Synthesis and Properties of Ortho-T-Buso2c6h4-Substituted Iodonium Ylides

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crystals Communication CommunicationSynthesis and Properties of ortho-t-BuSO2C6H4-Substituted Synthesis and Properties of ortho-t-BuSO C H -Substituted Iodonium Ylides 2 6 4 Iodonium Ylides Tomohiro Kimura 1, Shohei Hamada 2, Takumi Furuta 2, Yoshiji Takemoto 1,* and Yusuke Kobayashi 2,* Tomohiro Kimura 1, Shohei Hamada 2, Takumi Furuta 2, Yoshiji Takemoto 1,* and Yusuke Kobayashi 2,*

1 Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan; 1 Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan; [email protected] [email protected] 2 Department of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan; 2 Department of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan; [email protected] (S.H.); [email protected] (T.F.) [email protected] (S.H.); [email protected] (T.F.) * Correspondence: [email protected] (Y.T.); [email protected] (Y.K.); * Correspondence: [email protected] (Y.T.); [email protected] (Y.K.); Tel.: +81-75-753-4528 (Y.T.); +81-75-595-4666 (Y.K.) Tel.: +81-75-753-4528 (Y.T.); +81-75-595-4666 (Y.K.)

Abstract:Abstract: Iodonium ylides ylides have have recently recently attracted attracted much much attention attention on on account account of oftheir their synthetic synthetic ap- applications.plications. However, However, only only a alimited limited number number of of repo reportsrts concerning concerning the properties andand reactivityreactivity ofof iodoniumiodonium ylidesylides exist,exist, whichwhich isis partlypartly duedue toto theirtheir instability.instability. InIn thisthis study,study, we we synthesized synthesized several several iodoniumiodonium ylidesylides that that bear bear both both an an electron-withdrawing electron-withdrawing group group and and an an aromatic aromatic ring ring with with an anortho ortho-t-- t-BuSO2 group. Based on the crystal structures of the synthesized iodonium ylides in combination BuSO2 group. Based on the crystal structures of the synthesized iodonium ylides in combination with natural-bond-orbitalwith natural-bond-orbital (NBO) (NBO) calculations, calculations, we estimated we estimated the strength the strength of the intra-of the andintra- intermolecular and intermo- halogen-bondinglecular halogen-bonding interactions. interactions. In addition, In addition, we investigated we investigated the reactivity the reac oftivity theiodonium of the iodonium ylides underylides photoirradiation.under photoirradiation.

Keywords: halogen bonding; hypervalent iodine; NBO analysis; photochemistry; radical reactions Keywords: halogen bonding; hypervalent iodine; NBO analysis; photochemistry; radical reactions

Citation: Kimura, T.; Hamada, S.; Furuta,Citation: T.; Kimura, Takemoto, T.;Y.; Hamada, Kobayashi, S.; Y. SynthesisFuruta, T.; and Takemoto, Properties Y.; of Kobayashi, 1.1. IntroductionIntroduction Y. Synthesis and Properties of ortho-t-BuSO2C6H4-Substituted IodoniumIodonium ylides,ylides, aa classclass ofof hypervalenthypervalent iodineiodine compoundscompounds [[1],1], havehave attractedattracted muchmuch Iodoniumortho- t-BuSO Ylides.2C6HCrystals4-Substituted2021, 11 , attentionattention duedue toto theirtheir useuse asas carbenecarbene precursorsprecursors forfor C-H-insertionC‒H-insertion and and cyclopropanation cyclopropanation 1085.Iodonium https://doi.org/10.3390/ Ylides. Crystals 2021, 11, x. reactionsreactions (Scheme (Scheme1a) 1a) [ 2 ,[2,3].3]. Moreover, Moreover, iodonium iodonium ylides ylides have have been been used used for various for various synthetic syn- cryst11091085https://doi.org/10.3390/xxxxx applications,thetic applications, including including condensations condensations with thioamides with thioamides to produce to produce thiazole ringsthiazole in aqueous rings in mediaaqueous (Scheme media1 (Schemeb; Nu = 1b; thioamide) Nu = thioamide) [4,5], and [4,5], for and the for introduction the introduction of 18F of atoms 18F atoms into AcademicAcademic Editors: Editor: Sergiy RosokhaRosokha, − aromaticinto aromatic rings rings (Scheme (Scheme1c; Nu 1c;= Nu F )[ = 6F,−7)]. [6,7]. It has It alsohas also been been reported reported that that depending depending on the on andAtash Atash V. Gurbanov V. Gurbanov iodoniumthe iodonium ylide ylide and nucleophileand nucleophile that is that employed, is employed, the equilibrium the equilibrium between between the T-shaped the T- intermediatesshaped intermediates A and B canA and be inﬂuencedB can be influenc [6,7], anded thus,[6,7], theand ratio thus, of couplingthe ratio productsof coupling C Received:Received: 2020 August August 2021 2021 and D can be controlled. Accepted:Accepted: 3 3 September September 2021 2021 products C and D can be controlled. Published:Published: 7 7 September September 2021 2021

