JOM 13866                                                                                                         No. of P...
JOM 13866                                                                                                               No...
JOM 13866                                                                                                                 ...
JOM 13866                                                                                                            No. o...
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  1. 1. JOM 13866 No. of Pages 4, Model 5+ ARTICLE IN PRESS 5 December 2005; Disk Used 1 Journal of Organometallic Chemistry xxx (2005) xxx–xxx www.elsevier.com/locate/jorganchem 2 One-pot Pd-catalyzed hydrostannation/Stille reaction 3 with acid chlorides as the electrophiles F 4 Kyoungsoo Lee, William P. Gallagher, Elli A. Toskey, OO 5 Wenzheng Chong, Robert E. Maleczka Jr. * 6 Department of Chemistry, Michigan State University, 540 Chemistry, East Lansing, MI 48824, USA 7 Received 15 November 2005; accepted 16 November 2005 8 PR 9 10 Abstract 11 A one-pot hydrostannation/Stille coupling sequence amenable to the employment of acid chloride electrophiles has been developed. ED 12 In this protocol, palladium mediated alkyne hydrostannations using Me3SnF/PMHS as an in situ trimethyltin hydride source are fol- 13 lowed by the addition of the acid chloride to afford a variety of a,b-unsaturated ketones in a single pot. 14 Ó 2005 Published by Elsevier B.V. 15 CT 16 Pd-catalyzed cross-couplings of organostannanes and one pot hydrostannation/Stille protocol to include acid 37 17 various electrophiles are convenient and widely used reac- chlorides among the viable electrophiles (Scheme 2). 38 18 tions for r-bond construction [1]. Despite the well-estab- As it were, the prospect of adopting a straightforward 39 E 19 lished power of the Stille reaction, there are negative extension of our existing methodology with acid chlorides 40 20 issues associated with handling the often unstable and/or exposed a number of uncertainties. Unlike previously used 41 RR 21 toxic organostannanes used in these couplings [2]. To obvi- electrophiles, reactions with acid chlorides face a host of 42 22 ate direct manipulation of the stannane coupling partners, potential problems. For example, under our standard con- 43 23 our group has developed one-pot Pd-catalyzed hydrostan- ditions the triorganotin hydrides used in the hydrostanna- 44 24 nation/Stille coupling sequences [3] that begin with the tion step are prepared by the reduction of organotin halides 45 25 in situ generation of triorganotin hydrides [4]. The hydrides with polymethylhydrosiloxane (PMHS) in the presence of 46 CO 26 so formed react in situ with alkynes to form vinylstann- fluoride. Thus, we were confronted with the possibility of 47 27 anes, which without isolation undergo Stille cross-coupling residual tin hydride or PMHS reducing the acid chloride 48 28 reactions (Scheme 1). In earlier reports, we showed that [6] or the a,b-unsaturated ketone products [7]. In addition, 49 29 vinyl, aryl, and benzyl halides were all acceptable electro- while Stille reactions with acid chlorides have been done in 50 30 philes for this sequence [3]. Noticeably absent from this water [5b], we worried about acid chloride hydrolysis. Fur- 51 UN 31 group of electrophiles were acid