Chemoselective Transfer of Allyl Or Phenyl Group from Allyl(Phenyl)Germanes in Pd-Catalyzed Reactions with Aryl Halides

doi:10.1246/cl.2011.967 Published on the web September 5, 2011 967

Chemoselective Transfer of Allyl or Phenyl Group from Allyl(phenyl)germanes in Pd-catalyzed Reactions with Aryl Halides

Jean-Philippe Pitteloud, Yong Liang, and Stanislaw F. Wnuk* Department of Chemistry and Biochemistry, Florida International University, Miami,Florida 33199, USA

(Received May 27, 2011; CL-110451; E-mail: wnuk@ﬁu.edu)

Treatment of chloro(phenyl)germanes with allylmagnesium bromide yielded allyl(phenyl)germanes. Coupling of the allyl- GeCln MgBr (n equiv) Ge n (phenyl)germanes with aryl halides in 1,4-dioxane in the presence of aqueous NaOH and Pd catalyst resulted in Heck-type transfer of 4-nEt2O 4-n ° the allyl group providing the corresponding allylated aryls. On the 0 C or r.t. i f ll l l i i 1 n = 3 (85%) other hand, react on o a y (pheny )germanes w th SbF5 nterca- 2 n = 2 (94%) lated in graphite intoluene and subsequent treatment of the 3 n = 1 (92%) resulting germanylfluorides with TBAF generates reactive hyper- PhMgBr (5 equiv) GeCl valent fluorogermanates that undergo Stille-like Pd-catalyzed 3 3 (44%) Et O cross-coupling with aryl halides in wet toluene to provide biaryls. 2 Scheme 1. Synthesisof allyl(phenyl)germanes 13. The application of organogermanes to Pd-catalyzed couplings 1 has thus far received much less attention than the couplings Treatment of PhGeCl3,Ph2GeCl2,orPh3GeCl with 3, 2, or 1 involving organostannanes and organosilanes.2 This is due to the equivof allylmagnesium bromide yielded stabletriallyl(phenyl)- lower reactivity of tetracoordinated organogermanium species, the germane (1), diallyl(diphenyl)germane (2), or allyl(triphenyl)ger- less developed syntheses of vinyl/aryl germanyl derivatives, and mane (3), respectively (Scheme 1). Moreover, treatment of the higher cost of germanium relative to silicon.3 allyl(trichloro)germane with phenylmagnesium bromide also Based on the available knowledge on the susceptibility of produced allyl(triphenyl)germane (3) (44%).21 organogermanes toward coupling, it appears that the coupling is Attempted coupling of triallyl(phenyl)germane (1)with aryl promoted either by: (i) intramolecular chelation of a pendant iodides employing conditions used for the reactions of triallyl- 18 Lewis basic heteroatom which renders the Ge center “permanent- (phenyl)silanes (PdCl2/TBAF/PCy3/DMSO/H2O) or vinyltris- 47 12 ly” pentavalent or (ii) the presence of at least one heteroatom (trimethylsilyl)germanes (NaOH/H2O/H2O2/[Pd(PPh3)4]/THF) bound to the Ge center that renders the Ge center more susceptible with ArX failed to yieldbiaryl products and resulted in the to coordination by an external Lewis basic ligand (e.g., fluoride, recovery of 1. However, treatment of 1 with 1-butyl-4-iodoben- hydroxide, etc.), thereby also rendering the Ge center penta- zene (4a) (18 h, 95 °C), under conditions employed for the 817 9 valent. Although the effects offluoride/base activation and Pd- coupling of trichloro(phenyl)germanes [NaOH (8 equiv)/H2O/ catalyst/ligand combination on the coupling of organogermanes dioxane/Pd(OAc)2], yielded 1-allyl-4-butylbenzene (5a) resulting are still ambiguous, all but one4 successful exampleof germane from the transfer of the allyl group (Table 1, Entry 1). The ¡- couplings with aryl/alkenyl halides involved activation with either methyl vinylisomer 6a was also formed (5a/6a;55% total, 87:13). base or fluoride. These unexpected findings prompted us to examine the effect of Recently we reported that trichloro(phenyl)-, dichloro(diphen- reaction parameters on the transfer of allyl group from germane yl)-, and chloro(triphenyl)germanes undergo Pd-catalyzed cross- precursors 13. couplings with aryl bromides and iodides in the presence of TBAF Thus, treatment of 1 with 4a at higher concentrations of intoluene with addition of a measured amount of water. One NaOH afforded a regioisomericmixture of 5a and 6a inhigher chloride ligand on the Ge center issufficient to allow efficient yields (Entries 2 and 3). The combination of NaOH and Pd catalyst activation by fluoride and subsequent transfer of one, two or proved to be criticalfor the transfer of allyl groups from 1,since 16,17 three phenyl groups from the organogermane precursors. We reactions with only Pd(OAc)2 yielded product 5a in much lower showed that arylchlorogermanes can render a coupling efficiency yield (Entry 4). The use of different Pd catalysts also gave comparable to that of the more established stannane and silane coupling products with similar yields and regioselectivity (Entries counterparts and that their coupling efficiency reflected their 5 and 6). Reactions employing Et3N and TBAF afforded 5a in ability to generate reactive hypervalent intermediates upon fluoride moderate yields (Entries 7 and 8). The ratioofisomers 5a/6a activation.17 seems to be independent of the reaction conditions. For example, Hiyama and co-workers utilized tri-, di-, and monoallyl(aryl)- temperature has no effect on regioselectivity of the reaction of silanes in Pd-coupling with aryl halides to access biaryls.18 They allylgermane 1 with 4a. Thus, increasing the temperature from 50 suggested that allylsilanes spontaneouslycleave upon treatment to 70 to 95 °C increased the reaction rate but the same ratioof the with TBAF and an appropriate amount of water to provide an isomeric products 5a/6a (µ90:10) was observed after 1 h at all active silicate species that promotes transmetalation. Although the temperatures and remained constant after prolonged heating. chemistry of allylgermanes iswell established,19,20 the application To further investigate the transfer of the allyl group, the of allyl organogermanes as substrates for the Pd-catalyzed cross- reactions of allylgermanes 1, 2,or3 with other aryliodides 4a4c coupling with aryl halides has not been investigated. Herein, we (1.05 equiv) were carried out (Table 2). We found that triallyl- report chemoselective application of tri-, di-, and monoallyl- germane 1 gave higher yields of allylated aryl products 5a5c (phenyl)germanes toward Pd-catalyzed reactions. than diallylgermane 2,which in turn were more efficient than

Table1. Effect of the various reaction parameters on the efficiency of Table2. Allylation of aryliodides with allyl(phenyl)germanes 13a transferring allyl group from triallyl(phenyl)germane (1)a Ge n NaOH, Ar-I (4) I 4-n Pd, 1,4-dioxane Ar Ar Ge 3 Base, Pd 95 °C, 18 h 1,4-dioxane 1 n = 3 56 ° 2 n = 2 Series a Ar = 4-BuC H 95 C, 18 h 3 n = 1 6 4 Bu Bu Bu b Ar = 1-naphthyl c Ar = 4-MeOC6H4 1 4a 5a 6a i l i c Y e d Rat o Base Yield Ratioc Entry Germane Ar IPd /%b,c Entry Base Pd 5:6 /equiv /%b,c 5a:6a 1 14aPd(OAc)2 78 82:18 1 NaOH 8 Pd(OAc)2 55 87:13 2 24aPd(OAc)2 47 82:18 2 NaOH 10 Pd(OAc)2 60 89:11 3 34aPd(OAc)2 32 86:14 3 NaOH 12 Pd(OAc)2 84 82:18 4 14aPd2(dba)3 80 86:14 ® 4 NaOH Pd(OAc)2 15 94:6 5 24aPd2(dba)3 55 85:15 5 NaOH 12 Pd(PPh3)4 78 84:16 6 34aPd2(dba)3 33 85:15 6 NaOH 12 Pd2(dba)3 85 86:14 7 14bPd(OAc)2 73 90:10 7Et3N 10 Pd(OAc)2 32 83:17 8 24bPd(OAc)2 51 90:10 8 TBAF 10 Pd(PPh3)4 42 82:18 9 34bPd(OAc)2 29 91:9 aCouplings were performed on 0.16 mmol scaleof 1 (0.03 M) with 10 14bPd2(dba)3 88 91:9 1.05 equivof 4a and 0.08 equivof Pd catalyst indioxane (5 mL) and 11 24bPd2(dba)3 69 92:8 agiven stoichiometric amount of NaOH (2 M) or other bases. 