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Copyright: © 2021 by the authors. Copyright:Submitted for© 2021possible by theopen authors. access Licenseepublication MDPI, under Basel, the terms Switzerland. and con- Thisditions article of the is Creative an open Commons access article At- distributedtribution (CC under BY) license the (http://crea- terms and conditionstivecommons.org/licenses/by/4.0/). of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ Scheme 1. General synthetic utility of iodonium ylides. (a) Cyclopropanation of alkenes (b) Introduction 4.0/). of nucleophile into active methylene compound (c) Introduction of nucleophile into aromatic rings.

Crystals 2021, 11, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/crystals

Crystals 2021, 11, 1085. https://doi.org/10.3390/cryst11091085 https://www.mdpi.com/journal/crystals Crystals 2021, 11, x FOR PEER REVIEW 2 of 7

Scheme 1. General synthetic utility of iodonium ylides. (a) Cyclopropanation of alkenes (b) Intro- Crystals 2021, 11, 1085 duction of nucleophile into active methylene compound (c) Introduction of nucleophile2 of 7 into aromatic rings

However, to date, only a limited number of reports concerning the properties and However, to date, only a limited number of reports concerning the properties and reactivity of iodonium ylides have been published, which is at least in part due to their reactivity of iodonium ylides have been published, which is at least in part due to their instability (e.g.,instability degradation (e.g., via degradation intermediates via intermediates A and/or B) onA and/or account B) of on the account remaining of the remaining σ- σ-hole of intermediateshole of intermediates A and B, which A and can B, reactwhich with can nucleophilesreact with nucleophiles such as water. such We as water. We an- anticipate thatticipate the synthesis that the of asynthesis variety of of iodonium a variety ylidesof iodonium and the ylides investigation and the ofinvestigation their of their properties wouldproperties provide would essential provide information essential for informatio the advancementn for the ofadvancement synthetic applica- of synthetic applications such as chemoselectivetions such as chemoselective coupling reactions. coupling Of particular reactions. interest Of particular to us are interest iodonium to us are iodonium ylides that containylides a coordinatingthat contain aortho coordinatinggroup on ortho the aromatic group on ring the[ aromatic8], as such ring groups [8], as are such groups are known to stabilizeknown iodonium to stabilize ylides iodonium and other ylides hypervalent and othe iodiner hypervalent compounds iodine[5 –compounds9], thus [5–9], thus increasing theirincreasing solubility their via intramolecular solubility via intramolecular halogen bonding halogen (XB) [ bonding10]. In this (XB) study, [10]. we In this study, we synthesized severalsynthesized iodonium several ylides iodonium bearing bothylides an bearing electron-withdrawing both an electron-withdrawing group and an group and an 2 aromatic ring witharomatic an ortho ring- twith-BuSO an2 grouportho-t-BuSO [8,11]. Basedgroup on [8,11]. the crystalBased structureson the crystal of the structures of the synthesized iodoniumsynthesized ylides iodonium in combination ylides in with combination natural-bond-order with natural-bond-order (NBO) analysis, (NBO) we analysis, we also estimatedalso the strengthestimated of the the strength intra- and of intermolecularthe intra- and intermolecular XBs [12–23]. In XBs addition, [12–23]. we In addition, we investigated theinvestigated reactivity of the these reactivity iodonium of these ylides iodoni underum photoirradiation ylides under photoi [24–27rradiation]. [24–27].

