Stereoselectivity regiocontrol

In the intramolecular amidoalkylation of certain (Z)-allylsilanes, piperidine derivatives (n = 2) are formed less stereoselectively than the corresponding pyrrolidines (n = 1). The complete regiocontrol is induced by the /3-effect of the silicon atom. 

The Alder-ene reaction has traditionally been performed under thermal conditions—generally at temperatures in excess of 200 °C. Transition metal catalysis not only maintains the attractive atom-economical feature of the Alder-ene reaction, but also allows for regiocontrol and, in many cases, stereoselectivity. A multitude of transition metal complexes has shown the ability to catalyze the intramolecular Alder-ene reaction. Each possesses a unique reactivity that is reflected in the diversity of carbocyclic and heterocyclic products accessible via the transition metal-catalyzed intramolecular Alder-ene reaction. Presumably for these reasons, investigation of the thermal Alder-ene reaction seems to have stopped almost completely. For example, more than 40 papers pertaining to the transition metal-catalyzed intramolecular Alder-ene reaction have been published over the last decade. In the process of writing this review, we encountered only three recent examples of the thermal intramolecular Alder-ene reaction, two of which were applications to the synthesis of biologically relevant compounds (see Section 10.12.6). 

Treatment of the potentially electrophilic Z-xfi-unsaturated iron-acyl complexes, such as 1, with alkyllithium species or lithium amides generates extended enolate species such as 2 products arising from 1,2- or 1,4-addition to the enone functionality are rarely observed. Subsequent reaction of 2 with electrophiles results in regiocontrolled stereoselective alkylation at the a-position to provide j8,y-unsaturated products 3. The origin of this selective y-deproto-nation is suggested to be precoordination of the base to the acyl carbonyl oxygen (see structures A), followed by proton abstraction while the enone moiety exists in the s-cis conformation23536. 

The above described total synthesis features the first enantiodivergent approach to (+)- and (—)-scopadulcic acid A. The central transformations are the stereoselective carbonyl group reduction with (S)-Alpine Borane , the use of enolization stereoselection to dictate which enantiomer is produced, and the palladium-catalyzed bis-Heck cyclization which occurs with complete stereo- and regiocontrol to establish the scopadulan scaffold. 

The reactions of alkyl cuprates with allylic acetates are always stereospecifi-cally anti 5.114 —> 5.115, although the formation of racemic product shows that regiocontrol has been lost. These reactions are not mechanistically Sn2 reactions, since they involve in the first step coordination of the copper on the lower surface, followed by the formation of a re-allyl system at the same time as the acetate leaves. The delivery of the methyl group to the same surface, and equally to both ends of the allylic system, is a reductive elimination. It seems likely that the decisive step determining the stereoselectivity is that coordination of the copper anti to the nucleofugal group is needed before it will leave. 

The predominant formation of (lS, 47 )-42 from 4141 suggests that, in addition to excellent regiocontrol, a stereoselective transformation of vinyl epoxides with sodium azide is possible, but since the diastereomeric ratio of 41 is not reported, the degree of chirality transfer remains... 

There are essentially two selectivity problems when dealing with 1.3-dipolar cycloaddition reactions to alkenes regioselectivity and stereoselectivity. The issue of regiocontrol has received extensive coverage116 and will not be further discussed here. This chapter will deal with the problem of stereochemistry of the cycloaddition which can be addressed at three different levels. 

The cycloaddition of nitrile oxides to unpolarized (electron-rich) cycloalkenes suffers from a lack of regiocontrol, a drawback that limits the usefulness of this generally stereoselective process174 81. For instance, the reaction of 2-oxopropanenitrile oxide with (17i,57 )-7-oxabi-cyclo[3.2.1]oct-2-en-6-one gives a mixture of regio- and stereoisomers 79 ... 

Scheme 10-11 Cyclization of 34 proceeds with complete regiocontrol and moderate stereoselectivity.

The Patemo-Buchi reaction is one of the more predictable photocycloaddition reactions. Regiocontrol of the photoproduced oxetane is a function of the stepwise addition of the carbonyl chromophore to the alkene [30]. In the case of electron-rich alkenes, excitation of the carbonyl group produces a triplet species that adds to the alkene. The product regioselectivity is a result of addition that generates the most stable biradical, and the triplet lifetime of the intermediate biradical allows for substantial stereoselectivity prior to closing (see Scheme 2). Electron poor alkenes are more likely to undergo cycloaddition with carbonyl groups directly from an exciplex [31]. 

Radical cyclization of acetylenic esters." Cyclization of alkynyl esters 1 with Bu.ySnH/AIBN in refluxing benzene results in the (E)-exocyclic alkene, (E)-2, as the major product. In contrast, cyclization of 1 with tris(trimethyl-silyl)silane/AIBN provides a mixture of (E)- and (Z)-2, with the latter predominating. A different stereoselectivity obtains from cyclization of 1 with BuySnH or (TMSjySiH initiated by triethylborane/02. Actually the high (E)-selectivity in BujSnH/AlBN is a result of isomerization of (Z)-2 to (E)-2, promoted by BuySnH at high temperatures. In any case, this isomerization is an unexpected example of regiocontrol in radical cyclizations. 

Intramolecular hydrosilylation of allyl and homoallyl alcohols, with subsequent oxidative cleavage of the resultant C—Si bond, has provided a new approach to the regiocontrolled synthesis of 1,2-and/or 1,3-diols (see also Section 4.3.2.2.3). The example shown ° (Scheme 10) illustrates nicely the use of syn stereoselection in a reiterative manner. 

By using an unmodified system such as [Rh(OAc)2]2, the homoallylic phosphite 76 was converted into the formyl derivative 77 with total regio-and stereocontrol (Figure 23). In the open chain homoallylic phosphites 79, even though the stereoselectivity was low (60 40 for R= Me and 70 30 for R=Ph) regiocontrol was high which led to the formation of the branched... 

Lehman, J., and Lloyd-Jones, G. C. "Regiocontrol and Stereoselectivity in Tungsten-Bipyridine Catalyzed Allylic Alkylation." Tetrahedron, 8863-8874 (1995). 

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