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]
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.
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,
1999]
