Synthesis, Characterization, and Application of 1,4-Dienylindiums Toward Skipped Dienes

Communication Regio- and Stereoselective Allylindation of Alkynes Using InBr3 and Allylic Silanes: Synthesis, Characterization, and Application of 1,4-Dienylindiums toward Skipped Dienes

Yoshihiro Nishimoto 1,*, Junyi Yi 2, Tatsuaki Takata 2, Akio Baba 2 and Makoto Yasuda 2,* 1 Frontier Research Base for Global Young Researchers Center for Open Innovation Research and Education (COiRE), Graduate School of Engineering, Osaka University; Osaka 565-0871, Japan 2 Department of Applied Chemistry, Graduate School of Engineering, Osaka University; Osaka 565-0871, Japan; [email protected] (J.Y.); [email protected] (T.T.); [email protected] (A.B.) * Correspondence: [email protected] (Y.N.); [email protected] (M.Y.); Tel.: +81-6-6879-7386 (Y.N.); +81-6-6879-7384 (M.Y.) Received: 7 July 2018; Accepted: 27 July 2018; Published: 27 July 2018

Abstract: Regioselective anti-allylindation of alkynes was achieved using InBr3 and allylic silanes. Various types of alkynes and allylic silanes were applicable to the present allylindation. This sequential process used the generated 1,4-dienylindiums to establish novel synthetic methods for skipped dienes. The 1,4-dienylindiums were characterized by spectral analysis and treated with I2 to stereoselectively give 1-iodo-1,4-dienes. The Pd-catalyzed cross coupling of 1,4-dienylindium with iodobenzene successfully proceeded in a one-pot manner to afford the corresponding 1-aryl-1,4-diene.

Keywords: indium; allylmetalation; alkyne; allylic silane

1. Introduction Carbometalation is an important synthetic method in organic synthesis because organometallic compounds are produced with an expansion of the carbon framework [1–7]. In particular, the allylmetalation of alkynes provides metalated skipped dienes (1,4-diene), which are effectively transformed to functionalized skipped dienes via sequential reactions [8–18]. Skipped diene units are present in many biologically important natural products, and are also versatile synthetic building blocks in organic synthesis [19–22]. Therefore, various types of allylmetalation of alkynes have been developed. However, most reported reactions involve a syn-addition to alkynes, and few reports have focused on anti-allylmetalation (Scheme1). Allylmagnesations via direct anti-addition of allylic Grignard reagent were also reported (Scheme1A,B), in which a directing group such as hydroxy and amino groups nearby the alkyne moiety are required [23–29]. Yamamoto reported an allylsilylation of simple alkynes with allylic silanes catalyzed by either HfCl4 or EtAlCl2-Me3SiCl (Scheme1C) [ 16,30–32]. However, the produced 1,4-dienyl trialkylsilanes cannot be applied to sequential transformations such as Hiyama coupling without activation by a strong base because of their low reactivity. In this context, we achieved regioselective anti-allylindation of simple alkynes using InBr3 and allylic silanes (Scheme1D). To the best of our knowledge, anti-allylindation of alkynes has never been established, while several syn-allylindations using allylic indiums have [13,33–39]. The 1,4-dienylindium compounds can be excellent precursors for functionalized skipped dienes due to their moderate reactivity and high compatibility with many functional groups. In fact, the 1,4-dienylindiums synthesized by the present allylindation can be easily transformed to functionalized skipped dienes by iodination or Pd-catalyzed cross coupling without the addition of bases in contrast to 1,4-dienylsilanes produced via allylsilylation.

Molecules 2018, 23, 1884; doi:10.3390/molecules23081884 www.mdpi.com/journal/molecules Molecules 2018, 23, x 2 of 14

Moleculesskipped2018 dienes, 23, 1884 by iodination or Pd-catalyzed cross coupling without the addition of bases in contrast2 of 14 to 1,4-dienylsilanes produced via allylsilylation.

SchemeScheme 1.1. AntiAnti-allylmetalation-allylmetalation ofof alkynes.alkynes.

2. Results 2. Results Recently, we reported regioselective anti-carbometalations of alkynes using organosilicon Recently, we reported regioselective anti-carbometalations of alkynes using organosilicon nucleophiles nucleophiles and metal halides such as InBr3 [40], GaBr3 [41], BiBr3 [42], ZnBr2 [43], and AlBr3 [44]. In and metal halides such as InBr3 [40], GaBr3 [41], BiBr3 [42], ZnBr2 [43], and AlBr3 [44]. In our established our established carbometalations, a metal halide directly activates an alkyne, and then an carbometalations, a metal halide directly activates an alkyne, and then an organosilicon nucleophile organosilicon nucleophile adds to the alkyne from an opposite site of the metal halide. Therefore, we adds to the alkyne from an opposite site of the metal halide. Therefore, we applied a combination of applied a combination of indium trihalides and allylic silanes to establish anti-allylindation of indium trihalides and allylic silanes to establish anti-allylindation of alkynes. First, various indium salts alkynes. First, various indium salts were investigated for the reaction using alkyne 1a and methallyl were investigated for the reaction using alkyne 1a and methallyl trimethylsilane 2a (Table1). InBr 3, trimethylsilane 2a (Table 1). InBr3, 1a, and 2a were mixed in CH2Cl2, and then the reaction mixture 1a, and 2a were mixed in CH2Cl2, and then the reaction mixture was stirred at room temperature for was stirred at room temperature for 24 h. After an I◦2 solution in THF was added at −78 °C, alkenyl 24 h. After an I2 solution in THF was added at −78 C, alkenyl iodide 4aa was obtained as a single iodide 4aa was obtained as a single isomer in 89% yield (Entry 1). An iodine group was introduced isomer in 89% yield (Entry 1). An iodine group was introduced exclusively cis to the allylic group. exclusively cis to the allylic group. The production of 4aa by quenching with I2 suggested that anti- The production of 4aa by quenching with I2 suggested that anti-allylindation regioselectively proceeded allylindation regioselectively proceeded to give the corresponding 1,4-dienylindium 3aa. The use of to give the corresponding 1,4-dienylindium 3aa. The use of InCl3 instead of InBr3 afforded 4aa in a 42% InCl3 instead of InBr3 afforded 4aa in a 42% yield (Entry 2). On the other hand, examinations using yield (Entry 2). On the other hand, examinations using InF3, InI3, and In(OTf)3 resulted in no reaction InF3, InI3, and In(OTf)3 resulted in no reaction (Entries 3–5). The thermodynamic stability of a (Entries 3–5). The thermodynamic stability of a generated side product Me3SiX might influence the driving generated side product Me3SiX might influence the driving force of the reaction. An investigation of force of the reaction. An investigation of the solvent effect was carried out. The reaction performed in the solvent effect was carried out. The reaction performed in non-polar solvents such as toluene non-polar solvents such as toluene resulted in no product because InBr3 did not dissolve the solvent resulted in no product because InBr3 did not dissolve the solvent (Entry 6). Polar solvents such as (Entry 6). Polar solvents such as Et2O, CH3CN, and THF were not suitable to the present allylindation Et2O, CH3CN, and THF were not suitable to the present allylindation because of the deactivation of because of the deactivation of InBr3 by the solvent coordination (Entries 7–9). InBr3 by the solvent coordination (Entries 7–9).

MoleculesMolecules 2018, 23 2018, x , 23, x 3 of 14 3 of 14 MoleculesMolecules 2018, 23 2018, x , 23, x 3 of 14 3 of 14 Molecules 2018, 23, x 3 of 14 Table Table1. Optimization 1. Optimization of reaction of reaction condit conditions forions carboindation for carboindation of alkyne of alkyne 1a with 1a allylic with allylicsilane silane2a a. 2a a. Molecules 2018 23 a a Molecules Table2018, 23 Table1., x 1884Optimization 1. Optimization of reaction of reaction condit conditions forions carboindation for carboindation of alkyne of alkyne 1a with 1a allylic with allylicsilane silane2a 3. of 2a 14 . Table 1. Optimization of reaction conditions for carboindation of alkyne 1a with allylic silane 2a a.

Table 1. Optimization of reaction conditions for carboindation of alkyne 1a with allylic silane 2a a. Table 1. Optimization of reaction conditions for carboindation of alkyne 1a with allylic silane 2a a.

EntryEntry InX3 InX3 SolventSolvent Yield/%Yield/% EntryEntry InX3 InX3 SolventSolvent Yield/%Yield/% Entry1 1 InXInBr3 3 InBr3 SolventCH2ClCH 2 2Cl2 Yield/%89 89 1 1 InBr3 InBr3 CH2ClCH2 2Cl2 89 89 b b 3 2 2 12 2 b InBrInCl3 InCl3 CHCH2ClCl2CH 2Cl2 8942 42 Entry2 b 2 EntryInXInCl3 3 InCl InX33 SolventSolventCH2ClCH 2 Yield/%2Cl2 Yield/%42 42 2 b3 3 InClInF3 3 InF3 CHCH2Cl2Cl2CH 2 2Cl2 420 0 3 3 InF3 2 2CH2Cl2 0 1 3 1InBrInF 3 InBr3 CHCH2CHClCl22Cl 2 89 890 4 InI3 3 CH2Cl2 2 2 0 3b 4 bInF3 InI CH2Cl2CH Cl 0 0 2 4 4 2 InClInI3 3 InIInCl3 3 CHCH2CHCl2Cl22Cl2CH 2 2Cl422 420 0 5 In(OTf)3 CH2Cl2 0 4 5 3InI3 In(OTf) InF 3 CHCHCl2Cl2CH 2Cl0 2 0 0 3 5 5 In(OTf)InF3 In(OTf)3 3 3 CH2CH2Cl22Cl2CH 2 2Cl2 0 0 0 3 5 6 6 In(OTf)4InBr 3 InBr InI33 CHCHtoluene2Cl2Cl2 2toluene 0 0 0 0 4 6 6 InIInBr3 3 InBr3 CHtoluene2Cl2toluene 0 0 0 6 7 7 5InBrInBr3 3 In(OTf)InBr3 3 CHtoluene2ClEt22O Et2O0 0 0 0 5 7 7 In(OTf)6InBr3 InBr InBr3 tolueneCHEt2Cl2O2 Et2O 0 0 0 0 8 8 InBr3 3 InBr33 CH2 3CNCH 3CN 0 0 7 InBr 3 Et O 3 0 6 8 8 7InBrInBr3 3 InBr InBr3 EttolueneCH2O3CNCH CN 0 0 0 0 8 9 9 InBrInBr3 3 InBr3 CHTHF3CN THF 0 0 0 7 9 8InBr3 3 InBr InBr33 CH3EtCN2O THF 0 0 0 a 9 InBr THF 0 InX3 (1a InX mmol),39 (1 mmol), alkyne alkyne 1a (1 mmol), 1a9InBr (1 mmol),3 allylic InBr allylicsilane silane2a (2THF mmol),THF 2a (2 mmol), solvent 0 solvent (1 mL), (1 room mL), 0 temperature,room temperature, 24 24 a a InX3 (1 mmol), alkyne 1a (1 mmol),3 allylic3 silane 2a3 (2 mmol), solvent (1 mL), room temperature, 24 InX3 (1 mmol),8 alkyne 1a (1 mmol),InBr allylic silane 2a (2CH mmol),1CN solvent (1 mL), room0 temperature, 24 a h. I2 (1.5 mmol), THF (2 mL). Yields were determined via H-NMR1 using 1,1,2,2-tetrachloroethane as InX3 (1h. mmol), I2 (1.5 alkynemmol), 1aTHF (1 mmol),(2 mL). allylicYields silanewere determined2a (2 mmol), via solvent 1H-NMR (1 mL), using room 1,1,2,2-tetrachloroethane temperature, 24 as a h. I2 (1.5h. Immol),2 (1.59 mmol), THF (2 THF mL). (2 Yields mL).InBr Yields 3were determinedwere determined viaTHF 1H-NMR via H-NMR using using1,1,2,2-tetrachloroethane 1,1,2,2-tetrachloroethane 0 as as InX3 (1 mmol), alkyne 1ab(1 mmol),2 b allylic silane 2a (2 mmol), solvent (1 mL), room temperature, 24 h. I2 (1.5 mmol), an2 internalan internal standard; standard; Et O was Et2O used was instead used instead of THF. of THF.1 ah. I (1.5 mmol), THF (2 mL). bYields were1 determined via H-NMR using 1,1,2,2-tetrachloroethaneb as THF InXan (2internal3 (1 mL).an mmol), internal Yields standard; alkyne were standard; determinedb 1a Et 2(1O mmol),was Et2O viaused was allylicH-NMR instead used silane usinginstead of THF.2a 1,1,2,2-tetrachloroethane (2 of mmol), THF. solvent (1 asmL), an internalroom temperature, standard; Et 224O anwas internal used instead standard; of THF. b Et2O was used instead of THF. h. I2 (1.5 mmol), THF (2 mL). Yields were determined via 1H-NMR using 1,1,2,2-tetrachloroethane as The scopeThe scopeof the of alkynes the alkynes 1 is shown 1 is shown in Table in Table2. Sterically 2. Sterically hindered hindered aliphatic aliphatic alkynes alkynes 1b and 1b 1c and 1c anThe internal scopeThe standard; scope of the of alkynes b theEt2O alkynes was 1 isused shown 1 insteadis shown in Tableof THF.in Table 2. Sterically 2. Sterically hindered hindered aliphatic aliphatic alkynes alkynes 1b and 1b 1c and 1c (R The= (Rprimary scope = primary ofalkyl the alkynesalkylgroup) group) 1that is shown werethat inwereslightly Table slightly 2.larger Sterically larger than hindered than1a resulted 1a aliphaticresulted in lower alkynesin lower yields 1b yieldsand of 1cthe of the (R The= (Rprimary scope= primary of alkyl the alkynes alkylgroup) group)1 isthat shown werethat in were Tableslightly 2slightly. Sterically larger larger than hindered than1a resulted aliphatic1a resulted in alkynes lower in 1blower yieldsand yields1c of(R the = of the (Rcorresponding = primarycorresponding alkyl alkenyl group)alkenyl iodides thatiodides 4ba were and 4ba 4caslightly and, respectively 4ca ,larger respectively than(Entries 1a(Entries 1resulted and 12). and Cyclohexylacetylenein 2). lower Cyclohexylacetylene yields of 1dthe (R 1d (R primarycorrespondingThecorresponding alkylscope group) of alkenyl the thatalkynesalkenyl iodides were iodides1 slightlyis4ba shown and 4balarger 4ca inand ,Table respectively 4ca than, 2.respectively1a Stericallyresulted (Entries hindered(Entries in lower1 and 1 2). yieldsaliphatic and Cyclohexylacetylene 2). of Cyclohexylacetylene thealkynes corresponding 1b and 1d 1c (R 1d (R corresponding= secondary= secondary alkyl alkenyl group)alkyl iodides group) gave 4ba agave moderate and a moderate4ca, yieldrespectively (Entryyield (Entry 3),(Entries and 3), the 1and and allylindation the 2). allylindation Cyclohexylacetylene of tert of-butylacetylene tert-butylacetylene 1d (R (Ralkenyl= secondary= primary= iodidessecondary alkyl alkyl4ba alkylgroup) andgroup) group)4ca gave, respectivelythat agave moderate were a moderate slightly (Entries yield yield(Entrylarger 1 and (Entry 3), 2).than and Cyclohexylacetylene 3), 1athe and resultedallylindation the allylindation in lower of1d tert(R of-butylacetyleneyields =tert secondary-butylacetylene of the = 1esecondary did1e not did alkylproceed not group) proceed due gave todue large a moderateto largesteric steric hindranceyield hindrance(Entry (E 3),ntry and (E 4).ntry the These allylindation4). These results results showed of tert showed-butylacetylene that thethat steric the steric correspondingalkyl1e did group)1e not did gaveproceed not alkenyl aproceed moderate due iodides todue large yield4ba to andlargesteric (Entry 4ca sterichindrance, 3),respectively and hindrance the (E allylindationntry (Entries (E 4).ntry These 1 4).and of These tert2).results Cyclohexylacetylene-butylacetylene results showed showed that1e thethatdid 1d steric not the(R steric 1ehindrance did hindrancenot proceedon an onalkyne andue alkyne disturbsto large disturbs thesteric allylindation. thehindrance allylindation. (EThisntry allylindation This 4). allylindationThese results system system showed tolerated tolerated that functionalities the functionalities steric =proceed hindrancesecondaryhindrance due onalkyl to an large on group)alkyne an steric alkyne gavedisturbs hindrance adisturbs moderate the allylindation. (Entry the yield allylindation. 4). (Entry These This 3), results allylindation Thisand theallylindation showed allylindation system that system the tolerated of steric tert tolerated-butylacetylene hindrancefunctionalities functionalities on hindrancesuch assuch Ph on asand an Ph alkynealkyl and chloridealkyl disturbs chloride moieties the allylindation. moieties (Entries (Entries 5 Thisand 5allylindation6). and Aromatic 6). Aromatic alkynesystem alkyne 1htolerated was 1h also was functionalities applicable also applicable to to 1eansuch did alkyne assuchnot Phdisturbs proceed asand Ph alkyl andthe due alkylchloride allylindation. to chloridelarge moieties steric moieties This hindrance(Entries allylindation (Entries 5 and(Entry 5 6). and system Aromatic4). 6). These Aromatic tolerated alkyneresults functionalitiesalkyne 1hshowed was 1h also wasthat applicable suchalso the applicable assteric Ph to to suchthe presentasthe Ph presentand allylindation. alkyl allylindation. chloride In thismoieties In case, this (Entriesthecase, addition the 5 additionand of 6). Me Aromatic of2Si(OMe) Me2Si(OMe) alkyne2 effectively2 effectively1h was increased also increased applicable the yield the to yieldof of hindranceandthe alkylpresentthe chlorideonpresent allylindation.an alkyne allylindation. moieties disturbs In (Entries this Inthe case, this 5allylindation. and thecase, 6). addition the Aromatic addition This of Meallylindation alkyne of2Si(OMe) Me1h2Si(OMe)was2 systemeffectively also2 effectively applicable tolerated increased increasedfunctionalities to the the present yield the yieldof of thethe present desiredthe desired allylindation. alkenyl alkenyl iodide In iodide this4ha case,(Entries 4ha the(Entries 7addition and 7 8), and probablyof 8),Me probably2Si(OMe) because 2because effectively the MeO the increasedMeOgroup group of Methe of2 yieldSi(OMe) Me2 Si(OMe)of 2 2 suchallylindation.the asdesiredthe Ph desiredand alkenyl In alkyl this alkenyl case,chlorideiodide theiodide 4ha additionmoieties (Entries 4ha (Entries of(Entries 7 Me and2Si(OMe) 7 58), and and probably 8), 6).2 effectively probablyAromatic because because increasedalkyne the MeO 1hthethe was MeOgroup yield also group of ofapplicable Me the of2Si(OMe) desired Me2 Si(OMe)to 2 2 thecoordinated desiredcoordinated alkenyl to an toiodideindium an indium 4ha atom (Entries atomof the 7of andproduced the 8), produced probably 1,4-dienylindium 1,4-dienylindium because the 3 MeO to stabilize3 group to stabilize of3, Meand 23,Si(OMe) toand avoid to2 avoid thealkenylcoordinated presentcoordinated iodide allylindation. to4ha an(Entries toindium an Inindium 7 this andatom case, 8), atomof probably the of additionproduced the because produced of 1,4-dienylindium theMe2 MeOSi(OMe)1,4-dienylindium group2 effectively of 3 Me to2 Si(OMe)stabilize3 increasedto stabilize2 3,coordinated andthe 3, yield toand avoid of to avoid coordinatedprotonationprotonation to of an3 by indiumof alkyne 3 by alkyneatom 1h. of1h .the produced 1,4-dienylindium 3 to stabilize 3, and to avoid theanprotonation indiumdesiredprotonation atomalkenyl of 3 of by of theiodide alkyne 3 producedby alkyne4ha 1h . (Entries 1,4-dienylindium1h. 7 and 8), probably3 to stabilize because3, andthe MeO to avoid group protonation of Me2Si(OMe) of 3 by2 protonation of 3 by alkyne 1h. coordinatedalkyne 1h. to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid Table Table2. Scope 2. Scopeand limitation and limitation of alkyne of alkyne 1 in allylindation 1 in allylindation a. a. protonation of 3 by alkyneTable 1h. Table2. Scope 2. Scopeand limitation and limitation of alkyne of alkyne 1 in allylindation 1 in allylindation a. a. Table 2. Scope and limitation of alkyne 1 in allylindation a. Table 2. Scope and limitation of alkyne 1 in allylindation a. Table 2. Scope and limitation of alkyne 1 in allylindation a.

