Structure-Based Rationale for Selectivity in the Asymmetric Allylic Alkylation of Cycloalkenyl Esters Employing the Trost ‘Standard Ligand’ (TSL): Isolation, Analysis and Alkylation of the

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• 作者：Craig P. Butts ; Emane Filali ; Guy C. Lloyd-Jones ; Per-Ola Norrby ; David A. Sale ; York Schramm
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：July 29, 2009
• 年：2009
• 卷：131
• 期：29
• 页码：9945-9957
• 全文大小：536K
• 年卷期：v.131,no.29(July 29, 2009)
• ISSN：1520-5126

文摘

The solution-phase structures of the monomeric forms of the cationic Pd-ηp>3p>-allyl and Pd-ηp>3p>-cyclohexenyl complexes [Pd(R,R)-1(ηp>3p>-C₃H₅)]p>+p> (7p>+p>) and [Pd(R,R)-1(ηp>3p>-C₆H₉)]p>+p> (8p>+p>) bearing the trans-cyclohexylenediamine-based Trost ‘Standard Ligand’ (R,R)-1 have been elucidated by NMR, isotopic labeling and computation. In both complexes, (R,R)-1 is found to adopt a C₁-symmetric conformation, leading to a concave shape in the 13-membered chelate in which one amide group in the chiral scaffold projects its NH unit out of the concave surface in close vicinity to one allyl terminus. The adjacent amide has a reversed orientation and projects its carbonyl group out of the concave face in the vicinity of the opposite allyl terminus. Stoichiometric and catalytic asymmetric alkylations of [8p>+p>][Xp>−p>] by MCHE₂ (E = ester, M = ‘escort’ counterion, X = Pd allyl counterion) show the same selectivities and trends as have been reported for in situ-generated catalysts, and a new model for the enantioselectivity has been explored computationally. Three factors are found to govern the regioselectivity (pro-S vs pro-R) of attack of nucleophiles on the ηp>3p>-C₆H₉ ring in 8p>+p> and thus the ee of the alkylation product: (i) a pro-R torquoselective bias is induced by steric interaction of the ηp>3p>-C₆H₉ moiety with one phenyl ring of the ligand; (ii) pro-S delivery of the nucleophile can be facilitated by hydrogen-bonding with the concave orientated amide N−H; and (iii) pro-R delivery of the nucleophile can be facilitated by escort ion (M) binding to the concave orientated amide carbonyl. The latter two opposing interactions lead to the selectivity of the alkylation being sensitive to the identities of Xp>−p> and Mp>+p>. The generation of 8p>+p> from cyclohexenyl ester substrate has also been explored computationally. The concave orientated amide N−H is able to activate the leaving group of the allylic ester by hydrogen bonding to its carbonyl group. However, this interaction is only feasible for the (S)-enantiomer of substrate, leading to the prediction of a powerful kinetic resolution (k_S k_R), as is found experimentally. This new model involving two regiochemically distinct (NH) and (CO) locations for nucleofuge or nucleophile binding, may prove of broad utility for the interpretation of the selectivity in asymmetric allylic alkylation reactions catalyzed by Pd complexes of (R,R)-1 and related ligands.