Tetrahedron Letters 55 (2014) 2781–2788

Contents lists available at ScienceDirect

Tetrahedron Letters

journal homepage: www.elsevier .com/ locate/ tet le t

Digest Paper

Chemoselective reductions and iodinations using titaniumtetraiodide

http://dx.doi.org/10.1016/j.tetlet.2014.03.0520040-4039/� 2014 The Authors. Published by Elsevier Ltd.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

⇑ Tel.: +81 59 231 9414; fax: +81 59 231 9413 (I.H.); tel./fax: +81 59 231 9413(M.S.).

E-mail addresses: hachiya@chem.mie-u.ac.jp (I. Hachiya), mshimizu@chem.mie-u.ac.jp (M. Shimizu).

Iwao Hachiya ⇑, Makoto Shimizu ⇑Department of Chemistry for Materials, Graduate School of Engineering, Mie University, Tsu, Mie 514-8507, Japan

a r t i c l e i n f o

Article history:Received 24 February 2014Accepted 6 March 2014Available online 19 March 2014

Keywords:Titanium tetraiodideReductionIodinationChemoselectiveCarbonAcarbon bond forming reaction

a b s t r a c t

Titanium(IV) halides are extensively used in carbonAcarbon bond forming reactions as a Lewis acid andlow valent titanium halides promote reductive coupling reactions of carbonyl compounds. In most ofthese reactions, ligands of titanium halides are chloride or bromide. On the other hand, titanium(IV)tetraiodide had been rarely used in organic synthesis until the late 1990s. Since 2000 several useful syn-thetic reactions have been developed utilizing a moderate Lewis acidity, reducing and iodination abilitiesof titanium(IV) tetraiodide. This digest summarizes examples of chemoselective reductions and iodina-tions using titanium(IV) tetraiodide (TiI4).

� 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/3.0/).

Contents

Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2781Reduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2782

Pinacol coupling reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2782Reformatsky-type reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2782Reductive aldol and Mannich-type reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2783

Iodination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2786

Prins reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2786Iodoaldol reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2786Ring-opening reaction of epoxides and cyclopropanes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2787

2-Iodopyridine synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2787Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2788

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2788References and notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2788

Introduction

Titanium(IV) halides are extensively used in carbonAcarbonbond forming reactions; for examples, Mukaiyama aldol reactionsof aldehydes with silyl enol ethers, Diels–Alder reactions, and car-bonyl-ene reactions as a Lewis acid. Low valent titanium halidespromote reductive coupling reactions of carbonyl compounds. Inmost of these reactions, ligands of titanium halides are chloride

or bromide.1 Although titanium(IV) tetraiodide had been used forthe production of high purity metal titanium, its use was rare in or-ganic synthesis. Titanium(IV) tetraiodide has a moderate Lewisacidity and is used as a promoter and a catalyst in Mannich-typereactions,2 and 1,4- and 1,2-double nucleophilic addition of ketenesilyl acetals with a,b-unsaturated aldimines.3 On the other hand,titanium(IV) tetraiodide is different from titanium(IV) chloride orbromide in many reports and in particular shows reducing andiodination abilities in some useful organic reactions. Herein, thisdigest describes examples of chemoselective reductions and iodi-nations using titanium(IV) tetraiodide (TiI4).

http://crossmark.crossref.org/dialog/?doi=10.1016/j.tetlet.2014.03.052&domain=pdfhttp://creativecommons.org/licenses/by/3.0/http://dx.doi.org/10.1016/j.tetlet.2014.03.052http://creativecommons.org/licenses/by/3.0/mailto:hachiya@chem.mie-u.ac.jpmailto:mshimizu@chem.mie-u.ac.jpmailto:mshimizu@chem.mie-u.ac.jphttp://dx.doi.org/10.1016/j.tetlet.2014.03.052http://www.sciencedirect.com/science/journal/00404039http://www.elsevier.com/locate/tetlet

Scheme 5.

Scheme 6.

Scheme 1.

2782 I. Hachiya, M. Shimizu / Tetrahedron Letters 55 (2014) 2781–2788

Reduction

Pinacol coupling reaction

Reactions using reducing ability of iodide anion are well-known.4 Titanium(IV) tetraiodide is used as a chemoselectivereducing agent; for examples, reduction of sulfoxides to sulfides,5

a-diketones to a-hydroxy ketones,6 and a-imino ketones to a-ami-no ketones (Scheme 1).7

Titanium(IV) tetraiodide promoted diastereoselective pinacolcoupling reaction of aromatic aldehydes is reported; however,the reaction of aliphatic aldehydes does not proceed (Scheme 2).8

Nevertheless, the pinacol reaction of b-halogenated a,b-unsatu-rated aldehydes is promoted by titanium(IV) tetraiodide to give thecoupling products in good yields with high dl-selectivities, and thesubsequent reduction with H2/Pd-C gives saturated vic-diols ingood yields (Scheme 3).9 Although two steps are needed, this pina-col-coupling/hydrogenation of b-halogenated a,b-unsaturated

Scheme 2.

Scheme 3.

Scheme 4.

aldehydes can be regarded as the pinacol-coupling reaction of ali-phatic aldehyde to afford the saturated vic-diol in high dl-selectiv-ity. It is known that b-halo free enals do not always undergo theefficient pinacol coupling reaction.

A possible reaction pathway of titanium(IV) tetraiodide pro-moted pinacol coupling reaction is shown in Scheme 4. An initialiodination of the carbonyl group of the aldehyde 1 gives the iodin-ated intermediate 2, which is attacked by the iodide anion fromtitanium(IV) tetraiodide to form an anionic species. It has been re-ported that a similar halogenated intermediate was formed in thereaction of BCl3 with aromatic aldehydes.10 The species generatedfrom reductive dehalogenation in turn undergoes addition to an-other aldehyde to form a pinacol product 3. The formation of iodin-ated intermediate 2 appears to be easy in the case of aldehydeswith an electron-withdrawing substituent; therefore, the pinacolcoupling reaction proceeds readily with b-halogenated a,b-unsatu-rated aldehydes.

