Samarium diiodide based reactions
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Nucleophilic hydroxymethylation of carbonyl compounds provides a useful method for the synthesis of 1,2-diols.[Imamoto, 1991] Monoprotected 1,2-diols have been synthesized by alkoxymethylation of carbonyl compounds with a-halo ethers in the presence of SmI2.[Imamoto, 1984],[Sasaki, 1988], [Antonsen, 1992] The synthetic utility of this procedure has been demonstrated in a short synthesis of the pheromone (+) Frontalin (1) [Imamoto, 1991] and in the synthesis of the tetracylic diterpene 2-Desoxystemodinone (2).[White, 1987]
(1) Synthesis of Frontalin
The first step in the Frontalin synthesis, is a SmI2 mediated benzyloxymethylation of 2,6-heptadion with the a-chloro ether 1. The addition product 2 was isolated in 56 % yield.[Imamoto, 1991]
(2) Synthesis of Desoxystemodinone
Reaction of the sterically encumbered ketone 1 with methyllithium resulted only in enolate formation, while other nucleophilic reagents did not react.[White, 1987] The reaction of benzyloxymethyl chloride 2 in the presence of SmI2 gave, however, an excellent yield of the benzyloxymethylated compound 3.
(3) Monosilylated 1,2-diols
If for strategic reasons, it is desirable to have protecting groups that can be removed by fluoride ions, monosilylated 1,2-diols 5-7 can be made from the carbonyl compounds 1-3 and the a-chloro ether 4 by the method above.[Antonsen, 1992] The low yield in the case of hexanal 1 is not surprising since reductive coupling of aldehydes (pinacol formation) is a facile reaction with SmI2.[Souppe, 1983] The pinacol formation can, however, be suppressed to some extent by using a tetraethylene glycol ether as a co-solvent.[Imamoto, 1984]
It should be noted that an attempt to use the corresponding "lithium" approach to 1,2-monosilylated diols, only the rearranged silyl compound 8 was obtained. [Antonsen, 1992]
(4) a-Hydroxyacetyl anion equivalent
In the presence of 2,6-xylyl isocyanide 3 is benzyloxymethyl chloride 1 transformed into an a-hydroxyacetyl anion equivalent by SmI2.[Murakami, 1990] An (a-iminoalkyl) samarium(III) structure 4 has been proposed as this a-hydroxyacetyl anion equivalent. Some observations indicate that the a-hydroxyacetyl anion equivalent is formed by an a-addition of an alkylsamarium(III) species 2 to the isocyanide.[Murakami, 1993]
The a-hydroxyacetyl anion equivalent adds to aldehydes and ketones without enolization or reductions.[Murakami, 1993] For instance b-tetralone 5, which is exceptionally prone to enolization, is readily coupled with benzyloxymethyl chloride 1 and 2,4-xylyl isocyanide 3 in the SmI2-mediated three-component coupling to give the a,a'-dioxygenated imine 6. Treatment of 6 with HCl in benzene/MeOH/H2O at room temperature gave the corresponding a,a'-dioxygenated ketone 7.
With the a,b-unsaturated ketones, 1,2-adducts are selectively formed. The structure of the isocyanide is important in this reaction. Other isocyanides such as hexyl and 4-tolyl isocyanide gave complex reaction mixtures.
(5) 1,6-C-coupled disaccharide
The synthesis of a 1,6-C-coupled disaccharide was carried out via reaction of a glycosyl chloride with an aldehyde in the presence of samarium diiodide.[Hung, 1996]
(6) Reductive samaration of glycosyl iodides.
Reductive samaration of per-O-trimethylsilyl or benzyl glycopyranosyl iodides in the presence of carbonyl compounds provides the corresponding 1,2-trans-C-glycosyl compounds in good yields.[Miquel, 2000]
(7) Samarium diiodide mediated Barbier reaction of a-fluoro ethers with cyclohexanone
Reaction of the a-fluoro ethers with an excess of
samarium diiodide in tetrahydrofuran at room temperature in the presence of
cyclohexanone, gave the addition products in good yields. [Ringom,