Alkenes electrophilic addition, diastereoselectivity

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. 

To achieve diastereoselectivity in electrophilic additions to a double bond in acyclic compounds, there must be a facial preference for attack. An A strain provides such an element for conformational control, as exemplified by hydroboration of the alkene shown below.The hydration of a double bond via hydroboration involves (1) anti-Markovnikov addition of the B-H bond, (2) cis addition of the B-H bond, (3) addition of the B-H bond from the less hindered side of the double bond, and (4) oxidation with retention of configuration. 

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 addition of zinc enolates to alkenes in the intramolecular version finds several examples in recent literature. Thus, hydrazone 155, subjected to the same treatment reported for 151 (equation 80), undergoes diastereoselective 5-exo-trig (n = 1) or 6-exo-trig (n = 2) carbocyclization to yield -156, which on reaction with the electrophile E+ gives 157 (equation 81)174. 

In contrast to classical Meerwein arylations, non-activated alkenes are well suited for this reaction type for two reasons. First, due to the relatively slow formation of azo compounds by addition of aryl radical 49 to 48, this undesired pathway cannot compete successfully with the attack of 49 on the alkene to give radical adduct 50. Second, a nucleophilic alkyl radical 50 arises from the addition step, which is effectively trapped by electrophilic salt 48 to give azo compound 51. As a result of several improvements, the methodology is now applicable for a wide range of polar to non-polar alkenes with almost no restrictions on the substitution pattern of the diazonium salt [101, 102]. Moderate diastereoselectivities have been obtained in first attempts with chiral auxiliaries [103]. The azo compounds accessible, such as 51, can be converted to carboamination products 52 by hydrogenation and to various other heterocycles. 

We now turn to the stereochemistry governed by a ring system, and we shall look at both nucleophilic and electrophilic attack, since usually they have similar stereochemical preferences rather than contrasting preferences. In addition to several reactions that are straightforwardly electrophilic attack, we shall see several which can be described as electrophilic in nature, like the reactions of alkenes with osmium tetroxide, with peracids, with some 1,3-dipoles, and with boranes, and of dienes with dienophiles in Diels-Alder reactions. Some of these reactions are pericyclic, the pericyclic nature of which we shall meet in Chapter 6. For now, it is only their diastereoselectivity that will concern us. 

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. 

Diazoalkanes undergo smooth 1,3-dipolar cycloaddition. For additions to simple alkenes, this is presumably an electrophilic process. In the example illustrated, the overall process of electrocyclization of (142) followed by hydride shift proceeds with remarkable diastereoselectivity (equation 57). ... 

Electrophilic aldehydes have been also generated through a rhodium catalyzed hydroformylation process of alkenes, which has been combined with the aldol addition catalyzed by prohne (1,30 mol%) in a tandem reaction sequence, providing the aldol products 4 in good yields (59-86%) and enantioselectivities (71-83%), but with low diastereoselectivities [20]. 

As for the base-promoted thioetheriiication, Shen and Wang reported in 2005 that highly electrophilic alkenes such as fluorinated vinylstannanes 172 could be converted to fluorinated vinyl sulfides 173 with ( )-selectivity via a nucleophilic addition of thiols to alkenes and defluorination 174 followed by destannylation (Scheme 46.22). In 2008, Cordova developed an organocatalytic enantioselec-tive aminosulfenylation of a,(3-unsaturated aldehydes 175 using A -(benzylthio)succinimides 176 in the presence of a TMS-protected chiral diarylprolinol. ° The reaction proceeded with low diastereoselectivities but with excellent enantioselectivities. The reason for the low diastereoselec-tivity might lie in the rapid epimerzation of Ca-H bond under the enamine catalysis 178. 

Michaud et al. (1997) reported that nitromethane reacts via a diastereoselective double Michael addition with electrophilic alkenes in the presence of piperidine under solvent-free condition and focused microwave irradiation. It afforded functionalized cyclohexenes and there was no formation of cyclopropane. 

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