In 2008, titanium(IV) tetraiodide promoted pinacol couplingreaction of (Z)-3-iodo-3-trimethylsilylpropenal 4 was used forthe preparation of trans-4,5-bis[(Z)-2-iodo-2-(trimethyl-silyl)vinyl]-2,2-dimethyl-1,3-dioxolane 5, which was utilized forthe subsequent CAC bond forming reactions (Scheme 5).11

Reformatsky-type reaction

Reformatsky reaction of a-haloesters with carbonyl compoundsin the presence of zinc powder gives b-hydroxy carbonyl com-pounds and is well-known as one of the most importantcarbonAcarbon bond forming reactions. Reformatsky-type reac-tion promoted by some metal iodides such as AlI3,12 CeI3,13 andTiCl4/n-Bu4NI14 has been reported. Titanium enolates reductively

Scheme 7.

Scheme 8.

Table 1Deoxygenation of a-oxygenated ketone derivatives

R1 R2 R3 Yield (%)

4-MeC6H4 H Ac 744-MeC6H4 H Bz 744-MeC6H4 H Ts 80Ph Me Ts 85Ph Me Ms 80

Scheme 9.

Scheme 10.

Scheme 11.

Scheme 12.

Scheme 13.

I. Hachiya, M. Shimizu / Tetrahedron Letters 55 (2014) 2781–2788 2783

generated from a-iodoketones using titanium(IV) tetraiodide reactwith several aldehydes to give aldol products in good yields withgood diastereoselectivities (Scheme 6).15

Titanium tetraiodide promotes an aza-Reformatsky-type reac-tion of a-iodomethyl ketone O-alkyl oximes with carbonyl com-pounds to give b-hydroxy ketone O-alkyl oximes in good to highyields (Scheme 7).16

Aza-Mannich-type reaction proceeds between imines and theaza-enolates formed from a-iodomethyl ketone O-alkyl oximeswith titanium tetraiodide to give b-amino ketone O-alkyl oximesin good to excellent yields. Remarkable effects of added silica gelor molecular sieves (4 Å) are observed to promote the additionreactions (Scheme 8).17

In 2011, it was reported that titanium(IV) tetraiodide could re-duce a-aetyloxy, benzoyloxy, mesyloxy, and tosyloxy ketones toproduce deoxygenated ketones in good yields (Table 1). Reductivealdol reactions of a-tosyloxy ketones proceed with several alde-hydes to afford the aldol products (Scheme 9).18

Reductive aldol and Mannich-type reactions

Reactions utilizing both iodination and reducing abilities are re-ported. In 2000, it was reported that ring-opening reaction ofmethoxyallene oxide, which was prepared from methoxyallene 6with mCPBA in situ, with titanium(IV) tetraiodide generated thetitanium enolate, and the subsequent reaction with aldehydes oracetals proceeded to give 3-hydroxy-2-methoxy or 2,3-dialkoxy-ketones in good yields (Scheme 10).19

The hemiacetal 9 is isolated as a byproduct in the above reac-tion, suggesting that it would be one of the intermediates. The sub-sequent reaction of 9 with benzaldehyde under the influence ofTiI4-Ti(Oi-Pr)4 gives the aldol adduct 7 in high yield with highselectivity (Scheme 11).

A plausible reaction mechanism is shown in Scheme 12. Thetitanium enolate 11 would be formed via ring-opening reactionof methoxyallene oxide 10 with diiododiisopropoxytitanium de-rived from titanium(IV) tetraiodide and titanium(IV) tetraisoprop-oxide and undergoes protonation with 3-chlorobenzoic acid to giveiodo ketone 12. The iodo ketone 12 would be in turn regioselec-tively transformed into the titanium enolate 13 via reduction ofthe iodine with iodide anion, and the subsequent reaction withaldehyde gives the aldol adduct 7 in a regioselective manner.

Since the development of the above-mentioned reductive aldolreaction via the small ring-opening reaction, several reductive al-

Scheme 14.

Scheme 15.

Table 2Regioselectivity of the reductive ring-opening reaction of various 2-mono-substitutedazetidin-3-ones

R Yield (%) 15:16

Me 89 95.5Et 66 83:17i-Pr 76 77:23i-Bu 97 63:37Bn 82 92:8

Scheme 16.

Scheme 17.

2784 I. Hachiya, M. Shimizu / Tetrahedron Letters 55 (2014) 2781–2788

dol or Mannich-type reactions are reported via chemoselectivereductions (Scheme 13).20–22 These reductive carbonAcarbon bondforming reactions have an advantage of a procedure without isola-tion of unstable a-iodo carbonyl intermediates.

In 2006, reductive ring-opening of N-tosylaziridines was carriedout with titanium(IV) tetraiodide to form the titanium enolates,which in turn were subject to the aldol or the Manncich-type reac-tions with aldehydes or imines to give aldol or Manncich-type

products in good yields (Scheme 14).23 However, diastereoselectiv-ities are moderate and the reaction of 2-acetylaziiridine gives thealdol product in low yield with low diastereoselectivity.

In 2007, it was reported that aza-aldol reaction of aldehydeswith aza-enolates, which was generated via reductive ring-openingof 2-(1-benzyloxyiminoethyl)aziridines with titanium(IV) tetraio-dide, proceeded to give aza-aldol products in good yields with highdiastereoselectivities (Scheme 15).24

a-Amino ketones are one of the most important nitrogen-con-taining compounds because of their use as versatile building blocksand intermediates for the synthesis of the biologically active com-pound synthesis.25 In 2010, it was reported that titanium(IV)tetraiodide-promoted ring-opening reactions of 2-mono-substi-tuted azetidin-3-ones 14 gave a-amino ketones 15 in good yieldswith moderate to high regioselectivities (Table 2).26

On the other hand, reductive ring-opening reactions of 2,2-disubstituted azetidin-3-ones 17 proceed at the more substitutedbond to give the a-amino ketones 19 as sole products (Scheme 16).