chlorides. thermore, adventitious formation of HCl from the acid 52 32 We considered this omission problematic because acid chlorides could promote competitive protiodestannylation 53 33 chlorides represent an important class of Stille electrophiles of the vinyltin intermediates [8]. Lastly, decarbonylation 54 34 [5]. In StilleÕs earliest studies, he showed that reactions with [5a] of the palladium(II) oxidative addition intermediate 55 35 these compounds could efficiently produce a,b-unsaturated was also one of our concerns. Nonetheless, provided these 56 36 ketones [5a]. Thus, we sought to expand the scope of the problems could be defeated, achieving the synthesis of var- 57 ious a,b-unsaturated ketones from alkynes and acid chlo- 58 * Corresponding author. Tel.: +1 517 355 9715x124; fax: +1 517 353 rides in a single pot using an organotin salt as the initial 59 1793. tin source, a single load of catalyst, and unpurified vinyltin 60 E-mail address: maleczka@chemistry.msu.edu (R.E. Maleczka Jr.). intermediates would be attractive. 61 0022-328X/$ - see front matter Ó 2005 Published by Elsevier B.V. doi:10.1016/j.jorganchem.2005.11.041
  2. 2. JOM 13866 No. of Pages 4, Model 5+ ARTICLE IN PRESS 5 December 2005; Disk Used 2 K. Lee et al. / Journal of Organometallic Chemistry xxx (2005) xxx–xxx Bu3SnF, PHMS, Table 1 cat. TBAF, One-pot hydrostannation/Stille with acid chlorides using Bu3SnF R H R Ph 1.5 equiv Bu3SnF, O 1 mol% (Ph3P)2PdCl2; 1.6 equiv PMHS, Ph, THF R' Cl Br 1 mol % Pd2dba3, R 4 mol % TFP, (1.3 equiv) O Scheme 1. cat. TBAF R' R 65 ˚C THF, 2 h, rt O Entry R Acid chloride Stille rxn Yielda cat. Pd O time (h) (%) Bu3SnH R R' Cl F R Bu3Sn R' R 1 CH3 COCl 6 96 2 CH(CO2Me)2 6 84 OO Bu3SnF COCl Scheme 2. 3 CH3 6 56 4 CH(CO2Me)2 F 3C 2 74 b 62 In starting our exploration of this putative one-pot 5 CH3 57 6 COCl PR 63 sequence, we opted to use an ‘‘anhydrous’’ variation for S 64 the in situ generation of tributyltin hydride [4]. Thus, CH3 6 63 65 Bu3SnF, PMHS, and a catalytic amount of TBAF were 6 COCl O 66 reacted in the presence of an alkyne and an acid chloride. 67 Not surprisingly, this procedure gave little of the desired 7 CH3 1-Naphthoyl acid 10 31 68 a,b-unsaturated ketone as the acid chloride was consumed chloride ED 69 by the Bu3SnF/PMHS/TBAF combination in advance of 8 CH3 COCl 10 91 70 the cross-coupling. To avoid this trouble, we simply added 9 CH(CO2Me)2 6 58 71 the acid chloride (without any additional Pd-catalyst) after a Average isolated yield over two runs. 72 vinylstannane formation was complete (1 mol% Pd2dba3, b The decarbonylated product was also observed. 73 4 mol% TFP, 1.5 equiv. Bu3SnF, 2.5 equiv. PMHS, cat. CT 74 TBAF, THF, r.t., ca. 2 h or until complete by GC). Under 75 this two-step one-pot procedure a variety of a,b-unsatu- 76 rated ketones could be formed (Table 1). 77 This first generation study only employed alkynes that 1.5 equiv Bu3SnF, E 78 were tri-substituted at the propargylic position so that 2.5 equiv PMHS, 1 mol % Pd2dba3, 79 our evaluation of the process would not be complicated (71 %) 4 mol % TFP, cat. TBAF, Cl RR 80 by the formation of regioisomers. The protocol proved THF, 2 h, rt; then + 81 workable with a variety of acid chlorides. Typically cross- CHO 82 couplings were achieved after 6–10 h at 65 °C and the 2-chlorobenzoyl chloride (1.3 equiv), 65 oC, 6 h (32 %) 83 yields could be very high. However, in some cases intrusive Cl 84 amounts of side products were observed. For example, CO Scheme 3. 