Abstract
The alkyl electrophiles with β-hydrogens have been scarcely employed in the transition-metal-catalyzed cross-coupling reactions until recently. This is due to their low electrophilicity and the facile occurrence of β-hydrogen elimination under standard conditions. However, in recent years, the alkyl electrophiles have received a marked increase in attention; numerous synthetic examples using the alkyl electrophiles as coupling partners have been reported. This chapter classifies the recently reported cross-coupling reactions of these alkyl electrophiles, grouping the reactions by organometallic reagent. Introductions to representative synthetic examples are given.
Keywords
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Kochi JK, Tamura M (1971) Mechanism of the silver-catalyzed reaction of Grignard reagents with alkyl halides. J Am Chem Soc 93:1483–1485
Kochi JK, Tamura M (1971) Alkylcopper(I) in the coupling of Grignard reagents with alkyl halides. J Am Chem Soc 93:1485–1487
Tamura M, Kochi JK (1972) Copper-catalyzed coupling of Grignard reagents and alkyl halides in tetrahydrofuran solutions. J Organomet Chem 42:205–228
Nunomoto S, Kawakami Y, Yamashita Y (1983) Cross-coupling reaction of 2-(1,3-butadienyl)magnesium chloride with alkyl or aryl halides by lithium chloride-cupric chloride (Li2CuCl4), a superior catalyst. J Org Chem 48:1912–1914
Wright ME, Jin M-J (1990) Bis(pyridyl)-silane and -methanol ligands IV. Catalytic application of nickel(II) complexes in the Kumada cross-coupling reaction. J Organomet Chem 287:373–379
Castle PL, Widdowson DA (1986) New developments in palladium catalysed cross coupling: the coupling of alkyl iodides with alkyl Grignard reagents. Tetrahedron Lett 27:6013–6016
Donkervoort JG, Vicario JL, Jastrzebski JTBH, Gossage RA, Cahiez G, van Koten G (1998) Novel tridentate diamino organomanganese(II) complexes as homogeneous catalysts in manganese(II)/copper(I) catalyzed carbon–carbon bond forming reactions. J Organomet Chem 558:61–69
Cahiez G, Chaboche C, Jezequel M (2000) Cu-catalyzed alkylation of Grignard reagents: a new efficient procedure. Tetrahedron 56:2733–2737
Terao J, Watanabe H, Ikumi A, Kuniyasu H, Kambe N (2002) Nickel-catalyzed cross-coupling reaction of Grignard reagents with alkyl halides and tosylates: remarkable effect of 1,3-butadienes. J Am Chem Soc 124:4222–4223
Terao J, Naitoh Y, Kuniyasu H, Kambe N (2003) Pd-catalyzed cross-coupling reaction of alkyl tosylates and bromides with Grignard reagents in the presence of 1,3-butadiene. Chem Lett 32:890–891
Uemura M, Yorimitsu H, Oshima K (2006) Synthesis of Cp*CH2PPh2 and its use as a ligand for the nickel-catalyzed cross-coupling reaction of alkyl halides with aryl Grignard reagents. Chem Commun, 4726–4728
Vechorkin O, Proust V, Hu X (2009) Functional group tolerant Kumada–Corriu–Tamao coupling of nonactivated alkyl halides with aryl and heteroaryl nucleophiles: catalysis by a nickel pincer complex permits the coupling of functionalized Grignard reagents. J Am Chem Soc 131:9756–9766
Frisch C, Shaikh N, Zapf A, Beller M (2002) Palladium-catalyzed coupling of alkyl chlorides and Grignard reagents. Angew Chem Int Ed 41:4056–4059
Frisch AC, Rataboul F, Zapf A, Beller M (2003) First Kumada reaction of alkyl chlorides using N-heterocyclic carbene/palladium catalyst systems. J Organomet Chem 687:403–409
Tamura M, Kochi JK (1971) Vinylation of Grignard reagents. Catalysis by iron. J Am Chem Soc 93:1487–1489
Fürstner A, Leitner A (2002) Iron-catalyzed cross-coupling reactions of alkyl-Grignard reagents with aryl chlorides, tosylates, and triflates. Angew Chem Int Ed 41:609–612
Martin R, Fürstner A (2004) Cross-coupling of alkyl halides with aryl Grignard reagents catalyzed by a low-valent iron complex. Angew Chem Int Ed 43:3955–3957
