Syngas‐Free Highly Regioselective Rhodium‐Catalyzed Transfer Hydroformylation of Alkynes to α,β‐Unsaturated Aldehydes

Abstract

The hydroformylation of alkynes is a fundamental and important reaction in both academic research and industry. Conventional methods focus on the conversion of alkynes, CO, and H2 into α,β‐unsaturated aldehydes, but they often suffer from problems associated with operation, regioselectivity, and chemoselectivity. Herein, we disclose an operationally simple, mild, and syngas‐free rhodium‐catalyzed reaction for the hydroformylation of alkynes via formyl and hydride transfer from an alkyl aldehyde. This synthetic method uses inexpensive and easy‐to‐handle n‐butyraldehyde to overcome the challenge posed by the use of syngas in traditional approaches and employs a commercially available catalyst and ligand to transform a broad range of internal alkynes, especially alkynyl‐containing complex molecules, into versatile stereodefined α,β‐unsaturated aldehydes with excellent chemo‐, regio‐, and stereoselectivity.

Palladium-catalysed carboformylation of alkynes using acid chlorides as a dual carbon monoxide and carbon source

“…Several internal alkynes tethered with a polar functional group such as phthalimides, esters, carbamates and ethers were also probed to explore whether directing effects could influence the reaction´s regioselectivity. While most of them resulted in only slightly improved or negligible regioselectivity, an ester at the β-position relative to the alkyne led to a synthetically useful ratio of separable isomers (up to 3:1, 42-44) 19 . Additionally, high regioselectivity was obtained when a highly sterically encumbered alkyne is reacted with a bulky aroyl chloride (35), displaying preferential aryl insertion at the distal position relative to the bulky group, presumably to minimize steric repulsion.…”

“…Simultaneously, significant research has focused on vanquishing the hazards associated with the use of toxic and highly flammable CO, as well as avoiding the use of pressurized reactors to facilitate laboratory use. Among these strategies, the use of CO surrogates and two-chamber systems operating under mild conditions, as well as CO transfer by shuttle catalysis and single bond metathesis strategies, have emerged as valuable alternatives [15][16][17][18][19][20][21][22] . Among all carbonylation reactions, catalytic hydroformylation, the addition of CO and H2 across unsaturated substrates, is an essential reaction to access a wide set of functionalized aldehyde products.…”

Palladium-Catalyzed Carboformylation Enabled by a Molecular Shuffling Process

“…Several internal alkynes tethered with a polar functional group such as phthalimides, esters, carbamates and ethers were also probed to explore whether directing effects could influence the reaction´s regioselectivity. While most of them resulted in only slightly improved or negligible regioselectivity, an ester at the β-position relative to the alkyne led to a synthetically useful ratio of separable isomers (up to 3:1, 42-44) 18 . Additionally, high regioselectivity was obtained when a highly sterically encumbered alkyne is reacted with a bulky aroyl chloride (35), displaying preferential aryl insertion at the distal position relative to the bulky group, presumably to minimize steric repulsion.…”

“…Simultaneously, significant research has focused on vanquishing the hazards associated with the use of toxic and highly flammable CO, as well as avoiding the use of pressurized reactors to facilitate laboratory use. Among these strategies, the use of CO surrogates and two-chamber systems operating under mild conditions, as well as CO transfer by shuttle catalysis and single bond metathesis strategies, have emerged as valuable alternatives [14][15][16][17][18][19][20][21] .…”

Ligand-Controlled Regiodivergent Hydroformylation of Ynamides: A Stereospecific and Regioselective Access to 2- and 3-Aminoacroleins

“…In our opinion, this point was crucial as the selectivity of our catalytic systems is based on the directing abilities of this moiety. Substrates bearing a carbamate group such as Boc (1f), Moc (1g) or an oxazolidone (1h & 1i) gave relatively similar results as the tosylated ynamide 1a both in terms of selectivity and yield (entries [11][12][13][14][15][16][17][18]. Then the effect of the last point of diversity, i.e.…”