12 34bPd2(dba)3 40 93:7 d bOverall yieldof 5a and 6a. cDetermined by GC-MS of the crude 13 14cPd(OAc)2 90 79:21 e reaction mixture. 14 24cPd(OAc)2 37 76:24 f 15 34cPd(OAc)2 15 73:27 a li f l l f ll l i f i ll l i Coup ngs were per ormed on 0.16 mmo sca eo germanes 1 3 a y germane 3 n trans err ng a y groups (e.g., Entr es 1 3). The i i f l li i f f ff i li l i (0.03 M) w th 1.05 equ vo ary ha des, 12 equ vo NaOH, and use o Pd2(dba)3 a orded the products 5a 5c nsght yhgher i f l b ll i l f c i l i l i i i 0.08 equ vo Pd cata yst. Overa y e do 5a and 6a. Based on y e ds, though the 5 to 6 reg ose ect v ty was not mproved (e.g., GC-MS and 1H NMR of the purified reaction mixture. dWith Entries 13 vs. 46). The bulkier 1-iodonaphthalene (4b) showed a e f [Pd2(dba)3] (56%, 81:19). With [Pd2(dba)3] (39%, 79:21). With small enhancement in the regioselectivity as compared to 4a (e.g., [Pd2(dba)3] (14%, 80:20). Entry 1 vs. 7). Transfer of the allyl group from allylgermanes also occurred efficientlywith p-MeOC6H4I(4c) (Entries 1315) but failed with p-CF3C6H4I. I Since triallylgermane 1 could transfer up to three allyl n 4b substituents in the reaction with aryl halides, experiments with 3 Ge (3 equiv) equivof 1-iodonaphthalene (4b) were attempted. Thus, treatment 4-n NaOH/Pd(OAc)2 of 1 with 4b under the optimized conditions [NaOH (12 equiv)] 1,4-dioxane/95 °C/18 h 5b gave a mixture of 5b/6b (92%, 87:13, Scheme 2). Couplings of 1 n = 3 6b i ll l ll l i i f i 2 n = 2 5b/6b (92%, 87:13) from 1 d a y germane 2 or a y germane 3 w th 3 equ vo 4b prov ded 3 n = 1 5b/6b (78%, 89:11) from 2 isomers 5b/6b in78% and 38%, respectively, in addition to 5b/6b (38%, 92:8) from 3 unchanged 4b.Itis noteworthy that coupling yields increased li f ll l l i f proportionallywith the number of allyl groups present at the Ge Scheme 2. Coup ng o a y (pheny )germanes 1 3 w th excess o 1-iodonaphthalene (4b). center (38% ¼ 78% ¼ 92%)while the isomeric ratios 5b/6b remained similar. Since the overall yield for the couplings with allylgermanes 1 and 2 never exceeded 100% (based on germanes (phenyl)germanes 3 or 2 with SbF5 (0.250.5 equiv) intercalated in as limiting reagents), it seems likely that only one allyl group from graphite23 intoluene (0.51 h, 50 °C) resulted indisappearance of the germane substrates participated in the couplings. the germane substrates (TLC, 1H NMR) and clean formation24,25 of 19 It seems feasible that the formation of products 5 and 6 from the fluorogermanes Ph3GeF (s, ¤ ¹202.3, F NMR) or Ph2GeF2 allyl(phenyl)germanes 13 in the presence of NaOH might follow (2 © s, ¤ ¹165.2, and ¹167.4), respectively, with spectroscopic a Heck coupling mechanism. Allylgermatranes5 and allyltri- data in agreement with the reported values.15,17 Analogous methylsilanes22 were reported to undergo Heck reaction with aryl treatment of 1 gave cluster of peaks at ¤ ¹140.2 to ¹159.7. halides via the initial addition of the arylPd complex to a double Treatment of the fluorogermane generated insitu from 2/SbF5 bond of the