2. Results 2. Results We began by synthesizingWe began by iodonium synthesizi ylidesng iodonium2 via the ylides condensation 2 via the of condensation iodosobenzene of iodosobenzene 1 [11] with a variety1 [11] ofwith active a variety methylene of active compounds methylene (Table compounds1). The reaction (Table 1). of The1 and reaction the of 1 and the ◦ active methyleneactive compounds methylene proceeded compounds at 0proceededC in etheric at 0 solvents°C in etheric such solvents as THF such or Et 2asO THF or Et2O to to furnish thefurnish corresponding the corresponding iodonium ylidesiodonium (2) as ylides precipitates (2) as precipitates with H2O, with as the H sole2O, as the sole by- byproduct. Theproduct. desired productsThe desired were products collected were by simple collected suction by simple filtration suction and, followingfiltration and, following an n-hexane wash,an n-hexane produced wash, the produced pure compounds the pure incompounds acceptable in yield acceptable (for details, yield (for see details, see the the SupplementarySI). The Materials). major advantage The major that advantage this method that [28] this has method over the [28 conventional] has over the method that uses conventional methodiodoarene that diacetate uses iodoarene and an active diacetate methylene and an activecompound methylene under compoundbasic conditions is that it under basic conditionseliminates is thatthe need it eliminates to remove the the need formed to remove salt (e.g., the formed KOAc saltor NaOAc) (e.g., KOAc with an H2O wash or NaOAc) with[29]. an HWe2O tested wash [a29 wide]. We range tested of a active wide range meth ofylene active compounds, methylene which compounds, produced iodonium which producedylides iodonium 2a–h in ylides 27–89%2a–h yieldin 27–89% without yield significant without significantdecomposition decomposition during the purification. during the purification.This is presumably This is presumably due to the enhanced due to the el enhancedectrophilicity electrophilicity of the iodosobenzene of the compound iodosobenzeneand compound the increased and the stability increased of stabilitythe product of the due product to the due presence to the presenceof the coordinating of ortho- the coordinatingsulfonylortho-sulfonyl group. group.

Table 1. Synthesis of various iodonium ylides that bear an ortho-t-BuSO2 group on the aromatic ring Table 1. Synthesis of various iodonium ylides that bear an ortho-t-BuSO2 group on the aromatic ring (2) from iodosobenzene 1. (2) from iodosobenzene 1.

Entry ActiveEntry Methylene Active Methylene Compound Compound Solvent Solvent Time Time Product Product Yield (%) a Yield (%) a 1 1 R = R’ = OMe R = R’ = OMe THF THF 22 22 h h 2a 2a 67 67 2 2 R = Me, R’ R = = OEt Me, R’ = OEt THF THF 4 4h h 2b 2b 43 43 3 3R = CF3, R’ R = = OEt CF3, R’ = OEt Et2O Et 2O 2323 h h 2c 2c 78 78 Crystals 2021, 411, x FOR PEER REVIEW R = R’ = Me THF 16 h 2d 57 3 of 7 4 R = R’ = Me THF 16 h 2d 57 5 R = R’ = CF3 THF 1 min 2e 27 5 6 R = R’ = CF Dimedone3 THF THF 1.51 min h 2f 2e 89 27 6 7Dimedone Meldrum’s acidTHF THF 101.5 min h 2g 2f 56 89 7 Meldrum’s acid THF 10 min 2g 56 8 8 THFTHF 15 min 152h min 74 2h 74

a Isolated yields. a Isolated yields.

We also succeeded in obtainingWe also succeeded single crystals in obtaining of 2e and single2g thatcrystals were of suitable 2e and 2g for that were suitable for an

