Stereocontrol in Diels-Alder

D. Horton and D. Koh, Stereocontrol in Diels-Alder cycloaddition to aneainratnd sugars Reactivities of acyclic seven-carbon trims dfenophttea derived hoot aldopeotoees, Carbohydr. Res. 250 249 (1993). 

C. Bumouf, J. C. Lopez, F. G. Calvo-Flores, M. D. Laborde, A. Olesker, and G. Lukacs, ir-Facial selectivity in Diels-Alder reactions of 2-C-vinylglycals. Stereocontrolled route to annulted C-glycopyranosides, J. Chem. Soc. Chem. Commun. p. 823 (1990). 

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,... 

Recently, Aggarwal et al. have found that MBH adducts 179 are excellent dienophiles in Diels-Alder reactions, providing essentially complete diaster-eocontrol with all dienes. Although exojendo stereoisomers 180 were formed with cyclopentadiene and no regioisomers were obtained with isoprene, the emerging asymmetric MBH reaction coupled with these new Diels-Alder reactions rapidly builds up complex architectures in a stereocontrolled process from very simple and inexpensive starting materials, and this will no doubt find applications in synthesis (Scheme 3.72). ... 

Applications in Diels-Alder Chemistry. Alkyldihaloboranes have also been used as chiral catalysts for the stereocontrolled Diels-Alder Chemistry. High ewdo-selectivity is observed for this reaction although the ee s are only in the range of 5-50% (eq 20). 

For the aza-Diels-Alder reaction illustrated above, water works better than LP-DE as a reaction medium, providing the cycloadducts in good yield with outstanding stereocontrol. 

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... 

Grieco investigated the intramolecular Diels-Alder reaction of imi-nium ions in polar media such as 5.0 M lithium perchlorate-diethyl ether and in water129 to form carbocyclic arrays. They showed that water as the solvent provided good-to-excellent yields of tricyclic amines with excellent stereocontrol (Eq. 12.58). 

The readily available enantiopure acyclic hydroxy 2-sulfinyl butadiene 585 undergoes a highly face-selective Diels-Alder cycloaddition with PTAD to generate the densely functionalized cycloadduct 586 (Equation 84). The complete reversal of facial selectivity is observed when sulfonyl derivative 587 is treated with PTAD under identical conditions (Equation 85). These results demonstrate that the sulfinyl functionality is not just synthetically useful but also an extremely powerful element of stereocontrol for intermolecular Diels-Alder cycloadditions. On the other hand, the corresponding ( , )-hydroxy-2-sulfinyldienes treated with PTAD affords the cycloadducts in high yield but with moderate 7i-facial selectivity <1998CC409, 2005CEJ5136>. 

Diels-Alder disconnection will have been eliminated, and the rctrosynthetic search becomes highly focused. Having selected both the transform and the mapping onto the TGT, it is possible to sharpen the analysis in terms of potentially available dienophile or diene components, variants on the structure of the intermediate for Diels-Alder disconnection, tactics for ensuring stereocontrol and/or position control in the Diels-Alder addition, possible chiral control elements for enantioselective Diels-Alder reaction, etc. 

Because the Diels-Alder reaction allows the construction of six-membered rings with the introduction of up to four new stereocenters in a stereocontrolled fashion in one single step, it is a very important tool for the synthesis of six-membered rings containing natural compounds and derivatives. In many synthetic strategies toward these types of compounds, the Diels-Alder reaction is a crucial step, as illustrated by the following examples. 

Tandem pericyclic processes offer the opportunity to synthesize complex highly substituted cyclic molecules in a completely stereocontrolled fashion in a few consecutive steps. As a consequence, tandem processes have been studied extensively. Some tandem processes involving Diels-Alder reactions have recently been reviewed38,40,107. 

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). 

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