Regarding the different regioselectivity, two different pathwaysare proposed including an SN2-like process by titanium(IV) tetraio-dide or a one-electron transfer promoted by low-valent titaniumspecies. In the case of 2-mono-substituted azetidin-3-ones 14,the reaction would prefer an SN2-like process rather than one elec-tron transfer, because radical stabilization is more depressed ascompared with that of 2,2-disubstited cases. Initially, a-iodoketone20 is generated via the ring-opening of azetidin-3-ones 14A or 14Battacked by the iodide anion at the less hindered site and subse-quently another iodide anion attacks to the iodine to generatethe titanium enolate species 21. Hydrolysis of the enolate 21 withwater to quench the reaction gives the a-amino ketone 15(Scheme 17).

In the case of 2,2-dimethyl-azetidin-3-one 17a, it seems that anelectron-transfer reaction would play a significant role(Scheme 18). Initially, the disproportionation of TiI4 gives low-valent titanium species. One-electron transfer to azetidin-3-one17a at the C-3 position gives a radical intermediate 22. A ring-opening reaction proceeds via a fragmentation at the NAC(2) orNAC(4) bond. At this point, the fragmentation at the NAC(2) bondis favored because of the electronically more stabilized 2,2-di-methyl substitution. Further reduction of the intermediate leadsto the corresponding titanium enolate. Also, the homolysis of theNAC(4) bond gives the less substituted enolate 24 (path A). Alter-natively, the homolysis of the NAC(2) bond leads to the moresubstituted enolate 26 (path B). In path A, the enolate 24 could re-verse to the azetidine 17a via a re-cyclization under an equilib-rium.27 However, path B may not involve such a cyclizationbecause of the steric hindrance. Finally, the more thermodynami-cally stable enolate 26 would predominate. The enolate 26 ishydrolyzed with water to give the a-amino ketone 19a.

Enolates prepared by the reduction of 2-mono- or 2,2-disubsti-tuted azetidin-3-ones react with an aldehyde or an imine to affordthe aldol or Mannich-type products. This methodology provides a

Scheme 18.

Scheme 19.

Table 3TiI4–TiX4 (X = Br or Cl) promoted ring-opening reaction of 2-mono-substitutedazetidin-3-ones

R X Temp Yield (%) 15:16

Me Br �78 �C to rt 26 25:75Et Br �78 �C to rt 30 4:96i-Pr Br �78 �C to rt 56 0:100i-Bu Br �20 to 10 �C 90 16:84Me Cl 0 �C to rt 63 9:91Et Cl 0 �C to rt 78 4:96i-Pr Cl �78 �C to rt 84 0:100i-Bu Cl �78 �C to rt 88 0:100

Scheme 20.

Scheme 21.

Table 4TiI4-promoted ring-opening reaction of azetidin-3-one O-alkyloximes

R Yield (%)

31 32 15 16

Me 0 0 2 51Et 0 0 1 35i-Bu 0 0 0 28

I. Hachiya, M. Shimizu / Tetrahedron Letters 55 (2014) 2781–2788 2785

straightforward access to 1,4-amino alcohols or diamines in a reg-ioselective manner (Scheme 19).

In 2012, it was reported that the ring-opening of 2-mono-substituted azetidin-3-ones at the more substituted bond occurredwith the combined use of titanium(IV) tetraiodide and tita-nium(IV) tetrachloride or tetrabromide to give the a-amino ke-tones in moderate to high yields with high regioselectivities(Table 3).28

A proposed reaction mechanism is shown in Scheme 20. Thedisproportionation of titanium(IV) tetraiodide and titanium(IV)tetrachloride gives low-valent titanium species. A one-electrontransfer to 2-mono-substituted azetidin-3-one 14 at the C-3 posi-tion gives a radical intermediate 27. The ring-opening reaction of27 would proceed via a fragmentation at the NAC(2) bond to givethe more substituted titanium enolate 29, which is more stablethan the less substituted one, and the subsequent protonation withwater to quench the reaction would give the corresponding a-ami-no ketone 15.

The reductive aldol reaction of azetidin-3-one with chloral iscarried out using titanium(IV) tetraiodide and titanium(IV) tetra-chloride in the presence of Pd(O2CCF3)2 as a Lewis acid additiveto afford the aldol product in good yield with syn-selectivity(Scheme 21).

Scheme 22.

Scheme 23.

Scheme 25.

Table 5Prins reaction of alkyne with benzaldehyde dimethylacetal: comparison of tita-nium(IV) tetrahalide

X Yield (%) Ratio (Z,Z)/(Z:E)

F 0 —Cl 67 4:96Br 68 11:89I 68 91:9

Scheme 26.

Table 6Iodoaldol reaction with different aldehydes

Ph

O Til4 (1.3 equiv)RCHO (1.0 equiv)

CH2Cl2, –50 °C, 2 h

Ph

O

I

R

OH

34 Z-35

+Ph

O

I

R

OH

E-35

OEt

OEt EtO

OEt

OEt

OEt

R Yield (%) E/Z

Ph 65 97:3p-ClC6H4 52 100:0p-MeOC6H4 61 100:0p-MeC6H4 64 89:111-Naphthyl 34 100:02-Thienyl 52 100:0Cl3C 41 100:0n-Pentyl 35 100:0

2786 I. Hachiya, M. Shimizu / Tetrahedron Letters 55 (2014) 2781–2788

Titanium(IV) tetraiodide promoted ring-opening reaction of 2-mono-substituted azetidin-3-one O-alkyloximes 30 proceeds atthe more hindered site to give a-amino ketones (Table 4). In everyreaction, a-amino ketones 15 and 16 are obtained instead of thedesired a-amino ketone O-alkyloximes 31 or 32 probably due tothe reductive cleavage of the NAO bond by titanium(IV) tetraio-dide and subsequent hydrolysis with water to quench the reaction.Although the yields are low to moderate, it is of interest that theregioselectivity of the ring-opening reaction of 2-mono-substi-tuted azetidin-3-one O-alkyloximes is different from that of theparent 2-mono-substituted azetidin-3-ones 14.29