an X-ray diffraction analysis;X-ray thediffraction molecular analysis; structures the molecular of these compounds structures of are these shown compounds in are shown in Fig- ures 1 and 2, while pertinent crystallographic parameters are summarized in Table 2. As expected, the distance between the iodine atom (I1) and the oxygen atom (O5) of the ortho- sulfonyl group in 2e (2.737(3) Å) is within the sum of the van der Waals radii, implying the presence of an intramolecular XB interaction [10,19]. In addition, the analysis of the packing structure suggested the presence of an intermolecular XB in the solid state, in which the carbonyl oxygen (O11) and sulfonyl oxygen (O5) interact with the hypervalent iodine atom of 2e (Figure 1A). It is probably due to these interactions that 2e aligns to form the dimeric columnar structure shown in Figure 1B. The X-ray structure of 2g, which contains a residual molecule of chloroform, shows an intermolecular XB interaction in addition to the intramolecular XB with the ortho-t-BuSO2 group seen in 2e (Figure 2). This implies that this iodonium ylide may be able to recognize the substrates in coupling reactions via XB interactions. To estimate the interaction energies of the intra- and intermolecular XBs, we performed an NBO analysis based on the crystal structure of 2e, using the gaussian software package (Figure 3) [30,31]. The analysis demonstrated that the C14‒I1 σ* orbital of the hypervalent iodine moiety in 2e overlaps with the three types of lone pairs (LPs) of the intramolecular sulfonyl oxygen (O5) (See the Supplementary Materials for the details of orbitals). The energies of these interactions were calculated to be 3.15, 0.79, and 4.73 kcal/mol, respectively (Figure 3A). Moreover, the intermolecular XB energies were estimated to be 0.70 and 0.29 kcal/mol, respectively (Figure 3B). These interaction energies may contribute to the relative stability of this type of iodonium ylide. The corresponding results of the NBO analysis performed for iodonium ylide 2g are summarized in Figure 4. The interaction energies seem to be stronger when the interaction distance is shorter and the interaction angle is closer to 180º, which is an ideal situation for XB interactions (Table 2).

Figure 1. Crystal structure of iodonium ylide 2e: (A) sideview of 2e; (B) dimeric columnar structure formed by two stacked columns of 2e.

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8 THF 15 min 2h 74

a Isolated yields.

We also succeeded in obtaining single crystals of 2e and 2g that were suitable for an X-ray diffraction analysis; the molecular structures of these compounds are shown in Fig- ures 1 and 2, while pertinent crystallographic parameters are summarized in Table 2. As expected, the distance between the iodine atom (I1) and the oxygen atom (O5) of the ortho- sulfonyl group in 2e (2.737(3) Å) is within the sum of the van der Waals radii, implying the presence of an intramolecular XB interaction [10,19]. In addition, the analysis of the packing structure suggested the presence of an intermolecular XB in the solid state, in which the carbonyl oxygen (O11) and sulfonyl oxygen (O5) interact with the hypervalent iodine atom of 2e (Figure 1A). It is probably due to these interactions that 2e aligns to form the dimeric columnar structure shown in Figure 1B. The X-ray structure of 2g, which contains a residual molecule of chloroform, shows an intermolecular XB interaction in addition to the intramolecular XB with the ortho-t-BuSO2 group seen in 2e (Figure 2). This im- Crystals 2021, 11, 1085 plies that this iodonium ylide may be able to recognize the substrates in coupling reactions3 of 7 via XB interactions. To estimate the interaction energies of the intra- and intermolecular XBs, we performed an NBO analysis based on the crystal structure of 2e, using the gaussian software Figures1 and2, while pertinent crystallographic parameters are summarized in Table2 . As package (Figure 3) [30,31]. The analysis demonstrated that the C14‒I1 σ* orbital of the expected, the distance between the iodine atom (I1) and the oxygen atom (O5) of the ortho- hypervalent iodine moiety in 2e overlaps with the three types of lone pairs (LPs) of the sulfonyl group in 2e (2.737(3) Å) is within the sum of the van der Waals radii, implying the intramolecular sulfonyl oxygen (O5) (See the Supplementary Materials for the details of presence of an intramolecular XB interaction [10,19]. In addition, the analysis of the packing orbitals). The energies of these interactions were calculated to be 3.15, 0.79, and 4.73 structure suggested the presence of an intermolecular XB in the solid state, in which the carbonylkcal/mol, oxygenrespectively (O11) (Figure and sulfonyl 3A). Moreover, oxygen (O5) the intermolecular interact with the XB hypervalent energies were iodine esti- atommated of to2e be(Figure 0.70 and1A). 0.29 It is kcal/mol, probably respective due to thesely (Figure interactions 3B). These that 2e interactionaligns to formenergies the dimericmay contribute columnar to structurethe relative shown stability in Figure of this1B. type The of X-ray iodonium structure ylide. of The2g, which corresponding contains aresults residual of the molecule NBO analysis of chloroform, performed shows for aniodonium intermolecular ylide 2g XB are interaction summarized in additionin Figure to 4. The interaction energies seem to be stronger when the interaction distance is shorter and the intramolecular XB with the ortho-t-BuSO2 group seen in 2e (Figure2). This implies thatthe interaction this iodonium angle ylide is closer may to be 180º, able towhich recognize is an ideal the substrates situation for in couplingXB interactions reactions (Table via XB2). interactions.