allyl group. Addition of the aryl group to a less with 4b in TBAF/toluene resulted in transfer of phenyl groups hindered £-carbon of the allyl substituent on germanes could from Ge producing biaryl 7b in addition to the homocoupling by- account for the observed regioselectivity. Coupling of vinyl- product 8b with no formation of the allylated product 5b (or 6b) tributylgermanes with aryl halides has recently been shown to (Table 3). We found that addition of at least 3 equivof TBAF occur more efficiently under Heck than Stille conditions.7 was required to produce 7b in maximum yield (Entries 15). In our search to find suitable conditions for the cleavage of Apparently, selective cleavage of the Geallyl bond with SbF5 and Geallyl bond and to generate reactive germanate species for subsequent treatment of the resulting germanylfluorides with subsequent transmetalation, we found that treatment of allyl- TBAF generates reactive hypervalent fluorogermanates that pro-

a Table3. SbF5-promoted coupling of diallyl(diphenyl)germane (2)with Table4. SbF5-promoted coupling of germanes 13 with aryl halides 1-iodonaphthalene (4b): Transfer of the phenyl groups from Gea Ge n 1. SbF5/C ° 1. SbF /C toluene/50 C/1 h m Ar 5 + m ArX Ph toluene/50 °C/1 h 2. Pd/TBAF/100 °C Ge 2 4-n Ar 2. 1-iodonaphthalene (4b, 2 equiv) 18 h/(H2O) Ph ° [Pd2(dba)3]/TBAF/100 C/18 h 1 n = 3 m = 1 (for 1) Ar 2 n = 2 m = 2 (for 2) 7b-d8b-d 2 3 n = 1 m = 3 (for 3) 7b 8b Yield Ratioc Entry Germane ArX Product TBAFb Yield Ratiod 7/%b,c 7:8 Entry Germane /equiv 7b/%c,d 7b:8b 1 1 1-Iodonaphthalene 7b 52 (45) 10:1 1 2 1 43 4.4:1 2 1 1-Bromonaphthalene 7b 42 15:1 2 2 2 53 3.9:1 3 1 4-CH3OC6H4I 7c 82 (71) 20:1 3 2 3 60 (54) 3.8:1 4 1 4-CF3C6H4I 7d 46 (41) 1.9:1 4 2 4 47 2.0:1 5 2 1-Iodonaphthalene 7b 72 (62) 5.6:1 5 2 5 44 1.3:1 6 2 1-Bromonaphthalene 7b 34 2.3:1 e 6 2 3 67 (59) 5.2:1 7 2 4-CH3OC6H4I 7c 45 2.8:1 f 7 2 3 72 (62) 5.6:1 8 2 4-CF3C6H4I 7d 33 1:1 8 2 3g 68 6.1:1 9 3 1-Iodonaphthalene 7b 71 (63) 4:1 10 3 1-Bromonaphthalene 7b 14 3.3:1 aCouplings were performed on 0.14 mmol scaleof germanes 2 11 3 4-CH OC H I 7c 32 1.6:1 (0.04 M) with 2 eqiuv of 4b and 0.05 equivof Pd catalyst. 3 6 4 b c 12 3 4-CF3C6H4I 7d 22 1:1.5 Commercial 1 M THF solution containing 5% H2O. Based upon transferring of two phenyl groups from 2. Isolated yield in aCouplings were performed on 0.14 mmol scaleof germanes (13; d e parenthesis. Based on GC-MS of the crude reaction mixture. With 0.04 M) with 0.05 equivof Pd2(dba)3 catalyst and 1.0 (for 1), 2.0 (for f g f i f li / / i / 25 ¯Lof H2O added. With 50 ¯LH2O. With 75 ¯LH2O. 2), or 3.0 ( or 3) equ vo ha des and TBAF (1 M THF, 3 equ v) water (50 ¯L). bBased upon transferring of one, two, or three phenyl mote transmetalation viaaStille-like mechanism. Treatment of 2 groups from 1, 2,or3, respectively. Isolated yield in parenthesis. cDetermined by GC-MS of the crude reaction mixture. with SbF5/Calone, as a fluoride source, failed to produce cross- coupling product 7b. The yield increased when couplings were performed with addition of a measured amount of water (µ1030 Rappoport, John Wiley & Sons, Chichester, 2002,Vol.2. i i f f li i 4 M. Kosugi, T. Tanji, Y. Tanaka, A. Yoshida, K. Fugami, M. Kameyama, equ v; Entr es 6 8), as observed be ore or coup ngs w th T. Migita, J. Organomet. Chem. 1996, 508, 255. l l 16,17 / i i i ch oro(pheny )germanes. The SbF5 TBAF comb nat on n 5J.W.Faller, R. G. Kultyshev, Organometallics 2002, 21, 5911. moist toluene allowed transfer