Stereocontrol, 4-pyrones

Regiocontrolled and stereocontrolled Diels-Alder cycioadditions of 2-pyrones and unactivated unbranched 1 -alkenes [73]... 

Posner G. H. Stereocontrolled Synthesis of Functionalized Cyclohexenes Via Diels-Alder Cycloadditions of 2-Pyrones and 2-Pyridones-Applications to Synthesis of Physiologically Active Compounds in Stereocontrolled Org. Synth. 1994 177, Ed. Trost B. M., Pb. Blackwell Oxford... 

Okamura and Nakatani [65] revealed that the cycloaddition of 3-hydroxy-2-py-rone 107 with electron deficient dienophiles such as simple a,p-unsaturated aldehydes form the endo adduct under base catalysis. The reaction proceeds under NEtj, but demonstrates superior selectivity with Cinchona alkaloids. More recently, Deng et al. [66], through use of modified Cinchona alkaloids, expanded the dienophile pool in the Diels-Alder reaction of 3-hydroxy-2-pyrone 107 with a,p-unsaturated ketones. The mechanistic insight reveals that the bifunctional Cinchona alkaloid catalyst, via multiple hydrogen bonding, raises the HOMO of the 2-pyrone while lowering the LUMO of the dienophile with simultaneous stereocontrol over the substrates (Scheme 22). 

Cycloaddition Yamamoto s MAD Lewis acid promoted very mild and highly stereocontrolled [4-1-2] cycloaddition between the pyrone sulfone and enantiomerically pure vinyl ether 56 by use of 50 mol% MAD, cycloadducts were isolated on a 1.5-g scale in 93% yield as a 98 2 ratio of endo diastereomers with 57 being a major isomer (Scheme 6.37) [59]. 

In a much more complicated piece of work recently disclosed, two stereospecific aldehyde Diels-Alder reactions have been used in preparation of hikosamine derivative 29, a component of the antibacterial compound hizikimycin (Scheme 4-XIII).45k Diene 25 reacted with furfural to give cw-y-pyrone 26, which was transformed in several steps to aldehyde 27. Condensation of 27 with 25 using magnesium bromide as catalyst afforded only adduct 28, presumably via chelated intermediate 27A. Compound 28 was converted in a series of steps to acetylhikosamine 29. The methodlogy described here allowed total synthesis of this unusual sugar having 10 contiguous chiral centers with complete stereocontrol. 

This chapter focuses on recent advances in the scope, stereocontrol, and synthetic utility of 2-pyrones in Diels-Alder reactions. Special attention is given to the development of new, mild reaction conditions and electronically matched reaction partners which allow isolating the initially formed bicyclic lactone adducts. Relative reactivities and selectivities of differently substituted pyrones are compared. Finally,... 

More recently it was demonstrated that Lewis acid catalysis combined with high pressure coaxes 3-bromo-2-pyrone into [4+2] cycloadditions with unactivated terminal alkenes leading to cycloadducts, as shown in Table 5. As in the case of 3-methoxycar-bonyl-2-pyrone vide supra), reaction with unactivated dienophiles generally leads to decreased levels of stereocontrol compared to reaction with activated dienophiles. 

Markd and co-workers reported low levels of stereocontrol in the cycloaddition of 3-methoxycarbonyl-2-pyrone and butyl vinyl ether when TADDOL ligands are used in conjunction with YbfOTOj. ... 

Markd and co-workers also explored the use of binol complexes as Lewis acid catalysts for [4-t-2] cycloadditions of 3-methoxycarbonyl-2-pyrone. Marko reported modest to excellent levels of stereocontrol in the cycloadditions of a variety of vinyl ethers with this pyrone (Table 1 i)."b-d,6i gjjjj better results are reported when vinyl thioethers function as the dienophile. It is important to note that these impressive stereochemical results are obtained with catalytic amounts (0.1-0.2 equivalents) of Lewis acid. 

After obtaining the requisite intermediate 98, we then directed our attention to the synthesis of target 6 as shown in Scheme 22. The sequence involved the stereocontrolled formation of the tetrahydrofuran ring and subsequent conversion of the y-pyrone moiety into a-pyrone as the crucial steps. To this end, the removal of the TES protecting group from 98 followed by treatment with TsCl resulted in the formation of the desired cyclized product 99 in 80% overall yield as a single stereoisomer. We believe that the cyclized product 99 was formed from intermediate tosylate 88 (not isolated)... 

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