Δ-amino Alcohols Research Articles

Copper-Catalyzed γ-C(sp3)-H Lactamization and Iminolactonization.

Despite extensive efforts to develop γ-lactamization reactions for pyrrolidinone synthesis using either cyclometallation, C-H insertion, or radical C-H abstraction strategies, γ-lactamization reactions of aliphatic amides using practical catalysts and common protecting groups remain extremely rare. Herein we report copper-catalyzed γ-C(sp3)-H lactamization and iminolactonization of tosyl-protected aliphatic amides using inexpensive Selectfluor as the sole oxidant. A switchable selectivity of γ-Lactams or γ-iminolactones can be obtained by using two different sets of reaction conditions. Notably, structurally diverse spiro-, fused-, and bridged-lactams and iminolactones, as well as isoindolinones are accessible by this method. Further derivatization of the γ-lactam products enables the synthesis of a range of biologically important motifs, including γ-amino acids, δ-amino alcohols, and pyrrolidines.

Visible-Light Photocatalytic Barbier-Type Reaction of Aziridines and Azetidines with Nonactivated Aldehydes

AbstractBarbier-type reactions are a classic group of reactions for carbon–carbon bond formation; however, their common use of stoichiometric metals restricts their widespread application. Considering the ready availability and diversity of cyclic amines, we report a visible-light photocatalytic Barbier-type reaction of aziridines and azetidines with nonactivated aldehydes. A series of important γ- and δ-amino alcohols were synthesized in the presence of amines as electron donors. Moreover, this transition-metal-free protocol displays mild reaction conditions, broad functional-group tolerance, and a wide substrate scope. Mechanistic investigations indicated that carbon radicals and carbanions might be generated as key intermediates.

From Five to Seven: Ring Expansion of Monoazadiene Titanium Complexes by Insertion of Aldehydes, Ketones and Nitriles.

The ring enlargement reactions at ambient temperatures of non C-terminus substituted monoazabutadiene (η4 -RN=CHCH=CH2 ) titanium complexes 2 are investigated. The insertion of aldehydes/ketones (five examples) and nitriles (four examples) into the Ti-C bonds result in expansion of the five-membered rings to uncommon seven-membered titanacycles 3 and 4 in good yields. These new compounds are fully characterized by NMR spectroscopy and single-crystal X-ray diffraction. In subsequent reactions, the seven-membered ring systems are protolyzed and the released organic fragments are isolated. Whereas the aldehyde/ketone insertion products 3 form substituted δ-amino alcohols 5 after reduction with NaBH3 CN, the nitrile insertion products 4 form substituted pyrroles 6 via cyclization.

Photoredox-Catalyzed Cross-Coupling of Enamides for the Assembly of β-Difluoroimine Synthons.

A photoredox-catalyzed formal Csp3-Csp3 cross-coupling reaction of enamides with bromodifluoro compounds is established. The resulting gem-difluoromethylenated γ-imines indicated high stability, excellent E/Z control, and broad functional group tolerance. These synthetic intermediates can efficiently transfer to difluoromethylenated γ-amino acids or δ-amino alcohols. Mechanistic analysis indicates that a radical/SET mechanism proceeding via a difluoroalkyl radical may be involved in the catalytic cycle.

A Protocol for an Asymmetric Synthesis of γ-Amino Acids

A new and practical method for the asymmetric synthesis of γ-amino acids from β,γ-butenolides by an in situ esterification, condensation, and reduction in a one-pot procedure is described. This method is quite general for the preparation of both enantiomers of aryl or aliphatic γ-amino acids in high yields. These γ-amino-acid derivatives were also shown to be versatile synthetic intermediates for further transformations by their conversion to γ-lactams, δ-amino alcohols, and hydrolysis products in high yields with no racemization.

Stereocontrolled α-Alkylation of Oxime Ether Derived from Terpene: Efficient Synthesis of New Chiral γ- and δ-Amino Alcohols

The alkylation of (+)-nopinone oxime ether with various electrophiles afforded the corresponding adduct with a total stereoselectivity. Further reduction of the oxime ether afforded an easily access to new chiral γ-and δ-amino alcohols of high interest for catalysis and asymmetric synthesis.

