Copper-Catalyzed Formal Transfer Hydrogenation/Deuteration of Aryl Alkynes

Abstract

A copper-catalyzed reduction of alkynes to alkanes and deuterated alkanes is described under transfer hydrogenation and transfer deuteration conditions. Commercially available alcohols and silanes are used interchangeably with their deuterated analogues as the hydrogen or deuterium sources. Transfer deuteration of terminal and internal aryl alkynes occurs with high levels of deuterium incorporation. Alkyne-containing complex natural product analogues undergo transfer hydrogenation and transfer deuteration selectively, in high yield. Mechanistic experiments support the reaction occurring through a cis-alkene intermediate and demonstrate the possibility for a regioselective alkyne transfer hydrodeuteration reaction.

Highly Regioselective Copper‐Catalyzed Transfer Hydrodeuteration of Unactivated Terminal Alkenes

“…In a previous study by our group, we performed a Cucatalyzed alkyne transfer hydrogenation reaction using isopropanol as one of the H-sources. [41] This study revealed that hydrometalation of the alkene likely occurs in a reversible manner, similar to what is depicted for both the desired anti- We discovered that full conversion of alkene 1 can be achieved by increasing the catalyst loading to 3 mol% (entry 8, 90 % yield of 2 a, > 20 : 1 regioisomeric ratio). Consistent with entry 7, no alkene isomerization by-product was detected when using [D 8 ]isopropanol.…”

“…The role of the alcohol and/or silane in Cu-catalyzed alkene and alkyne hydrofunctionalization processes has been previously studied. [28,[38][39][40][41][42][43] Given that changing temperature, concentration and solvent did not lead to an optimal reaction, we decided to explore other alcohol-OD sources. The alcohol-OD reagent is important in the reaction because it is involved in the deuterodecupration of intermediates iii a and iii b (Scheme 2).…”

Catalytic Transfer Deuteration and Hydrodeuteration: Emerging Techniques to Selectively Transform Alkenes and Alkynes to Deuterated Alkanes

“…Notably, this early report employs an inexpensive deuterium source, which is often incompatible with metal-catalyzed transfer deuterations because of the potential for catalyst poisoning or undesirable side products. The authors demonstrated selective deuterium incorporation in the β-position of methylsuccinic acid dimethyl ester (31).…”

“…Another reaction that has been scarcely reported is a general alkyne transfer deuteration protocol. In 2020, the Clark group developed the first Cu‐catalyzed transfer deuteration of aryl alkynes [31] . The reaction employs dimethoxy(methyl)silane‐ d 1 and 2‐propanol‐OD (or ethanol‐OD) as the deuterium sources and ( R or S )‐DTBM‐SEGPHOS as a ligand for copper.…”

Correction: Room temperature iron catalyzed transfer hydrogenation using n-butanol and poly(methylhydrosiloxane)

“…The sentence that was intended to be included is as follows:Recently Clark has demonstrated a Cu-catalysed route for the preparation of alkanes and fully deuterated alkanes from alkynes. 1 The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.…”