Aza variant of intramolecular nucleophile-catalyzed aldol lactonization (NCAL): formal synthesis of (3 S,4 R) and (3 R,4 S) 4-(hydroxymethyl)pyrrolidin-3-ol (original) (raw)
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Angewandte Chemie International Edition, 2010
The ability to rapidly assemble complex carbocyclic frameworks in a catalytic, asymmetric manner has garnered great interest in recent years. This type of cascade process, which generates multiple C À C and C À X bonds and stereogenic centers, including quaternary carbon atoms, is highly useful in chemical biology, for example when attempting to synthesize a family of compounds around a natural product lead. We developed intramolecular nucleophile-catalyzed aldol lactonization (NCAL) processes that deliver bicyclic b-lactones from aldehyde acid substrates by using Cinchona alkaloid catalysts and modified Mukaiyama activating agents. [3] The NCAL methodology was more recently applied to keto acid substrates by using stoichiometric nucleophiles including 4-pyrrolidinopyridine (4-PPY), which led to a variety of racemic bi-and tricyclic b-lactones, and a nine-step enantioselective synthesis of salinosporamide A from d-serine. [5] Tricyclic-b-lactones (AE )-4 (Scheme 1) were also found to participate in a novel dyotropic process leading to spirocyclic g-lactones. In the latter report, we described a single example of an enantioselective NCAL process with keto acids leading to b-lactone (À)-4, by employing stoichiometric quantities of commercially available tetramisole (Scheme 1). Herein, we report a significant advance in the NCAL methodology with keto acids involving the use of catalytic homobenzotetramisole (S)-HBTM (6, Scheme 2) as chiral nucleophile (Lewis base), a tetramisole analogue, and p-toluenesulfonyl chloride rather than Mukaiyamas reagent, which led to bi-and tricyclic b-lactones in good yields and excellent enantioselectivities. In addition, we report transformations of these systems that lead to dramatically different topologies. Overall, the reported process provides an expedient route to useful templates for chemical biology through rapid synthesis of carbocyclic frameworks in optically active form. The resident b-lactone is also a versatile handle for further manipulations. Furthermore, the described methodology is the first example of catalytic desymmetrization reactions of cyclic diones by the NCAL process.
Tetrahedron, 2002
A variety of carbocycle-fused β-lactones are accessible via the intramolecular catalytic, asymmetric nucleophile catalyzed aldol-lactonization reaction recently developed in our laboratory. These bicyclic β-lactones undergo facile ring cleavage under mild conditions via both acyl C–O and alkyl C–O bond cleavage. Cleavage of the acyl C–O bond with hydroxylamine nucleophiles proceeds at ambient temperature and reductive cleavage is readily accomplished with aluminum and boron reducing agents. Alternatively, alkyl C–O cleavage with various nucleophiles leads to a variety of trans-β-substituted cyclopentane carboxylic acids. The utility of these transformations is demonstrated by the synthesis of protected (1S,2S)-transpentacin and a versatile diol for carbocyclic nucleoside synthesis.
Journal of Organometallic Chemistry, 1985
New catalytic processes which lead to the formation of N-acyl-a-amino acids promoted by homogeneous binary systems are described: (a) the isomerizationamidocarbonylation of allyllic alcohols catalyzed by transition metal binary systems, e.g., Co-Rh, Co-Pd, Co-Fe, giving various aliphatic N-acyl-a-amino acids; (b) the isomerization-amidocarbonylation of oxiranes catalyzed by cobalt-Lewis acid systems giving N-acyl-a-amino acids: The process is extremely effective for the synthesis of N-acetylphenylalanine from styrene oxide and (c) the hydroformylationamidocarbonylation of trifluoropropene catalyzed by cobalt-rhodium binary system giving N-acetyltrifluorovaline in excellent regioselectivity and yield. Possible mechanisms for these new processes are discussed. * This paper is dedicated to Professor Jack Halpem on the occasion of his 60th birthday and for his outstanding research and teaching in the field of organometallic, inorganic chemistry and catalysis.
Metal-Free Synthesis of N-Aryl Amides using Organocatalytic Ring-Opening Aminolysis of Lactones
ChemSusChem, 2017
Catalytic ring-opening of bio-sourced non-strained lactones with aromatic amines can offer a straightforward, 100% atom-economical and sustainable pathway towards relevant N-aryl amide scaffolds. We herein report the first general, metal-free and highly efficient N-aryl amide formation from poorly reactive aromatic amines and non-strained lactones under mild operating conditions using an organic bicyclic guanidine catalyst. This protocol has great application potential as exemplified by the formal syntheses of drug relevant molecules.
Molecules
Carbon–carbon bond forming reactions, such as aldol reaction and condensation, belong to extremely desired transformations as manifested by >25,000 entries in SciFinder. Their stereoselective variant requires the use of an appropriate catalyst with a strictly defined structure. Hence, chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested in a stereoselective aldol reaction between cyclic/acyclic ketone and p-nitrobenzaldehyde both in organic and aqueous media. Among catalysts containing a chiral bicyclic backbone, amide based on 2-azabicyclo[3.2.1]octane and pyrrolidine units showed the best catalytic activity and afforded aldol product in excellent chemical yields (up to 95%) and good diastereo- and enantioselectivity (dr 22:78, ee up to 63%).