Simple and Efficient Preparation of Ketones from Morpholine Amides

Martin, R. H.; Romea, Pedro; Tey, C.; Urpı́, Fèlix; Vilarrasa, Jaume

doi:10.1055/s-1997-1050

Cited by 112 publications

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“…The synthesis of 7 r is a facile way to convert aldehydes into morpholine amides, which are versatile reagents for further functionalizations. [18] Amidation with amine nucleophiles is not limited to benzaldehyde substrates and can be extended to electron-rich (7 s, 86 %) or electron-poor (7 t, 61%) aldehydes by using two equivalents of the aldehyde. Aliphatic aldehydes can also be converted into N-alkyl amides by using benzaldehyde as an inexpensive oxidant (7 u, 54 %).…”

mentioning

confidence: 99%

Nickel‐Catalyzed Dehydrogenative Cross‐Coupling: Direct Transformation of Aldehydes into Esters and Amides

Whittaker

Dong

2014

Angewandte Chemie

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By exploring a new mode of nickel-catalyzed crosscoupling, a method to directly transform both aromatic and aliphatic aldehydes into either esters or amides has been developed. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either a,a,a-trifluoroacetophenone or excess aldehyde. Mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C À H bond is also presented.Developing nickel catalysts for the selective oxidation of CÀH bonds is an emerging strategy that overcomes the need for precious metals and enables new transformations.[1] Our laboratory has previously focused on the oxidation of aldehydes under Rh, Ru, and Co catalysis.[2] Inspired by the promise of base metals, we considered that Ni-catalyzed cross-couplings of aldehydes could be classified into three general types: redox-neutral, reductive, and oxidative ( Figure 1). For example, Ogoshis cross-coupling between two aldehydes is a redox-neutral method that generates ester bonds.[3] In comparison, reductive coupling reactions generate carbon-carbon bonds in the presence of an external reductant (e.g., Et 2 Zn).[4] A complementary Ni-catalyzed cross-coupling in the presence of an external oxidant, however, represents an undeveloped mode of reactivity that warrants study.[5] Herein, we showcase a unified approach for transforming aldehyde CÀH bonds into both CÀO and CÀN bonds using Ni-catalyzed dehydrogenative cross-couplings. [6] The transformation of aldehydes into esters and amides in one step is an attractive goal that has been pursued using precious-metal catalysts, [7] base-metal catalysts with strong oxidants, [8] and N-heterocyclic carbene (NHC) catalysis.[9]Whereas these methods are promising, a method that couples aromatic and aliphatic aldehydes with alcohols, anilines, and amines has yet to be achieved. Towards addressing this challenge, we chose to examine carbonyl compounds as mild oxidants by hydrogen transfer.[10]Our initial studies focused on cross-coupling benzaldehyde (1 a) and 2-propanol (2 a) in the presence of various hydrogen acceptors. We discovered that NHC ligands in 1,4-dioxane produced the most promising results (Scheme 1). [11] In the absence of any Ni salts, we observed no reactivity. However, in the presence of [Ni(cod) 2 ] with benzaldehyde as both the substrate and hydrogen acceptor, we observed the formation of the desired ester 4 a and Tishchenko homodimer 5 a in a 5.9:1 ratio. To suppress the Tishchenko pathway, we sought an acceptor that undergoes reduction faster than benzaldehyde (1 a). Whereas the addition of acetone (3 a) and cyclobutanone (3 b) decreased the rate of the desired crosscoupling, both benzophenone (3 c) and a,a,a-trifluoroacetophenone (3 d) showed a remarkable enhancement in rate and selectivity for 4 a. As a result, we were able to use equimolar quantities of the coupling partners and 1

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confidence: 99%

Nickel‐Catalyzed Dehydrogenative Cross‐Coupling: Direct Transformation of Aldehydes into Esters and Amides

Whittaker

Dong

2014

Angewandte Chemie

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“…Morpholinyl amides are as useful as Weinreb amides. [41] A variety of organometallic reagents, such as Grignard reagents, alkyllithiums, and metal hydrides, react with morpholinyl amide through a reaction mechanism similar to that of the Weinreb amide, affording the corresponding ketone or aldehyde in good yield. When a,b-unsaturated morpholinyl amide 15 a was used as a substrate, in sharp contrast to the Weinreb amide 13, 10 mol % of (S)-Sm complex 9 afforded the corresponding a,b-epoxy morpholinyl amide 16 a in quantitative yield and excellent enantiomeric excess (99 % ee).…”

Section: Resultsmentioning

confidence: 99%

Strategy for Enantio‐ and Diastereoselective Syntheses of All Possible Stereoisomers of 1,3‐Polyol Arrays Based on a Highly Catalyst‐Controlled Epoxidation of α,β‐Unsaturated Morpholinyl Amides: Application to Natural Product Synthesis

Tosaki

Horiuchi

Nemoto

et al. 2004

Chemistry A European J

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We describe a new strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays. This strategy relies on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides promoted by the Sm-BINOL-Ph(3)As[double bond]O (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio- (up to >99 % ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5-10 mol % of the Sm complex to afford synthetically very useful, nearly optically pure alpha,beta-epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn- and anti-selective ketone reduction with the highly catalyst-controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3-polyol arrays. Eight possible stereoisomers of 1,3,5,7-tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3-polyol/alpha-pyrone natural products, for example, cryptocaryolone diacetate.

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“…Amides derived from morpholine can be readily transformed into ketones by reaction with organolithium reagents. [24] Thus, amide 2 c, was allowed to react with n-butyllithium at À78 8C for 3 h, obtaining the expected 1-aryl-2-hydroxyheptan-3-one 5, in 91% yield (Scheme 2).…”

Section: Synthesis Of Aromatic 2-hydroxy Amidesmentioning

confidence: 99%

Manganese‐Promoted Regioselective Ring‐Opening of 2,3‐Epoxy Acid Derivatives: A New Route to α‐Hydroxy Acid Derivatives

Concellón¹,

Bernad²,

Rodríguez‐Solla³

et al. 2009

Adv Synth Catal

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A simple and general methodology directed towards the synthesis 3-aryl-2-hydroxy amides, or esters with total regioselectivity from the easily available 2,3-epoxy amides or esters, promoted by active manganese is described. Utilizing enantiopure epoxy amides as starting materials, the corresponding 3-aryl-2-hydroxy amides in enantiopure form are also available. Some synthetic applications of selected examples of 3-aryl-2-hydroxy carboxylic acid derivatives are shown. A mechanism has been proposed to explain this novel reaction.

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Simple and Efficient Preparation of Ketones from Morpholine Amides

Cited by 112 publications

References 0 publications

Nickel‐Catalyzed Dehydrogenative Cross‐Coupling: Direct Transformation of Aldehydes into Esters and Amides

Nickel‐Catalyzed Dehydrogenative Cross‐Coupling: Direct Transformation of Aldehydes into Esters and Amides

Strategy for Enantio‐ and Diastereoselective Syntheses of All Possible Stereoisomers of 1,3‐Polyol Arrays Based on a Highly Catalyst‐Controlled Epoxidation of α,β‐Unsaturated Morpholinyl Amides: Application to Natural Product Synthesis

Manganese‐Promoted Regioselective Ring‐Opening of 2,3‐Epoxy Acid Derivatives: A New Route to α‐Hydroxy Acid Derivatives

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