Iodination

Prins reaction

Vinyl iodides are the most useful intermediates for the synthe-sis of multifunctionalized alkenes, which occur in biologically ac-tive compounds, and are applied to the metal-catalyzed cross-coupling and Nozaki–Hiyama–Kishi reactions as substrates.30 Iodi-nations of simple alkenes or phenyl acetylene with titanium(IV)tetraiodide give iodoalkanes and iodostylenes. On the other hand,iodinations of 1-alkynes afford 2,2-diiodoalkanes (Scheme 22).31

Titanium(IV) tetraiodide and iodine promote Prins-type reac-tion of acetals with alkenes to give 1,3-diiodopropopanes(Scheme 23).31

Intramolecular Prins reaction promoted by titanium(IV) tetraio-dide proceeds to give the iodo bicyclic product in high diastereose-lectivity (Scheme 24).32

Aza-Prins reactions of the imino ester 33 promoted by tita-nium(IV) tetraiodide and iodine with alkenes or alkynes proceedto give c-iodo-a-amino acid esters (Scheme 25).33

In 2010, titanium(IV) tetraiodide-promoted tandem Prins reac-tion of alkynes with acetals was reported. In the presence of tita-nium(IV) tetraiodide, tandem Prins reactions of alkynes proceedwith acetals to give (Z,Z)-1,5-diodo-1,3,5-triarylpenta-1,4-dienesin good yields, where an intriguing reversal of the stereoselectivityis observed among titanium(IV) tetrahalides (Table 5).34

Iodoaldol reaction

Since the iodoaldol reactions using TiCl4/n-Bu4NI or TiI4 re-ported by Tanigchi et al. in 1986 as shown in Scheme 26,35 severaliodoaldol reactions have been reported via b-iodoallenoate inter-mediates from alkynyl ketones and esters with several metal io-dides such as ZrCl4/n-Bu4NI,36 Et2AlI,37 MgI2,38 TMSI,39 BF3�OEt2/TMSI,40 CeCl3�7H2O/NaI,41 or GaI3.42 However, the diastereoselec-tive iodoaldol reactions of internal alkynyl ketones have been lim-ited to an intramolecular cyclization.43

In 2013, diastereoselective iodoaldol reaction of c-alkoxy-a,b-alkynyl ketone derivatives promoted by titanium(IV) tetraiodidewas reported. Iodoaldol reactions of the c-diethoxy alkynyl ketone

Scheme 24.

34 with several aldehydes proceed to give the iodoaldol products35 in moderate yields with high diastereoselectivities (Table 6).44

The iodoaldol reactions using c-methoxymethoxy alkynyl ke-tones 36 as a c-monoalkoxyalkynyl ketone also work well. Thereaction of c-methoxymethoxy alkynyl aryl ketones affords theiodoaldol products 37 in moderate to good yields with good to highdiastereoselectivities except in the case of 1-naphthaldehyde.Although the reaction of c-methoxymethoxy alkynyl methyl ke-tones proceeds, the iodo product 37 is obtained in low yield withlow diastereoselectivity (Table 7).

Ph

O

I

Ph

OH

E-38

EtO

OEt

Pd(PPh3)2Cl2 (5.0 mol%)CuI (0.2 equiv)phenylactetylene (2.0 equiv)

DMF/Et3N (1:1), 90 ºC, 20 h

Ph

O

Ph

OH

EtO

OEt39

Ph

PdCl2(CH3CN)2 (20 mol%)

THF, reflux, 2 h

Ph

O

EtO

OEt40

O

Ph

Ph

Ph

O

H

41

O

Ph

PhO

+

18% 36%

Ph

O

I

Ph

OH

MOMO

73%

4349%

E-42

Ph

O

O

Ph

PhMOMO

Pd(PPh3)2Cl2 (5.0 mol%)CuI (0.2 equiv)phenylactetylene (2.0 equiv)

DMF/Et3N (1:1), 60 ºC, 6 d

Scheme 27.

Scheme 28.

Scheme 29.

Scheme 30.

Table 7Iodoaldol reaction with different aldehydes

R2 R1 Yield (%) E/Z

Ph p-ClC6H4 72 75:25Ph p-MeOC6H4 56 88:12Ph p-MeC6H4 73 79:21Ph 1-Naphthyl 31 56:44Ph 2-Thienyl 33 85:15Ph n-Pentyl 48 70:302-Thienyl Ph 74 75:25Me Ph 32 56:44

Table 82-Iodopyridine synthesis

Scheme 31.

I. Hachiya, M. Shimizu / Tetrahedron Letters 55 (2014) 2781–2788 2787

The iodoaldol products are transformed into tetrasubstitutedfurans via the enynol intermediate. The Sonogashira coupling ofthe iodo product E-38 with phenylacetylene in the presence of[PdCl2(PPh3)2] and CuI proceeds to give the enynol 39 in 73% yield.The cyclization reaction of enynol 39 with [PdCl2(PPh3)2] affords

furans 40 and 41. The transformation of the iodo product E-42 di-rectly produces the furan 43 (Scheme 27).

Ring-opening reaction of epoxides and cyclopropanes

Titanium(IV) tetraiodide promotes the ring-opening reaction ofepoxides and cyclopropanes to give iodinated products. The ring-opening reaction of epoxide 44 with titanium(IV) tetraiodide givesiodohydrin 45 in high yield (Scheme 28).45

The ring-opening reaction of 1-hydroxyspiro[5.2]cyclooct-4-en-3-one 46 by titanium(IV) tetraiodide affords the iodoethylbenzoate47 (Scheme 29).46

The reaction of gem-aryl-disubstituted methylenecyclopropane48 with TiI4/diethyl azodicarboxylate gives the diiodo ring-openedproduct 49 in high yield (Scheme 30).47

2-Iodopyridine synthesisIn 2009, it was reported that highly substituted 2-iodopyridines

51 were synthesized from 2-(2-cyanoalk-1-enyl)-b-keto esters 50under the influence of titanium(IV) tetraiodide that worked effi-ciently for iodination–cyclization (Table 8).48

The present iodination–cyclization reaction most probably pro-ceeds as shown in Scheme 31. The titanium intermediate 52 wouldbe formed via a nucleophilic addition of iodide anion to a cyanogroup. Subsequent intramolecular cyclization of this species 52would give a titanium alkoxide intermediate 53, which would un-dergo aromatization via elimination of titanium oxide to give 2-iodopyridine 51.

