Enantioselective Addition Of Terminal Alkynes Research Articles

Dimethylzinc-mediated enantioselective addition of terminal alkynes to 1,2-diketones using perhydro-1,3-benzoxazines as ligands

A conformationally restricted perhydro-1,3-benzoxazine derived from (-)-8-aminomenthol behaves as a good chiral ligand in the dimethylzinc-mediated enantioselective monoaddition of aromatic and aliphatic terminal alkynes to 1,2-diketones. The corresponding α-hydroxyketones were obtained in good yields with high enantioselectivities starting from both aromatic and aliphatic 1,2-diketones. The alkynylation of unsymmetrical 1,2-diketones with electronically different substituents also proceeds with high regio- and enantioselectivity. This reaction provides a practical method to synthesize ketones bearing a chiral tertiary propargylic alcohol.

Diarylprolinol as a Ligand for Enantioselective Alkynylation of Cyclic Imines

AbstractAn easily accessible prolinol derived ligand, (S)‐bis(3,5‐bis(trifluoromethyl)phenyl)(pyrrolidin‐2‐yl)methanol, has been efficiently applied in the catalytic enantioselective addition of terminal alkynes to cyclic imines using dimethylzinc (Me2Zn) under mild reaction conditions. The developed catalytic system led to chiral propargylic sulfamidates with high yields (up to 97%) and excellent enantioselectivities (up to 97% ee).magnified image

Enantioselective Addition of Alkynes to α,α-Dichlorinated Aldehydes.

Enantioselective addition of terminal alkynes to α,α-dichlorinated aldehydes employing Zn(OTf)2/NME is disclosed. The propargylic alcohols obtained are accessed in good yields and high enantioselectivity from easily accessible α,α-dichloroaldehydes. The method opens new strategic opportunities for the synthesis of chlorinated natural products, such as the chlorosulfolipids.

Asymmetric synthesis and biological evaluation of natural or bioinspired cytotoxic C2-symmetrical lipids with two terminal chiral alkynylcarbinol pharmacophores.

Bidirectional syntheses of C2-symmetrical lipids embedding two terminal alkynylcarbinol pharmacophores are reported. Naturally occurring chiral alkenylalkynylcarbinol units were generated using Pu's procedure for enantioselective addition of terminal alkynes to aldehydes, allowing the first asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol, isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using Carreira's procedure adapted to ynal substrates. The dramatic effect of the carbinol configuration on cytotoxicity was confirmed with submicromolar IC50 values against HCT116 cells.

Enantioselective alkynylation of benzo[e][1,2,3]-oxathiazine 2,2-dioxides catalysed by (R)-VAPOL-Zn complexes: synthesis of chiral propargylic cyclic sulfamidates.

(R)-VAPOL-Zn(II) complexes catalysed the enantioselective addition of terminal alkynes to cyclic benzoxathiazine 2,2-dioxides, providing the corresponding chiral propargylic sulfamidates with high yields (up to 93%) and good enantiomeric excesses (up to 87%).

ChemInform Abstract: Application of Tartarate Derived Bidentate Bioxazolines in Enantioselective Addition of Terminal Alkynes to Imines.

AbstractA new class of bidentate bisoxazoline ligands is applied to the addition of alkynes to imines.

Application of tartarate derived bidentate bioxazolines in enantioselective addition of terminal alkynes to imines

A series of highly efficient and inexpensive bioxazoline ligands were easily synthesized from tartaric acid and further explored for enantioselective addition of terminal alkynes to imines in combination with copper(II) salts. This is the first ever report showing application of bidentate bioxazoline ligands in the synthesis of propargylamines with good enantioselectivity.

Chiral NCN Pincer Rhodium(III) Complexes with Bis(imidazolinyl)phenyl Ligands: Synthesis and Enantioselective Catalytic Alkynylation of Trifluoropyruvates with Terminal Alkynes

AbstractA series of new chiral C2‐symmetrical NCN pincer rhodium(III) complexes with bis(imidazolinyl)phenyl ligands have been conveniently synthesized from easily available materials. The complexes were subsequently applied in the enantioselective addition of terminal alkynes to trifluoropyruvates. With catalyst loading of 1.5–3.0 mol%, the alkynylation of ethyl or methyl trifluoropyruvate with a variety of electronically and structurally diverse terminal alkynes gave the optically active trifluoromethyl‐substituted tertiary propargylic alcohols with enantioselectivities of up to >99% ee and high yields. Although good to excellent enantioselectivities (85–98% ee) could be achieved only for some of the aliphatic terminal alkynes under the optimized conditions, the enantioselectivities were consistently excellent (94% to >99% ee) in the case of aromatic as well as heteroaromatic alkynes and enynes.

ChemInform Abstract: Enantioselective Addition of Terminal Alkynes to N‐(Diphenylphosphinoyl)imines Catalyzed by Zn—BINOL Complexes.

Abstract Chiral nonracemic N-(diphenylphosphinoyl)-protected propargylic amines have been prepared by addition of terminal alkynes to N-(diphenylphosphinoyl)aldimines in the presence of dimethylzinc and 3,3′-dibromo-BINOL as catalyst. The reaction works with a variety of aromatic and heteroaromatic aldimines and with different alkynes, providing the expected products in generally good yields and enantiomeric excesses (up to 96%).