Crystals 2021, 11, x FOR PEER REVIEW 4 of 7 FigureFigure 1.1. Crystal structurestructure ofof iodoniumiodonium ylideylide2e 2e:(: (AA)) sideviewsideview ofof 2e;(; (B)) dimeric columnar structurestructure formedformed byby twotwo stackedstacked columnscolumns ofof 2e2e..

FigureFigure 2. 2.Crystal Crystal structurestructure of of iodonium iodonium ylide ylide2g 2g:(: (AA)) sideview sideview of of2g 2g;(; (BB)) columnarcolumnar structurestructure formed formed by by one one stacked stacked column column ofof2g 2gand and residual residual chloroform chloroform molecules. molecules.

Table 2. Crystallographic parameters of the intra- and intermolecular XB interactions in the crystals of iodonium ylides 2e and 2g.

Compound C‒I•••O (or C‒I•••Cl) d(I•••O)/Å <(C‒I•••O) or <(C‒I•••Cl)/Deg 2e C14‒I1•••O5 (intramolecular) 2.737 (3) 164.0 C13‒I1•••O11 (intermolecular) 3.269 (4) 156.3 C14‒I1•••O5 (intermolecular) 3.451 (3) 132.5 2g C15‒I1•••O3 (intramolecular) 2.695 (3) 170.5 C9‒I1•••O8 (intermolecular) 3.411 (4) 159.5 C9‒I1•••Cl (intermolecular) 3.673 136.4

Figure 3. NBO analysis of iodonium ylide 2e. (A1) Intramolecular XB between a lone pair of the sulfonyl group (Orbital#71) and the C14-I1 σ* orbital (Orbital#136) (type 1). (A2) Intramolecular XB between a lone pair of the sulfonyl group (Or- bital#120) and the C14-I1 σ* orbital (Orbital#136) (type 2). (A3) Intramolecular XB between a lone pair of the sulfonyl group

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Table 2. Crystallographic parameters of the intra- and intermolecular XB interactions in the crystals of iodonium ylides 2e and 2g.

Compound C-I•••O (or C-I•••Cl) d(I•••O)/Å <(C-I•••O) or <(C-I•••Cl)/Deg 2e C14-I1•••O5 (intramolecular) 2.737 (3) 164.0 C13-I1•••O11 (intermolecular) 3.269 (4) 156.3 C14-I1•••O5 (intermolecular) 3.451 (3) 132.5 2g C15-I1•••O3 (intramolecular) 2.695 (3) 170.5 C9-I1•••O8 (intermolecular) 3.411 (4) 159.5 C9-I1•••Cl (intermolecular) 3.673 136.4

Figure 2. Crystal structure of iodoniumTo estimate ylide 2g the: (A interaction) sideview of energies 2g; (B) columnar of the intra- structure and intermolecular formed by one XBs,stacked we column performed of 2g and residual chloroform molecules. an NBO analysis based on the crystal structure of 2e, using the gaussian software package (Figure3)[ 30,31]. The analysis demonstrated that the C14-I1 σ* orbital of the hypervalent Table 2. Crystallographic parameters of the intra- and intermolecular XB interactions in the crystals of iodonium ylides 2e and 2g. iodine moiety in 2e overlaps with the three types of lone pairs (LPs) of the intramolecular sulfonyl oxygen (O5) (See the Supplementary Materials for the details of orbitals). The Compound C‒I•••Oenergies (or C‒I•••Cl) of these interactionsd(I•••O)/Å were calculated to be< 3.15,(C‒I•••O) 0.79, and or < 4.73(C‒I•••Cl)/Deg kcal/mol, respec- 2e C14‒I1•••O5tively (intramolecular) (Figure3A). Moreover, 2.737the intermolecular (3) XB energies were 164.0 estimated to be 0.70 C13‒I1•••O11and (intermolecula 0.29 kcal/mol,r) respectively3.269 (Figure (4) 3B). These interaction energies 156.3 may contribute to C14‒I1•••O5the (intermolecular) relative stability of this type 3.451 of iodonium (3) ylide. The corresponding 132.5 results of the NBO 2g C15‒I1•••O3analysis (intramolecular) performed for iodonium 2.695ylide (3) 2g are summarized in Figure 170.54 . The interaction C9‒I1•••O8energies (intermolecular) seem tobe stronger when 3.411 (4) the interaction distance is shorter 159.5 and the interaction angle is closer to 180º, which is an ideal situation for XB interactions (Table2). C9‒I1•••Cl (intermolecular) 3.673 136.4

