Recent developments in the stereoselective synthesis of α-aminoacids

ConspectusTransition-metal catalyzed C–H functionalizations became a complementary and efficient bond-forming strategy over the past decade. In this respect, Cp*Rh(III) complexes have emerged as powerful catalysts for a broad spectrum of reactions giving access to synthetically versatile building blocks. Despite their high potential, the corresponding catalytic enantioselective transformations largely lag behind. The targeted transformations require all the remaining three coordination sites of the central rhodium atom of the catalyst. In consequence, the chiral information on a competent catalyst can only by stored in the cyclopentadienyl unit. The lack of suitable enabling chiral cyclopentadienyl (Cpx) ligands is the key hurdle preventing the development of such asymmetric versions. In this respect, an efficient set of chiral Cpx ligands useable with a broad variety of different transition-metals can unlock substantial application potential. This Account provides a description of our developments of two...

Chiral Cyclopentadienyls: Enabling Ligands for Asymmetric Rh(III)-Catalyzed C–H Functionalizations

TADDOLs, which contain two adjacent diarylhydroxymethyl groups in a trans relationship on a 1,3-dioxolane ring, can be prepared from acetals or ketals of tartrate esters by reaction of the latter with aromatic Grignard reagents. They are extraordinarily versatile chiral auxiliaries. Here, a historical review of the subject is followed by discussion of the preparation of TADDOLs and analogous systems, including TADDOLs with N-, P-, O-, and S-heteroatom ligands appropriate for metals. Crystal structure analysis reveals that the heteroatoms on the diarylmethyl groups are almost always in close proximity to each other, joined together by H-bonds, and predisposed to form chelate complexes in which the metallic centers reside in propeller-like chiral environments. Applications of TADDOL derivatives in enantioselective synthesis extend from utilization as stoichiometric chiral reagents or in Lewis acid mediated reactions, to roles in catalytic hydrogenation and stereoregular metathesis polymerization. Derivatives and complexes based on the following metals have so far been investigated: Li, B, Mg, Al, Si, Cu, Zn, Ce, Ti, Zr, Mo, Rh, Ir, Pd, Pt. The number of stereoselective reactions already accomplished with TADDOLs is correspondingly large. It is also easy to prepare TADDOL derivatives that are readily polymerizable and graftable, and to transform them into immobilized solid-phase catalysts. The result is catalysts, simply or dendritically immobilized in polystyrene or on silica gel and characterized by unexpected stability even after multiple use in titanium TADDOLate mediated reactions. TADDOLs show further unusual characteristics that make them useful for applications in material science and supramolecular chemistry: they are the most effective doping agents known for phase transformations of achiral (nematic) into chiral (cholesteric) liquid crystals. The TADDOL OH group that is not involved in intramolecular H-bonding shows a strong tendency to associate intermolecularly with H-bond acceptors. In the process of crystallization this leads, enantioselectively, to the formation of inclusion compounds that lend themselves to the separation of racemic mixtures not otherwise suited to the classical method of crystallization through diastereomeric salts. The high melting points of TADDOLs even make possible the resolution of racemates by distillation! Host-guest compounds formed between TADDOLs and achiral partners can serve as platforms for enantioselective photoreactions. It seems safe to predict that many more applications will be discovered for the TADDOLs and their derivatives. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author.

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TADDOLs, Their Derivatives, and TADDOL Analogues: Versatile Chiral Auxiliaries

We thank the Spanish Ministerio de Ciencia e Innovacion (Grant Nos. CTQ2007-65218 and Consolider Ingenio 2010-CSD-2007-00006 and CTQ2011-24165), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER), and the University of Alicante for generous and continuous financial support.

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Diastereoselective allylation of carbonyl compounds and imines: application to the synthesis of natural products.

Total syntheses of the macrolides (R)-(+)-ricinelaidic acid lactone (6) and (−)-gloeosporone (7), a fungal germination self-inhibitor, are presented, which are distinctly shorter and more efficient than any of the previous approaches to these targets reported in the literature. Both of them benefit from the remarkable ease of macrocyclization of 1,ω-dienes by means of ring-closing olefin metathesis (RCM) using the ruthenium carbene 1a as catalyst precursor. The diene substrates are readily formed via the enantioselective addition of dialkylzinc reagents to aldehydes in the presence of catalytic amounts of Ti(OiPr)4 and bis-triflamide 18 and/or the stereoselective allylation of aldehydes developed by Keck et al. using allyltributylstannane in combination with a catalyst formed from Ti(OiPr)4 and (S)-(−)-1,1‘-bi-2-naphthol. Comparative studies show this latter procedure to be more practical than the stoichiometric allylation reaction employing the allyltitanium−α,α,α‘,α‘-tetraaryl-1,3-dioxolane-4,5-dimethan...

Total Syntheses of (+)-Ricinelaidic Acid Lactone and of (−)-Gloeosporone Based on Transition-Metal-Catalyzed C−C Bond Formations

The preparation, analysis, and reactions of novel, highly stereoselective cyclopentadienyldialkoxyallyltitanium reagents, available in both enantiomeric forms, are described. Chiral monochlorotitanates are readily prepared from CpTiCl 3 or Cp.TiCl 3 and chiral 1,4-diols, which in turn are obtained from tartrate ester acetals by Grignard addition. The resulting stable seven-membered titanacycles have been analyzed by 1 H, 13 C, and 49 Ti NMR spectroscopy. The structures of two representatives, the complexes 15 and 20, are confirmed by X-ray diffraction

Enantioselective syntheses with titanium carbohydrate complexes. Part 7. Enantioselective allyltitanation of aldehydes with cyclopentadienyldialkoxyallyltitanium complexes

Petra Rothe-Streit

Papers

Enantioselective syntheses with titanium carbohydrate complexes. Part 7. Enantioselective allyltitanation of aldehydes with cyclopentadienyldialkoxyallyltitanium complexes