Luz Cardona

Highly Enantioselective Zinc/Binol‐Catalyzed Alkynylation of N‐Sulfonyl Aldimines

The catalytic enantioselective formation of new C C bonds is an important class of organic reactions. Among them, the asymmetric additions of terminal alkynes to C=O and C=N bonds are two of the most important objectives in organic synthesis; the resulting chiral propargylic alcohols and amines are versatile building blocks for the synthesis of a wide range of natural products and pharmaceuticals. Some excellent work has been reported on the asymmetric addition of alkynes to carbonyl compounds resulting in high ee values. However, the practical enantioselective alkynylation of imines and imine derivatives to form propargylic amines is challenging because of the poor electrophilicity of the azomethine carbon. In this context, most of the studies reported so far deal with the catalytic enantioselective alkynylation of N-aryl imines by using Cu salts in combination with nitrogen-containing ligands. The leading studies of this reaction with N-aryl imines have been developed by Wei et al. , Bisai and Singh, and Benaglia and co-workers ; and Knochel and co-workers and Carreira and co-workers reported using iminium intermediates generated in situ in a three-component synthesis of propargylic amines. Other methods, which do not make use of copper complexes as the catalyst, have also been described. Hoveyda and co-workers have used peptide-based ligands in combination with Zr(OiPr)4·HOiPr to catalyze the addition of preformed mixed alkynylzinc reagents to various N-aryl aromatic imines, which gives good results with trimethylsilylethyne and lower enantioselectivities with aryl-substitued alkynes. Jiang and Si have described the addition of alkynes to a trifluoromethyl activated cyclic imine by using a stoichiometric amount of a chiral amino alcohol ligand. Recently, Bolm and co-workers have described the use of dimethylzinc to catalyze the addition of terminal alkynes toN-aryl andN-protected imines in the absence of ligands. An enantioselective version has been implemented by these authors for o-methoxyanilinederived imines by using a relatively large loading (40 mol%) of the amino alcohol ligands. In contrast, N-acyland Nsulfonyl-protected imines show enhanced reactivity because of the electron-withdrawing character of the protecting group. The alkynylation of these substrates lead to protected propargylic amines. The highly enantioselective alkynylation of N-acyl imines has been carried out by using chiral alkynylboronates and alkynylboranes, which are based on the binol and the borabicyclo[3.3.2]decane scaffolds, respectively, as reagents. However, to the best of our knowledge, the enantioselective alkynylation of N-tosyl imines has not been reported so far. Because of the increased reactivity of N-sulfonyl imines and the findings reported by Bolm and co-workers, we envisioned a dimethylzinc-mediated catalytic enantioselective alkynylation of N-sulfonyl imines by using an appropriate ligand (Scheme 1). Binol-type ligands were chosen in our study because they are known to give highly enantioselective reactions with a variety of metals, including zinc.

Sesquiterpene Lactones from Centaurea paui

Abstract A new elemanolide and two new heliangolides as well as (2R,3R)-(+)-3-hydroxy-2-methyl-butyrolactone have been isolated from Centaurea paui. The structures were elucidated by high field NMR techniques and chemical transformation.

6-Prenyloxy-7-methoxycoumarin, a coumarin-hemiterpene ether from Carduus tenuiflorus

Abstract From the acetone extract of Carduus tenuiflorus , a new coumarin-hemiterpene ether was isolated, which was identified as 6-(3,3-dimethylallyloxy)-7-methoxycoumarin. The synthesis of this coumarin and that of its positional isomer 7-(3,3-dimethylallyloxy)-6-methoxycoumarin were carried out from esculetin. Two other coumarins, three lignans and three flavonoids were also isolated.

Enantioselective zinc-mediated conjugate addition of terminal alkynes to enones.

Zinc for conjugate alkynylation: The enantioselective conjugate addition of terminal alkynes to 2-arylidene-1,3-diketones in the presence of diethylzinc and a catalytic amount of (R)-VANOL has been developed. The reaction can be applied to different aromatic and heteroaromatic alkynes and enones, giving the expected products in good yield and with enantiomeric excesses up to 91%. The products can be enantiomerically enriched up to 99% ee by crystallization (see scheme).

Ultrasound assisted reductive cleavage of eudesmane and guaiane γ-enonelactones. Synthesis of 1α,7α,10αH-guaian-4,11-dien-3-one and hydrocolorenone from santonin

Abstract Ultrasound enhances the rate of reductive cleavage of the C6–oxygen bond of sesquiterpene enonelactones. trans-Eudesmanolides 1c–1g, cis-eudesmanolides 2a–2c, and trans-guaianolides 4a–4d react with Zn in acetic acid–H2O under sonochemical conditions to afford the corresponding sesquiterpene acids 3a–3g and 5a–5d, respectively in good yields. Starting from 5d two natural guaianes 1α,7α,10αH-guaian-4,11-dien-3-one (6) and hydrocolorenone (7) have been prepared in good yields through a straightforward sequence.

Ring-opening aminolysis of sesquiterpene lactones: An easy entry to bioactive sesquiterpene derivatives. Synthesis of (+)-β-cyperone and (−)-eudesma-3,5-diene from santonin

Abstract Santonin ( 1 ) and other sesquiterpene lactones ( 2–3 ) react with pyrrolidine and other cyclic secondary amines to afford γ-hydroxyamides, which by elimination with mesyl chloride in pyridine-benzene at 80°C give unsaturated amides 4a-4c, 5a-5c and 6 . Starting from amides 5a-5c a series of bioactive compounds against Locusta migratoria have been prepared, differing in the oxidation states of the C-3 and C-12 carbon atoms. Starting from amides 5a and 6 two conjugated diene eudesmanes (+)-β-cyperone ( 15 ) and (−)eudesma-3,5-diene ( 19 ) have been prepared involving an elaboration of the amide group of the side chain of the eudesmane skeleton.

Synthesis of (+)-Isoalantolactone and (+)-Isoalloalantolactone from (−)-Santonin

Abstract This paper reports on the chemical conversion of (−)-santonin into (+)-isoalantolactone and (+)-isoalloalantolactone involving functionality transfer from C 6 to C 8 , refunctionalization of the ring A and the formation of the α-methylene-8 β,12-olide moiety.

Regio- and stereoselective oxyfunctionalization at C-1 and C-5 in sesquiterpene guaianolides

Abstract The regio- and stereoselective functionalization at C-1 and C-5 positions in a guaiane skeleton by allylic hydroxylation are described. The stereochemistry of the resulting compounds are identical to those of the majority of natural 1- and 5-hydroxy-guaianolides.

Polyoxygenated terpenes and cyanogenic glucosides from Centaurea aspera var. subinermis

Abstract From the methanol extract of Centaurea aspera var. subinermis three polyoxygenated terpenes and two cyanogenic glucosides were isolated. An eudesmane, an elemane and 6′-trans-2-butenoyl ester of prunasin are described for the first time.

A shorter route to the synthesis of (+)-junenol isojunenol, and their coumarate esters from (−)-santonin

Abstract This paper reports on the chemical conversion of (−)-santonin into (+)-junenol, isojunenol and their coumarate esters. The identity of (+)-junenol and 8-epi-β-verbesinol is also established.