2788 I. Hachiya, M. Shimizu / Tetrahedron Letters 55 (2014) 2781–2788

Conclusion

This digest describes several attractive reactions utilizingchemoselective reductions and iodinations using titanium(IV)tetraiodide. Although reducing ability of iodide anion is well-known, titanium(IV) tetraiodide promotes not only chemoselectivereduction but also reductively generates enolates or aza-enolates,which react with aldehydes, acetals, and imines to give useful syn-thetic intermediates. On the other hand, titanium(IV) tetraiodidealso promotes iodination reactions to give iodinated products.These iodination reactions will be applied to the synthesis of bio-logically active compounds and functional materials becauseiodinated products synthesized from unsaturated compounds canbe transformed into multi-functionalized compounds using transi-tion metal catalyzed coupling and Nozaki–Hiyama–Kishi reactions.

Acknowledgements

This work was supported by Grants-in Aid for Scientific Re-search (B) and Innovative Areas ‘Organic Synthesis Based on Reac-tion Integration. Development of New Methods and Creation ofNew Substances’ from JSPS and MEXT.

References and notes

1. (a) Mukaiyama, T. Org. React. 1982, 28, 203–331; (b) Reetz, M. T.Organotitanium Reagents in Organic Synthesis; Springer: Berlin, 1986; (c)Narasaka, K. Synthesis 1991, 1–11; (d) Mikami, K.; Shimizu, M. Chem. Rev.1992, 92, 1021–1050.

2. (a) Shimizu, M.; Kume, K.; Fujisawa, T. Tetrahedron Lett. 1995, 36, 5227–5230;(b) Shimizu, M.; Kume, K.; Fujisawa, T. Chem. Lett. 1996, 545–546.

3. Shimizu, M.; Morita, A.; Kaga, T. Tetrahedron Lett. 1999, 40, 8401–8405.4. (a) Zincke, T.; Baeuer, J. Liebigs Ann. Chem. 1918, 416, 86–112; (b) Reusch, W.;

Lemahieu, R. J. Am. Chem. Soc. 1964, 86, 3068–3072.5. Shimizu, M.; Shibuya, K.; Hayakawa, R. Synlett 2000, 1437–1438.6. Hayakawa, R.; Sahara, T.; Shimizu, M. Tetrahedron Lett. 2000, 41, 7939–7942.7. Shimizu, M.; Sahara, T.; Hayakawa, R. Chem. Lett. 2001, 792–793.8. (a) Hayakawa, R.; Shimizu, M. Chem. Lett. 2000, 724–725; Titanium(IV)

tetraiodide is reduced with copper to give low valent species which can beused for the pinacol coupling reaction, see: (b) Mukaiyama, T.; Yoshimura, N.;Igarashi, K. Chem. Lett. 2000, 838–839; (c) Mukaiyama, T.; Yoshimura, N.;Igarashi, K.; Kagayama, A. Tetrahedron 2001, 57, 2499–2506.

9. Hayakawa, R.; Goto, H.; Shimizu, M. Org. Lett. 2002, 4, 4097–4099.10. Kabalka, G. W.; Wu, Z. Tetrahedron Lett. 2000, 41, 579–581.11. Shimizu, M.; Okimura, H.; Manabe, N.; Hachiya, I. Chem. Lett. 2008, 37, 28–29.12. Borah, H. N.; Boruah, R. C.; Sandhu, J. S. J. Chem. Soc., Chem. Commun. 1991,

154–155.13. Fukuzawa, S.; Tsuruta, T.; Fujinami, T.; Sakai, S. J. Chem. Soc., Perkin Trans. 1

1987, 1473–1477.14. Tsuritani, T.; Ito, S.; Shinokubo, H.; Oshima, K. J. Org. Chem. 2000, 65, 5066–

5068.15. (a) Shimizu, M.; Kobayashi, F.; Hayakawa, R. Tetrahedron 2001, 57, 9591–9595;

Titanium(IV) tetraiodide is reduced with copper to give low valent specieswhich can be used for Reformatsky-type reaction, see: (b) Arai, H.; Shiina, I.;Mukaiyama, T. Chem. Lett. 2001, 118–119.

16. Shimizu, M.; Toyoda, T. Org. Biomol. Chem. 2004, 2, 2891–2892.17. Shimizu, M.; Tanaka, M.; Itoh, T.; Hachiya, I. Synlett 2006, 1687–1690.18. Hachiya, I.; Inagaki, T.; Ishihara, Y.; Shimizu, M. Bull. Chem. Soc. Jpn. 2011, 84,

419–421.19. Hayakawa, R.; Shimizu, M. Org. Lett. 2000, 2, 4079–4081.20. Shimizu, M.; Takeuchi, Y.; Sahara, T. Chem. Lett. 2001, 1196–1197.21. Shimizu, M.; Sahara, T. Chem. Lett. 2002, 888–889.

