Stereoselective reactions of acyclic alkenes

Earlier the chapter we discussed how to make single diastereoisomers by stereospecific additions to double bonds of fixed geometry. But if the alkene also contains a chiral centre there will be a stereoselective aspect to its reactions too its faces will be diastereotopic, and there will be two possible outcomes even if the reaction is fully stereo specific. Here is an example where the reaction is an 

In order to explain reactions of chiral alkenes like this, we need to assess which conformations are important, and consider how they will react, just as we have done for chiral carbonyl compounds. Much of the work on alkene conformations was done by K.N. Houk using theoretical computer models, and we will summarize the most important conclusions of these studies. The theoretical studies looked at two model alkenes, shown in the margin. 

The calculations found that the low-energy conformations in each case were those in which a substituent eclipses the double bond. For the simple model alkene 1, the lowest-energy conformation is the one that has the proton in the plane of the alkene. Another low-energy conformation—only 3.1 kj mol-1 higher—has one of the methyl groups eclipsing the double bond, so that when we start looking at reactions of this type of alkene, we shall have to consider both conformations. 

Houk works at the University of California in Los Angeles. He has provided explanations for a number of stereochemical results by using powerful computational methods. 

This effect—the control of conformation by a cis substituent—is known as allyllc strain or A1,3 strain. The groups involved are on carbons 1 and 3 of an a Hylic system. 

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Stereoselective reactions of acyclic alkenes 865 Fragmentations are controlled by stereochemistry 962... 

A typical example for stereoselective reactions of acyclic radicals occurs during the reaction of alkene 3 with BuHgCl/NaBH4. The reactions proceed by addition of a tert-hvXy radical to 3 and subsequent stereoselective H atom abstraction by radical 4 that leads to 5 as main product (Scheme 1). 

The stereoselective cyclopropanation of chiral alkenes can be divided into two classes cyclic and acyclic alkenes. Furthermore, within each class, a subdivision exists involving those that contain a proximal basic group that can direct the cyclopropanation reaction of zinc carbenoids and the others that do not. The discrimination of reactivity between alkenes that possess a proximal basic group and those that do not was first highhghted early on when Simmons and Smith noticed that the cyclopropanation of l-(o-methoxyphenyl)-l-propene was more efficient than that of the related meta and para isomers (equation 46). ... 

Control over regioselectivity and stereoselectivity in the formation of new C-C a-bond is required to utilize the Heck reaction in complex molecule synthesis. For the intramolecular Heck reaction, the size of the ring formed in the insertion step controls the regiochemistry, with 5-exo and 6-exo cyclization favoured. A mixture of regioisomers is formed from Heck insertions of acyclic alkenes, whereas cyclic alkenes such as cycloalkenes as a Heck substrate produce a a-arkylpalladium(II) intermediate A, which has only one syn-P-hydrogen. Syn-elimination of the hydrogen provides only product B (Scheme 5.6). 

With some catalysts the horizontal equilibria of (22) are established much more quickly than the vertical cis/trans equilibria and, in the initial stages, such metatheses may be very stereoselective. With other catalysts or with other substrates, the reverse is often true and there is little stereoselectivity. More complex still are the reactions involving more than two types of alkylidene moiety, derived from two or more reactant alkenes. Reactions of acyclic olefins are discussed in detail in Ch. 5-9. 

In both epoxidation examples, the stereoselectivity is due to the cyclic nature of the transition state the fact that there is a hydrogen bond or O-metal bond delivering the reagent to one face of the alkene. Effectively we have moved on from the tethered nucleophiles of the last section to (transiently) tethered reagents. This is a very important concept, and we revisit it in the next chapter cyclic transition states are the key to getting good stereoselectivity in reactions of acyclic compounds. 

In spite of the impressive variety of studies on the Ireland-Claisen rearrangement, several significant Hmitations to the reaction remain. A general solution to the problem of stereocontrolled formation of Cl,Cl-disubstituted silyl ketene acetals has yet to be reported. There is as yet no general catalytic enantioselective variant of the Claisen rearrangement There are as yet no reports of stereoselective generation of acyclic tetrasubstituted alkenes. 

