Application of aluminum triiodide in organic synthesis

2015 ARKIVOC  
The multifaceted reactivity of aluminum triiodide (AlI 3 ) is reviewed. The oxophilic character of the Lewis acid enables the formation of coordination complexes with esters, ethers, oxiranes, diols, Noxides, and sulfoxides that decompose spontaneously to afford acids, alcohols and olefins via ester and ether cleavage, deoxygenation of oxiranes, and deoxydehydration of diols, respectively. As an iodide ion source and hydrogen iodide precursor, the reagent allows iodination and reduction of
more » ... d reduction of Noxides, sulfoxides and azides as well as hydroiodination of alkenes and alkynes. Aluminum enolates, generated by treatment of -haloketones with AlI 3 , provide accesses to -hydroxy ketones, 1,5diones, and β-iodo Morita-Baylis-Hillman esters. AlI 3 exists as a dimer (Al 2 I 6 ) in the solid state and in aprotic apolar solvents, whereas planar monomer has also been observed in gas phase. 2 The reagent serves as an oxophilic Lewis acid 3,4 and coordinates with Lewis base ligands to form tetrahedral complexes. 5 Due to the unique oxophilicity and Lewis acidity nature, AlI 3 has been extensively applied in organic synthesis. Ester Cleavage The oxophilic character of AlI 3 enables coordination with esters by the Lewis acidic center (Al 3+ ) through the formation of donor-acceptor complexes. The complexes undergo cleavage at ambient temperature, and their decomposition could be accelerated at elevated temperatures. 6-8 The cleavages were complete within 0.5 hour and afforded corresponding acids in moderate to high yields. 9 Such kind of non-hydrolytic cleavage of esters features the advantage of avoiding strong acidic or basic conditions and is suitable for substrates containing sensitive functional groups. The transformation can be accessed alternatively with trimethyltin hydroxide, 10 lithium iodide, 11 lithium 1-propanethiolate, 12 lithium bromide, 13 and trimethylsilyl iodide (TMSI). 14 Scope of substrates The ester cleavage method was applied to a variety of substrates (1) including aromatic ester (1a), -unsaturated esters (1b, 1c), halogen-containing ester (1d), and aliphatic ester (1e), see scheme 1A. 9 When the method was applied to phenyl esters, however, ester cleavage was superceded by Fries rearrangement. For example, a mixture of benzophenols (p/o=2) were obtained in moderate yields after treatment of phenyl benzoate with AlI 3 . 9 Application in syntheses of pharmaceutical targets The method has been applied in syntheses of pharmaceutical targets: (I) A class of potent cholecystokinin B (CCK-B) receptor antagonists were accessed through AlI 3 induced ester cleavage. The cleavages of 4a and 4b were complete after refluxing in acetonitrile for several hours with AlI 3 and afforded 1,5-disubstituted benzodiazepines (6a and 6b) in low yields (scheme 1B). 15,16 Trace amount of meta-substituted phenol (7) was isolated, and was formed apparently through ether cleavage. 17 (II) Hexahydropyrrolo[1,2-c]imidazolones (9a and 9b), a family of effective MDM2-p53 interaction inhibitors and useful drug candidates for treating cancer, were prepared by AlI 3 induced cleavage of 8a and 8b in virtually quantitative yields. Microwave irradiation was used to assist the cleavage, and the conversions were complete efficiently in 15~30 minutes (scheme 1C). 18 Other applications An organic-inorganic hybrid material with free carboxylic groups over the surface was prepared by AlI 3 induced ester cleavage of corresponding methyl carboxylate groups. Hydrosilylation of 11 with triethoxysilane (10) gave 12. Sol-gel co-condensation between 12 and tetraethoxysilane (TEOS) afforded nanohybrid material 13. The surface of 13 was modified by AlI 3 to release terminal carboxylic groups (14) for uptake of lanthanide cations (Scheme 1D). 19 Reviews and Accounts ARKIVOC 2015 (vi) 446-493 Scheme 1. AlI 3 induced non-hydrolytic ester cleavage. A: Scope of substrates; B: syntheses of CCK-B receptor antagonists; C: syntheses of inhibitors for MDM2-p53 interactions; D: surface modification of an ester terminated silica nanohybrid. Ether Cleavage Ethers (15) tend to form ethereal-AlI 3 complexes (16) with AlI 3 as a result of its unique oxophilicity. The complexes underwent noticeable ether cleavages ( Figure 1A ) that afforded alcohols (18) and alkyl iodides. For example, methyl iodide, ethyl iodide and 4-iodobutanol were observed during decomposition of anisole, ethyl ether 20 and tetrahedronfuran complexes, respectively. 