EntryEntry AlkyneAlkyne 1 1 Product Product 4 4 Yield/% Yield/% EntryEntry Entry AlkyneAlkyne Alkyne 1 11 Product Product Product 44 4 Yield/% Yield/% Yield/% Entry Alkyne 1 Product 4 Yield/% Entry Alkyne 1 Product 4 Yield/% 1 1 64 64 1 1 1 64 64 64 1 64 1b 1b 4ba 4ba 1b 1b 4ba 4ba 1 1b 4ba 64

1b 4ba 2 2 41 41 2 41 2 41 2 4ca 4ca 41 1c 1c 4ca 4ca 1c 1c 4ca 2 1c 41 4ca 1c

Molecules 2018, 23, x 3 of 14

Table 1. Optimization of reaction conditions for carboindation of alkyne 1a with allylic silane 2a a.

Entry InX3 Solvent Yield/% 1 InBr3 CH2Cl2 89 2 b InCl3 CH2Cl2 42 3 InF3 CH2Cl2 0 4 InI3 CH2Cl2 0 5 In(OTf)3 CH2Cl2 0 6 InBr3 toluene 0 7 InBr3 Et2O 0 8 InBr3 CH3CN 0 9 InBr3 THF 0

a InX3 (1 mmol), alkyne 1a (1 mmol), allylic silane 2a (2 mmol), solvent (1 mL), room temperature, 24

h. I2 (1.5 mmol), THF (2 mL). Yields were determined via 1H-NMR using 1,1,2,2-tetrachloroethane as

an internal standard; b Et2O was used instead of THF.

The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonationMolecules 2018, 23of, 3 1884 by alkyne 1h. 4 of 14

a Table 2. Scope and limitationTable 2. ofCont. alkyne 1 in allylindation . Molecules Molecules2018, 23, x2018 , 23, x 4 of 14 4 of 14 Molecules 2018, 23, x 4 of 14 Molecules 2018, 23, x 4 of 14 Molecules 2018, 23, x 4 of 14 MoleculesMolecules 2018, 23 2018, x , 23, x 4 of 14 4 of 14 MoleculesMolecules 2018, 23 2018, x , 23, x 4 of 14 4 of 14 MoleculesMolecules 2018, 23 2018, x , 23, x 4 of 14 4 of 14 MoleculesMolecules 2018, 23 2018, x , 23, x 4 of 14 4 of 14 3 3 40 40 Entry3 EntryAlkyne Alkyne 1 1 Product Product 4 4 Yield/% Yield/%40

3 40 3 1d 1d 4da 4da 40 3 3 1d 4da 40 40 3 3 40 40 3 3 4da 40 40 3 3 3 1d 1d 4da 40 40 40 1 1d 1d 4da 4da 64 1d 1d 4da 4da 1d 1d 4da 4da 4 4 1b1d 1d 4ba4da 4da 0 0 4 0 4 1e 1e 0 4 1e 4ea 4ea 0 4 4 4ea 0 0 4 4 0 0 4 4 4 1e 1e 4ea 0 0 0 4 4 1e 1e 4ea 4ea 0 0 2 1e 1e 4ea 41 1e 1e 4ea 4ea 5 5 1e 1e 4ca4ea 4ea 59 59 5 1c 4ea 4ea 59 1f 1f 4fa 4fa 5 5 1f 4fa 59 59 5 5 59 59 5 5 5 59 59 59 5 5 1f 1f 4fa 4fa 59 59 5 5 1f 1f 4fa 4fa 59 59 1f 1f 4fa 4fa 6 6 1f 1f 4fa 4fa 80 80 1f 1f 4fa 4fa 6 80 1g 1g 4ga 4ga 6 6 1g 4ga 80 80 6 6 6 80 80 80 6 6 4ga 80 80 6 6 1g 1g 4ga 80 80 6 6 1g 1g 4ga 4ga 80 80 7 7 1g 1g 4ga 4ga 65 65 7 1g 1g 4ga 4ga 65 1g 1g 4ga 4ga 7 7 7 65 65 65 7 7 65 65 7 7 b 65 b65 8 7 8 7 78 65 78 65 8 7 1h 1h 4ha 4ha 7865 b 7 1h 65 4ha b b a 8 8 78 78 b Alkynea 1 (1 mmol), allylic8 silane 2a1h (2 mmol), InBr3 (1 mmol),3 CH2Cl2 (1 mL).2 2Yields were determinedb 78 b a Alkyne 1 (18 mmol), allylic silane1h 2a (2 mmol), InBr (14ha mmol), CH Cl (1 mL). Yields78 were determined Alkyne 1 (1 mmol), allylic8 silane1h 2a (2 mmol), InBr3 (1 mmol), CH4ha2Cl 2 (1 mL). Yields wereb 78determined b 1 8 8 1h 4ha b 78 b 78 by H-NMRby 1 H-NMRusing 81,1,2,2-tetrachloroeth using 1,1,2,2-tetrachloroethane as anane internal as an internalstandard;4ha standard; Me2Si(OMe) b Me2Si(OMe)2 78(1 mmol) 2 (1b wasmmol) was a 1 8 1h 1h 4ha 4ha b b 78 b by Alkyne H-NMRa 1 (1 using mmol), 1,1,2,2-tetrachloroeth allylic silane1h 2a 1h(2 mmol),ane as InBran internal3 (1 mmol), standard; CH2 Cl2 (1 Me mL). 2Si(OMe) Yields 2were (1 mmol) determined was a a Alkyne8 1 (1 mmol),8 allylic silane 2a (2 mmol), InBr4ha3 (1 mmol),4ha CH2Cl2 (1 mL).78 Yields 78 were 1 determined added.Alkyne Alkyne added.a1 Alkyne(1 1 mmol),(1 mmol), 1 (1 allylic mmol), allylic silane allylicsilane2a1h(2 mmol),silane2a 1h(2 mmol), 2a InBr (23 mmol),(1 InBr mmol),3 (1 InBr CHmmol),4ha23 Cl(12 mmol),(1 CH4ha mL).2Cl YieldsCH2 (1 2mL).Cl were2 (1 Yields mL). determined Yields were bydetermined wereH-NMR determined aby 1H-NMRa using 1,1,2,2-tetrachloroethane as an internal standard; b Me2Si(OMe)2 (1 mmol) was added.a Alkyne Alkyne 11 (1 mmol), 1 (1 mmol), allylic allylicsilane silane2a (2 mmol), 2a (2 mmol), InBrb 3 (1 InBr mmol),3 (1 mmol), CH2Cl CH2 (1 2mL).Cl2 (1 Yieldsb mL).2 Yields were determined were2 determined using Alkyne1 1,1,2,2-tetrachloroethanebya 11 H-NMR(1 mmol), using allylic 1,1,2,2-tetrachloroeth as silane an internal 2a (2 mmol), standard; InBraneMe 3 as(12Si(OMe) mmol),an3 internal2 (1CH mmol)2 Clstandard;2 (1 wasb 2mL). added.2 2 bYields Me Si(OMe) were2 determined (1 mmol) was bya H-NMRbya Alkyne H-NMR using 1 (1 mmol),using1,1,2,2-tetrachloroeth 1,1,2,2-tetrachloroeth allylic silane 2aane (2 mmol),asane an asinternal InBr an internal(1 standard;mmol), standard; CH ClMe (1 Si(OMe) mL).Me2Si(OMe) Yields (1 mmol) were2 (1 mmol)determined was was added. Alkyne1 Alkyne 11 (1 mmol), 1 (1 mmol), allylic allylicsilane silane2a (2 mmol), 2a (2 mmol), InBr3 (1 InBr mmol),3 (1 mmol), CH2Cl CH2 (1b 2mL).Cl2 2(1 bYields mL). Yields were2 determined were determined by 1H-NMRbyadded. 1H-NMR using using1,1,2,2-tetrachloroeth 1,1,2,2-tetrachloroethane asane an asinternal an internal standard; standard; b Me Si(OMe)b Me2Si(OMe) (1 mmol)2 (1 mmol) was was Next,added.by we Next,H-NMR evaluatedadded.by weH-NMR using evaluated the using1,1,2,2-tetrachloroeth scope the1,1,2,2-tetrachloroeth of scope allylic of silanes allylicane as 2silanesane anin theasinternal an 2allylindation in internal thestandard; allylindation standard; of Mealkyne2 Si(OMe) ofMe 1halkyne2Si(OMe) in2 (1 the mmol)1h 2presence (1in mmol)the was presence was Next,added.by 1H-NMR weadded.by evaluated1H-NMR using using1,1,2,2-tetrachloroeth the scope 1,1,2,2-tetrachloroeth of allylicane silanes asane an 2 asinternalin anthe internal allylindation standard; standard; b Me of2 Si(OMe)alkyneb Me2Si(OMe) 1h2 (1 in mmol) the2 (1 presencemmol) was was of Me2Si(OMe)ofNext,added. Me2 weSi(OMe)added.2 (Table evaluated 2 3).(Table Allylindation the 3). scope Allylindation of allylic using silanes the using simplest2 thein the simplest allylic allylindation silane allylic 2b ofsilane effectively alkyne 2b 1heffectivelyin proceeded the presence proceeded to of to of Me2Next,added.Si(OMe) added.Next,we 2evaluated (Table we evaluated 3). theAllylindation scope the scope of allylic using of allylic silanes the silanessimplest 2 in the 2 in allylicallylindation the allylindationsilane 2b of effectivelyalkyne of alkyne 1h in proceeded the1h in presence the presenceto giveMe theSi(OMe)give desiredNext, the Next,we desired(Tableproduct evaluated we3 ).evaluatedproduct 4hb Allylindation the in scope48%4hb the inyieldscope ofusing 48% allylic (Entryof yield the allylic silanes simplest 1).(Entry silanes Allylic 2 in allylic1). the 2 silaneAllylic in allylindation silanethe 2c allylindationsilane bearing2b effectively 2c of bearing alkynea Ph of alkynegroupproceeded 1ha Phin at1hthegroup the in presence to the2- giveat presencethe 2- of2 Me2Si(OMe)2 2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give theNext, desired Next,we2 evaluated productwe evaluated2 the4hb scope in the 48% scope of yieldallylic of allylic(Entry silanes silanes 1). 2 inAllylic the 2 in allylindation silanethe allylindation 2c bearing of alkyne ofa alkynePh 1h group in 1hthe inat presence the presence2- of MeNext,of2Si(OMe) Me Next,weSi(OMe) evaluated2 (Tablewe evaluated (Table 3). the Allylindation scope3). the Allylindation scope of allylic ofusing allylic silanes usingthe silanes simplest 2 thein the simplest 2 in allylindationallylic the allylindationallylic silane silane of2b alkyne effectively of2b alkyne effectively 1h in proceeded 1hthe in presence proceeded the presence to to positionthe desiredposition alsoNext,of Me affordedNext, productwe 2alsoSi(OMe) evaluated affordedwe a 4hb highevaluated2 (Tablein yieldthe a 48% high scope3). (Entthe yield Allylindationyield scope ryof (Entry 2). allylic(Ent Allylindationsofry allylic 1).silanes 2). using Allylic Allylindations silanes 2 thein silane using the simplest 2 in allylindation2c prenylsilanethe usingbearing allylindationallylic prenylsilane a silaneof Ph 2d alkyne groupand of2b alkyne cinnamylsilane 2deffectively 1h at and thein 1hthe cinnamylsilane 2-position in presence proceeded the presence to positionofgive Me theofgive2Si(OMe) alsoMe desired the2 affordedSi(OMe) desired2 (Table product2 a (Table highproduct3). 4hbAllylindation yield 3). in 4hbAllylindation (Ent48% inry yield48% 2).using Allylindations yield(Entry using the (Entry simplest1). the Allylic simplest 1). using allylicAllylic silane prenylsilane allylic silane silane 2c bearingsilane 2b 2c effectively 2dbearing 2b aand effectivelyPh cinnamylsilane groupa proceededPh group at proceeded the at to2- the to2- 2e, alsowhichgiveof Me afforded2e the,giveof 2 Si(OMe)havewhich Medesired the2 aSi(OMe)a high desiredhave2substituent (Table product yield a2 (Table productsubstituent3). (Entry 4hbAllylindation at 3). in the2). 4hbAllylindation 48%Allylindations 3-position,at in yieldthe48% using 3-position, yield(Entry usingtheef usingfectively (Entry simplest1). the Allylicef prenylsilane simplestfectively1). occurred allylicAllylic silane allylic occurredsilane 2d silane 2ctoand bearing givesilane 2b 2c cinnamylsilane to effectivelybearingthe 2b givea correspondingPheffectively thegroupa Phproceeded corresponding2e group at, proceeded which the at 2-to the 2-to 2egivepositionof, Mewhich thegiveofposition2Si(OMe) Mealsodesired havethe2Si(OMe) afforded alsodesired2 a(Table product substituentafforded2 (Tablea product3). high 4hbAllylindation a yield3). high in at 4hbAllylindation 48% the(Entyield in yield3-position,ry48% (Entusing 2). yield(EntryAllylindationsry using 2).the (EntryAllylindations ef simplest1). fectivelythe Allylic simplest1). using allylicAllylic occurredsilane usingprenylsilaneallylic silane silane 2c prenylsilanebearing tosilane 2b 2cgive effectivelybearing 2d2b athe and Pheffectively 2d corresponding groupacinnamylsilane and Phproceeded groupcinnamylsilane at proceeded the at 2-to the 2-to iodinatedhavepositiongiveiodinated athe positiongive substituentskipped alsodesired the affordedskipped alsodienesdesired product at afforded the 4hd dienesaproduct 3-position,high 4hband a yield 4hdhigh 4hein 4hb 48%and (Entyield effectivelyin in 72% 4he yieldry48% (Ent 2). andin yieldAllylindationsry(Entry 72% occurred 39%2). andAllylindations(Entry yields,1). 39%Allylic to 1). give respectively yields,using Allylic silane the usingprenylsilane respectively corresponding silane 2c prenylsilane (Entriesbearing 2c bearing 2d (Entries 3a and iodinatedandPh 2d groupcinnamylsilanea4). and 3Ph and groupcinnamylsilane skippedat 4). the at 2- the 2- iodinatedposition2egive, which thepositiongive2e, alsodesiredskippedwhich thehave afforded alsodesired have productadienes affordedsubstituent aproducta high 4hd substituent4hb a yieldhighand in 4hbat 48%4he yield(Entthe in atin yieldry48%3-position, (Ent 72% the2). yieldryAllylindations(Entry 3-position,and 2). Allylindations39%(Entry ef1).fectively yields,Allylic 1).ef fectivelyusing Allylic respectively silaneoccurred using prenylsilane silane occurred2c prenylsilane bearing to 2c(Entries give bearing 2dto a and thegivePh 3 2d and groupcinnamylsilaneacorresponding and thePh 4). cinnamylsilanegroup correspondingat the at 2- the 2- dienes2eposition, which2eposition4hd, alsowhich andhave afforded also4he havea affordedinsubstituent 72% aa high substituent and a yield high 39% at (Entyieldthe yields, at ry3-position, (Entthe 2). respectively Allylindationsry3-position, 2). Allylindations effectively (Entries ef fectivelyusing occurred 3 using andprenylsilane occurred 4). prenylsilane to give 2dto andthegive 2d cinnamylsilanecorresponding andthe cinnamylsilanecorresponding 2eiodinatedposition, whichposition also skippedhave afforded also a affordeddienessubstituent a high 4hd a yield high and at (Entyield4hethe ryin3-position, (Ent 2).72% Allylindationsry and2). Allylindations 39%effectively yields, using respectivelyoccurred usingprenylsilane prenylsilane to (Entriesgive 2d andthe 2d3 cinnamylsilaneandcorresponding and 4). cinnamylsilane 2e, which2eiodinated, which have skipped havea substituent aTable dienessubstituent 3. Scope4hdat the and ofat 3-position,allylic 4hethe in3-position, silane 72% 2ef and infectively allylindation 39%effectively yields, occurred a .occurred respectively toa give to (Entriesgivethe correspondingthe 3 andcorresponding 4). iodinatediodinated2e, whichskipped skipped have dienes a dienes substituent4hd and Table4hd 4he and 3.at Scopein 4hethe 72% inof3-position, and allylic72% 39% and silane yields, 39%ef fectively2 in yields, allylindationrespectively respectivelyoccurreda (Entries. to (Entriesgive 3 and the 34). andcorresponding 4). iodinated2e, whichiodinated2e, whichskipped have skipped havea dienessubstituent a dienessubstituent 4hdTable and 4hd at3. Scope4hethe and at in3-position, 4heofthe 72% allylic in3-position, and 72% silane 39% efandfectively 2 yields, in39%ef allylindationfectively yields, respectivelyoccurred respectivelyoccurred a . to (Entriesgive to (Entriesthegive 3 andcorresponding the 3 4). andcorresponding 4). iodinatediodinated skipped skipped dienes dienes 4hdTable and 4hd 3. Scope4he and in of4he 72% allylic in and 72% silane 39% and2 yields,in 39% allylindation yields, respectively respectively.a (Entries (Entries 3 and 34). and 4). iodinated skipped dienes 4hdTable and 3. 4he Scope in of72% allylic and silane 39% yields,2 in allylindation respectively . (Entriesa 3 and 4). iodinated skipped dienes 4hdTable and 3. 4he Scope in of72% allylic and silane 39% yields,2 in allylindation respectivelya . (Entries 3 and 4). Table Table3. Scope 3. Scopeof allylic of allylicsilane silane2 in allylindation 2 in allylindation . a. Table Table3. Scope 3. Scopeof allylic of allylicsilane silane2 in allylindation 2 in allylindation a. a. Table Table3. Scope 3. Scopeof allylic of allylicsilane silane2 in allylindation 2 in allylindation a. a. Table Table3. Scope 3. Scopeof allylic of allylicsilane silane2 in allylindation 2 in allylindation a. a.