Stereocontrolled α-Alkylation of Oxime Ether Derived from Terpene: Efficient Synthesis of New Chiral γ- and δ-Amino Alcohols

Stereocontrolled α-Alkylation of Oxime Ether Derived from Terpene: Efficient Synthesis of New Chiral γ- and δ-Amino Alcohols

New bicyclic γ- and δ-aminoalcohols as catalysts for the asymmetric diethylzinc addition to benzaldehyde

A new class of chiral non-racemic γ- and δ-amino alcohols based on bicyclo[2.2.1]heptane and bicyclo[2.2.2]octane have been synthesized and used as catalysts in the asymmetric diethylzinc addition to benzaldehyde.

Convenient Synthesis of Stable Aldimine−Borane Complexes, Chiral δ-Amino Alcohols, and γ-Substituted GABA Analogues from Nitriles

A one-pot synthesis of stable aldimine-trialkylborane adducts, the first synthesis of C- and N-deuterated imine-borane complexes, and their application for a highly enantioselective (84-99% ee) synthesis of delta-amino alcohols and gamma-substituted gamma-aminobutyric acids, including deuterated amino acids from nitriles, are described.

The role of conformational flexibility on the catalytic activity of norbornane-derived β-, γ- and δ-amino alcohols

Enantiopure norbornane-based γ-amino alcohols 1– 4 have been obtained from (+)-camphor and their catalytic behaviour as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde compared to these described for homologous β- and δ-amino alcohols. This has allowed the first study on the influence of the size of the catalytic zinc-chelate ring on the catalytic activity, which results in the unexpected observance of a non-linear correlation between enantioselectivity and chelate ring size (conformational flexibility). An empirical rationalisation of the observed phenomenon was realised on the basis of consideration of the energetically-favoured Noyori-type transition states.

Stereoselective synthesis of chiral precursors to cyclobutane carbocyclic nucleosides and oligopeptides

Versatile and highly efficient synthetic routes leading to optically active cyclobutanones, γ-amino acids and δ-amino alcohols are described. These compounds are relevant synthetic precursors to enantiopure cyclobutane carbocyclic nucleosides and oligopeptides. (−)-( S)-Verbenone is the chiral starting material used and the key synthetic steps involve concerted rearrangements in acidic medium.

Stereoselective synthesis of (±)-indolizidines 167B and 209D and theirtrans-isomers based on the reductive allylboration of pyridine

A general method for the synthesis of 5-substituted indolizidines based on intramolecular cyclization oftrans- andcis-2-allyl-6-R-1,2,3,6-tetrahydropyridines, obtained from pyridine and triallylborane, has been elaborated. The closure of the five-membered ring is carried out by hydroboration-oxidation followed by cyclization of the resulting δ-amino alcohols in the presence of the Ph3P−CBr4−Et3N system. (Pr2BH)2 and Pr3B are used as the hydroborating reagents, and H2O2 in an acid medium is used for the oxidation of 2-[3-(dipropylboryl]-Δ2-piperideines formed. This method has been used for the synthesis of two natural alkaloids: indolizidine 209D (cis-5-hexylindolizidine) and itstrans-isomer were prepared fromcis- andtrans-2-allyl-6-hexyl-1,2,3,6-tetrahydropiridine, respectively; indolizidine 167B andtrans-5-propylindolizidine were synthesized fromcis- andtrans-2,6-diallyl-1,2,3,6-tetra-hydropyridine, respectively.

Syntheses of new chiral 1,2-diamines and δ-amino-alcohols and their application in catalytic enantioselective CC bond formations at an elevated temperature of up to 110 °C

The syntheses of new chiral 1,2-diamines 6a-e and chiral δ-amino alcohols (−)- 10a-e, (+)- 10d-e and their use as ligands in catalytic asymmetric additions of diethylzinc to benzaldehyde are described. The diamines were found to be efficient catalysts which gave the corresponding alcohol in good to high ee's (e.g. 88% ee for Li-6a) at a reaction temperature of 110 °C. Also the δ-amino alcohols, particularly (−)- and (+)- 10e, gave ( S)- and ( R)-1-phenyl-1-propanol in high enantiomeric excesses (up to 91% ee) under mild reaction conditions.