22. Shimizu, M.; Inayoshi, K.; Sahara, T. Org. Biomol. Chem. 2005, 3, 2237–2238.23. Shimizu, M.; Kurokawa, H.; Nishiura, S.; Hachiya, I. Heterocycles 2006, 70, 57–

64.24. Shimizu, M.; Nishiura, S.; Hachiya, I. Heterocycles 2007, 74, 177–183.25. For examples, see: (a) Overhand, M.; Hecht, S. M. J. Org. Chem. 1994, 59, 4721–

4722; (b) Pace, R. D.; Kabalka, G. W. J. Org. Chem. 1995, 60, 4838–4844; (c)Langer, P.; Bodtke, A. Tetrahedron Lett. 2003, 44, 5965–5967; (d) Adam, I.;Orain, D.; Meier, P. Synlett 2004, 2031–2033; (e) Unthank, M. G.; Hussain, N.;Aggarwal, V. K. Angew. Chem., Int. Ed. 2006, 45, 7066–7069; (f) Anada, M.;Tanaka, M.; Washio, T.; Yamawaki, M.; Abe, T.; Hashimoto, S. Org. Lett. 2007, 9,4559–4562; (g) Frolova, L. V.; Evdokimov, N. M.; Hayden, K.; Malik, I.; Rogelj,S.; Kornienko, A.; Magedov, I. V. Org. Lett. 2011, 13, 1118–1121.

26. Hata, S.; Fukuda, D.; Hachiya, I.; Shimizu, M. Chem. Asian J. 2010, 5, 473–477.27. For an example of 4-endo-trig cyclization, see: Homsi, F.; Rousseau, G. J. Org.

Chem. 1999, 64, 81–85. and references therein.28. Hata, S.; Fukuda, D.; Hachiya, I.; Shimizu, M. Heterocycles 2012, 84, 301–307.29. Ariga, S.; Hata, S.; Fukuda, D.; Nishi, T.; Hachiya, I.; Shimizu, M. Heterocycles

2012, 86, 1187–1210.30. For recent examples, see: (a) Jessen, H. J.; Schumacher, A.; Schmid, F.; Phaltz,

A.; Gademann, K. Org. Lett. 2011, 13, 4368–4370; (b) Clause, D. J.; Wan, S.;Floreancig, P. E. Angew. Chem., Int. Ed. 2011, 50, 5178–5181; (c) Français, A.;Leyva-Pérez, A.; Etxebarria-Jardi, G.; Peña, J.; Ley, S. V. Chem. Eur. J. 2011, 17,329–343; (d) Français, A.; Leyva, A.; Etxebarria-Jardi, G.; Ley, S. V. Org. Lett.2010, 12, 340–343; (e) Pospísil, J.; Müller, C.; Fürstner, A. Chem. Eur. J. 2009, 15,5956–5968; (f) Jackson, K. L.; Henderson, J. A.; Motoyoshi, H.; Phillips, A. J.Angew. Chem., Int. Ed. 2009, 48, 2346–2350; (g) Tortosa, M.; Yakelis, N. A.;Roush, W. R. J. Org. Chem. 2008, 73, 9657–9667; (h) Dounay, A. B.; Humphreys,P. G.; Overman, L. E.; Wrobleski, A. D. J. Am. Chem. Soc. 2008, 130, 5368–5377;(i) Lee, S.; Hwang, G.-S.; Shin, S. C.; Lee, T. G.; Jo, R. H.; Ryu, D. H. Org. Lett. 2007,9, 5087–5089; (j) Maezaki, N.; Kojima, N.; Sakamoto, A.; Tominaga, H.; Iwata,C.; Tanaka, T.; Monden, M.; Damdinsuren, B.; Nakatomi, S. Chem. Eur. J. 2003, 9,390–399; (k) Kadota, I.; Takamura, H.; Ohno, A.; Matsuda, K.; Satake, M.;Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 11893–11899; (l) Trost, B. M.;Gunzner, J. L.; Dirat, O.; Rhee, T. H. J. Am. Chem. Soc. 2002, 124, 10396–10415;(m) Longbottom, D. A.; Morrison, A. J.; Dixon, D. J.; Ley, S. V. Angew. Chem., Int.Ed. 2002, 41, 2786–2790.

31. Shimizu, M.; Toyoda, T.; Baba, T. Synlett 2005, 2516–2518.32. Miles, R. B.; Davis, C. E.; Coates, R. M. J. Org. Chem. 2006, 71, 1493–1501.33. Shimizu, M.; Baba, T.; Toudou, S.; Hachiya, I. Chem. Lett. 2007, 12–13.34. Shimizu, M.; Okura, K.; Arai, T.; Hachiya, I. Chem. Lett. 2010, 39, 1052–1054.35. Taniguchi, M.; Hino, T.; Kishi, Y. Tetrahedron Lett. 1986, 27, 4767–4770.36. (a) Zhang, C.; Lu, X. Synthesis 1996, 586–588; (b) Lim, H. N.; Ji, S.-H.; Lee, K.-J.

Synthesis 2007, 2454–2460.37. Wei, H.-X.; Gao, J. J.; Li, G.; Paré, P. W. Tetrahedron Lett. 2002, 43, 5677–5680.38. (a) Kattuboina, A.; Kaur, P.; Timmons, C.; Li, G. Org. Lett. 2006, 8, 2771–2774;

(b) Timmons, C.; Kattuboina, A.; Banerjee, S.; Li, G. Tetrahedron 2006, 62, 7151–7154; (c) Wei, H.-X.; Hu, J.; Jasomi, R. L.; Paré, P. W. Helv. Chim. Acta 2004, 87,2359–2363; (d) Wei, H.-X.; Hu, J.; Purkiss, D. W.; Paré, P. W. Tetrahedron Lett.2003, 44, 949–952.

39. (a) Wei, H.-X.; Timmons, C.; Farag, M. A.; Paré, P. W.; Li, G. Org. Biomol. Chem.2004, 2, 2893–2896; (b) Deng, G.-H.; Hu, H.; Wei, H.-X.; Paré, P. W. Helv. Chim.Acta 2003, 86, 3510–3515.