Entry Entry Allylic AllylicSilane 2Silane 2 Product Product 3 3 Yield/% Yield/% Entry Allylic Silane 2 Product 3 Yield/% Entry Allylic Silane 2 Product 3 Yield/%

EntryEntry Allylic Allylic Silane Silane 2 2 Product Product 3 3 Yield/% Yield/% EntryEntry Allylic Allylic Silane Silane 2 2 Product Product 3 3 Yield/% Yield/% EntryEntry Allylic Allylic Silane Silane 2 2 Product Product 3 3 Yield/% Yield/% 1 Entry1Entry 1 Allylic Allylic Silane Silane 2 2 Product Product 3 483 48 Yield/% Yield/%48 Entry1 Allylic2b Silane2b 2 Product 3 Yield/%48 Entry 2b Allylic Silane 2 Product 3 Yield/% 1 4hb4hb 4hb 48 1 4hb 48 1 1 2b 2b 48 48 1 1 2b 2b 4hb 48 48 1 1 2b 2b 4hb 48 48 1 1 2b 2b 4hb 4hb 48 48 2b 2b 4hb 4hb 2 2 4hb 76 76 2 4hb 4hb 76 2c 2c 2 2c 4hc 4hc 76 2 4hc 76 2 2 76 76 2 2 2c 2c 76 76 2 2 2c 2c 4hc 4hc 76 76 2 2 4hc 4hc 76 76 2c 2c 4hc 4hc 2c 4hc 4hc 2c 2c 4hc 4hc

Molecules Molecules2018, 23, x2018 , 23, x 4 of 14 4 of 14

3 3 40 40 Molecules 2018, 23, x 4 of 14 1d 1d 4da 4da

4 3 4 0 40 0

1e 1d 1e 4ea4da 4ea

5 5 59 59 4 0 1f 1f 4fa 4fa 1e 4ea

6 6 80 80 5 59 1g 1g 4ga 4ga 1f 4fa

7 7 65 65 6 80

8 8 1g 4ga 78 b 78 b 1h 1h 4ha 4ha

a a Alkyne 1Alkyne (1 mmol), 17 (1 allylic mmol), silane allylic 2a silane (2 mmol), 2a (2 InBr mmol),3 (1 mmol),InBr3 (1 CH mmol),2Cl2 (1 CH mL).2Cl 2Yields (1 mL). were Yields65 determined were determined by 1H-NMRby 1 H-NMRusing 1,1,2,2-tetrachloroeth using 1,1,2,2-tetrachloroethane as anane internal as an internalstandard; standard; b Me2Si(OMe) b Me2Si(OMe)2 (1 mmol)2 (1 wasmmol) was added. added.

8 78 b Next, weNext, evaluated we evaluated the scope the 1hof scope allylic of silanes allylic 2silanes in the 4ha 2allylindation in the allylindation of alkyne of 1halkyne in the 1h presence in the presence of Me2Si(OMe)ofa Alkyne Me2Si(OMe)2 1(Table (1 mmol),2 3).(Table Allylindationallylic 3). silane Allylindation 2a using(2 mmol), the using InBr simplest 3 the(1 mmol), simplest allylic CH silane 2allylicCl2 (1 mL).2b silane effectively Yields 2b wereeffectively proceeded determined proceeded to to give thegiveby desired 1 H-NMRthe desired product using product 1,1,2,2-tetrachloroeth4hb in 48%4hb inyield 48% (Entryane yield as 1).an(Entry Allylicinternal 1). Allylicsilanestandard; 2c silane bearingb Me 2c2Si(OMe) bearing a Ph 2 group(1 a mmol)Ph atgroup thewas 2- at the 2- positionpositionadded. also afforded also afforded a high yield a high (Ent yieldry 2). (Ent Allylindationsry 2). Allylindations using prenylsilane using prenylsilane 2d and cinnamylsilane2d and cinnamylsilane 2e, which2e, havewhich a havesubstituent a substituent at the 3-position,at the 3-position, effectively effectively occurred occurred to give to the give corresponding the corresponding iodinatediodinatedNext, skipped we evaluatedskipped dienes 4hddienes the and scope 4hd 4he andof in allylic 72% 4he andin silanes 72% 39% and 2 yields, in 39%the allylindation respectivelyyields, respectively (Entriesof alkyne (Entries 3 and1h in 4). the3 and presence 4). of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired productTable 4hb 3.in TableScope 48% 3.yieldof Scope allylic (Entry of silane allylic 1). 2 insilaneAllylic allylindation 2 insilane allylindation a2c. bearing a. a Ph group at the 2- position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding Moleculesiodinated2018 skipped, 23, 1884 dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). 5 of 14

Table 3. Scope of allylic silane 2 in allylindation a. Table 3. Cont. Entry Entry Allylic AllylicSilane 2Silane 2 Product Product 3 3 Yield/% Yield/%

1 1 48 48 2b 2b 4hb 4hb Entry Entry Allylic Allylic Silane Silane 2 2 Product Product 3 3 Yield/% Yield/%

MoleculesMolecules 2018, 23, x2018 , 23, x 5 of 14 5 of 14 MoleculesMolecules 2018, 23,2 x2018 , 23,2 x 2 76 76 76 5 of 14 5 of 14

