Sustainable Alkylation of Unactivated Esters and Amides with Alcohols Enabled by Manganese Catalysis

Abstract

The first example of manganese catalyzed C-alkylation of the carboxylic acid derivatives is reported. The benchstable homogenous manganese complex enables the transformation of the renewable alcohol and carboxylic acid derivative feedstock to higher value esters and amides. The reaction operates via hydrogen autotransfer and, ideally produces water as the only side product. Importantly, aliphatic, benzylic, and heterocyclic containing alcohols could be used as alkylating reagents, eliminating the need of the mutagenic alkyl halides.

Sustainable and Selective Alkylation of Deactivated Secondary Alcohols to Ketones by Non‐bifunctional Pincer N‐heterocyclic Carbene Manganese

“…On the basis of our experimental observations and literature precedents, a plausible reaction pathway is proposed in Scheme . Initially, catalyst C1 reacts with a base to generate an unsaturated reactive species C1‐1 , similar to previous reports . The resulted reactive intermediate C1‐1 then reacts with primary or secondary alcohols to provide an alkoxo Mn intermediates ( C1‐2 and C1‐3 ).…”

“…Particularly impressive is the latest growth in Mn catalysis, as its reactivity towards hydrogenation and dehydrogenation reactions was demonstrated in 2016 . Progress on the α‐alkylation of ketones, esters, or amides using primary alcohols has been recently reported by Beller, Milstein, EI‐Sepelgy, Balaraman, and co‐workers using Mn catalysts (Scheme a). Very recently, we have also reported a phosphine‐free bis ‐NHC Mn promoted α‐alkylation of ketones with primary alcohols to α‐alkylated ketones …”

Bidentate Ru(II)‐NC Complexes as Catalysts for α‐Alkylation of Unactivated Amides and Esters

“…Compared to methyl ketones, the α-alkylation of unactivated amides and esters is more challenging, due to the lower acidity of their α-H, and the readily occurrence of side reactions for esters. [11][12][13][14][15] So far, the best catalyst for α-alkylation of unactivated amides and esters is the PCNÀ Ir complex discovered by Huang and coworkers (Scheme 1). [4] Later in 2013, Huang et al developed the α-alkylation of unactivated amides using an Ir-pincer complex (Scheme 1).…”

“…[4] Later in 2013, Huang et al developed the α-alkylation of unactivated amides using an Ir-pincer complex (Scheme 1). [5] Since then, several other transition-metal catalysts, including Ir, [6,7] Ru, [8][9][10] Co, [11] Ni [12] and Mn [13][14][15] complexes, have been developed, most of which are based on pincer-type ligands. For earth-abundant base metal catalysts, harsh reaction conditions and high catalyst loadings were needed for good conversion in most of the cases, and sometimes the substrates were limited.…”

“…For earth-abundant base metal catalysts, harsh reaction conditions and high catalyst loadings were needed for good conversion in most of the cases, and sometimes the substrates were limited. [11][12][13][14][15] So far, the best catalyst for α-alkylation of unactivated amides and esters is the PCNÀ Ir complex discovered by Huang and coworkers (Scheme 1). [6,7] For amide alkylation, the reactions proceeded well at 80°C with 0.5 mol% catalyst, [7] and when the substrates were esters, 60°C was even enough.…”