Cis addition

It is usually assumed that the epoxidation reaction proceeds initially by cis addition to the double bond. 

Tliis hydroxylation gives cis addition to the double bond (see Norman p.502-3 or Tedder vol. 1, p.61-2 if you re not sure about this). How then could you make TM 152 ... 

Diacetoxylation of various conjugated dienes including cyclic dienes has been extensively studied. 1,3-Cyclohexadiene was converted into a mixture of isomeric l,4-diacetoxy-2-cyclohexenes of unknown stereochemistry[303]. The stereoselective Pd-catalyzed 1,4-diacetoxylation of dienes is carried out in AcOH in the presence of LiOAc and /or LiCI and beiizoquinone[304.305]. In the presence of acetate ion and in the absence of chloride ion, /rau.v-diacetox-ylation occurs, whereas addition of a catalytic amount of LiCl changes the stereochemistry to cis addition. The coordination of a chloride ion to Pd makes the cis migration of the acetate from Pd impossible. From 1,3-cyclohexadiene, trans- and ci j-l,4-diacetoxy-2-cyclohexenes (346 and 347) can be prepared stereoselectively. For the 6-substituted 1,3-cycloheptadiene 348, a high diaster-eoselectivity is observed. The stereoselective cij-diacetoxylation of 5-carbo-methoxy-1,3-cyclohexadiene (349) has been applied to the synthesis of dl-shikimic acid (350). 

In MeOH, l,4-dimethoxy-2-cyclohexene (379) is obtainejl from 1,3-cydo-hexadiene[315]. Acetoxylation and the intramolecular alkoxylation took place in the synthesis of the naturally occurring tetrahydrofuran derivative 380 and is another example of the selective introduction of different nucleo-philes[316]. In intramolecular 1,4-oxyacetoxylation to form the fused tetrahy-drofurans and tetrahydropyrans 381, cis addition takes place in the presence of a catalytic amount of LiCI, whereas the trans product is obtained in its absence[317]. The stereocontrolled oxaspirocyclization proceeds to afford the Irons product 382 in the presence of Li2C03 and the cis product in the presence of LiCl[ 318,319]. 

The stereospecific synthesis of an A ring synthon of la-hydroxy vitamin D has been carried out. The ( )-allcene is cyclized to give the (E -c.xo-diene 155, and the (Z)-allcene affords the (Z)-e,xo-diene 156 stereospecifically[125,126]. These results can be understood by the cis addition and syn elimination mechanism. 

The intramolecular insertion of an internal alkyne into an aryl or alkenyl halide 727 generates aryl- or alkenylpalladium as an intermediate, which is trapped with an organozinc or organostannane to give 728. Overall cis addition to the alkyne takes place[595,596]. The reaction of the alkenylstannane 730 with the 2-bromomethylfuran 729 is used for the introduction of a prenyl group[597]. 

The reaction of allyl halides with terminal alkynes by use of PdClifFhCNji as a catalyst affords the l-halo-l,4-pentadienes 297. 7r-AlIylpalladium is not an intermediate in this reaction. The reaction proceeds by chloropalladation of the triple bond by PdCh, followed by the insertion of the double bond of the allyl halide to generate 296. The last step is the regeneration by elimination of PdCh, which recycles[148]. The cis addition of allyl chloride to alkynes is supported by formation of the cyclopentenone 299 from the addition product 298 by Ni(CO)4-catalyzed carbonylation[149]. 

The photolysis of a-diazosulfones dissolved in alkenes provides sulfonyl-substituted cyclopropanes in high yields. This is exemplified by the preparation of l-(p-methoxyphenylsulfonyl)-2,2,3,3-tetra-methylcyclopropane in 75% yield from -methoxybenzenesulfonyl-diazomethane and 2,3-dimethyl-2-butene. A similar addition to [Pg.101]

Me3Al-Cp2ZrCl2 or R2CuLi). In such cases of cis addition, stereoselectivity originates from a dominant cycloaddition mechanism. 

This reaction sequence proceeds by cis addition of deuterium and the reduction products usually exhibit high isotopic purity. For example, 5a-cholest-2-ene (136), which is known to give a product of very unsatisfactory isotopic purity when deuterated with heterogeneous catalysts (see section V-A), gives 2<, 3 -d2-5a-cholestane (137) with better than 95% isotopic purity in homogeneous solution. ... 

In a further extension of this reaction Winstein and Dauben showed that the action of the methylene-transfer reagent (1) on A -cycloal-kenols, e.g., (2), proceeds by stereospecific cis addition to give the cw-cyclo-propyl carbinol (5). It was also observed that both the rate and yield of the hydroxyl-assisted reaction are increased substantially. It has been suggested that the high stereoselectivity observed in these instances is best explained by complex formation or reaction of the reagent (1) with the hydroxyl group of (2) followed by intromolecular transfer of methylene. 

Both terminal and nonterminal acetylenes have been used. Activating groups oL to the acetylenic bond have included sulfone (131-135), sulfoxide (134), ester (28,133-139), and ketone (134,140). Whether adduct 183 Is designated as cis or trans depends on the investigators and the particular compound. If the addition reaction is carried out in aprotic solvents, the major isomer is 183 formed by cis addition (135,138,139). For example, the addition of aziridine to dimethyl acetylenedicarboxylate (182, X, Y = CO2CH3) in dimethyl sulfoxide (135) gave 75 % of a mixture containing 95 % of the Chester 185. Collapse of the intermediate zwitterion intermediate 186... 