1 2c 2c 48 2b 2c 4hc 4hc Molecules 2018, 23, x 4hb 5 of 14 3 3 72 72

3 3 3 2d 2d 72 72 72 4hd 4hd 2 2d 2d 76 3 4hd 4hd 72 2c2d 4hc 4hd 4 4 4 39 39 39 2e 4 4 2e 39 39 2e 2e 4 4he 4he 39 2e 4he 4he a a a AlkyneAlkyne 1aAlkyne 1a(1 (1mmol), mmol), 1a (1 allylicmmol), allylic silane silane allylic2 2(2 (2silane mmol), mmol), 2 (2 InBr InBrmmol),3 (13 mmol),(1 mmol),InBr Me3 (12 MeSi(OMe)mmol),4he2Si(OMe) 2 Me(1 mmol),2Si(OMe)2 (1 mmol), and2 (1 CH andmmol),2Cl 2CH(1 mL). 2andCl2 Yields(1CH 2Cl2 (1 a a 1 mL). Alkynewere YieldsmL). determined 1aAlkyne were(1 Yields mmol), 1adetermined by were(1 allylicH-NMRmmol), determined silane by usingallylic 1H-NMR 2 1,1,2,2-tetrachloroethane (2silane by mmol), 1H-NMR using 2 (2 InBrmmol), 1,1,2,2-tetrachloroeth using3 (1 mmol),InBr 1,1,2,2-tetrachloroeth as3 an(1 internalMemmol),2Si(OMe)anestandard. Me as2Si(OMe)2 an(1ane mmol),internal as2 an(1 and mmol),internalstandard. CH 2and Clstandard. 2 (1CH 2Cl 2 (1 a mL). YieldsmL). Alkyne were Yields 1a determined (1 were mmol), determined allylic by 1H-NMR silane by 2 1(2H-NMR using mmol), 1,1,2,2-tetrachloroeth usingInBr3 (1 1,1,2,2-tetrachloroeth mmol), Me2Si(OMe)ane as 2an (1ane mmol),internal as an and internalstandard. CH2Cl standard.2 (1 mL). Yields were determined by 1H-NMR using 1,1,2,2-tetrachloroethane as an internal standard. TheThe 1,4-dienylindiumThe 1,4-dienylindium 1,4-dienylindium 3 synthesized3 synthesized 3 synthesized by the by thepresent by presentthe present allylindation allylindation allylindation were were isolated were isolated isolated and and characterized and characterized characterized The 1,4-dienylindiumThe 1,4-dienylindium 3 synthesized 3 synthesized by the present by the present allylindation allylindation were isolated were isolated and characterized and characterized (Figure(Figure (Figure1).1 After).The After 1). 1,4-dienylindiumthe After the allylindation allylindation the allylindation 3 synthesizedof ofalkyne alkyne of alkyne1h by 1husing theusing present1h InBr using InBr3 allylindation and 3InBrand methallylsilane3 and methallylsilane weremethallylsilane isolated 2a, 2aandthe, the characterizedvolatiles2a, volatilesthe volatiles were were were (Figure (Figure1). After 1). the After allylindation the allylindation of alkyne of 1halkyne using 1h InBr using3 and InBr methallylsilane3 and methallylsilane 2a, the volatiles2a, the volatiles were were evaporatedevaporatedevaporated(Figure and 1). and the After and residual the thethe residual allylindation residual oil was oil oilwashed was ofwas alkyne washed washed with 1h hexanewithusing with hexaneInBr hexaneto 3obtain and to tomethallylsilane obtain theobtain desired the the desireddesired 1,4-dienylindium 2a, the 1,4-dienylindiumvolatiles1,4-dienylindium were 3ha 3ha asevaporated a3ha whiteasevaporatedevaporated a solid whiteand (Figure the solid and and residual the(Figure 1A).the residual residual Theoil 11A). A).was 1,4-dienylindium oil The The oil washedwas was 1,4-dienylindium washed washed with with hexane 3ha with hexane was hexaneto3ha3ha characterized toobtain wasobtainwas to characterized characterizedtheobtain the desired desired by the NMR desired 1,4-dienylindium by by spectroscopy. NMR NMR 1,4-dienylindium spectroscopy. spectroscopy. 3ha The3ha The3ha as a whiteas asolid white (Figure solid (Figure1A). The 1A).1 1,4-dienylindium The1 1,4-dienylindium1 3ha was 3ha characterized was characterized by NMR by spectroscopy. NMR spectroscopy. The The resonanceTheresonance as aof white a vinylic solidof of a a vinylicproton(Figure vinylic proton(H1A). proton) Theat the(H 1,4-dienylindium (H )α at)-position at the the α-positionα -positionof the3ha InBrwas of ofthe 2characterized group the InBr InBr2 appeared group2 group by appearedNMR at appeared δ spectroscopy. 5.99 at ppm δ at 5.99δ (Figure5.99 Theppm ppm (Figure 1 1 1B).resonance(Figure The1B).resonanceresonance 13 1ofC-NMR B).The a vinylic The 13 ofofC-NMR spectruma 13a vinylic C-NMRvinylicproton spectrum proton (Hprotonof spectrum )3ha at (H the (H1ofshowed) at α3ha) the ofat-position the3haαshowed -positiona αslightlyshowed-position of a theof slightly thebroad aInBr of slightlyInBr the2 group 2signalbroad groupInBr broad 2appeared groupforappearedsignal signalC1 appearedatfor atδ for Cδ134.1 15.995.99 Cat 1 atppm δppmatppm. δ134.1 δ5.99 (Figure134.1 (Figure These ppmppm. ppm. (Figure These 13 1313 11 1 chemical1B).These Thechemical1B).1B). chemicalshiftC-NMR The values shiftC-NMRC-NMR shiftspectrum valuesare values spectrum similarspectrum areof are 3ha similarto similarof thoseofshowed3ha 3ha toshowed toof thoseshowedthose pra eviouslyslightly aof ofslightly pra previously eviouslyslightly broad reported broad signalbroad reportedsignal reported alkenylindium for signalfor Calkenylindium C atatfor δ C 134.1134.1generated at ppm.δppm. 134.1 generated These byThese ppm. the by These the chemicalchemicalchemical shift values shiftshift valuesarevalues similar are are similar similarto those to thoseto of those pr ofeviously pr ofeviously previously reported reported reported alkenylindium alkenylindium alkenylindium generatedgenerated generated by by the the by the carboindationthe carboindationcarboindation of alkyne ofof alkyne alkyne1h with1h 1h InBrwith with3 InBrand InBr 3aand3 silyland a silylketenea silyl ketene keteneacetal acetal [41].acetal [ 41A ].[41].nuclear A nuclear A nuclear Overhauser Overhauser Overhauser effect effect effect carboindation of alkyne 1h with InBr3 and a silyl ketene acetal [41]. A nuclear Overhauser effect betweencarboindationbetweenbetweencarboindation H1 Hand1 ofand HH alkyne13 Handwas3 ofwas H observed, alkyne1h3 was observed, with observed, 1h InBrwhich with which3 and InBrshowedwhich showeda3 silyland showed that ketene thata silylantianti that-allylindation keteneacetal-allylindation anti -allylindation [41].acetal A proceeded [41].nuclear proceeded A proceeded nuclear Overhauser stereoselectively stereoselectively Overhauser stereoselectively effect toeffect between H1 and H3 was observed, which showed that anti-allylindation proceeded stereoselectively between H1 and H13 was observed,3 which showed that anti-allylindation proceeded stereoselectively to givegive to1,4-dienylindiumbetween 1,4-dienylindium give 1,4-dienylindium H and H with with was a a observed, transtranswith-configuration -conﬁgurationa trans which-configuration showed between between that between the the anti InBr InBr-allylindation the2 andand InBr allylic allylic2 and proceeded groups. groups.allylic groups. stereoselectively to give 1,4-dienylindium with a trans-configuration between the InBr22 and allylic groups. to give to1,4-dienylindium give 1,4-dienylindium with a transwith-configuration a trans-configuration between between the InBr the2 and InBr allylic2 and groups. allylic groups.

PPM 8 7 6 5 4 3 2 1 0PPM PPM PPM PPM 8 87 76 65 54 43 32 21 10 0 FigureFigure 1. Isolation 1. Isolation and characterizationand characterization of 1,4-dienylindium of 1,4-dienylindium synthesized synthesized by allylindation. by allylindation. (A) Isolation(A) 8 87 76 65 54 43 32 21 10 0 of 1,4-dienylindiumIsolation of 1,4-dienylindium3ha.(B) 1H-NMR 3ha. (B) spectrum 1H-NMR spectrum of 3ha. of 3ha. Figure 1.Figure Isolation 1. Isolation and characterization and characterization of 1,4-dien of ylindium1,4-dienylindium synthesized synthesized by allylindation. by allylindation. (A) (A) IsolationFigure Isolation1.FigureA of plausibleIsolation 1,4-dienylindium 1. of Isolation 1,4-dienylindiumreactionand characterization mechanism and3ha . (characterizationB) 3ha1H-NMR is. (illustratedBof) 1H-NMR1,4-dien spectrum of in ylindium1,4-dien Schemespectrum of 3haylindium 2.. synthesizedofA carbon-carbon3ha. synthesized by allylindation.triple by bond allylindation. of alkyne(A) (A) Isolation1 coordinatesIsolation of 1,4-dienylindium ofto 1,4-dienylindium InBr3, and 3ha then. (B) 3ha1H-NMRthe . positive(B) 1H-NMR spectrum charge spectrum ofon 3ha the. ofinternal 3ha. carbon atom of alkyne 1 is A plausibleincreased.A plausible reaction Allylic reactionsilane mechanism 2 adds mechanism to is the illustrated internal is illustrated carbon in Scheme atom in Scheme 2.from A carbon-carbon the 2. opposite A carbon-carbon side triple of InBr bond triple3 to giveof bond alkyne 1,4- of alkyne A plausible reaction mechanism is illustrated in Scheme 2. A2 carbon-carbon triple bond of alkyne 1 coordinates1dienylindium coordinatesA plausibleto InBr 3to3. ,The reactionandInBr iodination then3, and mechanism the then of positive 1,4-dienylindium the is positive illustrated charge charge on3 inwith the Scheme Ioninternal proceeds the 2. Ainternal carbon carbon-carbonwith retention carbonatom of of atomtriple thealkyne double bondof alkyne1 ofis alkyne 1 is 1 coordinatesbond configuration to InBr3, and of 3then 3to yield the alkenyl positive iodide charge 4 as aon single the isomer. internal carbon atom of alkyne 1 is increased.increased.1 coordinates Allylic silaneAllylic to 2 silaneInBr adds, to2and adds the then internal to the the internal carbonpositive carbonatom charge from atom on the fromthe opposite internal the opposite side carbon of InBrside atom 3of to InBr give of 3 alkyne1,4-to give 1,4-1 is increased. Allylic silane 2 adds to the internal carbon atom from the opposite side of InBr3 to give3 1,4- dienylindiumdienylindiumincreased. 3. The Allylic iodination3. The silane iodination 2 of adds 1,4-dienylindium to of the 1,4-dienylindium internal 3carbon with I3atom2 withproceeds from I2 proceeds thewith opposite retention with sideretention of ofthe InBr double of theto give double 1,4- bonddienylindium configurationbonddienylindium configuration 3. The of iodination3 3. toThe yieldof iodination 3 to alkenylof yield 1,4-dienylindium alkenyl ofiodide 1,4-dienylindium 4iodide as a 3single 4with as a isomer. I3single2 withproceeds isomer. I2 proceeds with retention with retention of the double of the double bond configurationbond configuration of 3 to yieldof 3 to alkenyl yield alkenyl iodide 4iodide as a single 4 as a isomer. single isomer.

Molecules 2018, 23, 1884 6 of 14

A plausible reaction mechanism is illustrated in Scheme2. A carbon-carbon triple bond of alkyne 1 coordinates to InBr3, and then the positive charge on the internal carbon atom of alkyne 1 is increased. Allylic silane 2 adds to the internal carbon atom from the opposite side of InBr3 to give 1,4-dienylindium 3. The iodination of 1,4-dienylindium 3 with I2 proceeds with retention of the double bond conﬁguration of 3 to yield alkenyl iodide 4 as a single isomer. Molecules 2018, 23, x 6 of 14 Molecules 2018, 23, x 6 of 14

SchemeScheme 2.2. Plausible reaction mechanism. Scheme 2. Plausible reaction mechanism. Finally, we applied the synthesized 1,4-dienylindium to Pd-catalyzed cross coupling [40,45,46]. Finally, we applied the synthesized 1,4-dienylindium to Pd-catalyzed cross coupling [40,45,46]. AfterFinally, 1,4-dienylindium we applied 3hathe wassynthesized produced 1,4-dienylindium via the allylindation to Pd-catalyzed of alkyne 1h cross with coupling allyl silane [40,45,46]. 2a and After 1,4-dienylindium 3ha was produced via the allylindation of alkyne 1h with allyl silane 2a and AfterInBr3 ,1,4-dienylindium iodobenzene, a catalytic 3ha was amount produced of Pd(PPh via the3 )allylindation4, and DMF were of alkyne added 1h to with the reaction allyl silane mixture 2a and in InBr , iodobenzene, a catalytic amount of Pd(PPh ) , and DMF were added to the reaction mixture InBra one-pot3, iodobenzene, manner. aThen, catalytic the amountPd-catalyzed of Pd(PPh coupling3)34, 4and reaction DMF were of 3ha added with to iodobenzenethe reaction mixture smoothly in in a one-pot manner. Then, the Pd-catalyzed coupling reaction of 3ha with iodobenzene smoothly aproceeded one-pot manner. at 100 °C Then, to give the the Pd-catalyzed desired skipped coupling diene 5reaction as a single of isomer.3ha with It shouldiodobenzene be noted smoothly that the proceeded at 100 ◦C to give the desired skipped diene 5 as a single isomer. It should be noted that the proceededcoupling product at 100 °C 5 towas give stereoselectively the desired skipped obtained diene with 5 as retention a single isomer. of the double It should bond be notedconfiguration that the coupling product 5 was stereoselectively obtained with retention of the double bond conﬁguration of couplingof the alkenylind productium 5 was (Scheme stereoselectively 3). obtained with retention of the double bond configuration ofthe the alkenylindium alkenylindium (Scheme (Scheme3). 3).

Scheme 3. Pd-catalyzed cross-coupling of alkenylindium with iodobenzene. Scheme 3. Pd-catalyzed cross-coupling of alkenylindium with iodobenzene. Scheme 3. Pd-catalyzed cross-coupling of alkenylindium with iodobenzene. 3. Materials and Methods 3. Materials and Methods 3. Materials and Methods 3.1. Analysis 3.1. Analysis NMR spectra were recorded on a JEOL JNM-400 (400 MHz for 1H-NMR and 100 MHz for 13C- 1 13 NMR)NMR spectrometer spectra spectra were were (JEOL recorded recorded Ltd., Tokyo, on on a aJEOL Japan). JEOL JNM-400 JNM-400 Chemical (400 (400 shifts MHz MHz were for for H-NMRreported1H-NMR andin ppm and100 100onMHz the MHz for δ scale forC- NMR) spectrometer (JEOL Ltd., Tokyo,1 Japan). Chemical shifts were reported in ppm13 on the δ scale 13relativeC-NMR) to tetramethylsilane spectrometer (JEOL (δ = Ltd., 0 for Tokyo, H-NMR) Japan). with Chemical the residual shifts CHCl were3 (δ reported = 77.0 for in C-NMR) ppm on theusedδ 1 13 relative to tetramethylsilane1 (δ = 0 13for H-NMR)1 with the residual CHCl3 (δ = 77.0 for C-NMR)13 used scaleas an relative internal to reference. tetramethylsilane H and (δC-NMR= 0 for H-NMR)signals of with all new the residual compounds CHCl were3 (δ = assigned 77.0 for byC-NMR) using 1 13 asusedHMQC, an asinternal an HMBC, internal reference. COSY, reference. and H and131HC andoff-resonanceC-NMR13C-NMR signals techniques. signals of all of allnew Infrared new compounds compounds (IR) spectra were were were assigned assigned recorded by by using on a 13 HMQC,JASCO FT/IR-6200HMBC, COSY, Fourier and transform 13C off-resonance infrared techniques. spectrophotometer Infrared Infrared (JASCO (IR) (IR) spectra spectra Co., Tokyo,were were recorded Japan). Silicaon a JASCOgel column FT/IR-6200 chromatography Fourier Fourier transform transform was performed infrared infrared using spec spectrophotometer antrophotometer automated flas (JASCO (JASCOh chromatography Co., Co., Tokyo, Tokyo, Japan). system Silica from gelthe columnYamazen chromatography Co. (W-Prep 2XY)was pe performed(Yamazenrformed using Co., anOsaka, automated Japan). flas ﬂash Gelh chromatography permeation chromatography system from the(GPC) YamazenYamazen was performed Co. Co. (W-Prep (W-Prep using 2XY) 2XY)a NEXT (Yamazen (Yamazen recycling Co., Co., Osaka,preparative Osaka, Japan). Japan). HPLC Gel permeationfromGel permeationthe Japan chromatography Analytical chromatography Industry (GPC) (GPC) was performed using a NEXT recycling preparative HPLC from the Japan Analytical Industry wasCo. (Tokyo, performed Japan) using (solvent: a NEXT CHCl recycling3; column: preparative JAIGEL-1HH HPLC and from JAIGEL-2HH). the Japan Analytical Reactions Industrywere carried Co. Co. (Tokyo, Japan) (solvent: CHCl3; column: JAIGEL-1HH and JAIGEL-2HH). Reactions were carried (Tokyo,out in dry Japan) solvents (solvent: under CHCl a nitrogen3; column: atmosphere, JAIGEL-1HH unless and otherwise JAIGEL-2HH). stated. ReactionsAll allylic weresilanes carried were outprepared in dry by solvents reported under methods. a nitrogennitrogen Other atmosphere,atmosphere, reagents we unlessreunless purchased otherwiseotherwise from stated.stated. Sigma-Aldrich All allylic Co. silanes (St. Louis, were preparedMO, USA), by the reported Tokyo methods. Chemical Other Industry reagents Co., we wereLtd.re (TCI) purchased (Tokyo, from Japan) Sigma-Aldrich or Wako PureCo. (St. Chemical Louis, Louis, MO,Industries, USA), Ltd.the (Osaka, Tokyo ChemicalChemical Japan), and Industry used after Co., purifica Ltd. (TCI) (TCI)tion by (Tokyo, (Tokyo, distillation Japan) Japan) or usedor or Wako without Pure purification Chemical Industries,for solid substrates. Ltd. (Osaka, Japan), and used after purification by distillation or used without purification for solid substrates. 3.2. Typical Procedure 3.2. Typical Procedure Alkyne 1 (1 mmol) was added to a solution of InBr3 (1 mmol) and allylic silane 2 (2 mmol) in 3 dichloromethaneAlkyne 1 (1 mmol) (1 mL). was The addedmixture to was a solution stirred ofat roomInBr temperature(1 mmol) and for allylic 24 h, silaneand then 2 (2 0.75 mmol) M I2 inin dichloromethaneTHF solution (2 mL) (1 mL). was Theadded mixture at −78 was °C. Thestirred resultant at room mixture temperature was stirred for 24 at h, − and78 °C then for 300.75 min. M I The2 in THFmixture solution was quenched(2 mL) was by added saturated at −78 Na °C.2S2 TheO3 aq resultant (10 mL), mixture and then was extracted stirred atwith −78 dichloromethane °C for 30 min. The (3 2 2 3 mixture× 10 mL). was The quenched collected by organic saturated layers Na S wereO aq dried (10 mL), over and MgSO then4 ,extracted and concentrated with dichloromethane under reduced (3 ×pressure. 10 mL). The collectedyield was organic determined layers bywere 1H-NMR dried overusing MgSO 1,1,2,2-tetrachloroethane4, and concentrated underas an reducedinternal pressure. The yield was determined by 1H-NMR using 1,1,2,2-tetrachloroethane as an internal

Molecules 2018, 23, 1884 7 of 14

Industries, Ltd. (Osaka, Japan), and used after puriﬁcation by distillation or used without puriﬁcation for solid substrates.

