Enantioselective DYKAT

In 2010, Cordova s group reported the first examples of one-pot highly chemo- and enantioselective DYKATs based on the reaetions between a,)S-unsaturated aldehydes and propargylated carbon acids, providing the... 

Ins(l,4,5)P3. A number of phosphates, e.g. (37), which act as inositol monophosphatase inhibitors have been synthesised from the l,6-epoxy-4-benzyloxycyc-lohexan-2-ol (36)7" Conduritol derivatives (39) are useful synthetic building blocks. However, the enantioselective palladium-catalysed allyl alkylation and similar reactions of (38) are complex due to C2 symmetry. It has now been reported that dynamic kinetic asymmetric transformation (DYKAT) of racemic... 

More recently, Trost el al. also examined the ability to use aliphatic alcohols as competent nucleophiles in the palladium-catalyzed DYKAT of MBH adducts. High yield and enantioselectivity were obtained for both the kinetic transformation and dynamic kinetic transformation to alford substituted pyran products. The utility of this method was further demonstrated in the context of a concise total synthesis of the gastrulation inhibitor ( + )-hippospongic acid A (Scheme 3.138). ° ... 

In 2009, Mangion et al. found that hydrazines and hydroxylamines eould be excellent nucleophiles for the Pd-catalysed allylic amination of butadiene monoepoxide in the presence of this ligand. The DYKATs afforded the corresponding amino alcohols in good yields and enantioselectivities, as shown in Scheme 2.50. The method was applicable to acyclic and heterocyclic amines, and applied towards a live-step synthesis of (f )-piperazic acid. 

By analogy to the DYKAT reactions with vinyl epoxides, Trost et al. have developed the Pd-eatalysed asymmetric dynamic kinetic allylic amination and acyl migration of vinyl aziridines with benzoyl imido carboxylates. As shown in Scheme 2.51, the process afforded the corresponding protected vicinal diamines in high yields and enantioselectivities of up to 93% ee. This methodology was demonstrated to be a platform for the formal synthesis of (-I- )-balanol and analogues. 

This ligand was also involved by Gais and colleagues in the Pd-catalysed enantioselective allylic alkylation of thiocarboxylate ions with allylic esters. " This novel DYKAT has allowed the access to highly enantio-enriched acyclic allylic thioesters in good to high yields, as shown in Scheme 2.56. 

In 2003, Trost and Frandrick developed a novel type of DYKAT based on the asymmetric palladium-catalysed cycloaddition between isocyanates and vinylaziridines. Performed in the presence of a chiral diphosphine as the ligand, the reaction allowed the access to a broad array of imidazolidin-2-ones with high yields and enantioselectivities of up to 95% ee, as shown in Scheme 2.58. In 2005, the same authors applied this methodology to the total synthesis of (-I- )-pseudodistomin D. ... 

Another type of DYKAT was reported by the same group on the basis of asymmetric palladium-catalysed alkylations of allenes with nucleophiles, such as amines and malonates. This methodology which employed a chiral diphosphine as the ligand provided the corresponding allenes and allenamines, respectively in high yields and enantioselectivities, as shown in Scheme 2.59. 

In 2009, Shibata s group achieved the first highly enantioselective direct K-hydroxylation of racemic malonates with oxaziridines through DYKAT catalysed by a chiral nickel catalyst to provide the corresponding chiral a-hydroxy malonates in high yields and enantioselectivities of up to 98% ee, as shown in Scheme 2.71. ° ... 

While a wide number of palladium-catalysed DYKATs have been developed, a much lower number of examples have dealt with the use of chiral copper catalysts. As an example, the copper-catalysed asymmetric allylic alkylation of cyclic substrates was reported for the first time by Langlois and Alexakis in 2010. Of particular interest was the addition of primary alkyl Grignard reagents to cyclic substrates, such as 3-bromocyclohex-l-ene, which afforded the corresponding alkylated products with excellent enantioselectivities of up to 99% ee, in the presence of a chiral copper catalyst (Scheme 2.81). These results constituted the first example of DYKAT in copper-catalysed asymmetric allylic alkylation. 

Very recently, Sun et al. developed a cascade reaction with a binary catalytic system combining a secondary amine and a palladium catalyst for the synthesis of dihydropyrrole enantioselectively [54]. The reaction began with a Jprgensen-Hayashi catalyst promoted N-Ts propargyl amine-involved aza-Michael addition to cinnamaldehydes and ended with subsequent PdCl and Jprgensen-Hayashi catalyst co-promoted car-bocyclization (Scheme 9.59). The chemistry presented here also involved a DYKAT process and provided an alternative to chiral dihyropyrrole synthesis. 

Enantioselective synthesis of syn-and anf/-1,3-aminoalcohols starting from aminoketones and subsequent reduction/DYKAT. 

Edin, M., Martin-Matute, B., and Backvall, J.-E. (2006). Ruthenium- and lipaseenantioselective synthesis of syn-l,2-diacetates. Tetrahedron Asymmetry, 17, 708-715. 

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