of two phenyl groups from germane 6J.W.Faller, R. G. Kultyshev, J. Parr, Tetrahedron Lett. 2003, 44, 451. i l 2, as expected based on the couplings of Ph2GeCl2 with aryl 7 N. M. Torres, J. M. Lav s, R. E. Ma eczka, Jr., Tetrahedron Lett. 2009, li 17 50, 4407. ha des promoted by TBAF. i i i i f i / 8 T. Nakamura, H. K nosh ta, H. Sh nokubo, K. Osh ma, Org. Lett. 2002, One-pot treatment o germanes 1, 2,or3 w th SbF5 C 4, 3165. followed by Pd-catalyzed (TBAF/moist toluene) reactions with 1, 9 T. Enokido, K. Fugami, M. Endo, M. Kameyama, M. Kosugi, Adv. 2, or 3 equivof aryl halides, respectivelyafforded various biaryls Synth. Catal. 2004, 346, 1685. 7b7d in good yields and regioselectivity (Table 4). Couplings 10 M. Endo, K. Fugami, T. Enokido, H. Sano, M. Kosugi, Adv. Synth. i l l ff l i l Catal. 2007, 349, 1025. w th 1-bromonaphtha ene a so a orded 7b a though n ower i i l i i l 11 S. F. Wnuk, P. I. Garc a, Jr., Z. Wang, Org. Lett. 2004, 6, 2047. y e ds than w th odonaphtha ene. 12 Z. Wang, S. F. Wnuk, J. Org. Chem. 2005, 70, 3281. In summary, we have developed two chemoselective Pd- 13 Z. Wang, A. Gonzalez, S. F. Wnuk, Tetrahedron Lett. 2005, 46, 5313. catalyzed reactions with allyl(phenyl)germanes. One reaction 14 A. C. Spivey, C.-C. Tseng, J. P. Hannah, C. J. G. Gripton, P. de Fraine, allows for the selective transfer of the allyl group in the reaction N. J. Parr, J. J. Scicinski, Chem. Commun. 2007, 2926. i l li i i i ll l l il 15 A. C. Spivey, C. J. G. Gripton, J. P. Hannah, C.-C. Tseng, P. de Fraine, w th ary ha des med ated by NaOH prov d ng a y ary s, wh e N. J. Parr, J. J. Scicinski, Appl. Organomet. Chem. 2007, 21, 572. the second reaction allows for the selective transfer of the phenyl 16 Z.-T. Zhang, J.-P. Pitteloud, L. Cabrera, Y. Liang, M. Toribio, S. F. group from Ge center yielding biaryls upon treatment with SbF5/C Wnuk, Org. Lett. 2010, 12, 816. and TBAF. 17 J.-P. Pitteloud, Z.-T. Zhang, Y. Liang, L. Cabrera, S. F. Wnuk, J. Org. Chem. 2010, 75, 8199. i l i f / 18 A. K. Sahoo, T. Oda, Y. Nakao, T. H yama, Adv. Synth. Cata . 2004, Th s work was supported by an award rom NIH NCI 346, 1715. (5SC1CA138176) and FIU University Graduate School Dis- 19 A. C. Spivey, C. M. Diaper, Sci. Synth. 2003, 5, 181. sertation Year Fellowship to JPP. 20 T. Akiyama, in Main Group Metals in Organic Synthesis, ed. by H. Yamamoto, K. Oshima, Wiley-VCH, Weinheim, 2004,Vol. 2, pp. 593 i i i l i f l i 619. Th s paper s nceebrat on o the 2010 Nobe Pr ze awarded 21 Supporting Information is availableelectronically on the CSJ-Journal to Professors Richard F. Heck, Akira Suzuki, and Ei-ichi Negishi. Web site, http://www.csj.jp/journals/chem-lett/index.html. 22 K. Karabelas, C. Westerlund, A. Hallberg, J. Org. Chem. 1985, 50, References and Notes 3896. 1A.C.Spivey, C. J. G. Gripton, J. P. Hannah, Curr. Org. Synth. 2004, 1, 23 R. J. P. Corriu, J. M. Fernandez, C. Guerin, J. Organomet. Chem. 1980, 211. 192, 347. 2 Metal-Catalyzed Cross-Coupling Reactions, ed. by A. de Meijere, F. 24 Activated C(sp3)Ge bonds inallylgermanes can be cleaved in the Diederich, Wiley-VCH, Weinheim, Germany, 2004. presence of Lewisacids.20,23 3 The Chemistry of Organic Germanium, Tin and Lead Compounds, ed. 25 Treatment of 115 or 2 with TBAF did not affect cleavage of Geallyl by S. Patai, John Wiley & Sons, Chichester, 1995,Vol.1; The bond(s) since formation offluorogermane(s) was not observed on 1Hor Chemistry of Organic Germanium, Tin and Lead Compounds, ed. by Z. 19F NMRs.