Cyclohexene derivative

Cyclopentene-l-carboxaldehydes are obtained from cyclohexene precursors by the sequence cyclohexene - cyclohexane-1,2-diol -> open-chain dialdehyde - cyclopentane aldol. The main advantage of this ring contraction procedure is, that the regio-and stereoselectivity of the Diels-Alder synthesis of cyclohexene derivatives can be transferred to cyclopentane synthesis (G. Stork, 1953 G. BUchi, 1968). 

Cyclohexene derivatives can be oxidatively cleaved under mild conditions to give 1,6-dicarbonyl compounds. The synthetic importance of the Diels-Alder reaction described above originates to some extent from this fact, and therefore this oxidation reaction is discussed in this part of the book. 

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

In antithetical analyses of carbon skeletons the synthon approach described in chapter I is used in the reverse order, e.g. 1,3-difunctional target molecules are "transformed" by imaginary retro-aldol type reactions, cyclohexene derivatives by imaginary relro-Diels-Alder reactions. 

To deduce the identity of the diene and dienophile that lead to a particular Diels-Alder adduct we use curved arrows in the reverse fashion to undo the cyclohexene derivative Start with the tt component of the double bond in the SIX membered ring and move electrons in pairs... 

Section 10 12 Conjugate addition of an alkene (the dienophile) to a conjugated diene gives a cyclohexene derivative in a process called the Diels-Alder reaction It is concerted and stereospecific substituents that are cis to each other on the dienophile remain cis m the product... 

Diels-Alder Reactions. The important dimerization between 1,3-dienes and a wide variety of dienoplules to produce cyclohexene derivatives was discovered in 1928 by Otto Diels and Kurt Alder. In 1950 they won the Nobel prize for their pioneering work. Butadiene has to be in the j -cis form in order to participate in these concerted reactions. Typical examples of reaction products from the reaction between butadiene and maleic anhydride (1), or cyclopentadiene (2), or itself (3), are <7 -1,2,3,6-tetrahydrophthaHc anhydride [27813-21 -4] 5-vinyl-2-norbomene [3048-64-4], and 4-vinyl-1-cyclohexene [100-40-3], respectively. 

Diels-Alder reaction (Section 10.12) Conjugate addition of an alkene to a conjugated diene to give a cyclohexene derivative. Diels-Alder reactions are extremely useful in synthesis. 

Once cyclization has occurred, the formed carbocation can lose a proton, and a cyclohexene derivative is obtained. This reaction is aided by the presence of an olefin in the vicinity (R-CH=CH2). 

The first mode of ring closure is usually observed for the cyclohexene derivatives 2.115... 

When 35 was heated in acetic acid containing hydrogen bromide, the tribromide 46 was obtained as a single product in 74% yield. Debromina-tion of 46 with zinc dust in acetic acid furnished the cyclohexene derivative 47, which was converted into compound 48 by osmium tetraoxide hydroxyl-ation and acetylation. The substitution reaction of 48 with acetate ions provided carba-a-DL-glucopyranose pentaacetate (49), which gave the carba-sugar 50 on hydrolysis. ... 

Thermal decarboxylation of 119 provided the cyclohexene derivative 120, which gave compound 121 by lithium aluminum hydride reduction. Hydroboration - oxidation of 121, followed by acetylation, gave carba-sugar derivatives (122 and 123) in equal yields. 

The crucial cyclization of 129 was accomplished by oxidation with pyri-dinium chlorochromate (PCC) and acetylation, providing two cyclohexane derivatives (130 and 131) in the ratio of 10 1. Thermal decarboxylation of 130 resulted in formation of the cyclohexene derivative 132, with concomitant elimination. Reduction of the ester group with diisobutylaluminum hydride converted 132 into 133. Hydroboration-oxidation of 133 gave the carba-sugar derivative 134 as a single product. 

Treatment of 51 with an excess of sodium benzoate in DMF resulted in substitution and elimination, to yield the cyclohexene derivative (228, 36%). The yield was low, but 228 was later shown to be a useful compound for synthesis of carba-oligosaccharides. <9-Deacylation of228 and successive benzylidenation and acetylation gave the alkene 229, which was oxidized with a peroxy acid to give a single epoxide (230) in 60% yield. Treatment of 230 with sodium azide and ammonium chloride in aqueous 2-methoxyeth-anol gave the azide (231,55%) as the major product this was converted into a hydroxyvalidamine derivative in the usual manner. On the other hand, an elimination reaction of the methanesulfonate of 231 with DBU in toluene gave the protected precursor (232, 87%) of 203. 

