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

Abstract

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.

A Straightforward Sequential Approach for the Enantioselective Synthesis of Optically Active α‐Arylmethanol‐1,2,3‐Triazoles

“…We started our studies by preparing the optically active TMS‐propargylic alcohol 2a following the procedure described by Wang using the inexpensive N ‐tosyl amino alcohol 5 as a chiral ligand (Table ). By using the reported protocol, the TMS‐propargylic alcohol 2a was acquired in a great yield, but a relatively low enantiomeric excess (75 %) was observed (entry 1).…”

“…Enantiomeric excess determined by chiral HPLC analysis (Chiralpak OD‐H colunm). The absolute configurations were assigned by comparasion with literature data …”

γ-Hydroxy-α,β-acetylenic esters: asymmetric syntheses and applications

“…The addition to aliphatic and α,β-unsaturated aldehydes resulted in lower enantioselectivity. Comparable enantioselectivity can be obtained by using DIPEA as the Lewis base additive after further tuning of the reaction conditions [44].…”

Highly Enantioselective Addition of Trimethylsilylacetylene to Aldehydes Catalyzed by a Zinc–Amino‐Alcohol Complex

“…In particular, by using catalytic systems such as Trosts prolinederived dinuclear Zn, [4i] Wolfs bisoxazolidine-Zn, [4j] Pus BINOL-Ti, [9b] Wangs sulfonamide alcohol-Ti, [11] and Nishiyamas bis(oxazolinyl)-phenyl-Ru, [4q] excellent enantioselectivity (> 90 % enantiomeric excess (ee)) can be achieved in the addition of trimethylsilylacetylene to aldehydes. Among the catalytic systems reported so far for the alkynylation of aldehydes, the amino-alcohol-Zn system is particularly noteworthy in terms of its operational simplicity and mild reaction conditions.…”

“…[5] A variety of effective catalytic systems including amino-alcohol-Zn, [6] iminoalcohol-Zn, [7] hydroxyl-carboxyamide-Zn, [8] proline-derived dinuclear Zn, [4i] bisoxazolidine-Zn, [4j] 1,1'-bi-2-naphthol (BINOL)-Ti, [9] bisphosphine-Cu I , [10] sulfonamide-alcoholTi, [11] and bis(oxazolinyl)phenyl-Ru [4q] have been developed for the addition of trimethylsilylacetylene to aldehydes. In particular, by using catalytic systems such as Trosts prolinederived dinuclear Zn, [4i] Wolfs bisoxazolidine-Zn, [4j] Pus BINOL-Ti, [9b] Wangs sulfonamide alcohol-Ti, [11] and Nishiyamas bis(oxazolinyl)-phenyl-Ru, [4q] excellent enantioselectivity (> 90 % enantiomeric excess (ee)) can be achieved in the addition of trimethylsilylacetylene to aldehydes.…”