85 reactions with either 4-trifluoromethylbenzoyl chloride 86 (entry 4) or 2-chlorobenzoyl chloride (Scheme 3) witnessed 87 the formation of the corresponding benzaldehydes and the to 2 h [10]. More importantly; the observed increases in 103 88 decarbonylated coupling products [5a]. Moreover, despite reaction rates were generally met with substantially higher 104 89 our best efforts at reaction optimization some of the prod- yields and fewer visible side reactions. For example, the 105 UN 90 uct yields remained moderate at best. previously failed coupling of 2-chlorobenzoyl chloride 106 91 We attributed some of these problems to the relatively (entry 3) could now be achieved in an over all yield of 107 92 slow cross-coupling times. In our previously reported tin 86%. Other entries worthy of further comment include 108 93 catalyzed hydrostannation/Stille sequence with other sp2- the reaction of 4-bromobenzoyl chloride (entry 6). Despite 109 94 halides, switching from Bu3SnCl to the less sterically its two potential coupling sites (acid chloride and aryl bro- 110 95 demanding Me3SnCl gave faster reaction times and mide) this substrate chemoselectively reacted with the 111 96 decreased byproduct formation [9]. Looking for a similar in situ generated vinyl stannane at the acid chloride site 112 97 outcome for the two-step one-pot acid chloride coupling to afford the product in near quantitative yield [11]. Fur- 113 98 sequence, the initial tin species was changed from Bu3SnF thermore, that product did not suffer from any unwanted 114 99 to Me3SnF. In doing so, we were gratified to observe a sig- dehalogenation of the aryl bromide [12]. Likewise, cinna- 115 100 nificantly improved process. moyl chloride afforded the 1,4-diene-3-one in 81% yield 116 101 As illustrated in Table 2, using Me3SnF in place of without any 1,4-reduction [7] of this activated dienone 117 102 Bu3SnF typically decreased cross-coupling times from 6 (entry 12). 118
  3. 3. JOM 13866 No. of Pages 4, Model 5+ ARTICLE IN PRESS 5 December 2005; Disk Used K. Lee et al. / Journal of Organometallic Chemistry xxx (2005) xxx–xxx 3 Table 2 One-pot hydrostannation/Stille with acid chlorides using Me3SnF [10] O 1.5 eq. Me3SnF, 2.5 eq. PMHS, (1.3 equiv) O 1 mol % Pd2dba3, 4 mol % TFP, R Cl Me3Sn R cat. TBAF, THF, 2 r, rt 65 ˚C Entry Acid Stille Product Yielda Entry Acid chloride Stille Product Yielda chloride rxn (%) rxn (%) time (h) time (h) O F COCl 1 2 94 7 2 99 COCl OO S S O O MeO COCl MeO 2 2 96 8 COCl 2 95 MeO MeO O O O PR OMe OMe O O COCl COCl 3 2 86 9 2 92 Cl Cl ED COCl O 4 2 72 10 COCl 2 90 NO 2 NO2 6 6 CT O NC COCl O NC COCl 5 2 98 11 4 92 E O O COCl COCl RR 6 4 98 12 4 80 Br Br a Average isolated yield over two reactions. CO 119 Unfortunately, even under these conditions not all sub- the Stille reaction time to 8 h to achieve the reported yield. 