Substitution disubstituted alkenes

Monosubstituted and disubstjtuted alkenes have characteristic =C—H out-ofplane bending absorptions in the 700 to 1000 cm-1 range( thereby allowing the substitution pattern on a double bond to be determined. Monosubstituted alkenes such as 1-hexene show strong characteristic bands at 910 and 990 cm-1, and 2,2-disubstituted alkenes (R2C=CH2) have an intense band at 890 cm-1. 

Double bonds tend to migrate to more highly substituted positions within a substrate that is, terminal alkenes isomerize to disubstituted or trisubstituted alkenes, disubstituted alkenes tend to migrate to trisubstituted, and trisubstituted to tetrasubstituted alkenes. Of course, migration can go both ways, and adsorbed surface species may not exhibit the same thermodynamic stability as their desorbed relatives. (The rate of migration is strongly catalyst dependent for example, it frequently occurs rapidly on Pd and slowly on Pt.)... 

Nenajdenko et al. described the first example of addition of a 1,2-dication to C-C mutiple bonds. The only S-S dication found to participate in this reaction was the highly strained dication 115 derived from 1,4-dithiane. The reaction with alkenes 119 proceeded under mild conditions and led to derivatives of dithioniabicyclo[2.2.2]octane 120 as shown in Equation (33) and Table 21 <1998JOC2168>. This reaction was sensitive to steric factors and proceeded only with mono and 1,2-disubstituted ethylenes. Only alkenes conjugated with aromatic or cyclopropane moieties underwent this reaction. For the 1,2-disubstituted alkenes used in this study, the relative configuration of substitutents at the double bond was preserved and only one diastereomer was formed (see entries 2 and 3). 

Reaction with alkenes is sensitive to steric factors - in the case of dication 49, only reaction with mono- and 1,2-disubstituted ethylenes afforded identifiable reaction products. Only alkenes conjugated with aromatic or cyclopropane moiety undergo this reaction. In the case of 1,2-disubstituted alkenes, the relative configuration of substitutents at the double bond is preserved and only one diastereomer is formed. 

The reaction tolerated a variety of functionality, including ester and ether groups on the alkyl-substituted alkene at least two carbons away from the double bond, and raefa-nitro or para-methoxy substituents on the styrene. As expected, cross-metathesis occurred selectively at the less hindered monosubsti-tuted double bond of dienes also containing a disubstituted alkene (Eq. 8). 

Enantioselective hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alky-lidene-substituted carbocycles and heterocycles [27 b, 41, 42]. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. For systems that embody 1,2-disubstituted alkenes, competitive /9-hydride elimination en route to products of cycloisomerization is observed. However, related enone-containing substrates cannot engage in /9-hydride elimination, and undergo reductive cyclization in good yield (Table 22.12). 

Lowenthal and Masamune (44) investigated the cyclopropanation of trisubsti-tuted alkenes leading to a chrysanthemic acid synthesis. They found that ligand 50c provided poor selectivities in this case (24% de for the trans isomer). Substitution in the 5 position of the oxazolines leads to increased selectivities, with excellent results provided by the BHT ester (94 6, 94% ee), Eq. 32. This ligand proved to be applicable to other trisubstituted and several cis-disubstituted alkenes, providing the corresponding cyclopropanes in ee values of 82-95%. These authors note that catalysts generated from CuOTf, CuOf-Bu, and Cu(II) precursors (with activation) provided similar yields and enantioselectivities. 

Arylalkenes [23] and alkenes with electron withdrawing substituents [24] can be bis-alkylated across the alkene bond by electrochemical reaction with dflialoal-kanes giving 3- to 6-membered carbocyclic products in good yields. ITie best reaction conditions use an undivided cell with a nickel cathode and a sacrificial aluminium anode in dimethylformamide or N-methylpyrrolidone containing a tetraalkylammonium salt. Anodically generated aluminium ions are essential for the reaction. 1,2-Disubstituted alkenes, regardless of their stereochemistry, are converted to the tranj-substituted cycloalkane. 

The reaction is versatile and proceeds with a variety of cyclic and acylic alkenes substituted with alkyl, aryl, vinyl and heteroatom substituents. Allene derivatives also undergo cycloaddition with nitrones ". A variety of cyclic and acyclic aliphatic nitrones bearing aliphatic and aromatic substituents has been tested. The reaction is, however, relatively sensitive to steric constraints and proceeds easily only for mono- and disubstituted alkenes. Steric requirements for a nitrone molecule are similar and, although several reactions with R, R2 are known, good yield has been achieved only with R = H (equation 105). 

