Synthesis And Transformation Of [Difluoro(Phenylseleno)Methyl]Trimethylsilane

The application of fluorinated organosulfur compounds as useful synthetic intermediates has intrigued a widespread interest in the construction of fluorinated building blocks. Difluoromethyl phenyl sulfone could be regarded as a difluoromethyl anion equivalent, a selective difluoromethylene dianion equivalent, as well as a difluoromethylidene equivalent. However, very little attention has been paid to the fluoroselenium compounds. It is well known that sulfur and selenium have similar chemical reactivity, but differ in size, electronegativity and nucleophilicity. Based on the aforementioned cases, we are very interested in the synthesis and transformation of fluoroselenium compounds.In this paper, we described a novel and efficient synthesis of bromodifluoromethyl phenyl selenide (PhSeCF₂Br, 1) by the addition of sodium borohydride to prevent the formation of diphenyl diselenide. [Difluoro(phenylseleno)methyl]trimethylsilane (PhSeCF₂TMS, 2) wasconveniently prepared by the coupling reaction of PhSeCF2Br and TMSC1 in the presence of magnesium. The resulting fluoroalkylated silane 2, in the presence of a fluoride initiator, could act as a "PhSeCF2^" equivalent and reacted with a series of aldehydes and ketones to furnish the corresponding a,a-difluoro-P-hydroxy selenides 3, which could be deselenylated to afford difluoromethyl alcohols via a classical procedure. In our opinion, difluoroalkylation of carbonyl compounds with 2 provided an optional method for the preparation of wide ranges of a,a-difluoro-(3-hydroxy selenides and difluoromethyl alcohols.As a vinylic pseudohalide group, the phenylselenium compounds were reported to undergo reductive radical cyclization, radical deselenylation and intermolecular radical addition in the manner similar to the Bu3SnH-mediated reaction of alkyl halides, which reflected the great potential of PhSeCF2TMS as fluorinated building block. Exhilaratingly, a convenient and nontoxic system NaBH4/InCl3, in which indium hydride (Cl2InH) was in situ generated, was recently reported by Baba group to be effective as an alternative to tributyltin hydride. Based on our ongoing project in the utilization of PhSeCF2TMS and as an extension of utilization scope of NaBH4/InCl3 system, herein we also report the NaBH4/InCl3-mediated radical intramolecular cyclization, radical deselenylation and radical intermolecular addition of gem-difluoromethyl-containing phenylseleno compounds. We firstly synthesized a series of a,a-difluoro-|3-hydroxy selenides 3, which wassupposed to be converted to cyclization precursors (0-allylated p-hydroxy-a,a-dlfluoro-alkyl phenyl selenides, 5) by allylation with allylic bromide. Considering the strong basicity of NaH would result in dehydrofluorination of a,a-difluoro-P-hydroxy selenides, inorganic base KOH was used in the allylation of alcohol 3 and the desired organoseleno compounds 5 were provided in 85-92% yields. We investigated the NaBH4/InCl3-mediated radical intramolecular cyclization of 5 and found reaction proceeded well to afford 3,3-difluoro-4-methyl tetrahydrofuran derivatives 6 in high cis/trans selectivity. In addition, NaBH4/InCl3-mediated radical deselenylation and radical intermolecular addition of gew-difluoromethyl-containing phenylseleno compounds were also addressed. These studies demonstrated that, NaBH4/InCl3 system could not entirely substitute for Bu3SnH/AIBN system in radical reactions despite its nontoxicity. That is, NaBH4/InCl3 system and Bu3SnH/AIBN system could be efficiently utilized in different radical reactions, respectively, and they could supplement each other in some radical reactions.Qin Ying-Ying (Applied Chemistry) Supervised by Qing Feng-Ling...