Asymmetric HDA reaction

Synthesis of a key 3,4-dihydropyran 196 during synthetic studies towards reveromycin B is achieved using an asymmetric hDA reaction. No chiral Lewis acid catalysts or auxiliaries are necessary as the stereochemistry at the spirocentre is controlled by the anomeric effect (Equation 93) <1997JOCl 196>. 

The synthesis of dihydropyranones by the asymmetric HDA reaction <07SL2147> and advances in approaches to natural product-based analogues <07EJO225> have been reviewed. 

The majority of metal-based Lewis acid catalysts used in the HDA reaction are moisture sensitive and are thus usually prepared in situ. The stable and storable zirconium-BINOL Lewis acids developed by Kobayashi and coworkers, effective in the aldol reaction (see Section 7.1) can also be used as asymmetric catalysts in the HDA reaction of aliphatic and aromatic aldehydes with dioxygenated dienes. Metal-free catalytic asymmetric HDA reactions have been developed, utilising enantiomerically pure protic molecules that activate the aldehyde component by hydrogen bonding to the carbonyl group. Rawal and coworkers have achieved up... 

Asymmetric hDA reaction of Danishefsky s dienes with a-carbonyl esters catalyzed by an indium(III)-pybox complex affords 2,3-dihydro-4f/-pyran-4-ones with good to excellent enantioselectivity (Scheme 57) (130L2914). 

In 1995, Katsuki and Yamashita [11a] found that Mg-salen complex and Co- or Cr-salen complexes served as Lewis acid catalysts for asymmetric Diels-Alder reactions and hetero Diels-Alder (HDA) reaction of Danishefsky s diene (l-methoxy-3-trimethylsilyloxy-l,3-butadiene) with aldehydes. Later on, they found that second-generation (R,S)-(ON )Ru-salen complex bearing chiral binaphthyl and ethylenediamine units also served as a catalyst for asymmetric HDA reaction between Danishefsky s diene and benzaldehyde [llbj. Recently, in 2001 they reported that (R,S)-Ru(II)-salen complex served as a good catalyst for... 

There are two main HDA approaches to stereocontrolled THP synthesis. The first uses a chiral auxiliary to direct ir-facial selectivity and generally proceeds through an endo transition state to give 2,6-cis cycloadducts. The second approach uses coordination of a chiral Lewis acid to activate the carbonyl while directing the approach of the diene to one face of the carbonyl dienophile. Several catalysts have been developed for the asymmetric HDA reaction with Jacobsen s Cr(lll) complexes [111, 112] exhibiting good to excellent enantioselectivities with a variety of substrates [113]. 

Scheme 5.3 A chiral diol ligand Iibra7 for solvent-free asymmetric HDA reaction.

Combinatorial Approach for Homogeneous Asymmetric Catalysis 1157 Table 5.2 Solvent-free asymmetric HDA reaction of aldehydes 1 with Danishefsky s diene 2. ... 

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