3.2. Typical Procedure

Alkyne 1 (1 mmol) was added to a solution of InBr3 (1 mmol) and allylic silane 2 (2 mmol) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h, and then 0.75 M I2 in THF solution (2 mL) was added at −78 ◦C. The resultant mixture was stirred at −78 ◦C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL), and then extracted with dichloromethane (3Molecules× 10 mL).2018, 23 The, x collected organic layers were dried over MgSO , and concentrated under reduced7 of 14 Molecules 2018, 23, x 4 7 of 14 pressure. The yield was determined by 1H-NMR using 1,1,2,2-tetrachloroethane as an internal standard. Thestandard. crude The product crude was product puriﬁed was by purified ﬂash chromatography by flash chromatography (spherical (spherical silica gel 60silicaµm, gel 30 60 g, μ diameterm, 30 g, diameter2.7 cm) and 2.7 GPC cm) and to give GPC the to product. give the product. (E)-4-(Iodomethylene)-2-methyldodec-1-ene(E)-4-(Iodomethylene)-2-methyldodec-1-ene ((4aa4aa))

The alkyne 1-decyne (0.980 mmol, 0.1354 g) was added to a solution of InBr3 (0.996 mmol, 0.3530 The alkyne 1-decyne1-decyne (0.980(0.980 mmol,mmol, 0.1354 0.1354 g) g) was was added added to to a a solution solution of of InBr InBr(0.9963 (0.996 mmol, mmol, 0.3530 0.3530 g) g) and methallyl trimethylsilane (2.07 mmol, 0.2654 g) in dichloromethane (1 3mL). The mixture was g)and and methallyl methallyl trimethylsilane trimethylsilane (2.07 (2.07 mmol, mmol, 0.2654 0.2654 g) g) in in dichloromethane dichloromethane (1(1 mL).mL). TheThe mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF stirred at room temperature for 24 h. The reaction mixture was cooled to −78− °C, and◦ 0.75 M I2 in THF stirredsolution at (2 room mL) temperaturewas added. The for resultant 24 h. The mixture reaction was mixture stirred was at − cooled78 °C for to 3078 min.C, The and mixture 0.75 M Iwas2 in THFsolution solution (2 mL) (2 was mL) added. was added. The resultant The resultant mixture mixture was wasstirred stirred at −78 at °C−78 for◦C 30 for min. 30 min.The mixture The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane mL). The collected organic layer was dried over MgSO4. The solvent was evaporated, and the residue mL).× The collected organic layer was dried over MgSO4. The solvent was evaporated, and the residue (was3 purified10 mL). Theby column collected chromatography organic layer was (hexane, dried over column MgSO length4. The 10 solvent cm, diameter was evaporated, 26 mm silica and gel) the wasresidue purified was puriﬁed by column by column chromatography chromatography (hexane, (hexane, column column length length 10 cm, 10 diameter cm, diameter 26 mm 26 silica mm silica gel) and GPC (CHCl3) to give the product (0.279 g, 89%). and GPC (CHCl3) to give the product (0.279 g, 89%). gel) and GPC (CHCl3) to give the product (0.279 g, 89%). IR: (neat) 1650, 1457 cm−1; 1H-NMR: (400 MHz, CDCl3) 5.92 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 (s, IR: (neat) 1650, 1457 cm−−11; 11H-NMR: (400 MHz, CDCl3) 5.92 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 (s, IR: (neat) 1650, 1457 cm ; H-NMR: (400 MHz, CDCl3) 5.92 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 (s, 1H, 1-H), 2.87 (s, 2H, 3-H2), 2.16 (t, J = 7.8 Hz, 2H, 5-H), 1.65 (s, 3H, 2-Me), 1.43–1.23 (m, 14H), 0.88 (t, 1H, 1-H), 2.87 (s, 2H, 3-H2), 2.16 (t, J = 7.8 Hz, 2H, 5-H), 1.65 (s, 3H, 2-Me), 1.43–1.23 (m, 14H), 0.88 (t, 1H, 1-H), 2.87 (s,13 2H, 3-H2), 2.16 (t, J = 7.8 Hz, 2H, 5-H), 1.65 (s, 3H, 2-Me), 1.43–1.23 (m, 14H), 0.88 (t, J = 6.8 Hz, 3H); 13C-NMR: (100 MHz, CDCl3) 149.4 (s, C-4), 142.5 (s, C-2), 113.0 (t, C-1), 76.2 (d, 4-CHI), J = 6.8 Hz, 3H); 13C-NMR: (100 MHz, CDCl3) 149.4 (s, C-4), 142.5 (s, C-2), 113.0 (t, C-1), 76.2 (d, 4-CHI), 45.8= 6.8 (t, HzC-3),, 3H); 36.4 (t,C-NMR: C-5), 31.9 (100 (t), MHz, 29.43 CDCl (t), 29.383) 149.4 (t), (s,29.22 C-4), (t), 142.5 27.0 (s,(t), C-2), 22.7 113.0(t), 21.8 (t, (q, C-1), 2-Me), 76.2 (d,14.1 4-CHI), (q, C- 45.8 (t, C-3), C-3), 36.4 36.4 (t, (t, C-5), C-5), 31.9 31.9 (t), (t), 29.43 29.43 (t), (t), 29.38 29.38 (t), (t), 29.22 29.22 (t), (t), 27.0 27.0 (t), (t), 22.7 22.7 (t), (t), 21.8 21.8 (q, (q,2-Me), 2-Me), 14.1 14.1 (q, C- (q, 12); HRMS: (EI, 70 eV) Calculated (C14H25I) 320.1001 (M+), Found: 320.1000. 12); HRMS: (EI, 70 eV) Calculated (C14H25I) 320.1001 (M+), Found:+ 320.1000. C-12); HRMS: (EI, 70 eV) Calculated (C14H25I) 320.1001 (M ), Found: 320.1000. (E)-4-(Iodomethylene)-2,7-dimethyloct-1-ene (4ba) (E)-4-(Iodomethylene)-2,7-dimethyloct-1-ene(E)-4-(Iodomethylene)-2,7-dimethyloct-1-ene ((4ba4ba))

The alkyne 5-methylhex-1-yne (1.02 mmol, 0.0985 g) was added to a solution of InBr3 (0.983 The alkyne 5-methylhex-1-yne (1.02 mmol, 0.0985 g) was added to a solution of InBr3 (0.983 mmol,The 0.3485 alkyne g) 5-methylhex-1-yneand methallyl trimethylsilane (1.02 mmol, (1.94 0.0985 mmol, g) was 0.2487 added g) to in a dichloromethane solution of InBr3 (0.983 (1 mL). mmol, The mixture0.3485 g) was and stirred methallyl at room trimethylsilane temperature (1.94 for mmol, 24 h. 0.2487The reaction g) in dichloromethane mixture was cooled (1 mL). to The−78 mixture°C, and ◦ was0.75 stirredM I2 in atTHF room solution temperature (2 mL) for was 24 added. h. The reactionThe resultant mixture mixture was cooled was stirred to −78 at C,−78 and °C 0.75for 30 M min. I in 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min.2 ◦ THFThe mixture solution (2was mL) quenched was added. by Thesaturated resultant Na mixture2S2O3 aq was (10 stirred mL). atThe− 78mixtureC for 30was min. extracted The mixture with The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with wasdichloromethane quenched by (3 saturated × 10 mL). Na TheS O collectedaq (10 mL).organic The layer mixture was wasdried extracted over MgSO with4. dichloromethaneThe solvent was dichloromethane (3 × 10 mL). The2 2 collected3 organic layer was dried over MgSO4. The solvent was × (evaporated3 10 mL). and The the collected residue organic was purified layer was by column dried over chromatography MgSO4. The solvent (hexane, was column evaporated length and 10 cm, the residuediameter was 26 puriﬁedmm silica by gel) column and GPC chromatography (CHCl3) to give (hexane, the product column (0.0930 length 10g, cm,33%). diameter 26 mm silica diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.0930 g, 33%). gel) and GPC (CHCl3) to give the product (0.0930 g, 33%). IR: (neat) 1650, 1467, 1455 cm−1; 1H-NMR: (400 MHz, CDCl3) 5.90 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 IR: (neat) 1650, 1467, 1455 cm−1; 1H-NMR: (400 MHz, CDCl3) 5.90 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 −1 1 IR:(s, 1H, (neat) 1-H), 1650, 2.88 1467, (s, 2H, 1455 3-H cm2), 2.18–2.16; H-NMR: (m, 2H, (400 5-H MHz,2), 1.65 CDCl (s, 3H,) 5.90 2-Me), (s, 1H, 1.62–1.52 4-CHI), (m, 4.83 1H, (s, 7-H), 1H, 1.30– 1-H), (s, 1H, 1-H), 2.88 (s, 2H, 3-H2), 2.18–2.16 (m, 2H, 5-H2), 1.65 (s, 3H,3 2-Me), 1.62–1.52 (m, 1H, 7-H), 1.30– 4.751.24 (s,(m, 1H, 2H, 1-H), 6-H2), 2.88 0.93 (s, (d, 2H, J = 3-H 6.3 Hz,), 2.18–2.16 6H, 8-H (m,3 and 2H, 7-Me); 5-H ),13C-NMR: 1.65 (s, 3H, (100 2-Me), MHz, 1.62–1.52 CDCl3) 149.5 (m, 1H, (s, 7-H),C-4), 1.24 (m, 2H, 6-H2), 0.93 (d, J = 6.32 Hz, 6H, 8-H3 and 7-Me);2 13C-NMR: (100 MHz, CDCl3) 149.5 (s, C-4), 13 1.30–1.24142.4 (s, C-2), (m, 2H,113.1 6-H (t,2 C-1),), 0.93 75.9 (d, J(d,= 4-CHI), 6.3 Hz, 6H,45.8 8-H (t, C-3 and3), 36.0 7-Me); (t, C-6),C-NMR: 34.5 (t, (100 C-5), MHz, 28.2 (d, CDCl C-7),3) 149.522.5 (q, (s, C-8 and 7-Me), 21.8 (q, 2-Me); HRMS: (EI, 70 eV) Calculated (C11H19I) 278.0531 (M+), Found: 278.0529. C-8 and 7-Me), 21.8 (q, 2-Me); HRMS: (EI, 70 eV) Calculated (C11H19I) 278.0531 (M+), Found: 278.0529. (E)-4-(Iodomethylene)-2,6-dimethylhept-1-ene (4ca)

Molecules 2018, 23, x 7 of 14 standard. The crude product was purified by flash chromatography (spherical silica gel 60 μm, 30 g, diameter 2.7 cm) and GPC to give the product. (E)-4-(Iodomethylene)-2-methyldodec-1-ene (4aa)

The alkyne 1-decyne (0.980 mmol, 0.1354 g) was added to a solution of InBr3 (0.996 mmol, 0.3530 g) and methallyl trimethylsilane (2.07 mmol, 0.2654 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated, and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.279 g, 89%).

IR: (neat) 1650, 1457 cm−1; 1H-NMR: (400 MHz, CDCl3) 5.92 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 (s, 1H, 1-H), 2.87 (s, 2H, 3-H2), 2.16 (t, J = 7.8 Hz, 2H, 5-H), 1.65 (s, 3H, 2-Me), 1.43–1.23 (m, 14H), 0.88 (t, J = 6.8 Hz, 3H); 13C-NMR: (100 MHz, CDCl3) 149.4 (s, C-4), 142.5 (s, C-2), 113.0 (t, C-1), 76.2 (d, 4-CHI), 45.8 (t, C-3), 36.4 (t, C-5), 31.9 (t), 29.43 (t), 29.38 (t), 29.22 (t), 27.0 (t), 22.7 (t), 21.8 (q, 2-Me), 14.1 (q, C- 12); HRMS: (EI, 70 eV) Calculated (C14H25I) 320.1001 (M+), Found: 320.1000. (E)-4-(Iodomethylene)-2,7-dimethyloct-1-ene (4ba)

The alkyne 5-methylhex-1-yne (1.02 mmol, 0.0985 g) was added to a solution of InBr3 (0.983 mmol, 0.3485 g) and methallyl trimethylsilane (1.94 mmol, 0.2487 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.0930 g, 33%). Molecules 2018, 23, 1884 8 of 14 IR: (neat) 1650, 1467, 1455 cm−1; 1H-NMR: (400 MHz, CDCl3) 5.90 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 (s, 1H, 1-H), 2.88 (s, 2H, 3-H2), 2.18–2.16 (m, 2H, 5-H2), 1.65 (s, 3H, 2-Me), 1.62–1.52 (m, 1H, 7-H), 1.30– 13 C-4),1.24 (m, 142.4 2H, (s, 6-H C-2),2), 0.93 113.1 (d, (t, J C-1),= 6.3 Hz, 75.9 6H, (d, 4-CHI),8-H3 and 45.8 7-Me); (t, C-3), C-NMR: 36.0 (t, (100 C-6), MHz, 34.5 CDCl (t, C-5),3) 149.5 28.2 (d,(s, C-7),C-4), 142.4 (s, C-2), 113.1 (t, C-1), 75.9 (d, 4-CHI), 45.8 (t, C-3), 36.0 (t, C-6), 34.5 (t, C-5), 28.2 (d, C-7),+ 22.5 (q, 22.5 (q, C-8 and 7-Me), 21.8 (q, 2-Me); HRMS: (EI, 70 eV) Calculated (C11H19I) 278.0531 (M ), Found: + 278.0529.C-8 and 7-Me), 21.8 (q, 2-Me); HRMS: (EI, 70 eV) Calculated (C11H19I) 278.0531 (M ), Found: 278.0529. (E)-4-(Iodomethylene)-2,6-dimethylhept-1-ene(E)-4-(Iodomethylene)-2,6-dimethylhept-1-ene ((4ca4ca))