Very recently, the coupling of tributyl(phenyl) and tributyl(vinyl) stannanes with cyclohexene derivatives was successfully carried out using a similar catalytic cocktail prepared from Pdj(dba)3 CHCl, IPr HCl and Cs CO as base. Outstanding results... 

Neier and coworkers have used a domino Diels-Alder/Ireland-Claisen process for the synthesis of (rac)-juvabione 4-46 and (rac)-epijuvabione [15]. Since neither the Diels-Alder reaction of the acetal 4-44 and methyl acrylate nor the sigmatropic rearrangement seemed to be stereoselective, these authors obtained the cyclohexene derivative 4-45 as a mixture of three diastereomers (Scheme 4.9). 

Triphenylphosphine was obtained from Nakarai Chemicals, Japan. When the reaction is carried out without additional triphenylphosphine, the yield of coupling product may drop to 60-70% and the product is accompanied by the by-products, phenyl vinyl sulfide and 4-viny 1-1 -cyclohexene, derived from 3-hydride elimination. 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

Retro-Diels-Alder reactions can be used to regenerate dienes or alkenes from Diels-Alder protected cyclohexene derivatives under pyrolytic conditions144. Most of the synthetic utility of this reaction comes from releasing the alkene by diene-deprotection. However, tetralin undergoes cycloreversion via the retro-Diels-Alder pathway to generate o-quinodimethane under laser photolysis (equation 89)145. A precursor of lysergic acid has been obtained by deprotection of the conjugated double bond and intramolecular Diels Alder reaction (equation 90)146. 

Using a protocol for tandem carbonylation and cycloisomerization, Mandai et al.83 were able to synthesize cyclopentene and cyclohexene derivatives in high yield, including fused and 5/>/>0-bicycles (Scheme 25). The cyclohexene Alder-ene products were not isolable methanol addition across the exocyclic double bond (in MeOH/ toluene solvent) and olefin migration (in BuOH/toluene solvent) were observed. The mechanism of methanol addition under the mild reaction conditions is unknown. In contrast to many of the other Pd conditions developed for the Alder-ene reaction, Mandai found phosphine ligands essential additionally, bidentate ligands were more effective than triphenylphosphine. 

The thermal ring opening of the cyclobutene in the heterocycle (339) led also to cyclohexene derivatives (340) through intermolecular Diels-Alder reaction 119). 

Novel thermal and metal-catalyzed di-tert-butylsilylene 161 transfer reactions have been reported by Woerpel < / /.308-312 The transfer reactions required the inital preparation of cyclohexene-derived silacyclopropanes 169-171, which has been achieved by trapping of di-fert-butylsilylenoid, generated from /-Bu2SiCl2 and lithium, with cyclohexenes (Scheme 26).305 It is noteworthy that these reactions occur with remarkably high diastereoselectivities when 2-substituted cyclohexenes are used. The silacyclopropanation of 169 with functionalized cyclopentenes under thermal conditions (115°C) has provided /razy-silacyclopropanes, such as 172, with diastereoselectivities up to 96 4, whereas no silacyclopropanes were obtained from the direct reaction of the same cyclopentenes with /-Bu2SiCl2 in the presence of lithium (Scheme 26).308... 

In connection with the behavior of the eight-membered ring system, it is interesting to mention that the uncatalyzed thermolysis of the open-chain tetraene ether 230 in toluene at 150 °C (11 h) gives rise to a mixture of four intramolecular Diels-Alder products 231-234 in 80% total yield (equation 74)88. The thermolysis of dimethyl homologue 235 (toluene, 150 °C, 11 h, 81%) affords the c/s-fused cyclohexene derivative 236 and... 

The Diels-Alder reaction is the reaction of a diene with a mono-ene to form a cyclohexene derivative, an important reaction for the construction of organic intermediates. One of its attractions is the atom efficiency of 100%, no by-products being formed. The mono-ene, or dienophile which may also be an alkync, has a LUMO of low energy while the diene is usually electron rich with a high lying HOMO. The interaction of these two orbitals starts the reaction between the two molecules (Figure 2.33) [26],... 

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