FigureFigure 3.3. NBO analysis of iodonium ylide 2e.(. (A1) Intramolecular XB between a lone pair of the sulfonyl sulfonyl group (Orbital#71) andand thethe C14-I1 C14-I1σ *σ orbital* orbital (Orbital#136) (Orbital#136) (type (type 1). (1).A2 )(A2 Intramolecular) Intramolecular XB between XB between a lone a pair lone of pair thesulfonyl of the sulfonyl group (Orbital#120) group (Or- andbital#120) the C14-I1 and σthe* orbital C14-I1 (Orbital#136) σ* orbital (Orbital#136) (type 2). (A3 (type) Intramolecular 2). (A3) Intramolecular XB between aXB lone between pair of a the lone sulfonyl pair of group the sulfonyl (Orbital#119) group and the C14-I1 σ* orbital (type 3) (Orbital#136). (B1) Intermolecular XB between a lone pair of the carbonyl group and the C13-I1 σ* orbital. (B2) Intermolecular XB between a lone pair of sulfonyl group and the C13-I1 σ* orbital.

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Crystals 2021, 11, 1085 5 of 7 (Orbital#119) and the C14-I1 σ* orbital (type 3) (Orbital#136). (B1) Intermolecular XB between a lone pair of the carbonyl group(Orbital#119) and the andC13-I1 the σ C14-I1* orbital. σ* (orbitalB2) Intermolecular (type 3) (Orbital#136). XB between (B1 a )lone Intermolecular pair of sulfonyl XB between group and a lone the pairC13-I1 of σthe* orbital. carbonyl group and the C13-I1 σ* orbital. (B2) Intermolecular XB between a lone pair of sulfonyl group and the C13-I1 σ* orbital.

FigureFigure 4. NBO 4. NBOanalysis analysis of iodonium of iodonium ylide ylide 2g. (A12g.() IntramolecularA1) Intramolecular XB between XB between a lone a lone pair pair of the of thesulfonyl sulfonyl group group (Orbital#58) (Orbital#58) and the Figure 4. NBO analysis of iodonium ylide 2g. (A1) Intramolecular XB between a lone pair of the sulfonyl group (Orbital#58) and the C15-I1and σ* orbital the C15-I1 (Orbital#123)σ* orbital (type (Orbital#123) 1). (A2) Intramolecular (type 1). (A2 XB) Intramolecular between a lone XB pair between of the sulfonyl a lone group pair of (Orbital#105) the sulfonyl and group the C15- I1C15-I1 σ* orbital σ* orbital (Orbital#123) (Orbital#123) (type (type2). (A3 1).) Intramolecular (A2) Intramolecular XB between XB between a lone a pair lone of pair the ofsulfonyl the sulfonyl group group (Orbital#104) (Orbital#105) and the and C15-I1 the C15- σ* (Orbital#105) and the C15-I1 σ* orbital (Orbital#123) (type 2). (A3) Intramolecular XB between a lone pair of the sulfonyl orbitalI1 σ* orbital (Orbital#123) (Orbital#123) (type 3).(type (B1 2).) Intermolecular (A3) Intramolecular XB between XB between a lone apair lone of pair the ofcarbonyl the sulfonyl group group and the (Orbital#104) C9-I1 σ* orbital. and the (B2 C15-I1) Inter- σ* group (Orbital#104) and the C15-I1 σ* orbital (Orbital#123) (type 3). (B1) Intermolecular XB between a lone pair of the molecularorbital (Orbital#123) XB between (type a lone 3). pair (B1 )of Intermolecular the Cl group and XB thebetween C9-I1 aσ lone* orbital. pair of the carbonyl group and the C9-I1 σ* orbital. (B2) Inter- molecularcarbonyl XB group between and a the lone C9-I1 pairσ of* orbital.the Cl group (B2) Intermolecular and the C9-I1 XBσ* betweenorbital. a lone pair of the Cl group and the C9-I1 σ* orbital. Finally, we investigated the reactivity of the synthesized iodonium ylides under pho- Finally, we investigated the reactivity of the synthesized iodonium ylides under toirradiationFinally, conditionswe investigated (Schem thee reactivity2) [9,24–27]. of the When synthesized ylide 2a iodoniumand ten equivalents ylides under of pho- N- photoirradiation conditions (Scheme2)[ 9,24–27]. When ylide 2a and ten equivalents of methylpyrroletoirradiation conditions were irradiated (Schem ate 365 2) [9,24–27].nm, the active When methylene ylide 2a andgroup ten was equivalents introduced of atN - Nmethylpyrrole-methylpyrrole were were irradiated irradiated at at 365 365 nm, nm, the the active methylene groupgroup waswas introducedintroduced at at the C2 position of N-methylpyrrole in 61% yield (Scheme(Scheme2 2a).a). Unexpectedly,Unexpectedly, whenwhen ylideylide 2ethe–g C2and position ten equivalents of N-methylpyrrole of N-methylpyrrole in 61% yield were (Schemirradiatede 2a). at 365Unexpectedly, nm, the aryl when group ylide (2- 2e2e––ggand and ten ten equivalents equivalents of ofN N-methylpyrrole-methylpyrrole were were irradiated irradiated at at 365 365 nm, nm, the the aryl aryl group group (2- (2-t- t-BuSO2C6H4) of the ylide was exclusively introduced at the C2 position of N-methylpyr- BuSO2C6H4) of the ylide was exclusively introduced at the C2 position of N-methylpyrrole rolet-BuSO (Scheme2C6H 42b).) of the ylide was exclusively introduced at the C2 position of N-methylpyr- (Schemerole (Scheme2b). 2b).