Nagano T, Hayashi T (2004) Iron-catalyzed Grignard cross-coupling with alkyl halides possessing β-hydrogens. Org Lett 6:1297–1299
Nakamura M, Matsuo K, Ito S, Nakamura E (2004) Iron-catalyzed cross-coupling of primary and secondary alkyl halides with aryl Grignard reagents. J Am Chem Soc 126:3686–3687
Bedford RB, Bruce DW, Frost RM, Goodby JW, Hird M (2004) Iron(III) salen-type catalysts for the cross-coupling of aryl Grignards with alkyl halides bearing β-hydrogens. Chem Commun, 2822–2823
Bedford RB, Bruce DW, Frost RM, Hird M (2005) Simple iron-amine catalysts for the cross-coupling of aryl Grignards with alkyl halides bearing β-hydrogens. Chem Commun, 4161–4163
Bedford RB, Betham M, Bruce DW, Danopoulos AA, Frost RM, Hird M (2006) Iron-phosphine, -phosphite, -arsine, and -carbene catalysts for the coupling of primary and secondary alkyl halides with aryl Grignard reagents. J Org Chem 71:1104–1110
Cahiez G, Habiak V, Duplais C, Moyeux A (2007) Iron-catalyzed alkylations of aromatic Grignard reagents. Angew Chem Int Ed 46:4364–4366
Chowdhury RR, Crane AK, Fowler C, Kwong P, Kozak CM (2008) Iron(III) amine-bis(phenolate) complexes as catalysts for the coupling of alkyl halides with aryl Grignard reagents. Chem Commun, 94–96
Ohmiya H, Yorimitsu H, Oshima K (2006) Cobalt(diamine)-catalyzed cross-coupling reaction of alkyl halides with arylmagnesium reagents: stereoselective constructions of arylated asymmetric carbons and application to total synthesis of AH13205. J Am Chem Soc 128:1886–1889
Ohmiya H, Wakabayashi K, Yorimitsu H, Oshima K (2006) Cobalt-catalyzed cross-coupling reactions of alkyl halides with aryl Grignard reagents and their application to sequential radical cyclization/cross-coupling reactions. Tetrahedron 62:2207–2213
Yasuda S, Yorimitsu H, Oshima K (2008) Vanadium-catalyzed cross-coupling reactions of alkyl halides with aryl Grignard reagents. Bull Chem Soc Jpn 81:287–290
Tucker CE, Knochel P (1993) Cross-coupling between functionalized alkylcopper reagents and functionalized alkyl halides. J Org Chem 58:4781–4782
Devasagayaraj A, Stüdemann T, Knochel P (1995) A new nickel-catalyzed cross-coupling reaction between sp3 carbon centers. Angew Chem Int Ed Engl 34:2723–2725
Giovannini R, Stüdemann T, Dussin G, Knochel P (1998) An efficient nickel-catalyzed cross-coupling between sp3 carbon centers. Angew Chem Int Ed 37:2387–2390
Giovannini R, Knochel P (1998) Ni(II)-catalyzed cross-coupling between polyfunctional arylzinc derivatives and primary alkyl iodides. J Am Chem Soc 120:11186–11187
Giovannini R, Stüdemann T, Devasagayaraj A, Dussin G, Knochel P (1999) New efficient nickel-catalyzed cross-coupling reaction between two Csp3 centers. J Org Chem 64:3544–3553
Zhou J, Fu GC (2003) Palladium-catalyzed Negishi cross-coupling reactions of unactivated alkyl iodides, bromides, chlorides, and tosylates. J Am Chem Soc 125:12527–12530
Zhou J, Fu GC (2003) Cross-couplings of unactivated secondary alkyl halides: room-temperature nickel-catalyzed Negishi reactions of alkyl bromides and iodides. J Am Chem Soc 125:14726–14727
Organ MG, Avola S, Dubovyk I, Hadei N, Kantchev EAB, O’Brien CJ, Valente C (2006) A user-friendly, all-purpose Pd-NHC(NHC = N-heterocyclic carbene) precatalyst for the Negishi reaction: a step towards a universal cross-coupling catalyst. Chem Eur J 12:4749–4755
Krasovskiy A, Duplais C, Lipshutz BH (2009) Zn-mediated, Pd-catalyzed cross-couplings in water at room temperature without prior formation of organozinc reagents. J Am Chem Soc 131:15592–15593
Nakamura M, Ito S, Matsuo K, Nakamura E (2005) Iron-catalyzed chemoselective cross-coupling of primary and secondary alkyl halides with arylzinc reagents. Synlett, 1794–1798
