Palladium catalyzed reactions desymmetrization

This methodology has been used to provide efficient protocols for the asymmetric allylic alkylation of p-keto esters, ketone enolates, barbituric acid derivatives, and nitroalkanes. Several natural products and analogs have been accessed using asymmetric desymmetrization of substrates with carbon nucleophiles. The palladium-catalyzed reaction of a dibenzoate with a sulfonylsuccinimide gave an advanced intermediate in the synthesis of L-showdomycin (eq 3). ... 

The enantioselective desymmetrization strategy can also be used for the palladium-catalyzed cross-coupling reactions with Grignard reagents. Thus, in the... 

Reactions with Nitrogen Nucleophiles. The palladium(O)-catalyzed asymmetric desymmetrization of cw-3,5-dibenzoyloxy-1-cyclopentene, with 6-chloropurine and 2-amino-6-chloropurine as nucleophiles, has been utilized in the synthesis of (-)-carbovir and (—)-neplanocin. In these examples, the diphenylethanediamine and the anthracenyldiamine based ligands were found to be superior to the standard ligand. 

For the desymmetrization, 448 was transformed into the monoenoltriflate, which in a palladium-catalyzed couphng reaction provided tetraolefin 450, ready for a Grubbs-Hoveyda cydization generating the cycloheptene moiety of449. 

Radhakrishnan and coworkers reported desymmetrization of bicyclic hydrazines, derived from the [4+2] cycloaddition of fulvene 27 with diethy-lazodicarboxylate, followed by a palladium/Lewis acid-catalyzed reaction with allyl and vinyl stannane to provide the alkylidene cyclopentenes 106 and 107, respectively (Scheme 7.25) [26]. 

Azide salts are a class of versatile nitrogen nucleophiles that can be readily employed as reaction partners in palladium-catalyzed allylic displacement reactions. A telling example was documented by Trost in the desymmetrization of bis-carbonate 51 to give azide 52 in an excellent 95% ee (Scheme 14.10) [66]. The fact that the reaction proceeds under mild conditions ensures that any undesired rearrangement of the allylic azide 52 is suppressed. 

Trost has reported enhanced enantioselectivity in the desymmetrization of mero-biscarbamates in the presence of triethylamine. Under these conditions, high yields (>80%) and enantiomeric excesses (93-99% ee) are obtained. This methodology has been applied to the synthesis of (—)-swainsonine. a-Amino esters have been used as nucleophiles in the reaction with acyclic allylic esters and isoprene monoepoxide, providing access to diastereoselective N-alkylated a-amino esters. By employing the feature ligand, asymmetric palladium(0)-catalyzed cychzation of 2-(tosylamino)phenol with ( -l,4-bis[(methoxycarbonyl)oxy]but-2-ene provides 2-vinylbenzomorpholine in 79% ee. A number of alternative diphosphine ligands were studied and found to be inferior. 

Lautens has spearheaded the study of a range of metal-catalyzed methods for the desymmetrization of various meso-oxabicyclooctanes [40]. In initial work, enantioselective nickel-catalyzed hydroalumination reactions of substrates such as 148 proved effective for the generation of cycloheptene 150 (95% ee, Scheme 14.24) [118], as also described in Section 7.5. The related desymmetrization reactions could be effected with carbon nucleophiles as well [119, 120], Thus, asymmetric ring-opening of 145 with Me2Zn mediated by a palladium catalyst prepared in situ with ligand 146 [121] led to the C3-C9 fragment (147) of the polyether antibiotic ionomycin (151) [120]. 

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