40. Alcaide, B.; Almendros, P.; Aragoncillo, C.; Rodríguez-Acebes, R. J. Org. Chem.2004, 69, 826–831.

41. Yadav, J. S.; Reddy, B. V. S.; Gupta, M. K.; Eeshwaraiah, B. Synthesis 2005, 57–60.42. Yadav, J. S.; Reddy, B. V. S.; Gupta, M. K.; Pandey, S. K. J. Mol. Cat. A: Chem. 2007,

264, 309–312.43. (a) Ciesielski, J.; Cariou, K.; Frontier, A. J. Org. Lett. 2012, 14, 4082–4085; (b)

Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952–9955; (c) Ciesielski, J.; Canterbury, D. P.; Frontier, A. J. Org. Lett. 2009, 11, 4374–4377; (d) Douelle, F.; Capes, A. S.; Greaney, M. F. Org. Lett. 2007, 9, 1931–1934.

44. Hachiya, I.; Ito, S.; Kayaki, S.; Shimizu, M. Asian J. Org. Chem. 2013, 2, 931–934.45. Shah, S. T. A.; Abdel-Jalil, R. J.; Khan, K. M.; Heinrich, A. M.; Richter, M.; Voelter,

W. Zeitschrift für Naturforschung, B Chem. Sci. 2004, 59, 337–340.46. (a) Bose, G.; Langer, P. Tetrahedron Lett. 2004, 45, 3861–3863; (b) Bose, G.;

Bracht, K.; Bednarski, P. J.; Lalk, M.; Langer, P. Bioorg. Med. Chem. 2006, 14,4694–4703.

47. Shao, L.-X.; Zhao, L.-J.; Shi, M. Eur. J. Org. Chem. 2004, 4894–4900.48. Hachiya, I.; Minami, Y.; Shimizu, M. Heterocycles 2009, 79, 365–371.