6 Ether cleavage reaction was applied in deprotection of alkoxybenzene, 1,3-benzodioxole, and alkylthiophenyl alkyl ether to afford corresponding phenol, pyrocatechol and alkylthiophenol, respectively. 21 Reviews and Accounts ARKIVOC 2015 (vi) 446-493 Page 450 © ARKAT-USA, Inc. Regioselectivity Cleavage of ethers is commonly carried out with Brønsted acids (such as HI-anhydride, 22 HBr-HOAc 23 or HCl-pyridine 24 ) or Lewis acids (boron, silicon and metal halides). AlI 3 showed an inversed regioselectivity in ether cleavage compared to boron and silicon halides when a dialkyl ether group and an alkyl aryl ether group coexisted in a substrate. For example when 19 was cleaved by AlI 3 , phenol (20) was the exclusive product ( Figure 1B ). By contrast, boron chloride (BCl 3 ), boron bromide (BBr 3 ), TMSI and trichlorosilyl iodide preferentially cleaved the aliphatic ether bond and gave 2-phenoxy ethanol (21) in moderate yields. 25 ARKIVOC 2015 (vi) 446-493 Page 451 © ARKAT-USA, Inc. resorcinol (30). 30 was further transformed into an organoirridium catalyst loaded on silica (31) for converting low molecular weight alkanes into higher molecular weight fuel (Scheme 2C). 30 As an inhibitor of 17-hydroxylase-C 17,20 -lyase and 5-reductase for treatment of hormone-dependent prostatic carcinoma, 33 was obtained as a mixture of stereoisomers (E/Z=91:9) by demethylation of 32 with AlI 3 in CS 2 (Scheme 2D). 31 1,5-Dialkyl-1,5-benzodiazepine (35), a potent CCK-B receptor antagonist, was synthesized by demethylation of ether 34 with AlI 3 in reflux acetonitrile. Alhough the transformation was sluggish, a large excess of AlI 3 furnished the deprotection in moderate yield (Scheme 2E). 32 The method was applied in syntheses of four coumarin analogues (39~42) applicable to organic light emitting displays as fluorescent dyes. Key intermediate 3hydroxytriphenylamine (38) was prepared in a two-step procedure: Ulmann coupling of iodobenzene and m-anisidine (36) furnished anisole 37; demethylation of 37 with AlI 3 afforded 38 in 93% yield (Scheme 2F). 33 Exhaustive demethylation AlI 3 was applied in syntheses of several naturally occurring phenols (Scheme 3). (I) Anacardic acids (44), a class of salicylic acids bearing a long alkyl chain, were achieved by demethylation of relevant ethers (43 and 46). The substrates were refluxed with AlI 3 in acetonitrile for 0.5 hour to complete the deprotection and afforded 44 in moderate to high yields (Scheme 3A). For two substrates with (8Z,11Z)-aliphatic substituent, limonene was used as hydrogen iodide (HI) scavenger. 34 (II) Plumbagic acid (48) was prepared in 77% yield by exhaustive demethylation of ether 47 with AlI 3 . The conversion was complete in 0.5 hour in refluxing acetonitrile. 35 It is noteworthy that the generation of I 2 complicated the work-up (Scheme 3B). 36 (III) Elliptinone (51), a biaryl natural product, was achieved by exhaustive deprotection of a 2,2'-binaphthol (BNAP, 50) followed by air oxidation. The BNAP was synthesized by tin tetrachloride (SnCl 4 ) mediated oxidative coupling of -naphthol (49), see Scheme 3C. 37 Deprotection of such 1,4dimethoxybenzene is typically achieved by cerium ammonium nitrate (CAN) mediated oxidation. 38-39 (IV) In a similar manner (±)-plumbazeylanone (54), a trimer of naphthoquinone, was achieved by exhaustive demethylation of ether 53 followed by air oxidation in 65% yield (Scheme 3D). 40 (V) Resveratrol (56b) and its derivatives such as oxyresveratrol (56c) and piceatannol (56d) were obtained by exhaustive deprotection of related phenolic methyl ethers (55). The transformations were complete after 3 hours of refluxing in acetonitrile, and afforded polyphenols (56a~56d) in 68~83% yields. 41-43 Surprisingly, E-stilbenes were obtained after treatment of Z-stilbenes with AlI 3 (Scheme 3E). 44 Conjugation of Z-4-styrylphenolates, a reactive species derived from 4-methoxystilbenes, may account for the E/Z stereoisomerization. Reviews and Accounts ARKIVOC 2015 (vi) 446-493
doi:10.3998/ark.5550190.p009.309 fatcat:bksfgkfxhffjpi4yky7mltkpcu