The First Sequential Reaction Promoted by Manganese:  Complete Stereoselective Synthesis of (E)-α,β-Unsaturated Esters from 2,2-Dichloroesters and Aldehydes

Abstract

Alpha,beta-unsaturated esters were obtained with complete control of stereoselectivity utilizing a sequential reaction of dichloroesters with a variety of aldehydes, promoted by active manganese. This methodology is generally applicable, and the C-C double bond can be di- or trisubstituted. A mechanism based on a successive aldol-type reaction/beta-elimination is proposed to explain these results.

Manganese-mediated reductive functionalization of activated aliphatic acids and primary amines

“…Under the above standard reaction conditions, the decarboxylative C-Se and C-Te bond formation reactions proceeded smoothly to afford the desired products (45)(46)(47)(48)(49). In order to showcase the virtues of our protocol in generating structural diversity for late-stage application, we applied this strategy to different natural products and drug molecules containing a carboxylic acid functional group (50)(51)(52)(53). Thus, derivatives of pregabalin (50), probenecid (51), steroids (52) and gemfibrozil (53) were successfully converted into the desired thiolated products in moderate to good yields.…”

“…In order to showcase the virtues of our protocol in generating structural diversity for late-stage application, we applied this strategy to different natural products and drug molecules containing a carboxylic acid functional group (50)(51)(52)(53). Thus, derivatives of pregabalin (50), probenecid (51), steroids (52) and gemfibrozil (53) were successfully converted into the desired thiolated products in moderate to good yields. Our protocol thus offers a valuable alternative to the previous light-promoted decarboxlative thiolations by providing broader substrate scope 62 .…”

“…It should be noted, however, in the typical Barbier coupling reactions, commercial Mn powder reacts only with the most reactive substrates (allylic halides, αhalogenoesters) 42,47,48 . The less reactive alkyl halides require the use of activated manganese metal, which is often too reactive to be sufficiently chemoselective when complex starting materials are employed 42,[49][50][51][52][53][54][55] .…”

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

“…[17] After the appearance in the literature of the aforementioned procedures for the preparation of Mn*, the number of contributions reporting new synthetic applications of this metal has increased. [18] Recently, we reported the first sequential processes promoted by Mn*, in which, starting from aldehydes and 2,2-dichloro esters or amides, (E)-a,b-unsaturated esters [19] or amides, [20] were obtained, respectively, with complete or total diastereoselectivity. In a similar manner we have also reported the synthesis of (Z)-a,b-unsaturated 2-halo esters or amides with high stereoselectivity, [21] promoted by Mn* from aldehydes and trihalo esters or amides.…”

Stereoselective synthesis of (Z)-α-haloacrylic acid derivatives, and (Z)-haloallylic alcohols from aldehydes and trihaloesters or amides promoted by Rieke manganese

“…de Química Orgánica e Inorgánica, Facultad de Química, Universidad de Oviedo, 33071 Oviedo, Spain. E-mail: jmcg@uniovi.es; Fax: +34 98 510 34 46; Tel: +34 98 510 34 57 † Electronic Supplementary Information (ESI) available: Copies of 1 H and 13 C NMR spectra for all new compounds 3, 5 and 9-11. See DOI: 10.1039/b803449d with a,a-dihaloesters 13 or amides, 14 yielding (E)-a,b-unsaturated esters or amides, respectively.…”