Asymmetric tertiary stereocenter

The potential substrates for the Strecker reaction fall into two categories ald-imines (derived from aldehydes, for which cyanide addition results in formation of a tertiary stereocenter) and ketoimines (derived from ketones, for which addition results in a quaternary stereocenter). As in the case of carbonyl cyanation, significant differences are observed between the substrate subclasses. To date, while a few catalyst systems have been found to display broad substrate scope with respect to aldimine substrates, successful Strecker reactions of ketoimines have been reported in only two cases. As is the case for all asymmetric catalytic methodologies, the breadth of the substrate scope constitutes a crucial criterion for the application of the Strecker reaction to a previously unexplored substrate. 

New asymmetric polymetallic catalysts were reported for the ring-opening reaction of ffieso-aziridines with TMSCN <07T5820>. Three contiguous tertiary stereocenters were generated via the reaction of active methylene nucleophiles with tosylated aziridines under mild phase-transfer catalyzed conditions. For example, reaction of aziridine 61 with the anion derived from 62 provided substituted cyclopentane 63 in excellent yield <07OL4677>. 

Asymmetric intramolecular conjugate addition of chiral enolates to form pyrrolidine, piperidine, indoline, and tetrahydroisoquinoline derivatives with contiguous quaternary and tertiary stereocenters 06YZ617. 

A direct catalytic asymmetric aldol-type reaction of 3-substituted-2-oxindoles with glyoxal derivatives was catalyzed by a similar chiral )V,A -dioxide-Sc(OTf)3 complex (eq 33). The complex efficiently catalyzed the aldol reaction affording the 3-(a-hydroxy-/3-carbonyl) oxindoles with vicinal quaternary-tertiary stereocenters, in up to 93% yield, 99 1 dr, and >99% ee under mild conditions. 

Zhou SJ, Huang Z (2013) Chiral phosphines for palladium-catalyzed asymmetric alpha-arylation of ester enolates to produce tertiary stereocenters in high enantioselectivity. WO/2013/028132 http //ww w. google. com/patents/WO2013028132A1 cl=en... 

The first step of the proposed synthesis is the intermolecular Michael reaction of 2-substituted p-ketoesters and p-substituted enones, which results in vicinal quaternary and tertiary stereocenters. Michael reactions of this type are challenging, due to the increased sterics. In fact, only a few asymmetric examples have been reported to constract these motifs (Scheme The only success-... 

With the catalyst of choice and optimal reaction conditions identified, the scope and limitations of the enantioselective Michael reaction were investigated (Schemes 6-10). As examples of asymmetric Michael reactions of 2-substituted p-ketoesters and p-substituted enones resulting in vicinal quaternary and tertiary stereocenters are limited (vide supra), demonstrating the utility of these reaction conditions would be beneficial. 

Asyimnetric catalytic method to generate C-C bond with adjacent quatemaiy-tertiary stereocenters ranains a challenging synthetic task. In this regard, the use of 3-substituted oxindoles as carbon-nucleophiles has attracted intensive interests due to their relevance in synthesizing bioactive indole alkaloids. Melchiorre recently reported asymmetric Michael addition of 3-substituted oxindoles to a,P-unsaturated aldehydes catalyzed by a primary amine thiourea catalyst 114 (Scheme 5.29). Good diasteieoselectivity and enantioselectivity have been achieved in most cases. However, the reactions were generally sluggish [56]. 

The first asymmetric total synthesis of (+)-lycorine is outlined in Scheme 15. While our earlier applications of the Birch reduction-alkylation of chiral benzamide 5 were focused on target structures with a quaternary stereocenter derived from C(l) of the starting benzoic acid derivative, the synthesis of 64 demonstrates that the method also is applicable to the construction of chiral six-membered rings containing only tertiary and trigonal carbon atoms. s... 

During the asymmetric total synthesis of (+)-pravastatin by A.R. Daniewski et al., one of the stereocenters was introduced with the Eschenmoser-Claisen rearrangement. The tertiary alcohol intermediate was heated in neat N,N-dimethylacetamide dimethyl acetal at 130 °C for 48h, during which time the by-product methanol was distilled out of the reaction mixture to afford the desired amide in 92% yield. 

Strecker reaction to establish a new stereocenter is subject to asymmetric induction, capable of creating either a tertiary" or quaternary carbon atom in the presence of 59. The peptido-imine 60 proves to be an excellent ligand for the Ti(IV)-mediated cyanation of aldimines. On catalysis of the bicyclic guanidine 61 the addition of HCN to A-benzhydrylaldimines affords a-amino nitrile derivatives with moderate to good ee. ... 

The use of palladium(II) 7i-allyl complexes in organic chemistry has a rich history. These complexes were the first examples of a C-M bond to be used as an electrophile [1-3]. At the dawn of the era of asymmetric catalysis, the use of chiral phosphines in palladium-catalyzed allylic alkylation reactions provided key early successes in asymmetric C-C bond formation that were an important validation of the usefulness of the field [4]. No researchers were more important to these innovations than Prof. B.M. Trost and Prof. J. Tsuji [5-10]. While most of the early discoveries in this field provided access to tertiary (3°) stereocenters formed on a prochiral electrophile [Eq. (1)] (Scheme 1), our interest focused on making quaternary (4°) stereocenters on prochiral enolates [Eq. (2)]. Recently, we have described decarboxylative asymmetric allylic alkylation reactions involving prochiral enolates that provide access to enantioenriched ot-quatemary carbonyl compounds [11-13]. We found that a range of substrates (e.g., allyl enol carbonates,... 

Enantioenriched a-arylcarboxylic acids with a tertiary a stereocenter are an important class of chiral building blocks that serve as useful intermediates in the synthesis of bioactive compounds. For the synthesis of enantioriched a-arylcarbonyl compounds, Lundin and Fu developed a nickel-catalyzed method for the asymmetric Suzuki aryla-tion of racemic a-chloroamides." Efficient reactivity was observed with NiBr2- diglyme and ligand 88, that are both commercially available. Thus, treatment of racemic... 

Palomo C, Oiarbide M, Dias F, Lopez R, Linden A. Construction of C—S bonds with a quaternary stereocenter through a formal Michael reaction asymmetric synthesis of tertiary thiols. Angew. Chem. Int. Ed. 2004 43 3307-3310. 

---