Levoglucosenone, cycloaddition

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... 

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... 

Levoglucosenone (287), readily available by the pyrolysis of cellulose, when heated with a variety of dienes in the absence of a Lewis acid provided exclusively products (289) resulting from cycloaddition to its convex face (Scheme 69, Table 15)7 ... 

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]. 

Another interesting dicnophile, l,6-anhydro-3,4-dideoxy-/ -D-g7)-rm>-hex-3-enopyranose-2-ulose (levoglucosenone, 9), is readily available by pyrolysis of waste papers. [4 + 2] Cycloaddition of cyclic28,29 and acyclic28,30 dienes to 9 proceeds with selective attack of the diene molecule to the face opposite the 1,6-anhydro bridge giving a mixture of endo- and exo-adducts. 

The Yohimbe alkaloids such as alloyohimbane (1) and the antihypertensive drug reserpine constitute attractive goals for synthetic chemists. Syntheses of Yohimbe alkaloids from noncarbohydrates have been reported. " Synthesis of 1 from cellulose has also been achieved (Scheme 1). Pyrolysis of cellulose gave the levoglucosenone (l,6-anhydro-3,4-dideoxy- 3-D-glycero-hex-3-enopyrano-2-ulose, 2), which underwent Diels-Alder cycloaddition with... 

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. 

Paton and coworkers (45) reported a highly regio- and stereospecific cycloaddition reaction of benzonitrile oxide to levoglucosenone leading to the formation of two exo-isomers and the endo- adduct in 70 % yield. A similar approach to functionalized levoglucosenone was based on the stereoselective construction of fused heterocyclic systems (45-49). 

Regio- and steroselective dipolar cycloadditons of benzonitrile oxide and C -diphenylnitrone to levoglucosenone have been recently reported (47). In both cases, the major product results from the addition of the l,3>dipole to the face of the enone opposite the 1,6-anhydro bridge, with the dipole oxygen becoming attached to the p-carbon of the enone. Facial selectivities of 100 1 were observed in the nitrile oxide cycloaddition). 

The cycloaddition of various 13-dipoles to levoglucosenone has been described (Scheme 7) The rhodium catalyzed hydroformylation of glycals in the presence of xn ortho-tert-butylphenyl) phosphite to afford 2-formyl derivatives such as 33 has appeared. ... 

The 1,3-dipolar cycloadditions of benzonitrile oxide and C,N-diphenylnitrone to levoglucosenone were highly regio- and face-selective giving essentially the single products (81) and (82) respectively. ... 

Cycloaddition of a-diqulnodimethane and levoglucosenone gave the adduct (10), potentially useful for making pyranonaphthoquinones. Diels-... 

Bromo-levoglucosenone 31 provides a functionalized dienophile which undergoes cycloaddition to give, after straightforward manipulation, ketone 32. The hindered ketone unit of 32 underwent nucleophilic attack using an alkynylborate complex in a synthetic approach directed towards tetrodotoxin (Scheme 6). Ketone 32 was found to be extremely sensitive and the precise nature of the alkynyl nucleophile was crucial to the success of the key addition step. ... 

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