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

Abstract

The hydroformylation of alkynes is af undamental and important reaction in both academic researcha nd industry.C onventional methods focus on the conversion of alkynes,C O, and H 2 into a,b-unsaturated aldehydes,b ut they often suffer from problems associated with operation, regioselectivity,and chemoselectivity.Herein, we disclose an operationally simple,m ild, 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 acommercially available catalyst and ligand to transform ab road range of internal alkynes, especially alkynyl-containing complex molecules,into versatile stereodefined a,b-unsaturated aldehydes with excellent chemo-,regio-, and stereoselectivity. Scheme 1. Hydroformylation of alkynes to a,b-unsaturated aldehydes.

Palladium‐Catalyzed Hydroformylation of Alkenes and Alkynes

“…In contrast to the transition-metal-catalyzed hydroformylation of olefins, which is among the most extensively studied catalytic reactions, hydroformylation of alkynes gained rather limited attention over the years. [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] This disparity might be surprising, considering that the products, the α,β-unsaturated aldehydes are important intermediates in organic synthesis, particularly for the synthesis of bioactive compounds, flavors, and fragrances. One challenge that hinders the development of efficient hydroformylation protocols is the high reactivity of starting materials and products.…”

“…During the past two decades, several methods of rhodium-catalyzed hydroformylation of alkynes were reported, demonstrating that the selective production of α,β-unsaturated aldehydes from alkynes is feasible. [62][63][64][65][66]68,69,71,72,[75][76][77]79] Hereafter, only the palladium-catalyzed hydroformylation of alkynes will be discussed.…”

“…Besides the above-mentioned Pd-based protocols, methods involving other catalysts, including Co- [60] and Rh-based complexes [61][62][63][64][65][66]68,69,71,72,[75][76][77] , were reported to undergo hydroformylation of internal alkynes. However, the counterpart methods for terminal alkynes with adequate activity and chemoselectivity remain rather rare.…”

“…In contrast to the transition‐metal‐catalyzed hydroformylation of olefins, which is among the most extensively studied catalytic reactions, hydroformylation of alkynes gained rather limited attention over the years [60–78] . This disparity might be surprising, considering that the products, the α,β‐unsaturated aldehydes are important intermediates in organic synthesis, particularly for the synthesis of bioactive compounds, flavors, and fragrances.…”

A General and Highly Selective Palladium‐Catalyzed Hydroamidation of 1,3‐Diynes

“…Clearly, carbonylations of unsymmetrical internal alkynes are more demanding because of their low reactivity and the difficulty in achieving high regioselectivity. Notable exceptions include the recent works on hydroformylation and alkoxycarbonylation reported by the groups of Breit, [8a] You [8b] and Ma, [9] respectively. In these studies, regioselectivity could be controlled by hydrogen bonding interactions between substrates and catalysts, steric hinderance and/or chelation.…”