Tether-directed allylation

Scheme 10-102 Tether-directed allylation provides a diastereoselective route to precursors in the synthesis of tricyclic jS-lactam antibiotics.

Scheme 6.186) [347]. The condensation of O-allylic and O-propargylic salicylalde-hydes with a-amino esters was carried out either in the absence of a solvent or - if both components were solids - in a minimal volume of xylene. All reactions performed under microwave conditions rapidly proceeded to completion within a few minutes and typically provided higher yields compared to the corresponding thermal protocols. In the case of intramolecular alkene cycloadditions, mixtures of hexa-hydrochromeno[4,3-b]pyrrole diastereoisomers were obtained, whereas transformations involving alkyne tethers provided chromeno[4,3-b]pyrroles directly after in situ oxidation with elemental sulfur (Scheme 6.186). Independent work by Pospisil and Potacek involved very similar transformations under strictly solvent-free conditions [348]. 

In order to increase interactions between the incoming nucleophile and the ligand, a chiral functional group capable of coordinating to the carbanion has been tethered to a bidentate phosphane. The resulting enhanced steric repulsion between the enolate and the chiral phos-phane now allows efficient differentiation between the enantiotopic faces of the prostereogenic enolate in favorable cases. Furthermore, directing the nucleophile accelerates the allylation process. 

Controlled radical cyclization directly onto a ring junction is less easy. Lejeune and Lallemand envisaged that a tethered radical cyclization of a (bromomethyl)dimethylsilyl ether onto an allylic double bond could be used to incorporate a hydroxymethyl functionality into an angular position at the ring junction of a decalin system [53]. This would then provide an interesting entry into a variety of natural products containing this skeletal functionality, such as the insect antifeedant clerodin 132 (Scheme 10-45). 

Ionic liquids ([BMIM][PF6]) are suitable media for the Co2(CO)8-catalyzed intramolecular and intermolecular Pauson-Khand aimulation, provided that the reaction is carried out under a CO pressure of 10 bar [299]. Two diethyl allyl propargyl malonates were quantitatively converted into the relevant cydopentenones, whereas heteroatom tethered enynes gave lower yields in their cydocarbonjiation products. An example is shown in Scheme 5.2-138. The reaction also works with the direct addition of ethyldiazoacetate to imines in [BMIM][BF4] and [BMIMjfPFe] [300]. 

Oxygen atoms, such as in an alcohol, are not sufficiently good ligands to have this effect. The best ligands are phosphoms based, but this atom is almost never required in the final product of the synthesis. The solution is to attach the phosphorus ligand, L to the alcohol in the substrate by a temporary tether that may be subsequently cleaved (Scheme 4.62). The reaction can proceed with useful diastereoselectivity and regioselectivity and, when allylic alcohols are the substrate, this represents an alternative to aldol chemistry. The directing effect can also involve stereochemical issues (Schemes 4.63. 65). ... 

Homoallylic alcohol 9 is readily prepared by palladium-catalyzed directed cyanoboration followed by Suzuki-Miyaura cross-coupling (Scheme 5.15) [15]. Palladium-catalyzed allyl transfer from 9 to aryl bromide results in removal of the hydroxymethyl directing group and concomitant formation of 3,4-diaryl-2-butenenitrile albeit the lack of regio- and stereospecificity. The overall transformation proposes a concept of intramolecular reaction with a carbon tether removable through retro-allylation. 

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