Copper-Mediated Cross-Coupling of Organostannanes with Organic Iodides at or below Room Temperature

and, Gary D. Allred; Liebeskind, Lanny S.

doi:10.1021/ja9541239

Cited by 466 publications

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“…As anticipated, this transformation was experimentally challenging due to the sterically damanding nature of both vinyl iodide and stannane fragments. After screening of several reaction conditions, we were delighted to find the optimal conditions using a combination of copper thiophene-2-carboxylate (CuTC) [24] and [Pd(PPh3)4] in the presence of tetrabutylammonium diphenylphosphonate salt, [25] giving the diene 17 in very high yield of 77% (Scheme 5). In this step, the only significant side reaction was the selfdimerization of the vinyl iodide 3 (~10%).…”

Section: Communicationmentioning

confidence: 99%

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

2014

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Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic that is used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have excellent bactericidal activity against multidrug-resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has been reported to date. The enantioselective synthesis of the central 18-membered macrolactone is reported herein. The key reactions include ring-closing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis involves three medium-sized fragments, thus leading to a flexible yet convergent synthetic route. COMMUNICATION Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)Hideki Miyatake-Ondozabal, Elias Kaufmann and Karl Gademann* Dedication ((optional)) Abstract: Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have an excellent bactericidal activity against multi-drug resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has ever been reported to date. Herein, we report the enantioselective synthesis of the central 18-membered macrolactone. The noteworthy reactions include ringclosing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis comprises of three medium sized fragments leading to a flexible yet convergent synthetic route.

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Section: Communicationmentioning

confidence: 99%

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

2014

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“…1 H NMR chemical shifts (d) 6 were distilled from anhydrous MgSO 4 , sparged with N 2 , and stored over activated 4 Å molecular sieve pellets overnight. CD 3 OD was distilled from activated Mg and sparged with N 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Sc(OTf) 3 was obtained from Sigma-Aldrich and was dried under vacuum at 150°C for 12 h. Pd(PPh 3 ) 4 and B(C 6 F 5 ) 3 were obtained from Strem Chemicals; Bu 3 SnCl, CsF, DIBAL-H, nBuLi, NaHMDS, trans-cinnamaldehyde, 2,6-di-tert-butyl-4-methylpyridine, Cu(OTf) 2 , Me 3 Al, Me 2 AlCl, BF 3 ·OEt 2 , AlI 3 , TfOH, and 2,6-bis[(4R)-4-phenyl-2-oxazolinyl]pyridine were obtained from Sigma-Aldrich; these reagents were used without further purification. Copper(I) thiophene-2-carboxylate, 6 (iodomethyl)triphenylphosphonium iodide, 16 a-iodocinnamaldehyde (6), 17 abromocinnamaldehyde (9), 18 ethyl 2-tributylstannyl-2-butenoate (15), 4 4-iodo-2-methyl-1-phenyl-1,3-butadiene (18), 4 manganese dioxide, 19 phenylaluminum dichloride, 20 2-tributylstannylpropenol (22), 21 2-tributylstannyl-2-cyclopentenone (33), 4 hexatriene 2, 4 and cyclohexadiene 36, 4 were synthesized according to literature proce- dures. Characterization data for these compounds agree with literature values.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, formyl hexatriene 7 was synthesized by subjecting stannane 5 and iodide 6 to modified Liebeskind coupling conditions (Scheme 2). 6,7 The synthesis and purification of stannane 5 was complicated by its propensity to undergo protodestannylation as well as the sensitivity of iodide 4. Therefore, 4 and 5 were carried through to the coupling reaction with minimal purification.…”

Section: Variation Of Lewis Basic Hexatrienesmentioning

confidence: 99%

“…Synthesized in a fashion analogous to that of cyclohexadiene 8, using hexatriene 34 (1.6 mL, 24 mM in benzene-d 6 , 0.038 mmol; containing 5 mol% hexamethylbenzene as an internal standard), with the exception that the reaction mixture was heated for 20 h at 100°C. The crude product was purified by silica gel chromatography (EtOAc-hexanes, 20→23%) yielding cyclohexadiene 35.…”

Section: Cyclohexadiene 35mentioning

confidence: 99%

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On the Development of Catalytic Carba-6π Electrocyclizations

