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. 2011 Dec 21;133(50):20552-60.
doi: 10.1021/ja208935u. Epub 2011 Nov 29.

Palladium-catalyzed allylic substitution with (η6-arene-CH2Z)Cr(CO)(3)-based nucleophiles

Jiadi Zhang  1 , Corneliu Stanciu, Beibei Wang, Mahmud M Hussain, Chao-Shan Da, Patrick J Carroll, Spencer D Dreher, Patrick J Walsh
Affiliations

Palladium-catalyzed allylic substitution with (η6-arene-CH2Z)Cr(CO)(3)-based nucleophiles

Jiadi Zhang et al. J Am Chem Soc. .

Abstract

Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to "α-2-propenyl benzyl" motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (η(6)-C(6)H(5)CHLiR)Cr(CO)(3) nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to η(6)-toluene complexes, benzyl amine and ether derivatives (η(6)-C(6)H(5)CH(2)Z)Cr(CO)(3) (Z = NR(2), OR) are also viable pronucleophiles, allowing C-C bond-formation α to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetalation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions.

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Figures

Figure 1
Figure 1
Selected bioactive compounds and natural products containing the “α-2-propenyl benzyl” motif.
Scheme 1
Scheme 1
Palladium-catalyzed Benzylic Allylations.
Scheme 2
Scheme 2
Allylation at Multiple Benzylic Sites.
Scheme 3
Scheme 3
Allylic Substitution with Retention of Configuration.
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