Preparation of Aryl and Heteroaryl Indium(III) Reagents by the Direct Insertion of Indium in the Presence of LiCl

Abstract

Functionalized organometallic compounds are key intermediates in organic synthesis. [1] In particular, organozinc reagents are compatible with a wide range of functional groups and have broad application in synthesis.[2] However, sensitive functional groups, such as aldehyde or ketone functionalities with a acidic hydrogen atoms, are only tolerated in special cases.[3] Furthermore, the reactivity of unsaturated zinc reagents toward acidic hydrogen atoms of alcohols and phenols precludes the performance of Negishi cross-coupling reactions [4] of aromatic iodides containing these functionalities. In contrast to organozinc reagents, organoindium reagents have been shown to be compatible with water and several important functionalities.[5] However, in classical syntheses of these organoindium compounds through Li/In or Mg/In transmetalation, the corresponding organometallic precursors require protecting groups. Recently, we reported that LiCl accelerates dramatically the insertion of zinc [6] or magnesium [7] into organic halides. Herein, we report a preparation of polyfunctional aryl and heteroaryl indium(III) reagents 1 through the direct insertion of indium metal in the presence of LiCl into iodides 2. To the best of our knowledge, only allyl, propargyl, [5] pentafluorophenyl, [8] and benzyl indium(III) reagents [9] have been prepared by the direct treatment of the corresponding halides with indium metal. Commercially available indium does not react with aryl iodides. However, when LiCl (2-4 equiv) [10] was added to indium powder (2-4 equiv) that had been activated with 1,2-dibromoethane and TMSCl [11] in THF, an efficient insertion occurred within 20 min to 24 h at 30-50 8C to provide polyfunctional aryl and heteroaryl indium(III) species 1 in 70-97 % yield (Scheme 1).Thus, the treatment of 4-iodoacetophenone (2 a) with activated indium powder (4 equiv) in the presence of LiCl (4 equiv) in THF at 50 8C for 24 h provided the desired aryl indium(III) reagent 1 a in 96 % yield, as indicated by iodolysis (Table 1). [12] No insertion occurred in the absence of LiCl.Similarly, the iodoketones 2 b and 2 c were converted into the corresponding keto-substituted indium derivatives 1 b (50 8C, 24 h) and 1 c (35 8C, 2 h) in 93 and 90 % yield, respectively. The functionalized aryl iodides 2 d-g with an ester or aldehyde functionality also reacted smoothly with indium metal in the presence of LiCl to give the organoindium(III) reagents 1 d-g in 70-86 % yield. The presence of an electronwithdrawing group or metalation-directing group increased the insertion rate considerably. This method was extended to the preparation of heteroaryl indium(III) reagents. Heterocyclic iodides (and a heterocyclic bromide), some of which contained a ketone, aldehyde, or ester functionality, reacted smoothly with indium powder in the presence of LiCl to furnish the heteroaryl indium(III) compounds 1 h-m in 78-97 % yield (Table 1, entries 8-13). This method provides access to organoindium reagents containing a range of important and sensitive funct...

The Barbier–Grignard-type arylation of aldehydes using unactivated aryl iodides in water

“…On the basis of our previous experience 39 and other literature studies 40 , we proposed a plausible mechanism for this transformation. We hypothesized that under certain conditions, the organometallic reagents generated in situ 41,42 in water could be temporarily stabilized briefly, for example organozinc reagents (Fig. 5b).…”

Coupling of Epoxides and Lactones by Cationic Indium Catalysts To Form Functionalized Spiro‐Orthoesters

“…SOE1 was purified by distillation;h owever,p rior to this, all trace amounts of the catalyst needed to be removed by passing the reactionm ixture through as ilica gel columnt op reventp olymerization during distillation. Characterization of SOE1 by 1 HNMR, 13 C{ 1 H} NMR, HSQC, and HMBC spectroscopy provided results that were consistent with the formation of two discrete diastereomers of SOE1 with the absence of ac orrelation between each set of signals ( Figures S24-S28). GC-MS analysis of SOE1 showedt wo signals with a2 .22:1.00 ratio closely distributed on the chromatogram, with ap arentm ass of m/z = 240.1, which is consistent with the calculatedm ass of SOE1 ( Figure S29).…”

“…[5a, 9] The reaction of (AE)-H(NN i O) with In(CH 2 SiMe 3 ) 3 in Et 2 Oa t2 58Cr esulted in the formation of the dialkyl complex (NN i O)In(CH 2 SiMe 3 ) 2 (1)i n7 8% yield (Scheme 1). The solid-state structure of 1,d etermined by single-crystal X-ray crystallography,f eatures ad istorted square pyramidal indium center (t = 0.36) [10] with a k 3 -bound ancillary ligand.T he 1 HNMR and 13 Figures S5-S16). In particular, the 1 HNMR spectrum of 2·THF shows an AB doublet centered at d = À0.25 ppm corresponding to one In-CH 2 SiMe 3 ligand, and this signal is shiftedd ownfield relative to the signal for the corresponding protons of complex 1.A sc omplex 2·THF was isolated more readily and in highery ield, all catalytic experiments were attempted with this species.…”

“…[12] The lack of reactivity of the InÀC bond with the coordinated water molecule is at estamentt o the degree of its covalency and is similart oo ther water-soluble indiumalkyl complexes. [13] Under optimized conditions (Table S4), the reaction of a1 :1 mixture of e-caprolactone (e-CL) with 1,2-epoxy-7-octene (EOE) at 60 8Ci nb enzene with a2 .5 %l oading of 2·THF resulted in the formationo f2 -(hex-5-en-1-yl)-1,4,6-trioxaspiro[4.6]undecane (SOE1)asaracemic mixture of diastereomersw ith quantitative conversions for both e-CL and EOE after 24 h[ Eq. (1)].…”

Pd‐Catalyzed Functionalization of the Thenoyltrifluoroacetone Coligands by Aromatic Dyes in Bis(cyclometallated) IrIII Complexes: From Phosphorescence to Fluorescence?­

“…The products were purified by silica gel column chromatography. {5-[3-(Trifluoromethyl)phenyl]thiophen-2-yl}ethanone (th-PhCF 3 , 1a): [20] Method B. From 1-bromo-3-(trifluoromethyl)benzene (1.35 g, 6 mmol) and 2-acetylthiophene (2.27 g, 18 mmol), the product was obtained in 55 % yield (0.891 g).…”