The alkyne 4-methylpent-1-yne (1.06 mmol, 0.0872 g) was added to a solution of InBr3 (1.02 mmol, The alkyne 4-methylpent-1-yne (1.06 mmol, 0.0872 g) was added to a solution of InBr3 (1.02 mmol, 0.3606 g) and methallyl trimethylsilane (2.03 mmol, 0.2620 g) in dichloromethane (1 mL). The mixture 0.3606 g) and methallyl trimethylsilane (2.03 mmol, 0.2620 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 ◦C, and 0.75 M I in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture2 THFMolecules solution 2018,, 23 (2,, xx mL) was added. The resultant mixture was stirred at −78 ◦C for 30 min. The mixture8 of 14 was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue waswas puriﬁedpurified by by column column chromatography chromatography (hexane, (hexane, column column length length 10 cm, 10 diametercm, diameter 26 mm 26silica mm silica gel) and GPC (CHCl3) to give the product (0.0560 g, 20%). gel) and GPC (CHCl3) to give the product (0.0560 g, 20%). −1 1 IR: (neat) 1650, 1463 cm−−11; 1H-NMR:1 (400 MHz, CDCl3) 6.01 (s, 1H, 8-H), 4.84 (s, 1H, 1-H), 4.74 (s, 1H, IR: (neat) 1650, 1463 cm ; H-NMR: (400 MHz, CDCl3) 6.01 (s, 1H, 8-H), 4.84 (s, 1H, 1-H), 4.74 (s, 1H, 1-H), 2.87 (s, 2H, 3-H2), 2.09 (d, J = 8.0 Hz, 2H, 5-H2), 1.90 (septet, J = 8.0 Hz, 1H, 6-H), 1.65 (s, 3H, 2- 1-H), 2.87 (s, 2H, 3-H2), 2.09 (d, J = 8.0 Hz, 2H, 5-H2), 1.90 (septet, J = 8.0 Hz, 1H, 6-H), 1.65 (s, 3H, 13 Me), 0.93 (d, J = 0.8 Hz, 6H, 7-H3 and 6-Me); 13C-NMR:13 (100 MHz, CDCl3) 148.4 (s, C-4), 142.4 (s, C-2), 2-Me), 0.93 (d, J = 0.8 Hz, 6H, 7-H3 and 6-Me); C-NMR: (100 MHz, CDCl3) 148.4 (s, C-4), 142.4 (s, 113.2C-2), 113.2(t, C-1), (t, C-1),77.5 (d, 77.5 C-8), (d, C-8),46.1 (t, 46.1 C-3), (t, C-3), 44.7 44.7(t, C-5), (t, C-5), 26.8 26.8(d, C-6), (d, C-6), 22.4 22.4 (q, C-7 (q, C-7 and and 6-Me), 6-Me), 21.8 21.8 (q, (q,2- + Me); HRMS: (EI, 70 eV) Calculated (C10H17I) 264.0375 (M+), Found:+ 264.0370. 2-Me); HRMS: (EI, 70 eV) Calculated (C10H17I) 264.0375 (M ), Found: 264.0370. (Z)-(1-Iodo-4-methylpenta-1,4-dien-2-yl)cyclohexane(Z)-(1-Iodo-4-methylpenta-1,4-dien-2-yl)cyclohexane ((4da4da))

Ethynylcyclohexane (1.01 mmol, 0.1094 g) was added to a solution of InBr3 (0.968 mmol, 0.3432 Ethynylcyclohexane (1.01 mmol, 0.1094 g) was added to a solution of InBr3 (0.968 mmol, 0.3432 g) g)and and methallyl methallyl trimethylsilane trimethylsilane (1.98 (1.98 mmol, mmol, 0.2540 0.2540 g) g) in in dichloromethane dichloromethane (1(1 mL).mL). TheThe mixturemixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and◦ 0.75 M I2 in THF stirred at room temperature for 24 h. The reaction mixture was cooled to −78 C, and 0.75 M I2 in THFsolution solution (2 mL) (2 was mL) added. was added. The resultant The resultant mixture mixture was wasstirred stirred at −78 at °C−78 for◦C 30 for min. 30 min.The mixture The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the wasresidue purified was puriﬁed by column by column chromatography chromatography (hexane, (hexane, column column length length 10 cm, 10 diameter cm, diameter 26 mm 26 silica mm silica gel) and GPC (CHCl3) to give the product (0.0607 g, 21%). gel) and GPC (CHCl3) to give the product (0.0607 g, 21%). −1 1 IR: (neat) 1650, 1448 cm−−11; 11H-NMR: (400 MHz, CDCl3) 5.83 (s, 1H, 11-H), 4.87 (s, 1H, 10-H), 4.77 (s, IR: (neat) 1650, 1448 cm ; H-NMR: (400 MHz, CDCl3) 5.83 (s, 1H, 11-H), 4.87 (s, 1H, 10-H), 4.77 (s, 1H, 1H, 10-H), 2.81 (s, 2H, 8-H2), 2.63–2.56 (m, 1H, 1-H), 1.79–1.55 (m, 8H), 1.4–1.23 (m, 4H), 1.20–1.09 (m, 10-H), 2.81 (s, 2H, 8-H2), 2.63–2.56 (m, 1H, 1-H), 1.79–1.55 (m, 8H), 1.4–1.23 (m, 4H), 1.20–1.09 (m, 1H); 13 131H); 13C-NMR: (100 MHz, CDCl3) 151.8 (s, C-7), 142.8 (s, C-9), 113.7 (t, C-10), 76.0 (d, C-11), 47.3 (d, C- C-NMR: (100 MHz, CDCl3) 151.8 (s, C-7), 142.8 (s, C-9), 113.7 (t, C-10), 76.0 (d, C-11), 47.3 (d, C-1), 1), 42.1 (t, C-8), 29.9 (t), 26.3 (t), 26.0 (t), 22.0 (t, C-12); HRMS: (EI, 70 eV) Calculated (C12H19I) 290.0531 42.1 (t, C-8), 29.9 (t), 26.3 (t), 26.0 (t), 22.0 (t, C-12); HRMS: (EI, 70 eV) Calculated (C12H19I) 290.0531 + (M+),), Found: Found: 290.0530. 290.0530. (E)-(3-(Iodomethylene)-5-methylhex-5-en-1-yl)benzene(E)-(3-(Iodomethylene)-5-methylhex-5-en-1-yl)benzene ((4fa4fa))

−1 1 IR: (neat) 1649, 1604, 1494, 1454 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.31–7.17 (m, 5H, Ph), 6.00 (s, 1H, 3-CHI), 4.85 (s, 1H, 6-H), 4.76 (s, 1H, 6-H), 2.86 (s, 2H, 4-H2), 2.72–2.68 (m, 2H, 1-H2), 2.48–2.44 (m, 2H, 13 2-H2), 1.64 (s, 3H, 5-Me); 13C-NMR: (100 MHz, CDCl3) 148.4 (s, C-3), 142.2 (s, C-5), 141.4 (s, i), 128.39 (d), 128.35 (d), 126.0 (d, p), 113.3 (t, C-6), 77.2 (d, 3-CHI), 46.3 (t, C-4), 38.6 (t, C-2), 33.3 (t, C-1), 21.8 (q, + 5-Me); HRMS: (EI, 70 eV) Calculated (C14H17I) 312.0375 (M+), Found: 312.0377. (E)-7-Chloro-4-(iodomethylene)-2-methylhept-1-ene (4ga)

Molecules 2018, 23, 1884 9 of 14

Pent-4-yn-1-ylbenzene (1.01 mmol, 0.1314 g) was added to a solution of InBr3 (0.979 mmol, 0.3471 g) and methallyl trimethylsilane (2.00 mmol, 0.2560 g) in dichloromethane (1 mL). The mixture ◦ was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 ◦C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was puriﬁed by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.1357 g, 43%). −1 1 IR: (neat) 1649, 1604, 1494, 1454 cm ; H-NMR: (400 MHz, CDCl3) 7.31–7.17 (m, 5H, Ph), 6.00 (s, 1H, 3-CHI), 4.85 (s, 1H, 6-H), 4.76 (s, 1H, 6-H), 2.86 (s, 2H, 4-H2), 2.72–2.68 (m, 2H, 1-H2), 2.48–2.44 (m, 13 2H, 2-H2), 1.64 (s, 3H, 5-Me); C-NMR: (100 MHz, CDCl3) 148.4 (s, C-3), 142.2 (s, C-5), 141.4 (s, i), 128.39 (d), 128.35 (d), 126.0 (d, p), 113.3 (t, C-6), 77.2 (d, 3-CHI), 46.3 (t, C-4), 38.6 (t, C-2), 33.3 (t, C-1), + 21.8 (q, 5-Me); HRMS: (EI, 70 eV) Calculated (C14H17I) 312.0375 (M ), Found: 312.0377. (E)-7-Chloro-4-(iodomethylene)-2-methylhept-1-eneMolecules 2018,, 23,, xx (4ga) 9 of 14

The alkyne 5-chloropent-1-yne (1.01 mmol, 0.1031 g) was added to a solution of InBr33 (0.983(0.983 The alkyne 5-chloropent-1-yne (1.01 mmol, 0.1031 g) was added to a solution of InBr3 (0.983 mmol, mmol,0.3486 g)0.3486 and methallylg) and methallyl trimethylsilane trimethylsilane (1.99 mmol, (1.99 0.2557 mmol, g) 0.2557 in dichloromethane g) in dichloromethane (1 mL). The(1 mL). mixture The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled◦ to −78 °C, and was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 C, and 0.75 M I2 in THF0.75 M solution I22 inin THFTHF (2 mL) solutionsolution wasadded. (2(2 mL)mL) Thewaswasresultant added.added. TheThe mixture resultantresultant was mixture stirredmixture at waswas−78 stirredstirred◦C for atat 30 − min.78 °C The for mixture30 min. The mixture was quenched by saturated Na22S22O33 aqaq (10(10 mL).mL). TheThe mixturemixture waswas extractedextracted withwith was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO44.. TheThe solventsolvent waswas (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the evaporatedresidue was and puriﬁed the residue by column was chromatography purified by column (hexane, chromatographychromatography column length (hexane,(hexane, 10 cm, column diametercolumn lengthlength 26 mm 1010 silica cm,cm, diametergel) to give 26 the mm product silica gel) (0.1676 to give g, 59%).the product (0.1676 g, 59%).

IR: (neat) 1649, 1443 cm−−−111;; 11H-NMR:1 (400 MHz, CDCl33) 6.01 (s, 1H, 4-CHI), 4.84 (s, 1H, 7-H), 4.76 (s, IR: (neat) 1649, 1443 cm ; H-NMR: (400 MHz, CDCl3) 6.01 (s, 1H, 4-CHI), 4.84 (s, 1H, 7-H), 4.76 (s, 1H, 7-H), 3.54 (t, J == 7.37.3 Hz,Hz, 2H,2H, 1-H1-H22), 2.88 (s, 2H, 5-H22), 2.31 (t, J == 7.37.3 Hz,Hz, 2H,2H, 3-H3-H22), 1.88 (quintet, J == 1H, 7-H), 3.54 (t, J = 7.3 Hz, 2H, 1-H2), 2.88 (s, 2H, 5-H2), 2.31 (t, J = 7.3 Hz, 2H, 3-H2), 1.88 (quintet, 7.3 Hz, 2H, 2-H22), 1.64 (s, 3H, 6-Me); 1313C-NMR:13 (100 MHz, CDCl33) 147.6 (s, C-4), 141.9 (s, C-6), 113.4 (t, J = 7.3 Hz, 2H, 2-H2), 1.64 (s, 3H, 6-Me); C-NMR: (100 MHz, CDCl3) 147.6 (s, C-4), 141.9 (s, C-6), 113.4C-7), 77.6 (t, C-7), (d, 4-CHI), 77.6 (d, 4-CHI),46.0 (t, C-5), 46.0 (t,44.5 C-5), (t, C-1), 44.5 (t,33.9 C-1), (t, C-3), 33.9 (t,30.0 C-3), (t, C-2), 30.0 (t,21.7 C-2), (q, 21.76-Me); (q, HRMS: 6-Me); HRMS:(EI, 70 eV) Calculated (C99H1414ClI) 283.9829 (M++), Found:+ 283.9823. (EI, 70 eV) Calculated (C9H14ClI) 283.9829 (M ), Found: 283.9823. (Z)-(1-Iodo-4-methylpenta-1,4-dien-2-yl)benzene(Z)-(1-Iodo-4-methylpenta-1,4-dien-2-yl)benzene (((4ha4ha))

Phenylacetylene (1.08 mmol, 0.110 g) was added to a solution of InBr33 (1.00(1.00 mmol,mmol, 0.35410.3541 g),g), methallylPhenylacetylene trimethylsilane (1.08 mmol, (1.99 0.110 mmol, g) was 0.2552 added g), to aand solution Me22Si(OMe) of InBr3 (1.0022 (1.02(1.02 mmol, mmol,mmol, 0.3541 0.12300.1230 g), methallyl g)g) inin dichloromethanetrimethylsilane (1.99 (1 mmol,mL). The 0.2552 mixture g), and was Me stirred2Si(OMe) at roomroom2 (1.02 temperaturetemperature mmol, 0.1230 forfor g) 2424 in h. dichloromethaneh. TheThe reactionreaction mixturemixture (1 mL). − ◦ Thewas mixturecooled to was −78 stirred °C, and at 0.75 room M temperature I22 inin THFTHF solutionsolution for 24 h.(2(2 ThemL)mL) reaction waswas added.added. mixture TheThe wasresultantresultant cooled mixturemixture to 78 waswasC, − ◦ stirredand 0.75 at M −78I2 °Cin for THF 30 solutionmin. The (2 mixtur mL)e was was added. quenched The by resultant saturated mixture Na22S22O was33 aqaq stirred(10(10 mL).mL). at TheThe78 mixturemixtureC for was30 min. extracted The mixture with dichloromethane was quenched by (3 saturated × 10 mL). Na TheThe2S2 collectedcollectedO3 aq (10 organicorganic mL). The layerlayer mixture waswas dried wasdried extracted overover MgSOMgSO with44.. Thedichloromethane solvent was (3evaporated× 10 mL). and The the collected residue organic was purified layer was by dried column over chromatography MgSO4. The solvent (hexane, was columnevaporated length and 10 the cm, residue diameter was 26 purified mm silica by gel) column and chromatographyGPC (CHCl33) to give (hexane, the product column (0.169 length g,10 55%). cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.169 g, 55%). IR: (neat) 1650, 1490, 1442 cm−−11;; 11H-NMR: (400 MHz, CDCl33) 7.38–7.30 (m, 3H, Ar), 7.21 (d, J == 6.86.8 Hz,Hz, −1 1 2H,IR: (neat) Ar), 6.35 1650, (s, 1490, 1H, 1-H), 1442 cm4.78 (s,; H-NMR:1H, 5-H), (400 4.66 MHz, (s, 1H, CDCl 5-H),3) 3.20 7.38–7.30 (s, 2H, (m, 3-H), 3H, 1.70 Ar), (s, 7.21 3H, (d, 4-Me);J = 6.8 1313 HzC-, NMR:2H, Ar), (100 6.35 MHz, (s, 1H, CDCl 1-H),33) 150.1 4.78 (s), (s, 141.9 1H, 5-H), (s), 141.5 4.66 (s), (s, 128.1 1H, 5-H), (d), 127.9 3.20 (s,(d), 2H, 127.6 3-H), (d),1.70 113.7 (s, (t, 3H, C-5), 4-Me); 77.6 (d, C-1), 48.6 (t, C-3), 21.9 (q, 4-Me); Calculated (C1212H1313I) 284.0062 (M++), Found: 284.0062. (Z)-(1-Iodopenta-1,4-dien-2-yl)benzene (4hb)

Phenylacetylene (1.00 mmol, 0.102 g) was added to a solution of InBr33 (1.11(1.11 mmol,mmol, 0.39210.3921 g),g), allylallyl trimethylsilanetrimethylsilane (1.96(1.96 mmol,mmol, 0.22360.2236 g),g), andand MeMe22Si(OMe)22 (1.00(1.00 mmol,mmol, 0.12020.1202 g)g) inin dichloromethanedichloromethane (1(1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I22 inin THFTHF solutionsolution (2(2 mL)mL) waswas added.added. TheThe resultantresultant mixturemixture waswas stirredstirred atat −78 °C for 30 min. The mixture was quenched by saturated Na22S22O33 aqaq (10(10 mL).mL). TheThe mixturemixture waswas extractedextracted withwith dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO44.. TheThe solventsolvent waswas evaporated and the residue was purified by column chromatographychromatography (hexane,(hexane, columncolumn lengthlength 1010 cm,cm, diameter 26 mm silica gel) and GPC (CHCl33) to give the product (0.102 g, 38%).

