the reaction of 169 with acryloyl chloride connects the chiral sultam to the acrylic acid substrate, and subsequent cycloaddition yields product 170 with a diastereoselectivity of 90 10.84... 

Compound 388 is an acylating agent for electron-deficient alkenes, in a Michael addition process. It is formed by treating molybdenum hexacarbonyl with an organolithium compound, followed by quenching the intermediate 387 with boron trifluoride (equation 104). The structure of 388 (R = Ph) can be elucidated by NMR spectroscopy. Other examples of enantioselective and diastereoselective Michael-type additions involving lithium-containing intermediates in the presence of chiral additives can be found elsewhere in the literature . 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

The stereochemistry of 1,3-dipolar cycloadditions of azomethine ylides with alkenes is more complex. In this reaction, up to four new chiral centers can be formed and up to eight different diastereomers may be obtained (Scheme 12.4). There are three different types of diastereoselectivity to be considered, of which the two are connected. First, the relative geometry of the terminal substituents of the azomethine ylide determine whether the products have 2,5-cis or 2,5-trans conformation. Most frequently the azomethine ylide exists in one preferred configuration or it shifts between two different forms. The addition process can proceed in either an endo or an exo fashion, but the possible ( ,Z) interconversion of the azomethine ylide confuses these terms to some extent. The endo-isomers obtained from the ( , )-azomethine ylide are identical to the exo-isomers obtained from the (Z,Z)-isomer. Finally, the azomethine ylide can add to either face of the alkene, which is described as diastereofacial selectivity if one or both of the substrates are chiral or as enantioselectivity if the substrates are achiral. 

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