Stereoselectivity cyclic alkenes

The preferred stereochemistry of addition to cyclic alkenes is anti The additions are not as highly stereoselective as hydrogen bromide addition, however. 

As is true for most reagents, there is a preference for approach of the borane from the less hindered face of the alkene. Because diborane itself is a relatively small molecule, the stereoselectivity is not high for unhindered alkenes. Table 4.4 gives some data comparing the direction of approach for three cyclic alkenes. The products in all cases result from syn addition, but the mixtures result from both the low regioselectivity and from addition to both faces of the double bond. Even 7,7-dimethylnorbornene shows only modest preference for endo addition with diborane. The selectivity is enhanced with the bulkier reagent 9-BBN. 

With cyclic alkenes, the reaction proceeds with variable regiose-lectivity and stereoselectivity depending on the substituents, although the overall reaction proceeds in moderate to good yield. The approach is of particular value for those systems where regiochem-istry and stereochemistry are not variable. 

Catalytic ring-closing metathesis makes available a wide range of cyclic alkenes, thus rendering a number of stereoselective olefin functionalizations practical. The availability of effective metathesis catalysts has also spawned the development of a variety of methods that prepare specially-outfitted diene substrates that can undergo catalytic ring closure. The new metathesis catalysts have already played a pivotal role in a number of enantioselective total syntheses. 

In the steric course of olefin metathesis, acyclic and cyclic alkenes exhibit opposite behavior. The stereoselectivity of the transformation of most acyclic olefins is low and usually goes to equilibrium. In some systems there is a strong initial preference for retention of stereochemistry, that is for the transformation of cis to cis and that of trans to tram isomers.88 This means that geometric isomers of an olefin give different isomeric mixtures of the same product ... 

The stereoselectivity of this hydration process has been studied on a number of alkenes. Acyclic alkenes and most cyclic alkenes give exclusively trans addition (equations 214 and 2 1 5).331,332 However, some strained cyclic alkenes, such as rrans-cyclooctene and trans-cyclononene, give cis adducts.332... 

Griesbeck and colleagues proposed a reliable model that would predict the stereoselectivity in the PB reaction of the dihydrofuran derivatives (Scheme 7.16). Thus, the Griesbeck Model [33] explains the stereoselectivity of oxetanes formed in the PB reactions of cyclic alkenes. 

In cyclic alkenes such as cyclohexene and cycloheptene trans addition was also highly stereoselective [7]. However, cis cyclooctene afforded both cis and trans adducts in the ratio 1 3 in the presence of oxygen 1,4-dichlorides were also formed [8]. In cyclodecenes, both cis and trans, the main product was the allylic chloride, with some formation of transannular dichlorides [9]. In some substrates with an exocyclic double bond, such as methylene cyclobutane, only (dichloroiodo)benzene was suitable for a clean addition [10]. 

Epoxidation of cyclic alkenes is stereoselective, with reaction taking place on the less hindered face, or directed by hydrogen bonding to a hydroxyl group OAc OAc OH OH... 

Substituents occupying sites more remote from the alkenic center than the allylic position may also influence the direction of attack on an alkene with diastereotopic Tr-faces. Thus, cyclic alkenes with a sul-foximine group attached to an exocyclic homoallylic carbon atom and a hydroxy group at the allylic position, for example (Iti) in equation (5), undergo syn hydroxylation with a very high degree of dia-stereoselectivity, diol (17) being produced as the sole diastereoisomer. ... 

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). 

W(NAr)(=CHBuO(OR)2 (R = CMe(CF3)2, 50) are highly active catalysts for the metathesis of internal alkenes (equation 16), and also effect the stereoselective olefmation of hydroxy ketones (equation 17). The reactivity of these catalysts can be tuned by varying the aUcoxide ligands for example, when R = Bn, the complex acts only upon strained cyclic alkenes and is a highly effective ring-opening metathesis polymerization (ROMP) catalyst (see Metathesis Polymerization Processes by Homogeneous Catalysis). 

