An Asymmetric Catalytic Darzens Reaction between Diazoacetamides and Aldehydes Generates cis‐Glycidic Amides with High Enantiomeric Purity

Abstract

Titanium strength: The title reaction was catalyzed by a chiral titanium complex formed in situ from commercially available Ti(OiPr)4 and (R)‐binol, and gave cis‐glycidic amides with excellent enantiomeric purity (see scheme). This new method has been applied to the preparation of chiral building blocks used for the synthesis of the side chain of taxol and (−)‐bestatin.

Catalytic Asymmetric Darzens and Aza‐Darzens Reactions for the Synthesis of Chiral Epoxides and Aziridines

“…A few examples have been applied to the preparation of enantiomerically enriched epoxides, which proceed through the nucleophilic attack of the diazo carbon to the carbonyl compound. In 2009, Gong et al . reported the first highly cis ‐selective and enantioselective DR between diazoacetamides and aldehydes catalyzed by a BINOL/titanium (IV) complex.…”

“…A few examples have been applied to the preparation of enantiomerically enriched epoxides, which proceed through the nucleophilic attack of the diazo carbon to the carbonyl compound. In 2009, 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 Gong et al [34] reported the first highly cis-selective and enantioselective DR between diazoacetamides and aldehydes catalyzed by a BINOL/titanium (IV) complex. N,N-Dimethyl diazoacetamide and N-benzyl diazoacetamide showed no reactivity and decomposed under the reaction conditions.…”

Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL‐Derived Chiral Borate Catalysts

“…A third method involving the formation of epoxides from the reactions of diazo compounds are not that common and have not been particularly useful . However, efficient catalytic asymmetric versions have been more recently reported by Gong and co‐workers for the reactions of aldehydes with secondary α‐diazoacetamides ,. These reactions gave high asymmetric inductions with chiral complexes of titanium or zirconium with BINOL and BINOL derivatives.…”

Heterocyclic chemistry

“…Scheme 5 55 The use of the N-amino-tetrahydrophthalimide shown in Scheme 6 in the oxidative aminoaziridation of alkenes was found to give excellent yields of trans-aziridines from trans-alkenes, whereas lower reactivity was observed with cis-alkenes. 6 This reaction is believed to proceed via an intermediate aminonitrene which arises from the action of the PhI(OAc) 2 in Scheme 7, the first time that such a process has been observed (previous reactions of azides with enol ethers proceed via 1,3-dipolar cycloaddition). 7 Aziridine formation via intramolecular 1,3-dipolar cycloaddition and nitrogen extrusion led to the aziridinopyrrolobenzodiazepines shown in Scheme 8, where the products are of interest as DNA-intercalating antitumour antibiotics.…”

“…25 Optically pure epoxides are available via a highly diastereoselective and enantioselective Darzens reaction involving a chiral titanium complex which is generated in situ from titanium isopropoxide and (R)-binol, as shown in Scheme 2. 2 The range of aldehydes includes aromatic, aliphatic and unsaturated substrates and hence allows access to a wide range of cis-glycidic amides. …”