Molecules 2018, 23, x 9 of 14

The alkyne 5-chloropent-1-yne (1.01 mmol, 0.1031 g) was added to a solution of InBr3 (0.983 mmol, 0.3486 g) and methallyl trimethylsilane (1.99 mmol, 0.2557 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) to give the product (0.1676 g, 59%).

IR: (neat) 1649, 1443 cm−1; 1H-NMR: (400 MHz, CDCl3) 6.01 (s, 1H, 4-CHI), 4.84 (s, 1H, 7-H), 4.76 (s, 1H, 7-H), 3.54 (t, J = 7.3 Hz, 2H, 1-H2), 2.88 (s, 2H, 5-H2), 2.31 (t, J = 7.3 Hz, 2H, 3-H2), 1.88 (quintet, J = 7.3 Hz, 2H, 2-H2), 1.64 (s, 3H, 6-Me); 13C-NMR: (100 MHz, CDCl3) 147.6 (s, C-4), 141.9 (s, C-6), 113.4 (t, C-7), 77.6 (d, 4-CHI), 46.0 (t, C-5), 44.5 (t, C-1), 33.9 (t, C-3), 30.0 (t, C-2), 21.7 (q, 6-Me); HRMS: (EI, 70 eV) Calculated (C9H14ClI) 283.9829 (M+), Found: 283.9823. (Z)-(1-Iodo-4-methylpenta-1,4-dien-2-yl)benzene (4ha)

Phenylacetylene (1.08 mmol, 0.110 g) was added to a solution of InBr3 (1.00 mmol, 0.3541 g), methallyl trimethylsilane (1.99 mmol, 0.2552 g), and Me2Si(OMe)2 (1.02 mmol, 0.1230 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.169 g, 55%). Molecules 2018, 23, 1884 10 of 14 IR: (neat) 1650, 1490, 1442 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.38–7.30 (m, 3H, Ar), 7.21 (d, J = 6.8 Hz, 2H, Ar), 6.35 (s, 1H, 1-H), 4.78 (s, 1H, 5-H), 4.66 (s, 1H, 5-H), 3.20 (s, 2H, 3-H), 1.70 (s, 3H, 4-Me); 13C- 13NMR: (100 MHz, CDCl3) 150.1 (s), 141.9 (s), 141.5 (s), 128.1 (d), 127.9 (d), 127.6 (d), 113.7 (t, C-5), 77.6 C-NMR: (100 MHz, CDCl3) 150.1 (s), 141.9 (s), 141.5 (s), 128.1 (d), 127.9 (d), 127.6 (d), 113.7 (t, C-5), (d, C-1), 48.6 (t, C-3), 21.9 (q, 4-Me); Calculated (C12H13I) 284.0062 (M+), Found:+ 284.0062. 77.6 (d, C-1), 48.6 (t, C-3), 21.9 (q, 4-Me); Calculated (C12H13I) 284.0062 (M ), Found: 284.0062. (Z)-(1-Iodopenta-1,4-dien-2-yl)benzene(Z)-(1-Iodopenta-1,4-dien-2-yl)benzene ((4hb4hb))

Phenylacetylene (1.00 mmol, 0.102 g) was added to a solution of InBr3 (1.11 mmol, 0.3921 g), allyl trimethylsilanePhenylacetylene (1.96 mmol, (1.00 mmol, 0.2236 0.102 g), and g) was Me2 addedSi(OMe) to2 a (1.00 solution mmol, of InBr0.12023 (1.11 g) in mmol, dichloromethane 0.3921 g), allyl (1 trimethylsilanemL). The mixture (1.96 was mmol, stirred 0.2236at room g), temperature and Me2Si(OMe) for 24 h.2 (1.00 The reaction mmol, 0.1202 mixture g) was in dichloromethane cooled to −78 °C, (1and mL). 0.75 The M I mixture2 in THF was solution stirred (2 atmL) room was temperature added. The resultant for 24 h. Themixture reaction was mixturestirred at was −78 cooled°C for 30 to ◦ ◦ −min.78 TheC, and mixture 0.75 M was I2 in quenched THF solution by saturated (2 mL) was Na added.2S2O3 aq The (10 resultant mL). The mixture mixture was was stirred extracted at −78 withC fordichloromethane 30 min. The mixture (3 × 10 was mL). quenched The collected by saturated organic Na layer2S2 Owas3 aq dried (10 mL). over The MgSO mixture4. The was solvent extracted was withevaporated dichloromethane and the residue (3 × 10was mL). purified The collected by column organic chromatography layer was dried (hexane, over column MgSO4 length. The solvent 10 cm, wasdiameter evaporated 26 mm andsilica the gel) residue and GPC was (CHCl puriﬁed3) to by give column the product chromatography (0.102 g, 38%). (hexane, column length Molecules 2018, 23, x 10 of 14 10Molecules cm, diameter 2018, 23, x 26 mm silica gel) and GPC (CHCl3) to give the product (0.102 g, 38%). 10 of 14 −−1 11 1 IR: IR: (neat) 1638 1638 cm cm ; ;H-NMR:H-NMR: (400 (400 MHz, MHz, CDCl CDCl3) 7.42–7.7.313) 7.42–7.7.31 (m, (m,3H, 3H,Ar), Ar), 7.24–7.22 7.24–7.22 (m, 2H, (m, Ar), 2H, 6.35 Ar), IR: (neat) 1638 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.42–7.7.31 (m, 3H, Ar), 7.24–7.22 (m, 2H, Ar), 6.35 6.35(t, J = (t, 1.5J =Hz, 1.5 1H, Hz, 1-H), 1H, 1-H),5.78 (m, 5.78 1H, (m, 4-H), 1H, 4-H),5.11–5.06 5.11–5.06 (m, 2H, (m, 5-H), 2H, 5-H),3.25 (dq, 3.25 J (dq,= 6.8,J 1.5= 6.8, Hz, 1.5 2H, Hz, 3-H 2H,2); (t,13 J = 1.513 Hz, 1H, 1-H), 5.78 (m, 1H, 4-H), 5.11–5.06 (m, 2H, 5-H), 3.25 (dq, J = 6.8, 1.5 Hz, 2H, 3-H2); 3-HC-NMR:2); C-NMR: (100 MHz, (100 CDCl MHz,3) CDCl 150.83 )(s, 150.8 C-2), (s, 142.1 C-2), (s), 142.1 134.3 (s), (d, 134.3 C-4), (d, 128.2 C-4), (d), 128.2 127.8 (d), (d), 127.8 127.6 (d), (d), 127.6 117.5 (d), 13 C-NMR: (100 MHz, CDCl3) 150.8 (s, C-2), 142.1 (s), 134.3 (d, C-4), 128.2 (d), 127.8 (d), 127.6+ (d), 117.5 117.5(t, C-5), (t, C-5),77.1 77.1(d, C-1), (d, C-1), 44.3 44.3 (t, (t,C-3); C-3); HRMS: HRMS: (EI, (EI, 70 70 eV) eV) Calculated Calculated (C 11HH1111I)I) 269.9905 269.9905 (M ),), Found: Found: (t, C-5), 77.1 (d, C-1), 44.3 (t, C-3); HRMS: (EI, 70 eV) Calculated (C11H11I) 269.9905 (M+), Found: 269.9903. 269.9903. (Z)-1-Iodo-2,4-diphenylpenta-1,4-diene(Z)-1-Iodo-2,4-diphenylpenta-1,4-diene ((4hc4hc)) (Z)-1-Iodo-2,4-diphenylpenta-1,4-diene (4hc)

Phenylacetylene (1.03 mmol, 0.1053 g) was added to a solution of InBr3 (0.98 mmol, 0.3497 g), 2- Phenylacetylene (1.03 mmol, 0.1053 g) was added to a solution of InBr3 (0.98 mmol, 0.3497 g), 2- phenylallylPhenylacetylene trimethylsilane (1.03 mmol, (2.00 0.1053mmol, g)0.3813 was addedg), and to aMe solution2Si(OMe) of2 InBr (1.003 (0.98 mmol, mmol, 0.1207 0.3497 g) g),in phenylallyl trimethylsilane (2.00 mmol, 0.3813 g), and Me2Si(OMe)2 (1.00 mmol, 0.1207 g) in 2-phenylallyldichloromethane trimethylsilane (1 mL). The mixture (2.00 mmol, was stirred 0.3813 at g), room and temperature Me2Si(OMe) for2 24(1.00 h. The mmol, reaction 0.1207 mixture g) in dichloromethanewas cooled to −78 (1 °C, mL). and The 0.75 mixture M I2 in was THF stirred solution at room (2 mL) temperature was added. for The 24 h. resultant The reaction mixture mixture was was cooled to −78 °C,◦ and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was wasstirred cooled at −78 to °C− 78for 30C, min. and 0.75The mixtur M I2 ine THFwas quenched solution (2 by mL) saturated was added. Na2S2 TheO3 aq resultant (10 mL). mixtureThe mixture was stirred at −78 °C◦ for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture stirredwas extracted at −78 withC for dichloromethane 30 min. The mixture (3 × was 10 mL). quenched The collected by saturated organic Na2 layerS2O3 aqwas (10 dried mL). over The mixtureMgSO4. was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. wasThe extractedsolvent was with evaporated dichloromethane and the (3 ×residue10 mL). was The purified collected by organic column layer chromatography was dried over (hexane, MgSO4. Thecolumn solventsolvent length was was 10 evaporated cm,evaporated diameter and and 26 the mmthe residue silicaresidue was gel) was puriﬁed and purifiedGPC by (CHCl column by 3column) to chromatography give chromatographythe product (hexane, (0.153 (hexane, g, column 43%). column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.153 g, 43%). length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.153 g, 43%). IR: (neat) 1626, 1492, 1442 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.36–7.23 (m, 8H, Ar), 7.17–7.15 (m, 2H, −1 1 IR: (neat) 1626, 1492, 1442 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.36–7.23 (m,13 8H, Ar), 7.17–7.15 (m, 2H, IR:Ar), (neat) 6.33 (s, 1626, 1H, 1492,1-H), 14425.41 (s, cm 1H,; 5-H),H-NMR: 5.07 (s, (400 1H, MHz, 5-H), CDCl 3.65 3(s,) 7.36–7.232H, 3-H2); (m, C-NMR: 8H, Ar), (100 7.17–7.15 MHz, (m,CDCl 2H,3) Ar), 6.33 (s, 1H, 1-H), 5.41 (s, 1H, 5-H), 5.07 (s, 1H, 5-H), 3.65 (s, 2H, 3-H2); 13C-NMR: (100 MHz, CDCl3) Ar),149.9 6.33 (s), (s,143.9 1H, (s), 1-H), 142.2 5.41 (s), (s, 1H,140.1 5-H), (s), 128.3 5.07 (s, (d), 1H, 128. 5-H),1 (d), 3.65 127.8 (s, 2H, (d), 3-H 127.2); 6 (d),C-NMR: 126.0 (100(d), MHz,115.8 (t, CDCl C-5),3) 149.978.6 (d, (s), C-1), 143.9 45.6 (s), (t, 142.2 C-3); (s), HR 140.1MS: (EI,(s), 128.370 eV) (d), Calculated 128. 128.11 (d), (C 127.8 17H15 (d), I) 346.0218 127. 6 (d), (M +126.0 ) Found: (d), 346.0221.115.8 (t, (t, C-5), 78.6 (d, C-1), 45.6 (t, C-3); HRMS:HRMS: (EI, 70 eV) Calculated (C 17HH15I)I) 346.0218 346.0218 (M (M++) )Found: Found: 346.0221. 346.0221. (Z)-(1-Iodo-3,3-dimethylpenta-1,4-dien-2-yl)benzene (4hd) 17 15 (Z)-(1-Iodo-3,3-dimethylpenta-1,4-dien-2-yl)benzene ((4hd4hd))

Phenylacetylene (1.02 mmol, 0.104 g) was added to a solution of InBr3 (1.01 mmol, 0.3597 g), 3 prenylPhenylacetylene trimethylsilane (1.02 (1.96 mmol, mmol, 0.104 0.2788 g) was g), added and toMe a 2solutionSi(OMe) of2 (0.962InBr (1.01mmol, mmol, 0.1157 0.3597 g) g),in prenyldichloromethane trimethylsilane (1 mL). (1.96The mixturemmol, was0.2788 stirred g), atand room Me temperature2Si(OMe)2 for(0.962 24 h.mmol, The reaction 0.1157 mixture g) in dichloromethanewas cooled to −78 (1 °C, mL). and The 0.75 mixture M I2 in was THF stirred solution at room (2 mL) temperature was added. for The 24 h. resultant The reaction mixture mixture was 2 wasstirred cooled at −78 to °C −78 for °C, 30 andmin. 0.75 The Mmixtur I ine THF was solutionquenched (2 by mL) saturated was added. Na2S 2TheO3 aq resultant (10 mL). mixture The mixture was 2 2 3 stirredwas extracted at −78 °C with for dichloromethane30 min. The mixtur (3e ×was 10 mL).quenched The collected by saturated organic Na layerS O aq was (10 dried mL). overThe mixtureMgSO4. wasThe extractedsolvent was with evaporated dichloromethane and the (3 residue× 10 mL). was The purified collected by organic column layer chromatography was dried over (hexane, MgSO4. Thecolumn solvent length was 10 cm,evaporated diameter and 26 mmthe silicaresidue gel) was and purifiedGPC (CHCl by 3column) to give chromatographythe product (0.126 (hexane, g, 41%). column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.126 g, 41%). IR: (neat) 1638, 1490, 1462, 1442 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.41–7.7.32 (m, 3H, Ar), 7.04–7.00 −1 1 IR:(m, (neat) 2H, Ar), 1638, 6.53 1490, (s, 1H, 1462, 1-H), 1442 5.94 cm (dd,; H-NMR: J = 17.4, 10.6(400 Hz,MHz, 1H, CDCl 4-H),3) 5.097.41–7.7.32 (d, J = 10.6(m, 3H,Hz, 1H,Ar), 5-H),7.04–7.00 5.03 (m,(d, J2H, = 17.4 Ar), Hz, 6.53 1H, (s, 5-H), 1H, 1-H),1.21 (s, 5.94 6H, (dd, 3-Me J =2 );17.4, 13C-NMR: 10.6 Hz, (100 1H, MHz, 4-H), CDCl 5.09 3(d,) 159.7 J = 10.6 (s, C-2), Hz, 1H,145.2 5-H), (d, C-4), 5.03 2 13 3 (d,142. J =4 17.4(s), 128.9 Hz, 1H, (d), 5-H),127.8 1.21(d), 127.1(s, 6H, (d), 3-Me 112.3); (t,C-NMR: C-5), 80.2 (100 (d, MHz, C-1), CDCl45.1 (s,) C-3),159.7 26.4(s, C-2), (q, 3-Me 145.22); (d, HRMS: C-4), 2 142.(EI, 704 (s), eV) 128.9 Calculated (d), 127.8 (C 13(d),H15 127.1I) 298.0218 (d), 112.3 (M+ (t,), Found: C-5), 80.2 298.0219. (d, C-1), 45.1 (s, C-3), 26.4 (q, 3-Me ); HRMS: (EI, 70 eV) Calculated (C13H15I) 298.0218 (M+), Found: 298.0219. (Z)-1-Iodo-2,3-diphenylpenta-1,4-diene (4he) (Z)-1-Iodo-2,3-diphenylpenta-1,4-diene (4he)