Stereoselectivity in the dibromination of acyclic alkenes is explained by the same mechanism given for the reaction with cyclic alkenes. In cis-2-butene, the two methyl groups are locked on one side of the C=C unit because there is no rotation around those carbon atoms. The key to the stereoselectivity is the fact that the stereochemical relationship of the groups on the C=C unit is retained in the transition state that leads to the bromonium ion—in the bromonium ion and in the final product. When cis-2-butene reacts with bromine, bromonium ion 46 is formed, which is arbitrarily drawn with the bromine... 

A more practical, atom-economic and environmentally benign aziridination protocol is the use of chloramine-T or bromamine-T as nitrene source, which leads to NaCl or NaBr as the sole reaction by-product. In 2001, Gross reported an iron corrole catalyzed aziridination of styrenes with chloramine-T [83]. With iron corrole as catalyst, the aziridination can be performed rmder air atmosphere conditions, affording aziridines in moderate product yields (48-60%). In 2004, Zhang described an aziridination with bromamine-T as nitrene source and [Fe(TTP)Cl] as catalyst [84]. This catalytic system is effective for a variety of alkenes, including aromatic, aliphatic, cyclic, and acyclic alkenes, as well as cx,p-unsaturated esters (Scheme 28). Moderate to low stereoselectivities for 1,2-disubstituted alkenes were observed indicating the involvement of radical intermediate. 

According to the stepwise electrophilic reaction mechanism, the differences in the stereochemistries of the products from the reactions of alkenes with cyclic 49 and acyclic 51 disulfonium dications can be explained by the larger rates of the intramolecular reactions. In the case of a cyclic dication, the carbocationic center in intermediate 94, which is formed as the result of initial attack by a S-S dication on a double C=C bond reacts with nucleophile intramolecularly, thus conserving the configuration of the substituents at the double bond. On the other hand, an acyclic dication undergoes transformation to two separate particles (95 and dimethylsulfide) with a consequent loss of stereoselectivity. Additional experiments with deuteretad alkenes confirm that reaction is not stereoselective, lending further support to the stepwise mechanism (Scheme 36).106... 

The 1,3-dipolar cycloaddition of nitrones to vinyl ethers is accelerated by Ti(IV) species. The efficiency of the catalyst depends on its complexation capacity. The use of Ti( PrO)2Cl2 favors the formation of trans cycloadducts, presumably, via an endo bidentate complex, in which the metal atom is simultaneously coordinated to the vinyl ether and to the cyclic nitrone or to the Z-isomer of the acyclic nitrones (800a). Highly diastereo- and enantioselective 1,3-dipolar cycloaddition reactions of nitrones with alkenes, catalyzed by chiral polybi-naphtyl Lewis acids, have been developed. Isoxazolidines with up to 99% ee were obtained. The chiral polymer ligand influences the stereoselectivity to the same extent as its monomeric version, but has the advantage of easy recovery and reuse (800b). 

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. 

An example is the rhodium catalyzed hydroformylation reaction, which is an industrially important homogenous catalytic process [3]. In contrast, it is amazing that such an important transition-metal catalyzed C/C bond-forming process has been employed only rarely in organic synthesis [4]. Part of the reason stems from the difficulty in controlling stereoselectivity. Even though some recently developed chiral rhodium catalysts allow for enantio- and diastereoselective hydroformylation of certain specific classes of alkenes [5, 6], only little is known about the diastereoselective hydroformylation of acyclic olefins [7, 8]. 

The regioselectivity of the Paterno-Biichi reaction with acyclic enol ethers is substantially higher than with the corresponding unsymmetrically alkyl-substituted olefins. This effect was used for the synthesis of a variety of 3-alkoxyoxetanes and a series of derivatives [55]. The diastereoisomeric cis-and tnms-l-methoxy-l-butenes were used as substrates for the investigation of the spin state influence on reactivity, regio- and stereoselectivity [56]. The use of trimethylsilyloxyethene 62 as electron rich alkene is advantageous and several 1,3-anhydroapiitol derivatives such as 63 could be synthesized via photocycloaddition with l,3-diacetoxy-2-propanone 61 (Sch. 17) [57]. 

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