Enantioselective addition of terminal alkynes to N-(diphenylphosphinoyl)imines catalyzed by Zn–BINOL complexes

Chiral nonracemic N-(diphenylphosphinoyl)-protected propargylic amines have been prepared by addition of terminal alkynes to N-(diphenylphosphinoyl)aldimines in the presence of dimethylzinc and 3,3′-dibromo-BINOL as catalyst. The reaction works with a variety of aromatic and heteroaromatic aldimines and with different alkynes, providing the expected products in generally good yields and enantiomeric excesses (up to 96%).

Enantioselective Imine Alkynylation with Fe3O4-Supported Copper Pybox

Fe3O4 nanoparticle supported ­copper(I) pybox catalyst 3 was prepared by im­mobilization of pybox 2 onto alkylamine-tethered silica-coated nanoparticles 1 in the presence of CuBr and BINOL followed by treatment with (CuOTf)2˙toluene (eq. 1). The catalyst promoted the enantioselective addition of terminal alkynes to imines to give the corresponding adducts in 80-94% yield with 84-92% ee (6 examples, eq. 2).

Copper(I)-catalyzed enantioselective alkynylation of α-imino esters: ligand-to-metal ratio effects and mechanistic studies

An unprecedented effect of the ligand-to-metal ratio on the stereofacial selection in the copper-catalyzed enantioselective addition of terminal alkynes to N-PMP-α-imino esters was observed. An excess of ligand was found not to be beneficial, on the contrary, an excess of copper was found to be beneficial. Moreover, both enantiomers of the alkynylation product were obtained with almost the same enantiomeric excess with the same chiral ligand by simply adjusting the ligand-to-metal ratio. The investigation of the mechanism demonstrated the presence of a positive nonlinear effect [(+)-NLE].

ChemInform Abstract: Catalytic Enantioselective Addition of Terminal Alkynes to Aromatic Aldehydes Using Zinc—Hydroxyamide Complexes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Zinc‐Salen‐Catalyzed Asymmetric Alkynylation of Alkyl Acylsilanes

AbstractOptically active tertiary propargylic alcohols are useful and versatile building blocks in organic synthesis, and their direct access by enantioselective addition of alkyne nucleophiles to ketones has achieved significant progress over the last ten years. In view of the potential applications of acylsilanes as useful synthetic equivalents of aldehydes, we described a general catalytic enantioselective addition of terminal alkynes to alkyl acylsilanes. After reaction optimization involving variation of solvent, temperature, catalyst ratio and various catalysts screen, the in situ generated Zn‐salen complex was chosen as catalyst. With hexane as solvent, the silylated tertiary propargylic alcohols were obtained in satisfactory yields and ees for both aliphatic and aromatic alkynes.

ChemInform Abstract: Enantioselective Addition of Terminal Alkynes to Aromatic Aldehydes Catalyzed by Copper(I) Complexes with Wide‐Bite‐Angle Chiral Bisphosphine Ligands: Optimization, Scope, and Mechanistic Studies.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly Enantioselective Zinc/Amino Alcohol‐Catalyzed Alkynylation of Aldehydes

Meeting the challenge: The zinc/amino alcohol catalyzed enantioselective addition of terminal alkynes to aldehydes is effective with both phenylacetylene and methyl propiolate, leading to chiral secondary propargyl alcohols with very high enantioselectivity (see scheme).

Catalytic enantioselective addition of terminal alkynes to aromatic aldehydes using zinc-hydroxyamide complexes

A mandelamide ligand, derived from (S)-mandelic acid and (S)-phenylethanamine, catalyzes the addition of aryl-, alkyl- and silyl-alkynylzinc reagents to aromatic and heteroaromatic aldehydes with good yields and good to high enantioselectivities.

Enantioselective Addition of Terminal Alkynes to Aromatic Aldehydes Catalyzed by Copper(I) Complexes with Wide-Bite-Angle Chiral Bisphosphine Ligands: Optimization, Scope, and Mechanistic Studies

The addition of terminal alkynes to aromatic aldehydes was carried out in t-BuOH under mild conditions in the presence of a Cu-phosphine complex, which was prepared in situ from Cu(O-t-Bu) and TRAP chiral bisphosphine, to yield enantiomerically enriched propargyl alcohols with moderate enantioselectivities. Studies on the screening of various ligands showed that wide bite angles of bisphosphine ligands are important for the Cu catalysis. According to the analysis of stoichiometric reactions, the reaction presumably involves the nucleophilic addition of a TRAP-coordinated Cu(I) acetylide to an aldehyde: The alcoholic solvent participates in the addition through coordination to the Cu center and simultaneous protonation of the carbonyl oxygen. The C−C bond-forming addition step is reversible with a strong preference for the backward reaction.

Highly enantioselective addition of terminal alkynes to aldehydes catalyzed by a new chiral β‐sulfonamide alcohol/Ti(OiPr)4/Et2Zn/R3N catalyst system

A new catalytic system, generated from the readily available and inexpensive beta-sulfonamide alcohol L*, Ti(O(i)Pr)(4), Et(2)Zn, and tertiary amine base (R(3)N), effectively catalyzes the enantioselective addition of various terminal alkynes including some quite challenging alkynes to aldehydes in good yields and excellent enantioselectivities. Up to 96% yield and >99% enantioselectivity were achieved with the use of N,N-diisoproylethylamine (DIPEA) as an additive in this asymmetric addition.

ChemInform Abstract: Enantioselective Addition of Terminal Alkynes to Aldehydes Catalyzed by a Cu(I)—TRAP Complex.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.