Acetylenic esters react well witli copper-zinc compounds. Propiolic esters are especially reacive [83], but otier acetylenecarboxylic acid derivabves suci as di-nietliyl acetylenedicarboxylate or propiolaniide 118 undergo biglily stereoselecive cis addition (Scienie 2.47) [46]. 

Photolytically generated carbene, as mentioned above, undergoes a variety of undiscriminated addition and insertion reactions and is therefore of limited synthetic utility. The discovery (3) of the generation of carbenes by the zinc-copper couple, however, makes carbene addition to double bonds synthetically useful. The iodo-methylzinc iodide complex is believed to function by electrophilic addition to the double bond in a three-center transition state giving essentially cis addition. Use of the... 

The stereoisomers of olefin saturation are often those derived by cis addition of hydrogen to the least hindered side of the molecule (99). But there are many exceptions and complications (97), among which is the difficulty of determining which side of the molecule is the least hindered. Double-bond isomerization frequently occurs, and the hydrogenation product is the resultant of a number of competing reactions. Experimentally, stereochemistry has been found to vary, sometimes to a marked degree, with olefin purity, reaction parameters, solvent, and catalyst 30,100). Generalizing, it is expedient, when unwanted products arise as a result of prior isomerization, to avoid those catalysts and conditions that are known to favor isomerization. 

The addition of hydridosilanes across the triple bond of alkynes can be accomplished using a variety of catalysts, the best being chloroplatinic acid. cis-Addition, with terminal regioselectivity, is normally observed, with lower temperatures favouring a greater proportion of the terminal isomer (see also Chapter 17). 

The transition metal catalysed addition of a hydridosilane to a multiply-bonded system is known as hydrosilylation (1). Under such conditions, alkynes undergo clear cis-addition, so providing one of the most direct routes to vinylsilanes (Chapter 3). Hydridosilanes also add to the carbonyl group of saturated aldehydes and ketones, to produce alkyl silyl ethers. Fot example, under suitable conditions, 4-t-butylcyclohexanone (2) can be reduced with a high degree of stereoselectivity. 

Bordwell and Garbisch71 contested this conclusion since they found that nitric acid in acetic anhydride prepared at —10 °C contained a much less effective nitrating species (the nitric acid could be recovered quantitatively) than when mixed at 25 °C and cooled to —10 °C (the nitric acid being then mostly unrecoverable). Further, these latter solutions reacted with alkenes to give predominantly cis addition products (nitro-acetates), whi h indicates association of the nitronium ion with some other species. It has been argued72 that this does not necessarily follow, since nitration of aromatics may involve a different... 

Sulfonyl bromides and iodides react similarly217-218-225 copper-salt catalysis in these cases facilitates the additions but is not absolutely necessary however, it influences the stereochemistry of the additions. Addition of sulfonyl iodides226 as well as the uncatalyzed thermal addition of sulfonyl bromides227 to alkynes leads to an exclusive trans-addition, whereas CuBr2 catalysis in the latter case causes the formation of cis-addition products to some extent (11 16%) correspondingly, copper-salt catalysis in sulfonyl chloride additions to alkynes leads to the formation of a mixture of Z,E-isomers228-229 (equation 40). 

Jones and coworkers200 found that a variety of sulphenic acids may be generated by thermolysis of the readily available /J-cyanosulphoxides (equation 81) and observed their highly regiospecific addition also to non-conjugated alkynes (Table 12). As expected for a pericyclic mechanism, the reaction afforded the product of a stereospecific cis-addition. However, the regioselectivity of the addition suggests that the partial carbon-sulphur bond in the transition state 148 is polarized in such a way that the carbon atom has some cationic character (equation 82). 

Nucleophilic addition to acetylenic sulfoxides provides a,/ -ethylenic sulfoxides. Treatment of 181 with monoalkyl-copper afforded nearly quantitatively /J-alkylated a, / -ethylenic sulfoxides 182 through cis-addition to the triple bond. The reaction with lithium dimethylcuprate also afforded a similar adduct however, the reaction with lithium di-n-butylcuprate was found to give a small amount of ethyl n-butyl sulfoxide 183 besides the... 

The copper-catalyzed 1 1 additions of aliphatic and aromatic sulfonyl chlorides82,85 or bromides84 to acetylenes yielding mixtures of trans- and cis-/3-halovinyl sulfones have also been described. Highly polar solvents favored trans addition, while cis addition predominated in low polarity media84,85. A comparison between the thermal and the copper-catalyzed addition of sulfonyl bromides to phenylacetylene (cf. Scheme 6) enabled Amiel84 to suggest that the two stereoisomers do not have a common intermediate. That is, the trans addition product is a result of a normal radical chain, while the cis addition... 

Jackman, Hamilton, and Lawlor have studied the stereochemistry of the addition of [Co(CN)5D] to a,/3-unsaturated acids and identified the product of the addition of fumarate as the threo isomer, i.e., adduct formation has occurred by a stereospecific cis addition of Co—D across the double bond 94). 

But in neutral solution, where the complex is present mainly as the hydride, the only product was the a-phenylvinyl complex (CH2=CHPhCo). When the Co(I) complex was formed by reduction with D2 or NaBD4 in CH3OH the reaction in neutral solution gave a product containing a significant amount of deuterium in the position cis to cobalt. This establishes the mechanism as the stereospecific cis addition of Co—D across the double bond, i.e.,... 

Phenylacetylene is apparently one of thee few actylenes so far reported which is able to react via the cis addition of Co—H. Methyl propiolate, ethyl... 

The hydroboration reaction occurs stereospecifically, and the boron attacks from the less-hindered side of the molecule by normal cis addition, owing to the presence of the bulky benzyloxy group in the axial position. 

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