An alternative procedure for the preparation of /J-alkoxy selenides involves treatment of cyclic or acyclic alkenes with phenylselenenyl cyanide in the appropriate alcohol in the presence of catalytic amounts of copper(ri) or nickel(ll) halides. The reaction using methanol as the alcohol with cyclic alkenes is tram stereoselective giving /1-methoxy selenides 23 usually in high yield34. 

The reaction is also fully stereoselective when cyclohexene is the cyclic alkene and ethanol or 2-propanol is the solvent. ( )-2-Butene in methanol gives 2-methoxy-3-(phenylseleno)butane 24 in 82% yield containing more than 95% of the (25, 3.R )-isomer (by GC and 13C NMR). Similarly, the product obtained from (Z)-2-butene consists of more than 95% of the (25, 35 )-selenide34. 

It has been rationalized that these reactions proceed via a cyclic telluronium ion intermediate which undergoes a nucleophilic attack by the chloride ion giving the products with trans configuration. The addition of 2-naphthyltellurium trichloride to a variety of acyclic and cyclic alkenes is completely anti or trans stereoselective, but tellurium tetrachloride usually gives mixtures arising from syn (cis) and anti (trans) addition representative results are presented in Tables 15 and 16. 

Regardless of the mechanism, stereoselective cis cycloaddition is generally observed with cyclic alkenes. 

Free-radical hydrosilylation of alkenes with tris(trimethylsilyl)silane proceeds in high yields and with good stereoselectivity. In the case of cyclic alkenes the thermodynamically less stable c/.y-products (resulting from anti attack) arc formed preferentially, while in the case of acyclic alkenes the products are formed with opposite stereochemistry33. 

Reaction of cyclic sulfates or thionocarbonates, derived from 1,2-diols, with telluride results in stereospecific alkene formation <1995TL7209>. This is illustrated by the conversion of the cyclic sulfate OTitra-l,2-diphenyl-l,2-ethanediol 49 into fif-stilbene exclusively by Te, as shown in Equation (13). Treatment of the cyclic sulfate of 47-1,2-diphenyl-1,2-ethanediol with Te produces /ra r-stilbene exclusively. These results are accounted for by intermolecular Te Sn2 displacement followed by intramolecular Sn2 displacement to form the corresponding tellurirane. The tellurirane then thermally loses tellurium stereoselectively forming alkene. Cyclic sulfates need not be used dimethanesulfonates or di-/i-toluenesulfonates prepared from 1,2-diols also, stereospecifically, provide alkenes via telluriranes <1993CC923, 1996SL655>. 

The cycloadditions proceed stereoselectively with the geometry of ( )-alkenes being preserved, but that for (Z)-alkenes being partially lost (equations 1 and 2), Excellent diastereofacial selectivity has been observed in cycloadditions to cyclic alkenes, the major product resulting from the addition of the TMM-PdL2 complex to the least-hindered face of the alkene (equations 3-5). Modest (4 1) to high (>99 1) diastereoselectivity is also observed when enantiomerically pure acyclic alkenes are used (equations 6,7). ... 

In ketone-directed peroxy acid epoxidations of cyclic alkenes the actual epoxidizing agent has been shown by 180-labeling not to involve a dioxirane <94TL6155>. Instead, an a-hydroxy-benzoylperoxide or a carbonyl oxide is believed to be responsible for observed stereoselectivities in the intramolecular epoxidations. The extent of syn-selectivity is greater for ketones than with esters the syn/anti ratios increase when ether is used as solvent rather than CH2C12, the reverse situation for hydroxyl-directed epoxidations. Fused-ring oxiranes can also be prepared from acyclic precursors. Four different approaches are discussed below. 

Chiral olefins (racemic or enantiomerically pure) can provide two diastcreomers when carbene (carbenoid) CX2 is added, or four diastereomers when carbene (carbenoid) CXY is employed. Cyclic alkenes (on-ring stereoselection) are considered before acyclic olefins (acyclic stcrcosclcction) are discussed. 

A great variety of sulfones are available from the addition of RSO2X to alkenes, alkynes, and allenes [6, 8, 18, 27-30] (Eqs. 11-16). In the case of cyclic alkenes, the addition is highly stereoselective in favor of the trans adduct (Eq. 11). 

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