Asymmetric Hetero-Diels−Alder Reactions of N-Sulfinyl Dienophiles Using Chiral Bis(oxazoline)−Copper(II) and −Zinc(II) Triflates

Abstract

Asymmetric hetero-Diels-Alder (HDA) reactions of N-sulfinyl dienophiles using bis(oxazoline)-copper(II) and -zinc(II) triflates are described. The cycloadditions with cyclic and acyclic 1,3-dienes have been studied. In most cases, good enantioselectivities (70-98% ee) and yields (60-85%) were obtained with stoichiometric amounts of the Lewis acids. Cyclic dienes gave the endo adducts as major products, while acyclic dienes provided cis adducts. The HDA adducts have been transformed into N-protected alpha-amino acid methyl esters, amino alcohols, and homoallylic amines. A stereochemical model, which accounts for the enantiofacial selectivity of the HDA reaction by a tetrahedral metal center, has been proposed. Mechanistic studies revealed positive nonlinear effects, assumed to arise from the formation of less-reactive heterochiral complexes. Investigation of the temperature dependence of the enantioselectivity indicated that at least two selective reaction steps exist in the zinc-catalyzed reaction. Reactions run with 10 mol % chiral Lewis acid gave poor yields and selectivities. However, in combination with TMSOTf (100 mol %), high yields (68-86%) and enantioselectivities (97-98% ee) were obtained.

Mechanistic Insights into Stereoselective Catalysis—The Effects of Counterions in a CuII–Bissulfoximine‐Catalyzed Diels–Alder Reaction

“…A similar conclusion can be drawn from the X-band HYS-CORE spectra shown in Figure 7. In both spectra, peaks attributable to 14 N nuclei are labeled, with hyperfine couplings in the range j AA C H T U N G T R E N N U N G ( Cl hyperfine couplings is consistent with the broad signals observed in the ENDOR spectra. The low-frequency peaks in the X-band HYSCORE spectra can be assigned to 35,37 Cl from the solvent, with small hyperfine coupling constants j A(Cl) j % 2 MHz.…”

“…[5][6][7][8][9][10] Lewis acid type catalysts of this type lead to high conversions and excellent selectivities in a vast array of reactions of the Grignardtype, [11] aldol condensations, [7,8,12] fluorinations, [13] and, prominently, Diels-Alder or hetero-Diels-Alder reactions. [5,6,[14][15][16][17] Abstract: The initial steps of an enantioselective Diels-Alder reaction catalyzed by a Cu II -bissulfoximine complex were followed by EXAFS (EXAFS = extended X-ray absorption fine structure), EPR (EPR = electron paramagnetic resonance) spectroscopy (CW-EPR, FID-detected EPR, pulse ENDOR, HYSCORE; CW = continuous wave; ENDOR = electron nuclear double resonance; HYSCORE = hyperfine sublevel correlation; FID = free induction decay), and UV-visible spectroscopy. The complexes formed between the parent CuX 2 (X = Cl À , Br À , TfO À , SbF 6 À ) salts, the chiral bissulfoximine ligand (S,S)-1, and N-(1-oxoprop-2-en-1-yl)oxazolidin-2-one (2) as the substrate in CH 2 Cl 2 were investigated in frozen and fluid solution.…”

Nonlinear Effects in Asymmetric Catalysis

“…(31)]. [101,102] The NLE was greater in the case of the zinc catalyst. A precipitate was detected when partially resolved ligand 117 was employed; thus the involvement of dimeric or higher aggregated complexes was suggested.…”

Copper(II) Trifluoromethanesulfonate

“…By using stoichiometric amounts of the bis(oxazoline)-copper(II) triflate system as catalyst, asymmetric hetero-Diels-Alder (HDA) cycloaddition reactions were performed with cyclic and acyclic 1,3dienes. 22 The reported enantioselectivity (70-98% ee) and yields (60-85%) are satisfactory. Cyclic dienes gave the endo-adducts as major products (eq 24), and acyclic dienes gave the cis-adducts predominantly (eq 25).…”