et al. 2010

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Hexatriene substrates substituted in the 2-position with carbonyl groups were studied in the context of catalytic 6π electrocyclizations. The nature of the carbonyl group and the substitution pattern on the hexatriene have significant effects on the ability of these substrates to succumb to catalysis. A novel 2-formyl hexatriene dimerization was observed. The first example of a catalytic asymmetric carba-6π electrocyclization is reported along with the discovery of an unusual kinetic resolution via a catalytic photochemical electrocyclic ring-opening.Key words: electrocyclic reactions, catalysis, dimerization, asymmetric catalysis, kinetic resolution.The ability to catalyze pericyclic reactions has greatly increased their synthetic utility and has allowed for the development of asymmetric versions. Among the different types of these reactions, Diels-Alder cycloadditions, Claisen rearrangements, and Nazarov cyclizations have been rendered asymmetric by using a variety of chiral Lewis acids, Brønsted acids and aminocatalysts. 1,2 Our group has contributed to this topic by introducing 2-alkoxy-1,4-pentadien-3-ones as excellent substrates for Nazarov cyclizations, which have yielded the first highly enantioselective examples of these 4π electrocyclizations. 2 More recently, 6π electrocyclizations have come into focus. In 2009, List and Smith independently reported asymmetric catalysis in aza-6π electrocyclizations. 3 Prior to this, we demonstrated that carba-6π electrocyclizations could be catalyzed with Lewis acids (Scheme 1). 4,5 Using esters (e.g., 1) and ketones (e.g., 2) as Lewis bases and Me 2 AlCl as a Lewis acid, we showed that rate accelerations up to 55-fold could be achieved. Our experimental results were accompanied by theoretical calculations on simple aldehydes, such as 3, which indeed showed that placement of a formyl group in the 2-position should result in significant rate accelerations upon binding of a Lewis acid or a proton.It is generally believed that aldehydes are preferred substrates for asymmetric Lewis acid catalyzed reactions, since the geometry of their complexation is well-defined. In addition, unsaturated aldehydes, such as 3, allow for aminocatalysis, which is more problematic with ketones due to their decreased electrophilicity and increased steric hindrance. We have therefore investigated 2-formyl hexatrienes in the context of catalytic 6π electrocyclizations. Herein, we report on our experiences with these substrates and provide an update on our continued studies of catalytic and asymmetric catalytic carba-6π electrocyclizations. In the course of these investigations, we have established that certain substituents on the hexatriene system are required to promote electrocyclizations and prevent side reactions, such as double bond isomerizations or Prins-type cyclizations. Powerful new Lewis acid catalysts have been identified that have led to rate accelerations an order of magnitude higher than previously described. In addition, we have launched preliminary investigations ...

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Total Synthesis of (+)-Concanamycin F

et al. 2000

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The concanamycin group of macrolides, first isolated from a culture of Streptomyces diastatochromogenes Sp. S45 by Kinashi and co-workers and typified by concanamycin A (1, Figure 1) [1a±d] and its aglycone, concanamycin F 2), [1e,f] exhibit potent inhibition of vacuolar (H ) ATPase activity. [2] The of a variety of sluggishly reactive and/or sparsely soluble hypervalent iodine reagents in water under neutral conditions. Further studies on the application of this system are now in progress. Experimental SectionMethod A (for primary alcohols): PhIO (0.44 mmol; Tokyo Chemical Industry Co., Ltd.) was added at room temperature to a stirred mixture of 1 (0.20 mmol) and KBr (0.04 mmol) in water (1.0 mL), and the mixture was stirred for 2 h. The resulting mixture was extracted with AcOEt, washed with brine, dried over Na 2 SO 4 , evaporated in vacuo, and the residue was purified by column chromatography (EtOAc/n-hexane) to give pure 2. Intermolecular esterification through nucleophilic attack on the initially formed aldehyde also proceeds under the conditions of Method B.Method B (for secondary alcohols): Water (2.0 mmol) was added dropwise to a stirred mixture of 1 (0.2 mmol), PhIO (0.22 mmol), and KBr (0.2 mmol). The mixture was stirred or sonicated for several hours while checking the reaction progress by gas or thin-layer chromatography. After completion, n-hexane was added to the mixture, and then filtered. Evaporation of the solvent under vacuum afforded a crude product that was further purified by column chromatography (Et 2 O/n-hexane) to give pure 2.Method C (for the oxidation with PSDIB): PSDIB (22 mmol), used without any pretreatment, was added at room temperature to a stirred suspension of 1 (20 mmol) and KBr (14 mmol) in water (40 mL), and the mixture was then sonicated for several hours. The resulting mixture was filtered and the residue containing 2 was washed with water to remove KBr, then extracted with n-hexane or MeOH, and the filtrate was evaporated to give 2. The product was purified by column chromatography, when necessary. benzaldehyde quantitatively, however, only a trace amount of 2 e was obtained even after 48 h under their reaction conditions (PSDIB in CH 2 Cl 2 ). [14] PSDIB was prepared from polystyrene standard (M w 44 000) (Aldrich) via poly(iodostyrene) (78 % iodinated) following known procedures. Elemental analysis (C 45.86, H 3.93, I 37.41) revealed the resin loading to be 2.0 mmol g À1 , which indicated that 68 % of the iodophenyl rings in the resin was converted into (diacetoxyiodo)phenyl rings: Y. Yamada, M. Okawara, Makromol. Chem. 1972, 152, 153 ± 162. [15] J. J. Parlow, B. L. Case, M. S. South, Tetrahedron 1999, 55, 6785 ± 6796.[16] Intermolecular homoesterification mainly proceeds to give Ph(CH 2 ) 3 OCO(CH 2 ) 2 Ph (51 %) in the absence of NaHCO 3 (2 k: 38 %).[17] Even after stirring PSDIB in water for 4 d, the addition of 1 e and KBr to this suspension gave 2 e in 68 % yield.[18] 2 e was obtained only in 8 % yield, when the reaction was performed with PSDIB in CH 2 Cl 2 (cont...

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Copper-Mediated Cross-Coupling of Organostannanes with Organic Iodides at or below Room Temperature

Abstract: reactions of organo-metal compounds reactions of organo-metal compounds O 0350 -093Copper-Mediated Cross-Coupling of Organostannanes with Organic Iodides at or below Room Temperature.

Cited by 466 publications

References 24 publications

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

On the Development of Catalytic Carba-6π Electrocyclizations

Total Synthesis of (+)-Concanamycin F

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