Scheme 2. (a) Reactivity of iodonium ylide 2a under photoirradiation conditions. (b) Reactivity of iodoniumSchemeScheme 2. 2. ylide( a(a)) Reactivity Reactivity 2e–g under ofof iodoniumphotoirradiationiodonium ylideylide2a 2a conditions.under under photoirradiationphotoirradiation conditions.conditions. (b)) ReactivityReactivity of iodonium ylide 2e–g under photoirradiation conditions. iodonium ylide 2e–g under photoirradiation conditions. Based on these observations and recent related reports by other groups [7], the reaction seemsBasedBased to on on proceed these these observations observations via a T-shaped and and recenttri-coor recent relateddinated related reports intermediate, reports by otherby other which groups groups is [ 7different], the[7], reactionthe from reac- seemstion seems to proceed to proceed via a via T-shaped a T-shaped tri-coordinated tri-coordinated intermediate, intermediate, which which is different is different from from a free carbene species [32]. The T-shaped tricoordinated intermediate could be formed via

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a biradical species generated via photoirradiation [33]. The unexpected selectivity of the reductive elimination might be explained by the steric hindrance of the dimedone and Meldrum’s acid moieties in 2f and 2g, although a detailed mechanism for this transforma- tion, including the selectivity in the case of 2e, is not clear at this stage. Iodonium ylides 2c and 2h gave the coupling product 4 in 43% and 31%, respectively, while 2b and 2d did not afford any coupling products, presumably due to degradation under photoirradiation.

3. Conclusions We have synthesized a series of novel iodonium ylides that bear a coordinating ortho-t- BuSO2 group on their aryl rings, and we have analyzed the crystal structures of two of these molecules. Intra- and intermolecular halogen bonding (XB) interactions were observed in the crystal structures of two ylides that were structurally characterized by X-ray diffraction analysis. The synthesized iodonium ylides were found to serve as active transfer reagents of methylene or aryl groups. Further synthetic applications and mechanistic studies are currently under investigation in our laboratory.

Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/cryst11091085/s1: Detailed compound characterization data and copies of NMR charts. Author Contributions: Conceptualization, Y.K. and Y.T.; methodology, T.K.; software, S.H., T.F. and Y.K.; validation, S.H., T.F. and Y.K.; formal analysis, T.K.; investigation, T.K.; resources, T.K.; data curation, T.K.; writing—original draft preparation, Y.K.; writing—review and editing, S.H., T.F. and Y.T.; visualization, Y.K.; supervision, Y.K. and Y.T.; project administration, Y.K. and Y.T.; funding acquisition, Y.K. All authors have read and agreed to the published version of the manuscript. Funding: This work was partly supported by JSPS KAKENHI grant 19K06974, as well as a research grant from the Hoansha Foundation. Acknowledgments: We thank Kosuke Katagiri (Konan University) for assistance with preparing the graphics. Conﬂicts of Interest: The funders neither had a role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, nor in the decision to publish the results.

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