136 120 strates were universally accepted. As shown in entry 4, 4- In an attempt to circumvent the distal/proximal regiochem- 137 121 nitrobenzoyl chloride still gave the decarbonylated cou- ical matter, we first looked at performing the Pd-catalyzed 138 122 pling product, even when the reaction was run under an hydrostannation step on the 1-bromoalkyne derivative 139 UN 123 atmosphere of CO [5a]. [3b,8b]. However, for reasons that remain unclear, that 140 124 Finally, we examined a reaction sequence that started substrate did not work well in the hydrostannation/cross- 141 125 with an alkyne that was not fully substituted at the propar- coupling sequence. Another option involved running the 142 126 gylic position (Scheme 4). As previously mentioned such hydrostannation step under free radical conditions [4] 143 127 substrates afford measurable levels of the proximal vinylst- and then adding the acid chloride along with a Pd-catalysts 144 128 annanes under Pd-catalyzed conditions [4,8b,13]. Such to carry out the second step. Owing to the volatility [2] of 145 129 vinyltins are known to be sluggish Stille partners [1,14]. Me3SnH, we chose to run the radical hydrostannation with 146 130 This is reflected in the slightly diminished yield (71%) of Bu3SnH. While, this modified procedure was successful at 147 131 the cross-coupled product, which primarily arose from eliminating the proximal isomer (at the cost of some Z- 148 132 the selective cross-coupling of the distal vinyltin intermedi- vinylstannane formation), recourse to the tributyltin again 149 133 ate with the benzoyl chloride [15]. Furthermore, it must be gave the a,b-unsaturated ketone in only modest average 150 134 noted that for this substrate we were also required to add overall yield (42%). Usefully, the TBS ether survived the 151 135 an additional load of the palladium catalyst and extend fluoride present throughout both successful sequences. 152
  4. 4. JOM 13866 No. of Pages 4, Model 5+ ARTICLE IN PRESS 5 December 2005; Disk Used 4 K. Lee et al. / Journal of Organometallic Chemistry xxx (2005) xxx–xxx 1.5 equiv Me3SnF, OTBS [2] (a) P.J. Smith (Ed.), Chemistry of Tin, Blackie Academic and 178 2.5 equiv PMHS, benzoyl chloride Professional, New York, 1998; 179 cat. TBAF, (1.3 equiv), (b) A.G. Davies (Ed.), Organotin Chemistry, VCH, New York, 1997. 180 [3] (a) W.P. Gallagher, R.E. Maleczka Jr., J. Org. Chem. 70 (2005) 841– 181 1 mol % (Ph3P)4Pd, Me3Sn (Ph3P)2PdCl2 846; 182 4 mol % TFP, 1 mol %, 183 + proximal vinyltin (b) Also see: C.D.J. Boden, G. Pattenden, T. Ye, J. Chem. Soc., THF, 2 h, rt; then 65 oC, 8 h Perkin Trans. I (1996) 2417–2419. 184 (71%) [4] R.E. Maleczka Jr., L.R. Terrell, D.H. Clark, S.L. Whitehead, W.P. 185 Gallagher, I. Terstiege, J. Org. Chem. 64 (1999) 5958–5965. 186 OTBS OTBS [5] (a) J.W. Labadie, D. Tueting, J.K. Stille, J. Org. Chem. 48 (1983) 187 Ph 4634–4642; 188 (b) For selected recent examples, see: R. Lerebours, A. Camacho- 189 F O Soto, C. Wolf, J. Org. Chem. 70 (2005) 8601–8604; 190 (c) T. Ichige, S. Kamimura, K. Mayumi, Y. Sakamoto, S. Terashita, 191 E. Ohteki, N. Kanoh, M. Nakata, Tetrahedron Lett. 46 (2005) 1263– 192 OO benzoyl chloride 1267; 193 OTBS (1.3 equiv), (Ph3P)2PdCl2 (d) K.R. Dieter, Tetrahedron 55 (1999) 4177–4236. 194 1.5 equiv Bu3SnF, 2.5 equiv PMHS, 1 mol % [6] J. Lipowitz, S.A. Bowman, J. Org. Chem. 38 (1973) 162–165. 195 [7] J.A. Muchnij, R.E. Maleczka, Jr. Chemoselective Conjugate reduc- 196 cat. AIBN Bu3Sn 65 ˚C, 3 h (42%) tion of a,b-unsaturated carbonyl compounds with poly- 197 toluene, 70 ˚C, 2 h + Z-vinyltin methylhydrosiloxane. In: Proceedings of the 37th Organosilicon 198 PR Symposium, Philadelphia, PA, 2004; Poster P-34. 199 Scheme 4. [8] (a) S.A. Hitchcock, D.R. Mayhugh, G.S. Gregory, Tetrahedron Lett. 200 36 (1995) 9085–9088; 201 ´ (b) H.X. Zhang, F. Guibe, G. Balavoine, J. Org. Chem. 15 (1990) 202 153 In summary, we have expanded the one-pot hydrostan- 1857–1867. 