Levoglucosenone Diels-Alder reaction

Cycloaddition reactions of levoglucosenone (2) have been widely investigated and include the Diels-Alder reaction with various dienes such as cyclopentadiene, butadiene, and isoprene.11-14 In addition, 1,3-dipolar cycloadditions have been investigated.15... 

We studied the Diels-Alder reaction of levoglucosenone (2) with the very reactive diene 2,3-dimethylene-2,3-dihydrofuran (3),10 the fiiran-based orf/io-quinodimethane, which is readily available by the Flash Vacuum Pyrolysis (FVP) of ester 4.16 Diene 3 dimerizes very rapidly16... 

The thermal reaction produced 5 and 6 in a 3 2 ratio but the Lewis acid-catalyzed reaction gave a 1 1 ratio. We could not separate the two cycloadducts, but based the indicated constitution on analysis of the mass spectrum and lH NMR spectrum of the mixture of the two compounds. The stereochemistry was assigned on the basis that the Diels-Alder reaction is normally suprafacial-suprafacial18 and that for other cycloaddition reactions of levoglucosenone (2) the addition anti to the 1,6-anhydro bridge is favored.13 15... 

Easily prepared from glycols, enones have been investigated as dienophiles. They react with butadiene under Lewis acid catalysis to form chiral cyclohexenes used in the synthesis of compactin analogs [353]. Levoglucosenone has been used in a Diels-Alder reaction with acetoxy-butadiene to construct a part of the indole alkaloid reserpine [354], and in synthetic studies toward tetrodotoxin [355]. Analogs of the anthracycline rhodomycinone have been similarly prepared [356]. [4 + 2]-Cycloaddition of the same enone with silyloxydiene allowed the creation of the fused ring system present in actinobolin [357]. 

Two examples of electrocyclic reactions for synthesis of carbocycles were reported. Diels-Alder reaction of D-glucose-derived diene 20 with quinone 21 gave 22, which epimerized on base catalysis to the trans-fused analogue. Levoglucosenone-derived enediene 23, was elaborated to triene 25 (via 24), thermal [3+3] rearrangement giving cyclohexadiene 26, then converted to 27, an... 

Horton and Bhata reported the synthesis of functionalized carbocycles by the Diels-Alder reactions of cyclopentadiene with levoglucosenone 14). The addition of cyclopentadiene occurred predominantly form the face of the enone opposite the 1,6-anhydro bridge, in the endo mode. 

A Diels-Alder reaction between 3-bromo-levoglucosenone and butadiene gives rise to adduct (10), which could be converted into (11), which represents the guanidinium part of tetrodotoxin. An interesting intramolecular Diels-Alder reaction (Scheme 3) was a key step in a synthesis of (+)-isovelleral (12) from the L-erythuronic acid derivative (13) which is accessible from D-ribonolactone. The synthesis produced firstly the diastereomer (14) of (-f-)-isovelleral (12), but the two were thermally interconvertible by an ene-type opening and closing of the three-membered... 

This methodology was initially applied to a synthesis of (—)-alloyohimbane (82) (Scheme 3.13) (29). Readily available levoglucosenone (75), a product of cellulose pyrolysis, was the starting material. Diels-Alder reaction of 75 with 1,3-butadiene afforded adduct 76 which underwent Wolff-Kishner elimination and subsequent acylation to provide the bicyclic enol ether 77. Hydrolysis followed by oxidation and saponification afforded hydroxymethyl lactone 78 which was then condensed with tryptamine to yield the amide diol 79. Periodate cleavage of the diol was followed by conversion to chloride 80 which was cyclized to afford lactam 81. Subsequent Bischler-Napieralski cyclization followed by hydrogenation of the olefin moiety afforded the target ( )-alloyohimbane (82). 

This type of reaction has been explored in detail as the chemical character of the conjugated system and reactivity of levoglucosenone is highly suitable for functionalization though cycloaddition reactions. Horton s laboratory (43,44) was the first to explore the potential of levoglucosenone as a chiral dienophile in Diels-Alder cycioadditions. 

The diastereofacial selectivity of the Diels-Alder addition of A -phenyhnaleimide to dienopyranoside 21 to give adduct 22 has been compared with the reaction of the carbocyclic analogue of 21. It was shown that the dienophile added to the face opposite to the methoxy group in all cases. See Chapter 24 for the Diels-Alder addition of dienes to levoglucosenone derivatives. 

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