Double bond, exocyclic, selective hydrogenation

DITHIENYL SULFIDE, 50 75 1,3-Dithiolanes, 54, 37 Diynes, preparation, 50, 101 n-Dodecane, 53, 108 Double bond, exocyclic, selective hydrogenation, 53, 65 DURENE, I0D0—, 51, 94... 

Several generalities can be formulated regarding selective reduction of polyolefins. Usually the least hindered double bond is hydrogenated pre ferentially (123), and, with steric hindrance about equal, the most strained bond will be reduced first. Exocyclic olefins are reduced more easily than those in the ring (R)-(+ )-Limonene, 190 g, was shaken with W-4 Raney nickel (12 g) under hydrogen at atmospheric pressure. After 31.9 1 of hydrogen had been absorbed, the solution was filtered. Essentially, pure (R)-( -i- )-carvomenthene was obtained in 96% yield (58). 

An iridium catalyst was used in the selective hydrogenation of a steroid compound, where the exocyclic double bond was saturated in the presence of an endocyclic one (equation 67)161. 

The exocyclic C=C double bond of the 1,4-dithiafulvenes (263) can be selectively hydrogenated under controlled conditions in an acidic medium (Zn/glacial acetic acid), the product being 295. The ease with which the postulated intermediate 1,3-dithiolium salts (264) accept the hydride ion has been adduced as evidence that the resonance stabilization of these ions cannot be very strong.159... 

To study the effects of water and other solvents on titanocene(III)-mediated processes we used the transannular cychzation of epoxygerma-crolides as a model reaction [47]. Thus, we found that in anhydrous, non-halogenated solvents such as THF the reaction led selectively to decalins with an exocyclic double bond (Scheme 5). In an aqueous medium (THF/H2O), however, the characteristic lime green color of Cp2TiCl turned deep blue and the main product was a reduced decalin (Scheme 5). Under these conditions, water (either H2O or D2O) proved to be more effective than the toxic and expensive hydrogen-atom donor 1,4-cyclohexadiene for the reduction of tertiary radicals [47]. This is an unusual phenomenon in free-radical chemistry [48-50], subsequently exploited by us for the selective reduction of aromatic ketones as we shall see later [51,52]. 

Without conjugation of the olefmic double bond to the alkoxycarbonyl function, high selectivity and high reactivity are attained in some cyclic systems. Even ester function can be replaced with ether. Thus, (S)-BINAP-Ru-catalyzed high-pressure hydrogenation of four- and five-membered cyclic lactones or carbonates having an exocyclic methylene bond gives (R)-/3-methyl-/3-propiolactone in 92% e.e., (R)-y-methyl-y-butyrolactone in 95% e.e. [35], and the carbonate of (R)-3-methyl-2,3-buta-... 

Research in the laboratory of H.M.I. Osborn showed that the use of cyclohexene derivatives as nucleophiles in the Lewis acid-mediated Type I carbon-Ferrier reaction of 3-0-acetylated glycals can be used to prepare unsaturated 3-linked C-disaccharides. The incorporation of the alkene took place with one equivalent of glucal in the presence of boron-trifluoride etherate in 33% yield. The desired C-disaccharide was obtained by selective hydrogenation of the exocyclic double bond in the presence of an endocyclic one. 

Lithium-ethylamine reduction at one or both double bonds of carvone, and of carvenone (58) to carvomenthone only, is reported.The effect of solvent on the lithium or potassium amide-reduction of p-cymene to menthenes and menthadienes has been examined.Hydrogenation of carvone (Vol. 4, p. 32), using palladium-polysaccharide exchange resin, favours endocyclic over exocyclic double-bond reduction, more so than with Pd-C or Pd-BaS04, whereas platinum or rhodium on exchange resins exhibit no special selectivity.Optimum conditions for the catalytic hydrogenation of thymol, and the catalytic dehydrogenation of menthol, to menthone have been determined.Cathodic reduction of carvomenthone (to... 

Several syntheses are available to the 13,14-dihydroprostaglandins, some of which are metabolites of the E and F series. The first of these routes [143, 144] started from the formyl derivative (LVII) of the enol ether of cyclo-pentan-l,3-dione which on reaction with ethyl 6-bromosorbate and tri-phenylphosphine followed by selective catalytic reduction afforded the ester (LVIII). A second formylation followed by elaboration with n-hexanoyl-methylenetriphenylphosphonium chloride 1 to the ketone (LIX) which on reduction of the exocyclic double bond and acid-catalysed solvolysis in benzyl alcohol afforded the benzyl ether (LX) and its isomeric enol ether. Reduction with lithium tri-t-butoxyaluminium hydride to the corresponding 15-hydroxy-compound and palladium-charcoal catalysed hydrogenolysis followed by prolonged catalytic hydrogenation with rhodium-charcoal led to ( )-dihydro-PGEi ethyl ester. 

Elimination of selenoxides takes place through an intramolecular, syn elimination pathway. The carbon—hydrogen and carbon—selenium bonds are coplanar in the transition state. The reaction is highly traws-selective when acyclic a-phenylseleno carbonyl compounds are employed. The formation of conjugated double bonds is favored. Endocyclic double bonds tend to predominate over exocyclic ones, unless there is no syn hydrogen available in the ring. Some examples of selenoxide-mediated syn eUmination reaction are given in Scheme 6.23. 

The selective catalytic hydrogenation of exocyclic a,/3-unsaturated ketones was successfully utilized in the assymetric synthesis process of the chiral building blocks, a-hydroxy acids. The influence of the catalyst support, solvent and additives in the selective 1,4-reduction was studied in a series of exocyclic enone systems (Scheme The best conditions for the selective reduction of the exocyclic double bond were obtained in an apolar solvent like toluene over a range of Pd-supported catalysts (Pd black, Pd/Ti02, Pd/Al203, Pd/SiOa, Pd/C). The usage of polar solvents like methanol and DMF decreased the selectivity dramatically but addition of triethyl amine, pyridine or potassium acetate to the reaction mixtures revert this result successfully. 

A similar catalytic system was applied for the isomerizing hydroformylation-hydrogenation sequence using an excess of hydrogen (Scheme 1.38) [15]. Preferentially, linear 2-olefins gave corresponding linear alcohols with lib selectivities up to 86 14. Under these conditions, also 2,5-dihydrofuran and 2,3-dihydropyrrol were cleanly converted. The highest selectivity was noted in the reaction with l-methyl-4-(prop-l-en-2-yl)cyclohex-l-ene, where only the exocyclic double bond reacted. 

Propargylamlnes 14 were converted to 5-methyleneoxazolidin-2-ones 15 using supercriHcal CO2 as a reagent and solvent (Scheme 9) [25]. This eco-friendly method utilized catalysis by basic alumina, which can be used for at least seven runs without loss of the catalytic activity. Yields of 15 (R = Me, =Bn) for these seven consecutive runs varied within 94-97% range. It should be noted that the amine 14 with u-hydrogens (R = H, R =n-pentyl) also selectively afforded product 15 with the exocyclic double bond. 

Reactions. Birch reduction of 2-furoic acid with lithium in liquid ammonia gives the 2,5-dihydro-compound (131) in 90% yield. Hydrogenation of the vinyl-furans (132 R = CO2H, C02Me, Ac, or COPh) in the presence of nickel bromide occurs selectively at the exocyclic double bond. Anodic methoxylation of 2-(2-thienylmethyl)-furan yields a mixture of geometrically isomeric adducts... 

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