203 154 nation/Stille coupling method to allow acid chlorides to [9] R.E. Maleczka Jr., W.P. Gallagher, I. Terstiege, J. Am. Chem. Soc. 204 122 (2000) 384–385. 205 ED 155 serve as the electrophilic coupling partner. Problems asso- [10] Typical reaction procedure: Pd2dba3 (0.01 mmol, 9.2 mg) and TFP 206 156 ciated with the use of these reactive building blocks can be (0.04 mmol, 9.3 mg) were added to THF (5 mL) and the resulting 207 157 avoided by adding the acid chloride to the reaction after mixture was stirred at r.t. for 15 min. At that time, 3,3-dimethyl 1- 208 158 the vinylstannane has been produced in situ from butyne (1 mmol, 0.125 mL), Me3SnF (1.5 mmol, 274 mg), PMHS 209 159 Me3SnF/PMHS generated Me3SnH and a corresponding (2.5 mmol, 0.09 mL), and TBAF (1 drop of a 1 M solution in THF 210 CT 160 alkyne. Both aliphatic and electronically varied aromatic (0.008 mmol)) were added successively. The reaction was then 211 allowed to stirr at r.t. for 2 h, at which time the hydrostannation was 212 161 acid chlorides can be employed in this one-pot synthesis complete by GC. The acid chloride (1.3 mmol) was then added and 213 162 of a,b-unsaturated ketones. the mixture was allowed to stirr at reflux (65 °C) until the cross- 214 coupling was judged complete by TLC (2–4 h). At that time, the 215 reaction was diluted with saturated aq. KF (3 mL) and stirred for 0.5 216 E 163 Acknowledgments h. The reaction was extracted with Et2O and H2O and the aqueous 217 phase was back extracted with Et2O. The combined organics were 218 164 We thank the NIH (HL-58114), NSF (CHE-9984644), RR dried over MgSO4, filtered, and concentrated. The resulting residue 219 165 and the Yamanouchi USA Foundation for generous sup- was purified by silica gel chromatography to afford the corresponding 220 166 port. E.A.T. thanks the NSF REU Program (NSF a,b-unsaturated ketone. 221 167 0138932) at MSU for the opportunity granted. [11] Such chemoselectivity has been previously observed. See: Ref. [5b]. 222 [12] R.E. Maleczka Jr., R.J. Rahaim, R.R. Teixeira, Tetrahedron Lett. 43 223 (2002) 7087–7090. 224 CO 168 Appendix A. Supplementary data [13] (a) N.D. Smith, J. Mancuso, M. Lautens, Chem. Rev. 100 (2000) 225 3257–3282; 226 169 Supplementary data associated with this article can be (b) M.B. Rice, S.L. Whitehead, C.M. Horvath, J.A. Muchnij, R.E. 227 170 found, in the online version, at doi:10.1016/j.jorganchem. Maleczka Jr., Synthesis (2001) 1495–1504, and references cited; 228 171 2005.11.041. (c) K. Kikukawa, H. Umekawa, F. Wada, T. Matsuda, Chem. Lett. 229 (1988) 881–884; 230 UN ´ (d) H.X. Zhang, F. Guibe, G. Balavoine, Tetrahedron Lett. 29 (1988) 231 172 References 619–622; 232 (e) Y. Ichinose, H. Oda, K. Oshima, K. Utimoto, Bull. Chem. Soc. 233 173 [1] (a) J.K. Stille, Pure Appl. Chem. 57 (1985) 1771–1780; Jpn. 60 (1987) 3468–3470. 234 174 (b) J.K. Stille, B.L. Groh, J. Am. Chem. Soc. 109 (1987) 813–817; [14] X. Han, B.M. Stoltz, E.J. Corey, J. Am. Chem. Soc. 121 (1999) 7600– 235 175 (c) J.K. Stille, Angew. Chem., Int. Ed. Engl. 25 (1986) 508–523; 7605. 236 176 (d) V. Farina, V. Krishnamurthy, W.J. Scott, Org. React. 50 (1997) [15] The cross-coupling of 4-methoxybenzoyl chloride afforded the corre- 237 177 1–652. sponding a,b-unsaturated ketone in only 33% yield. 238 239

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