Ketones reactions with samarium diiodide

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

Two convenient methods have been developed for the preparation of trifluoro-methyl-substituted alkoxyallenes. Reductive elimination of allylic acetates 30 with samarium diiodide leads to 31 (Scheme 8.11) [38], whereas reaction of Wittig cumu-lene 32 with phenyl trifluoromethyl ketone (33) and thermolysis of the intermediate 34 provides 35 (Scheme 8.12) [39]. 

Transannular cyclization of ketoalkenes was first reported in 1965. Treatment of the conformationally restricted ketone (104) with sodium in moist ether gave the alcohol (105 equation 127). Similarly the ketoalkene (106) transannulated in 73% yield by exposure to sodium in refluxing propanol (equation 128). Conformational restriction is not a prerequisite for transannular reaction thus the caryophyllene (107) undergoes cyclization to the alcohol (108) with lithium in liquid ammonia (equation 129). Transannulation across a nine-membered ring has also been observed upon treatment of ketone (109 equation 130) with samarium diiodide, via cyclization of the ketoalkene (110). Of more practical importance, the electrochemical transannulation of the cyclooct-4-en-l-one gives the bicyclo[3.3.0]octanol (111 equation 131). ... 

Despite the tremendous amount of work on samarium diiodide mediated reactions, few examples of cyclic ketone reductions have been described. One example is a step in the synthesis of racemic atractyligenin49 where an annulated cyclohexanone was reduced efficiently with samarium diiodide in tetrahydrofuran/ water at 20 C to give the 2/J-alcohol equatorioselectively. 

The mechanism for the transformation of 5 to 4 was not addressed. However, it seems plausible that samarium diiodide accomplishes a reduction of the carbon-chlorine bond to give a transient, resonance-stabilized carbon radical which then adds to a Smni-activated ketone carbonyl or combines with a ketyl radical. Although some intramolecular samarium(n)-promoted Barbier reactions do appear to proceed through the intermediacy of an organo-samarium intermediate (i.e. a Smm carbanion),10 ibis probable that a -elimination pathway would lead to a rapid destruction of intermediate 5 if such a species were formed in this reaction. Nevertheless, the facile transformation of intermediate 5 to 4, attended by the formation of the strained four-membered ring of paeoniflorigenin, constitutes a very elegant example of an intramolecular samarium-mediated Barbier reaction. 

Molander and co-workers have studied the stereoselective intramolecular addition of ketyl radicals to olefins [95JOC872]. The ketyl radicals are generated from ketone by treatment with samarium(II) diiodide. A similar reaction sequence using 61 gave only elimination products. 

Ni(0) catalyst. A radical 5-exo cyclization to the potentially zinc or nickel-complexed ketone provides an alkoxyl radical that combines with the co-produced Ni(I) species. A transmetalation to a zinc alkoxide regenerates the catalyst and forms the zinc cyclopentoxide, from which products 79 are liberated on hydrolysis. A bimetallic Cu(I)-Mn(II) system provided similar results (see Sect. 8.4). Analogous samarium diiodide-mediated reactions require in contrast stoichiometric amounts of the reducing agent and are less diastereoselective [26, 27],... 

A more versatile reducing agent is samarium diiodide, which promotes chemoselective cyclizations of functionalized keto aldehydes in a stereodefined manner to form 2,3-dihydrocyclopentane carboxylate derivatives in good yields and with diastereoselectivities of up to 200 1 (equation 38)7 The reaction proceeds via selective one-electron reduction of the aldehyde component and subsequent nucleophilic attack on the ketone moiety. Stereochemical control is established by chelation of the developing diol (19) with Sm " " which thereby selectively furnishes cis diols (equation 39). The stereoselective M/-cyclization of 1,5-diketones to cis cyclopentane-1,2-diols using TiCU/Zn has been used to prepare stereodefined sterically hindered acyclic 1,2-diols when a removable heteroatom, such as sulfur or selenium, is included in the linking chain (equation 40). 

Studies by Molander et al. have demonstrated that samarium diiodide efficiently promotes the intramolecular coupling of ketones with distal epoxy olefins in the presence of HMPA, in good yields and often with high diastereoselec-tivity (Scheme 20). When tetramethylguanidine was used instead of HMPA, the desired carbocycle was obtained in good yield but the diastereoselectivity was diminished [55]. Evidence has been presented that suggests that the reaction proceeds via an initial radical cyclization route although reaction via an allyl samarium species cannot be ruled out. 

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