Magnesium bromide Diels-Alder reaction

A full report on the short stereocontrolled synthesis of racemic patchouli alcohol has been presented,362 the key steps of which are the Grignard addition of the magnesium derivative of the bromide (796) to the dienone (797) followed by an intramolecular Diels-Alder reaction. The preparation of the two enantiomers of... 

A different synthetic approach to benzoannelated [2.2]paracyclophanes was realized by the Diels-Alder reaction of bis (methylene) [2.2] paracyclophane (13) and tetrakismethylene[2.2]paracyclophane (15) with para-benzoquinone [20]. The bis(exomethylene)paracyclophane derivatives were obtained from 6 and 7 via a copper-mediated coupling with methyl magnesium bromide, bromination and debromination. The dienes 13 and 15 react readily to the bis- and tris-phanes 16 and 17 when heated with para-benzoquinone in dichlorobenzene. However, both compounds are extremely poorly soluble in organic solvents and... 

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. 

Danishefsky et al. have achieved a synthesis of a methyl peracetyl-oc-hikosaminide (216), an undecose degradation product of the anthelmintic hikizimycin, in which use is twice made of the siloxy-diene aldehyde Diels-Alder reaction. Thus, the reaction between the diene (211) and furfural with [EuCfod) ] catalysis leads to the pyrone (212) which, after elaboration to (213), is again condensed with (211), but this time with magnesium bromide catalysis, which causes addition of the remaining four carbon atoms of the undecose in a chelation-controlled and, notably, a topically exo reaction. Elaboration of (215) to the required protected hikosamine (216) then follows in a straightforward manner. 

The antitumor antibiotic phloeodictine A1 (171) has been synthesized by Snider s group (Scheme 15.37). The unstable azide derived from 167 was subjected to a polymer supported tandem Staudinger-aza-Wittig followed by a retro Diels-Alder reaction to afford intermediate 170. Addition of 11-dodecenyl magnesium bromide followed by alkylation reaction and deprotection completes an efficient synthesis of phloeodictine A1 (171). 

This particular reaction has been reported recently by Lukacs in the context of complex molecules synthesis by Diels-Alder cycloaddition [19]. A typical example is given in the experimental section. Note that the reaction of 5 with vinyl magnesium bromide gave a mixture of 4 and 6 because of epimerization of the axial methyl group at C-2 owing to the basicity of the reagents [20]. 

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