Addition of Hetero Allenyl Copper Reagents to Aldehydes: Scope and Behavior

Abstract

Cyanocuprates derived from propargylic amines or ethers react with aldehydes to give regioselectively the corresponding anti-homopropargylic alcohols with a high level of diastereoselectivity. Such selectivity could be obtained independently of the nature of the heteroatom (amine or ethers) or the acetylenic substituents. Excellent selectivities can be reached regardless of the aldehydes used, remarkably also with vinylic or acetylenic ones. A reactivity scale for the cuprates bearing different acetylenic substituents was established to be: SiMe3 >Ph> Et. The rate of the addition reaction to aldehydes was also found to be slowed down in the presence of HMPA underlining the crucial role of the Li counterion. DFT calculations have shown that the relationship between the rate and the acetylenic substituent is not connected to a possible metallotropic equilibrium but to the stability of the reactive allenic species compared to the less-stable propargylic isomer.

Copper(II) Triflate Catalyzed Regioselective and Enantioselective Propargylation of Isatin Derivatives by Using Allenylboronic Acid Pinacol Ester

“…Under the optimized condition, L4 (Table , Entry 13) with N ‐methyl isatin ( 3oa ) taken as a model substrate, we could achieve chiral propargylic alcohols in enantiomeric ratio 15:85. The use of strong base to suppress the formation allenyl products and formation of Cu‐alkoxide complex for smooth Cu/B exchange to form stable allenyl Cu‐species for asymmetric propargylation…”

“…To investigate the mechanism of the reaction NMR spectroscopic analysis was done. Smooth transmetallation of Cu/B exchange was observed by 11 B NMR spectroscopy (Figure ) with a new peak at δ = 21.31 ppm (Allene 11 B‐29.11 ppm). 13 C NMR spectra (Figure ) shows that the peak at δ = 218.04 ppm completely disappears.…”

“…However, these results could not compete with water (Table 2, Entry 7) except for tetrahydrofuran (THF; Table 2, Entry 9) that gave similar results but suffered a slightly more prolonged reaction time. Fast reaction rates could be attributed to the fact that transmetallation (B/Cu exchange) [11] occurred rapidly in aqueous media as a result of its high solubility in water to form stable allenyl intermediates to afford propargyl alcohols in high yields. With the optimized conditions in hand (5 mol-% of copper II triflate) and with 2a nucleophile in H 2 O as a green solvent, we investigated the different N-protected and unprotected isatins.…”

“…[10] However, the site selection for the formation of propargyl and allenyl substitutes remain a challenging task because of the formation of stable allenyl and less stable propargyl intermediates. [11] With these upsurge developments for regioselective and enantioselective propargylation, the substrate scope has been restricted to aldehydes, [5e,8b,9a,12] ketones, [1a,7a,12] imines, [7b,9d,12,13] and keto esters. [5b] However, the regioselective and enantioselective propargylation of isatin, i.e., alpha-keto lactams have rarely been explored.…”

2.05 Propargyl and Allenyl Organometallics

“…Mangeney, Vrancken et al considered the addition of hetero allenyl copper reagents to aldehydes; 28 it is noteworthy that until their reports, synthetically interesting aza-substituted allenylmetal compounds had been almost totally neglected. This approach allowed preparation of a-heteroatom-functionalized homopropargylic alcohols 52 and 54 with excellent anti-selectivity (equations 8-9, Tables 22 and 23).…”