http://refhub.elsevier.com/S0040-4039(14)00461-4/h0005http://refhub.elsevier.com/S0040-4039(14)00461-4/h0010http://refhub.elsevier.com/S0040-4039(14)00461-4/h0010http://refhub.elsevier.com/S0040-4039(14)00461-4/h0015http://refhub.elsevier.com/S0040-4039(14)00461-4/h0015http://refhub.elsevier.com/S0040-4039(14)00461-4/h0020http://refhub.elsevier.com/S0040-4039(14)00461-4/h0020http://refhub.elsevier.com/S0040-4039(14)00461-4/h0025http://refhub.elsevier.com/S0040-4039(14)00461-4/h0030http://refhub.elsevier.com/S0040-4039(14)00461-4/h0035http://refhub.elsevier.com/S0040-4039(14)00461-4/h0040http://refhub.elsevier.com/S0040-4039(14)00461-4/h0045http://refhub.elsevier.com/S0040-4039(14)00461-4/h0045http://refhub.elsevier.com/S0040-4039(14)00461-4/h0050http://refhub.elsevier.com/S0040-4039(14)00461-4/h0055http://refhub.elsevier.com/S0040-4039(14)00461-4/h0060http://refhub.elsevier.com/S0040-4039(14)00461-4/h0065http://refhub.elsevier.com/S0040-4039(14)00461-4/h0070http://refhub.elsevier.com/S0040-4039(14)00461-4/h0070http://refhub.elsevier.com/S0040-4039(14)00461-4/h0070http://refhub.elsevier.com/S0040-4039(14)00461-4/h0070http://refhub.elsevier.com/S0040-4039(14)00461-4/h0075http://refhub.elsevier.com/S0040-4039(14)00461-4/h0075http://refhub.elsevier.com/S0040-4039(14)00461-4/h0080http://refhub.elsevier.com/S0040-4039(14)00461-4/h0085http://refhub.elsevier.com/S0040-4039(14)00461-4/h0090http://refhub.elsevier.com/S0040-4039(14)00461-4/h0095http://refhub.elsevier.com/S0040-4039(14)00461-4/h0095http://refhub.elsevier.com/S0040-4039(14)00461-4/h0100http://refhub.elsevier.com/S0040-4039(14)00461-4/h0100http://refhub.elsevier.com/S0040-4039(14)00461-4/h0105http://refhub.elsevier.com/S0040-4039(14)00461-4/h0105http://refhub.elsevier.com/S0040-4039(14)00461-4/h0110http://refhub.elsevier.com/S0040-4039(14)00461-4/h0115http://refhub.elsevier.com/S0040-4039(14)00461-4/h0115http://refhub.elsevier.com/S0040-4039(14)00461-4/h0115http://refhub.elsevier.com/S0040-4039(14)00461-4/h0120http://refhub.elsevier.com/S0040-4039(14)00461-4/h0125http://refhub.elsevier.com/S0040-4039(14)00461-4/h0130http://refhub.elsevier.com/S0040-4039(14)00461-4/h0130http://refhub.elsevier.com/S0040-4039(14)00461-4/h0135http://refhub.elsevier.com/S0040-4039(14)00461-4/h0140http://refhub.elsevier.com/S0040-4039(14)00461-4/h0145http://refhub.elsevier.com/S0040-4039(14)00461-4/h0150http://refhub.elsevier.com/S0040-4039(14)00461-4/h0155http://refhub.elsevier.com/S0040-4039(14)00461-4/h0155http://refhub.elsevier.com/S0040-4039(14)00461-4/h0160http://refhub.elsevier.com/S0040-4039(14)00461-4/h0165http://refhub.elsevier.com/S0040-4039(14)00461-4/h0165http://refhub.elsevier.com/S0040-4039(14)00461-4/h0170http://refhub.elsevier.com/S0040-4039(14)00461-4/h0175http://refhub.elsevier.com/S0040-4039(14)00461-4/h0175http://refhub.elsevier.com/S0040-4039(14)00461-4/h0180http://refhub.elsevier.com/S0040-4039(14)00461-4/h0180http://refhub.elsevier.com/S0040-4039(14)00461-4/h0185http://refhub.elsevier.com/S0040-4039(14)00461-4/h0185http://refhub.elsevier.com/S0040-4039(14)00461-4/h0190http://refhub.elsevier.com/S0040-4039(14)00461-4/h0190http://refhub.elsevier.com/S0040-4039(14)00461-4/h0190http://refhub.elsevier.com/S0040-4039(14)00461-4/h0195http://refhub.elsevier.com/S0040-4039(14)00461-4/h0195http://refhub.elsevier.com/S0040-4039(14)00461-4/h0200http://refhub.elsevier.com/S0040-4039(14)00461-4/h0205http://refhub.elsevier.com/S0040-4039(14)00461-4/h0205http://refhub.elsevier.com/S0040-4039(14)00461-4/h0210http://refhub.elsevier.com/S0040-4039(14)00461-4/h0215http://refhub.elsevier.com/S0040-4039(14)00461-4/h0215http://refhub.elsevier.com/S0040-4039(14)00461-4/h0220http://refhub.elsevier.com/S0040-4039(14)00461-4/h0220http://refhub.elsevier.com/S0040-4039(14)00461-4/h0225http://refhub.elsevier.com/S0040-4039(14)00461-4/h0225http://refhub.elsevier.com/S0040-4039(14)00461-4/h0230http://refhub.elsevier.com/S0040-4039(14)00461-4/h0230http://refhub.elsevier.com/S0040-4039(14)00461-4/h0230http://refhub.elsevier.com/S0040-4039(14)00461-4/h0235http://refhub.elsevier.com/S0040-4039(14)00461-4/h0235http://refhub.elsevier.com/S0040-4039(14)00461-4/h0240http://refhub.elsevier.com/S0040-4039(14)00461-4/h0240http://refhub.elsevier.com/S0040-4039(14)00461-4/h0245http://refhub.elsevier.com/S0040-4039(14)00461-4/h0245http://refhub.elsevier.com/S0040-4039(14)00461-4/h0250http://refhub.elsevier.com/S0040-4039(14)00461-4/h0250http://refhub.elsevier.com/S0040-4039(14)00461-4/h0255http://refhub.elsevier.com/S0040-4039(14)00461-4/h0255http://refhub.elsevier.com/S0040-4039(14)00461-4/h0260http://refhub.elsevier.com/S0040-4039(14)00461-4/h0260http://refhub.elsevier.com/S0040-4039(14)00461-4/h0265http://refhub.elsevier.com/S0040-4039(14)00461-4/h0265http://refhub.elsevier.com/S0040-4039(14)00461-4/h0265http://refhub.elsevier.com/S0040-4039(14)00461-4/h0270http://refhub.elsevier.com/S0040-4039(14)00461-4/h0270http://refhub.elsevier.com/S0040-4039(14)00461-4/h0275http://refhub.elsevier.com/S0040-4039(14)00461-4/h0275http://refhub.elsevier.com/S0040-4039(14)00461-4/h0280http://refhub.elsevier.com/S0040-4039(14)00461-4/h0280http://refhub.elsevier.com/S0040-4039(14)00461-4/h0285http://refhub.elsevier.com/S0040-4039(14)00461-4/h0290http://refhub.elsevier.com/S0040-4039(14)00461-4/h0295http://refhub.elsevier.com/S0040-4039(14)00461-4/h0300http://refhub.elsevier.com/S0040-4039(14)00461-4/h0305http://refhub.elsevier.com/S0040-4039(14)00461-4/h0310http://refhub.elsevier.com/S0040-4039(14)00461-4/h0315http://refhub.elsevier.com/S0040-4039(14)00461-4/h0315http://refhub.elsevier.com/S0040-4039(14)00461-4/h0320http://refhub.elsevier.com/S0040-4039(14)00461-4/h0325http://refhub.elsevier.com/S0040-4039(14)00461-4/h0330http://refhub.elsevier.com/S0040-4039(14)00461-4/h0330http://refhub.elsevier.com/S0040-4039(14)00461-4/h0335http://refhub.elsevier.com/S0040-4039(14)00461-4/h0335http://refhub.elsevier.com/S0040-4039(14)00461-4/h0340http://refhub.elsevier.com/S0040-4039(14)00461-4/h0340http://refhub.elsevier.com/S0040-4039(14)00461-4/h0345http://refhub.elsevier.com/S0040-4039(14)00461-4/h0345http://refhub.elsevier.com/S0040-4039(14)00461-4/h0350http://refhub.elsevier.com/S0040-4039(14)00461-4/h0350http://refhub.elsevier.com/S0040-4039(14)00461-4/h0355http://refhub.elsevier.com/S0040-4039(14)00461-4/h0355http://refhub.elsevier.com/S0040-4039(14)00461-4/h0360http://refhub.elsevier.com/S0040-4039(14)00461-4/h0365http://refhub.elsevier.com/S0040-4039(14)00461-4/h0365http://refhub.elsevier.com/S0040-4039(14)00461-4/h0370http://refhub.elsevier.com/S0040-4039(14)00461-4/h0375http://refhub.elsevier.com/S0040-4039(14)00461-4/h0375http://refhub.elsevier.com/S0040-4039(14)00461-4/h0375http://refhub.elsevier.com/S0040-4039(14)00461-4/h0380http://refhub.elsevier.com/S0040-4039(14)00461-4/h0380http://refhub.elsevier.com/S0040-4039(14)00461-4/h0385http://refhub.elsevier.com/S0040-4039(14)00461-4/h0390http://refhub.elsevier.com/S0040-4039(14)00461-4/h0395http://refhub.elsevier.com/S0040-4039(14)00461-4/h0395http://refhub.elsevier.com/S0040-4039(14)00461-4/h0400http://refhub.elsevier.com/S0040-4039(14)00461-4/h0405http://refhub.elsevier.com/S0040-4039(14)00461-4/h0405http://refhub.elsevier.com/S0040-4039(14)00461-4/h0405http://refhub.elsevier.com/S0040-4039(14)00461-4/h0410http://refhub.elsevier.com/S0040-4039(14)00461-4/h0415

Chemoselective reductions and iodinations using titanium tetraiodideIntroductionReductionPinacol coupling reactionReformatsky-type reactionReductive aldol and Mannich-type reactions

IodinationPrins reactionIodoaldol reactionRing-opening reaction of epoxides and cyclopropanes2-Iodopyridine synthesis

ConclusionAcknowledgementsReferences and notes