Sequential Radical Cyclization/Organometallic Addition. On the Mechanism of the Samarium(II) Mediated Barbier Reaction in the Presence of Hexamethylphosphoric Triamide

Coupling of Organic Halides with Carbonyl Compounds Promoted by SmI2, the Kagan Reagent

“…The reaction is achieved with 2 molar equiv of SmI 2 and occurs by stepwise one-electron transfer to the organic halide (Scheme ) . Although conflicting mechanisms have been proposed, , the consensus 37 is that the intermolecular reaction usually proceeds via organosamarium species (with half-lives on the order of minutes to hours at room temperature) which then react with the carbonyl compounds ,− to produce the corresponding alcohols.

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“…The reactions have been performed (Scheme ) stepwise as in the Grignard reaction , (samarium Grignard reaction) by first reacting the organic halide with SmI 2 and then adding the carbonyl compound ,,, or in one single pot, as in the Barbier reaction ,, (samarium Barbier reaction), by mixing SmI 2 together with the organic halide and the carbonyl compound. ,− ,− ,,, The samarium-Barbier conditions offer several advantages over the classical Barbier conditions involving Mg or Li instead and have been used especially in intramolecular reactions (intramolecular samarium Barbier reaction: ISBR). ,− ,,, …”

Samarium(II) Mediated Radical Reactions

“…In one such example, haloacetals were cyclized and subsequently converted to the corresponding lactones (Eq. 2 Alkyl,Aryl,and Alkenyl Radical Addition Reactions 159 reactions promoted by SmI2 [3,23,241. Additionally, sequential reactions based upon this process have also been realized [ 151.…”

“…13). The rate constant of 5-ex0 cyclization of aryl radicals has been measured to be as high as 4 x lo9 s-' [23] making such cyclizations particularly attractive using this method. In one such cascade, radical cyclization ultimately leads to an organosamarium species that is trapped by an electrophilic isocyanide.…”

Cyclization into Hydrindanes Using Samarium Diiodide: Stereochemical Features Depending on the Protecting Group

“…We have been studying reductive cyclization reactions [2] affording guaianes [3], hydrindanes [4], perhydronaphthalenes [5], and other bicyclic systems using samarium diiodide (SmI 2 ) [6]. Organo samarium chemistry has been widely studied in detail [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Using samarium diiodide, monocyclic compounds having both an enone and a formyl group in the same molecule such as 3, without chiral centers, can cyclize into bicyclic compounds, such as ketol 4, bearing three consecutive chiral centers [4].…”