Stereoselective Olefination Reactions Promoted by Rieke Manganese

Abstract

A study of the advantages of using manganese, an inexpensive and nontoxic metal, to perform stereoselective b-elimination reactions and to promote sequential olefination reactions of aldehydes to obtain a,b-unsaturated esters and amides is presented. Various elimination reactions, all of them characterized by occurring with complete stereoselectivity and in high yields, were performed using active manganese (Mn*) as metalating agent. This ability of manganese has been applied to develop a novel and direct synthesis of (E)-a,b-unsaturated esters or amides and (Z)-a,b-unsaturated a-halo esters and a-choroamides through a Mn*-mediated sequential olefination protocol of aldehydes with dichloro esters or amides and trihalo esters or trichloroamides, respectively.Manganese is a nontoxic 1 and inexpensive 2 metal and the reduction potential of Mn 2+ /Mn 0 system (-1.03 V) 3 is adequate to reduce an important number of organic functions. According to these properties, extensive use of manganese in organic synthesis might be expected. However, in contrast to other metals, such as lithium, magnesium, zinc, or samarium, the application of manganese in organic synthesis has been scarcely developed. Among the main reasons for this lack of development are the inability of commercially available manganese to react directly with organic compounds as consequence of its passivity, 4 mainly because of the formation of an oxide layer on its surface. To overcome the lack of reactivity of manganese metal, different procedures have been describe to obtain active manganese (Mn*) by Rieke 5 and Fürstner 6 in 1996, by Oshima 7 in 1998, and by Cahiez 8 in 1999. Since then the number of reported transformations promoted by Mn* have increased. 9 It is important to note that all these transformations take place with high selectivity. Combining the aforementioned properties of manganese (reduction potential, selectivity, low price, and toxicity) with our interest in the development of novel highly selective organic reagents, including the use of selective metals, has prompted us to develop new synthetic applications of manganese.We decided to test the ability of manganese to promote highly stereoselective elimination reactions towards the synthesis of a,b-unsaturated esters or amides, based on: (a) the use of manganese to carry out elimination reactions has not been previously reported, and (b) despite there being a large number of contributions reporting the synthesis of a,b-unsaturated esters 10,11 or amides, 11,12 some of these methods take place without complete stereoselectivity (particularly when the double bond is trisubstituted) and are either tedious (multistep procedures) or imply the use of expensive starting materials.Based on these precedents, we reported the first transformation of 2-bromo-3-hydroxy esters into a,b-unsaturated esters with complete stereoselectivity promoted by commercial manganese activated by chlorotrimethylsilane. 13 Later, we described a novel manganese-mediated olefination reaction of aldehydes to obtain (E)-...

Diisopinocampheylborane‐Mediated Reductive Aldol Reactions: Highly Enantio‐ and Diastereoselective Synthesis of syn Aldols from N‐Acryloylmorpholine

“…[12] Morpholine amides are a safe alternative [13] to Weinreb amides but have similar modes of reactivity and comparable ease of manipulation. [14] We quickly found that excellent results were obtained when the hydroboration of 8 with ( l Ipc) 2 BH[15] was performed in Et 2 O at 0 °C for 2 h, followed by addition of 0.85 equiv of aldehyde at −78 °C (Scheme 2). By using this procedure, the syn -α-methyl-β-hydroxy morpholine amides 11a–f were obtained in good to excellent yields (68–91%) and with excellent enantio- and diastereoselectivities (96–98% ee, d.r.…”

“…[1–7,23] The morpholine amide unit in the aldol products exhibits Weinreb amide-like ease of manipulation in subsequent steps. [13,14] Our procedure requires only two steps, starting with the straightforward synthesis of diisopinocampheylborane. [15] Strikingly, the cost of raw materials required for the synthesis of enolborinate 9 Z (including the synthesis of diisopinocampheylborane) is less than $0.25 per mmol scale aldol reaction (2012 Sigma-Aldrich prices for bulk quantities of reagents).…”

“…[15] Strikingly, the cost of raw materials required for the synthesis of enolborinate 9 Z (including the synthesis of diisopinocampheylborane) is less than $0.25 per mmol scale aldol reaction (2012 Sigma-Aldrich prices for bulk quantities of reagents). [11] Integrating over cost, reagent accessibility, selectivity (both enantio- and diastereoselectivity), substrate scope and generality, and the ease of manipulation of the morpholine amide aldol products, [14] we submit that the new reductive aldol procedure described here is the least expensive [24] and ranks high among the most highly enantio- and diastereoselective, substrate-general methods for synthesis of syn aldols compared to all other currently available procedures.…”

Synthetic approaches to monofluoroalkenes

“…The reaction was also Z-selective but yields with the substrates tested were lower (62-64%). 146 In order to replace Cr II with a less expensive and less toxic metal, Falck studied the reaction of ethyl dichlorofluoroacetate with benzaldehyde using Fe. Thought the yield was lower (79%) than with the Cr II version (99%), the reaction was still Z-selective.…”

Deoxydichlorination of aldehydes catalyzed by Diphenyl sulfoxide

“…Dichlorides -important class of intermediates in organic synthesis. They were used for alkenylation of carbonyl compounds [15,16], cyclopropanation and epoxidation [17][18][19], dimerization [20,21] and others [22][23][24][25]. In addition, geminal dichlorides are encountered as structural motifs in polyhalogenated natural products [26,27] (Fig.…”