Ru(C. 35C(0)CH2C(0)C. j5)3] , a substituted (acac) complex, is made from the 1,3-diketone C j COCH COC Fu with RuClj (quoted as RuCl in the paper) in ethanol with KCHCOj). In biphasic solvents [Ru(C jjC(0)CH2C(0)C j3)3]7per-fluorodecaUn-toluene/O (1 atm)/65°C oxidised aldehydes to ketones, disubstituted alkenes (cyclo-octene, norbomene) to epoxides and sulfides to sulfoxides or sul-fones [821, 822],... 

The cycloaddition of substituted acrylates has been investigated with cyclic nitronate 24 (Table 2.49) (14). The cycloaddition of a 1,1-disubstituted dipolar-ophile (entry 2), proceeds in good yield, but both 1,2-disubstituted alkenes fail to react. The effect of substitution pattern on the dipolarophile was investigated with a slightly more reactive nitronate (Table 2.50) (228). Less sterically demanding alkenes such as cyclohexene, cyclopentene, and methyl substituted styrenes react, albeit at elevated temperature. The only exception is the 1,1-disubstituted alkene (entry 4), which reacts at room temperature. Both stilbene and dimethyl fumarate fail to provide the desired cycloadduct. In a rare example of the dipolar cycloaddition of tetra-substituted alkenes, tetramethylethylene reacts at 50 °C over 3 days to give a small amount of the cycloadduct (entry 7). 

Reactions of nitrile oxides with 1,1-disubstituted alkenes afford products in which the oxygen atom of the nitrile oxide gets attached to the most crowded carbon atom of the dipolarophile. This high regioselectivity does not seem to depend on the type of substituent present on the alkene (142-152). Some of the results cannot be satisfactorily interpreted on the basis of FMO theory (149,151). Both steric and electrostatic effects often counteract each other and contribute to the regioselectivity actually observed. With trisubstituted alkenes, the orientation of cycloaddition is apparently dominated by this phenomenon. The preference is for the more substituted carbon atom to end up at the 5-position of the heterocyclic product (153,154). However, cases of opposite regiodifferentiation are also found, in particular with donor-substituted alkenes (42,155-157) (Scheme 6.21). 

Allylic chlorides Actually the reaction of HOG with highly substituted alkenes is a convenient route to allylic chlorides if CH2G2 is used as the organic cosolvent. The reagent is prepared by addition of dry ice to calcium hypochlorite (70%) in water. The reaction of 1-methylcyclohexene is typical (equation I). Chlorohydrins arc the main products only in the case of 1-alkenes and 1,2-disubstituted alkenes. 

Simple mono- and disubstituted alkenes react to yield 1,3-diols, when the Prins reaction is carried out at elevated temperature. Diols originate from the attack of water on carbocation 18, or through the acidolysis of dioxanes under the reaction conditions. When the reaction is conducted in acetic acid, monoacetates are formed by acetate attack on 18. Dienes resulting from the dehydration of intermediate diols are the products of the transformation of more substituted alkenes. Monoacetates and diols may react further to yield 1,3-diol diacetates. When the Prins reaction... 

Substituted cycloalkenes usually react in the ring and not in the side chain. Internal alkenes with CH2 groups in both allylic positions yield a mixture of isomers, whereas terminal alkenes give primary alcohols as a result of allylic rearrangement. Later studies revealed, however, that the reactivity depends on both the structure of the alkene and reaction conditions.674 675 In alcoholic solutions, for example, racemic products are formed. Geminally disubstituted alkenes may exhibit a reactivity sequence CH > CH2 > CH3.675 676... 

A study of the scope of the reaction has shown that mono- and disubstituted alkenes and, particularly, aryl-substituted alkenes are the best substrates. Various limitations have been noted, some not unexpected (sensitivity to steric effects), others quite surprising (complex reactivity of cyclohexenes). Nevertheless, the exceptionally high stability of the reagent should make it available from the shelf, and in appropriate cases its use is to be considered as an alternative to the Simmons-Smith reaction. 

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