Molecules 2018, 23, 1884 11 of 14

Phenylacetylene (1.02 mmol, 0.104 g) was added to a solution of InBr3 (1.01 mmol, 0.3597 g), prenyl trimethylsilane (1.96 mmol, 0.2788 g), and Me2Si(OMe)2 (0.962 mmol, 0.1157 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to ◦ ◦ −78 C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was puriﬁed by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.126 g, 41%). −1 1 IR: (neat) 1638, 1490, 1462, 1442 cm ; H-NMR: (400 MHz, CDCl3) 7.41–7.7.32 (m, 3H, Ar), 7.04–7.00 (m, 2H, Ar), 6.53 (s, 1H, 1-H), 5.94 (dd, J = 17.4, 10.6 Hz, 1H, 4-H), 5.09 (d, J = 10.6 Hz, 1H, 5-H), 5.03 (d, 13 J = 17.4 Hz, 1H, 5-H), 1.21 (s, 6H, 3-Me2); C-NMR: (100 MHz, CDCl3) 159.7 (s, C-2), 145.2 (d, C-4), 142. 4 (s), 128.9 (d), 127.8 (d), 127.1 (d), 112.3 (t, C-5), 80.2 (d, C-1), 45.1 (s, C-3), 26.4 (q, 3-Me2); HRMS: + (EI, 70 eV) Calculated (C13H15I) 298.0218 (M ), Found: 298.0219. (Z)-1-Iodo-2,3-diphenylpenta-1,4-dieneMolecules 2018, 23, x (4he) 11 of 14

Phenylacetylene (1.02 mmol, 0.1044 g) was added to a solution of InBr3 (1.04 mmol, 0.3701 g), Phenylacetylene (1.02 mmol, 0.1044 g) was added to a solution of InBr3 (1.04 mmol, 0.3701 g), cinnamyl trimethylsilane (2.10 mmol, 0.4007 g), and Me2Si(OMe)2 (1.06 mmol, 0.1280 g) in cinnamyl trimethylsilane (2.10 mmol, 0.4007 g), and Me2Si(OMe)2 (1.06 mmol, 0.1280 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was was cooled to −78 ◦C, and 0.75 M I in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixtur2 e was quenched by saturated Na2S2O3 aq (10 mL). The mixture stirred at −78 °C◦ for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture stirred at −78 C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, The solvent was evaporated and the residue was puriﬁed by column chromatography (hexane, column column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.080 g, 23%). length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.080 g, 23%). IR: (neat) 1636 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.29–7.14 (m, 8H, Ar), 6.99 (dd, J = 7.8, 2.0 Hz, 2H, IR: (neat) 1636 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.29–7.14 (m, 8H, Ar), 6.99 (dd, J = 7.8, 2.0 Hz, 2H, IR: (neat) 1636 cm ; H-NMR: (400 MHz, CDCl3) 7.29–7.14 (m, 8H, Ar), 6.99 (dd, J = 7.8, 2.0 Hz, 2H, Ar), 6.42 (s, 1H, 1-H), 6.11 (ddd, J = 17.4, 10.1, 7.3 Hz, 1H, 4-H), 5.19 (d, J = 10.1 Hz, 1H, 5-H), 5.00 (d, Ar), 6.42 (s, 1H, 1-H), 6.11 (ddd, J = 17.4, 10.1, 7.3 Hz, 1H, 4-H), 5.19 (d, J = 10.1 Hz, 1H, 5-H), 5.00 (d, J = 17.4 Hz, 1H, 5-H), 4.47 (d, J = 7.3 Hz, 1H, 3-H); 13C-NMR: (100 MHz, CDCl3) 154.1 (s), 142.3 (s), J = 17.4 Hz, 1H, 5-H), 4.47 (d, J = 7.3 Hz, 1H, 3-H); 13C-NMR: (100 MHz, CDCl3) 154.1 (s), 142.3 (s), J = 17.4 Hz, 1H, 5-H), 4.47 (d, J = 7.3 Hz, 1H, 3-H); C-NMR: (100 MHz, CDCl3) 154.1 (s), 142.3 (s), 139.8 (s), 138.2 (d, C-4), 128.48 (d), 128.40 (d), 128.2 (d), 127.9 (d), 127.4 (d), 126.8 (d), 117.3 (t, C-5), 80.4 139.8 (s), 138.2 (d, C-4), 128.48 (d), 128.40 (d), 128.2 (d), 127.9 (d), 127.4 (d), 126.8 (d), 117.3 (t, C-5), 80.4 (d, C-1), 58.8 (d, C-3); HRMS: (EI, 70 eV) Calculated (C17H15I) 346.0218 (M+), Found: 346.0214. (d, C-1), 58.8 (d, C-3); HRMS: (EI, 70 eV) Calculated (C17H15I) 346.0218 (M +), Found: 346.0214. (d, C-1), 58.8 (d, C-3); HRMS: (EI, 70 eV) Calculated (C17H15I) 346.0218 (M ), Found: 346.0214. (Z)-(4-Methyl-2-phenylpenta-1,4-dien-1-yl)indium(III) bromide (3ha) (Z)-(4-Methyl-2-phenylpenta-1,4-dien-1-yl)indium(III) bromide (3ha)

All manipulations were carried out in a globe box filled with nitrogen gas. Phenylacetylene All manipulations were carried out in a globe box ﬁlled with nitrogen gas. Phenylacetylene (0.886 mmol, 0.0905 g) was added to a solution of InBr3 (1.00 mmol, 0.3550 g), methallyl (0.886 mmol, 0.0905 g) was added to a solution of InBr (1.00 mmol, 0.3550 g), methallyl trimethylsilane trimethylsilane (1.98 mmol, 0.2541 g), and Me2Si(OMe)3 2 (1.05 mmol, 0.1267 g) in dichloromethane (1 (1.98mL). mmol,The mixture 0.2541 was g), and stirred Me2 Si(OMe)at room2 temperature(1.05 mmol, 0.1267for 24 g)h. inThe dichloromethane volatiles were evaporated (1 mL). The mixtureand the wasresidual stirred oil was at room washed temperature with hexane for to 24 obtain h. The the volatiles desired were alkenylindium evaporated compound and the residual as a white oil solid was washed(0.106 g,with 26%). hexane to obtain the desired alkenylindium compound as a white solid (0.106 g, 26%). 11H-NMR: (400 MHz, CDCl ) 7.43–7.22 (m, 5H, Ar), 5.99 (s, 1H, 1-H), 4.83 (s, 1H, 5-H), 4.73 (s, 1H, 5-H), 1H-NMR: (400 MHz, CDCl33) 7.43–7.22 (m, 5H, Ar), 5.99 (s, 1H, 1-H), 4.83 (s, 1H, 5-H), 4.73 (s, 1H, 5- 3.30 (s, 2H, 3-H ), 1.72 (s, 3H, 4-Me); 13C-NMR:13 (100 MHz, CDCl ) 160.6 (s), 145.7 (s), 141.9 (s), 134.1 (d, H), 3.30 (s, 2H, 23-H2), 1.72 (s, 3H, 4-Me); 13C-NMR: (100 MHz, CDCl3 3) 160.6 (s), 145.7 (s), 141.9 (s), 134.1 C-1),(d, C-1), 129.5 129.5 (d), (d), 128.8 128.8 (d), (d), 126.5 126.5 (d), (d), 113.9 113.9 (t, C-5), (t, C-5), 48.1 48.1 (t, C-3), (t, C-3), 22.1 22.1 (q, 4-Me).(q, 4-Me). (Z)-4-Methy-1,2-diphenylpenta-1,4-diene (5)

Phenylacetylene (0.540 mmol, 0.0551 g) was added to a solutin of InBr3 (0.532 mmol, 0.1885 g), methallyl trimethylsilane (1.01 mmol, 0.1290 g), and Me2Si(OMe)2 (0.499 mmol, 0.060 g) in dichloromethane (0.5 mL). The mixture was stirred at room temperature for 3 h. DMF (1 mL) was added to the reaction mixture at −78 °C. Then, the »reaction mixture was warmed to room temperature. PhI (0.749 mmol, 0.1528 g) and Pd(PPh3)4 (0.028 mmol, 0.0325g) were added to the reaction mixture, and the mixture was heated at 100 °C for 3 h. The mixture was quenched by H2O (10 mL) and Et2O (20 mL) at room temperature. The organic layer was washed by H2O (3 × 10 mL), and was dried over MgSO4. The solvent was evaporated and the residue was purified by column

Molecules 2018, 23, x 11 of 14

Phenylacetylene (1.02 mmol, 0.1044 g) was added to a solution of InBr3 (1.04 mmol, 0.3701 g), cinnamyl trimethylsilane (2.10 mmol, 0.4007 g), and Me2Si(OMe)2 (1.06 mmol, 0.1280 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.080 g, 23%).

IR: (neat) 1636 cm−1; 1H-NMR: (400 MHz, CDCl3) 7.29–7.14 (m, 8H, Ar), 6.99 (dd, J = 7.8, 2.0 Hz, 2H, Ar), 6.42 (s, 1H, 1-H), 6.11 (ddd, J = 17.4, 10.1, 7.3 Hz, 1H, 4-H), 5.19 (d, J = 10.1 Hz, 1H, 5-H), 5.00 (d, J = 17.4 Hz, 1H, 5-H), 4.47 (d, J = 7.3 Hz, 1H, 3-H); 13C-NMR: (100 MHz, CDCl3) 154.1 (s), 142.3 (s), 139.8 (s), 138.2 (d, C-4), 128.48 (d), 128.40 (d), 128.2 (d), 127.9 (d), 127.4 (d), 126.8 (d), 117.3 (t, C-5), 80.4 (d, C-1), 58.8 (d, C-3); HRMS: (EI, 70 eV) Calculated (C17H15I) 346.0218 (M+), Found: 346.0214. (Z)-(4-Methyl-2-phenylpenta-1,4-dien-1-yl)indium(III) bromide (3ha)

All manipulations were carried out in a globe box filled with nitrogen gas. Phenylacetylene (0.886 mmol, 0.0905 g) was added to a solution of InBr3 (1.00 mmol, 0.3550 g), methallyl trimethylsilane (1.98 mmol, 0.2541 g), and Me2Si(OMe)2 (1.05 mmol, 0.1267 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The volatiles were evaporated and the residual oil was washed with hexane to obtain the desired alkenylindium compound as a white solid (0.106 g, 26%).

1H-NMR: (400 MHz, CDCl3) 7.43–7.22 (m, 5H, Ar), 5.99 (s, 1H, 1-H), 4.83 (s, 1H, 5-H), 4.73 (s, 1H, 5- MoleculesH), 3.302018 (s, 2H,, 23, 18843-H2), 1.72 (s, 3H, 4-Me); 13C-NMR: (100 MHz, CDCl3) 160.6 (s), 145.7 (s), 141.9 (s),12 134.1 of 14 (d, C-1), 129.5 (d), 128.8 (d), 126.5 (d), 113.9 (t, C-5), 48.1 (t, C-3), 22.1 (q, 4-Me).

(Z)-4-Methy-1,2-diphenylpenta-1,4-diene(Z)-4-Methy-1,2-diphenylpenta-1,4-diene( (55))

Phenylacetylene (0.540 mmol, 0.0551 g) was added to a solutin of InBr3 (0.532 mmol, 0.1885 g), methallylPhenylacetylene trimethylsilane (0.540 (1.01 mmol, mmol, 0.0551 0.1290 g) was g), added and to Me a solutin2Si(OMe) of2 InBr (0.4993 (0.532 mmol, mmol, 0.060 0.1885 g) g),in methallyldichloromethane trimethylsilane (0.5 mL). (1.01The mixture mmol, was 0.1290 stirre g),d at and room Me 2temperatureSi(OMe)2 (0.499 for 3 h. mmol, DMF 0.060(1 mL) g) was in dichloromethaneadded to the reaction (0.5 mL). mixture The mixture at −78 was°C. stirredThen, atthe room »reaction temperature mixture for was 3 h. warmed DMF (1 mL)to room was ◦ addedtemperature. to the reaction PhI (0.749 mixture mmol, at − 0.152878 C. Then,g) and the Pd(PPh »reaction3)4 (0.028 mixture mmol, was warmed0.0325g) to were room added temperature. to the PhIreaction (0.749 mixture, mmol, 0.1528and the g) mixture and Pd(PPh was3 heated)4 (0.028 at mmol, 100 °C 0.0325g) for 3 h. wereThe mixture added towas the quenched reaction mixture, by H2O ◦ and(10 mL) the mixtureand Et2O was (20 heatedmL) at atroom 100 temperature.C for 3 h. The The mixture organic was layer quenched was washed by H2 Oby (10 H2 mL)O (3 and× 10 EtmL),2O (20and mL) was at dried room over temperature. MgSO4. The The organicsolvent layerwas evaporated was washed and by Hthe2O residue (3 × 10 was mL), purified and was by dried column over MgSO4. The solvent was evaporated and the residue was puriﬁed by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl ) to give the product (0.0686 g, 54%). 3 −1 1 IR: (neat) 1650, 1599, 1494, 1444 cm ; H-NMR: (400 MHz, CDCl3) 7.29–7.20 (m, 3H, Ar), 7.15 (d, J = 6.8 Hz, 2H, Ar), 7.12–7.04 (m, 3H, Ar), 6.95 (d, J = 6.8 Hz, Ar), 4.79 (s, 1H, 5-H), 4.72 (s, 1H, 5-H), 13 3.18 (s, 2H, 3-H2), 1.76 (s, 3H, 4-Me); C-NMR: (100 MHz, CDCl3) 142.9 (s, C-4), 141.1 (s), 140.4 (s), 137.3 (s), 129.0 (d), 128.6 (d), 128.3 (d), 128.1 (d), 127.8 (d), 126.9 (d), 126.3 (d), 113.1 (t, C-5), 49.1 (t, C-3), + 22.1 (q, 4-Me); HRMS: (EI, 70 eV) Calculated (C18H18) 234.1409 (M ), Found: 234.1408.

4. Conclusions

We established a regioselective anti-allylindation of alkynes using InBr3 and allylic silanes. Many types of aliphatic and aromatic alkynes were applicable. The present allylindation has a wide scope of allylic silanes, and the reactions using allyl, methallyl, prenyl, cinnamyl silanes gave the desired products. A 1,4-dienyl indium compound generated by the present allylindation was successfully isolated and characterized by NMR spectroscopy. The synthesized 1,4-dienyl indiums were applicable to iodination and Pd-catalyzed cross-coupling with an aryl iodide in a one-pot manner to give the corresponding functionalized skipped dienes.

Supplementary Materials: The following are available online, Supporting Information of NOE Experiments and NMR Spectra. Author Contributions: Y.N., A.B. and M.Y. conceived and designed the experiments; J.Y. and T.T. performed the experiments; Y.N., J.Y. and T.T. analyzed the data; Yoshihiro Nishimoto, J.Y. and T.T. contributed reagents/materials/analysis tools; Y.N. and M.Y. wrote the paper. Funding: This research received no external funding. Acknowledgments: This work was supported by the JSPS KAKENHI Grant Numbers JP15H05848 in Middle Molecular Strategy, JP16K05719, and JP18H01977. Y.N. acknowledges support from the Frontier Research Base for Global Young Researchers, Osaka University, of the MEXT program. N.Y. acknowledges financial support from Mitsui Chemicals Award in Synthetic Organic Chemistry and Shorai Foundation for Science and Technology to Y.N. Conflicts of Interest: The authors declare no conflict of interest.

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Sample Availability: Samples of the compounds are not available from the authors.

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