Ejiri S, Odo S, Takahashi H, Nishimura Y, Gotoh K, Nishihara Y, Takagi K (2010) Negishi alkyl–aryl cross-coupling catalyzed by Rh: efficiency of novel tripodal 3-diphenylphosphino-2-(diphenylphosphino)methyl-2-methylpropyl acetate ligand. Org Lett 12:1692–1695
Shimizu R, Fuchikami T (1996) Palladium catalyzed coupling reactions of β-perfluoroalkyl-substituted alkyl halides with organostannanes. Tetrahedron Lett 37:8405–8408
Shimizu R, Fuchikami T (2001) Effect of fluorine substituents on functionalizations of alkyl halides with organostannanes. Tetrahedron Lett 42:6891–6894
Tang H, Menzel K, Fu GC (2003) Ligands for palladium-catalyzed cross-couplings of alkyl halides: use of an alkyldiaminophosphane expands the scope of the Stille reaction. Angew Chem Int Ed 42:5079–5082
Hosoya T, Sumi K, Doi H, Wakao M, Suzuki M (2006) Rapid methylation on carbon frameworks useful for the synthesis of 11CH3-incorporated PET tracers: Pd(0)-mediated rapid coupling of methyliodide with an alkenyltributylstannane leading to a 1-methylalkene. Org Biomol Chem, 410–415
Ishiyama T, Abe S, Miyaura N, Suzuki A (1992) Palladium-catalyzed alkyl-Alkyl cross-coupling reaction of 9-alkyl-9-BBN derivatives with iodoalkanes possessing β-hydrogens. Chem Lett, 691–694
Charette AB, Giroux A (1996) Palladium-catalyzed Suzuki-type cross-couplings of iodocyclopropanes with boronic acid: synthesis of trans-1,2-dicycopropyl alkenes. J Org Chem 61:8718–8719
Netherton MR, Dai C, Neuschütz K, Fu GC (2001) Room-temperature alkyl–alkyl Suzuki cross-coupling of alkyl bromides that possess β hydrogens. J Am Chem Soc 123:10099–10100
Kirchhoff JH, Dai C, Fu GC (2002) A method for palladium-catalyzed crosscouplings of simple alkyl chlorides: Suzuki reactions catalyzed by [Pd2(dba)3]/PCy3. Angew Chem Int Ed 41:1945–1947
Netherton MR, Fu GC (2002) Suzuki cross-couplings of alkyl tosylates that possess β hydrogen atoms: synthetic and mechanistic studies. Angew Chem Int Ed 41:3910–3912
Kirchhoff JH, Netherton MR, Hills ID, Fu GC (2002) Boronic acids: new coupling partners in room-temperature Suzuki reactions of alkyl bromides. Crystallographic characterization of an oxidative-addition adduct generated under remarkably mild conditions. J Am Chem Soc 124:13662–13663
Arentsen K, Caddick S, Cloke FGN, Herring AP, Hitchcock PB (2004) Suzuki–Miyaura cross-coupling of aryl and alkyl halides using palladium/imidazolium salt protocols. Tetrahedron Lett 45:3511–3515
Hills ID, Netherton MR, Fu GC (2003) Toward an improved understanding of the unusual reactivity of Pd0/trialkylphosphane catalysts in cross-coupling of alkyl electrophiles: quantifying the factors that determine the rate of oxidative addition. Angew Chem Int Ed 42:5749–5752
Terao J, Kambe N (2006) Transition metal-catalyzed C–C bond formation reactions using alkyl halides. Bull Chem Soc Jpn 79:663–672
Zhou J, Fu GC (2004) Suzuki cross-couplings of unactivated secondary alkyl bromides and iodides. J Am Chem Soc 126:1340–1341
Duncton MAJ, Estiarte MA, Tan D, Kaub C, O’Mahony DJR, Johnson RJ, Cox M, Edwards WT, Wan M, Kincaid J, Kelly MG (2008) Preparation of aryloxetanes and arylazetidines by use of an alkyl-aryl Suzuki coupling. Org Lett 10:3259–3262
González-Bobes F, Fu GC (2006) Amino alcohols as ligands for nickel-catalyzed Suzuki reactions of unactivated alkyl halides, including secondary alkyl chlorides, with arylboronic acids. J Am Chem Soc 128:5360–5361
Saito B, Fu GC (2007) Alkyl–alkyl Suzuki cross-couplings of unactivated secondary alkyl halides at room temperature. J Am Chem Soc 129:9602–9603
Rodríguez N, de Arellano CR, Asensio G, Medio-Simón M (2007) Palladium-catalyzed Suzuki–Miyaura reaction involving a secondary sp3 carbon: studies of stereochemistry and scope of the reaction. Chem Eur J 13:4223–4229
Saito B, Fu GC (2008) Enantioselective alkyl–alkyl Suzuki cross-couplings of unactivated homobenzylic halides. J Am Chem Soc 130:6694–6695
Lu Z, Fu GC (2010) Alkyl–alkyl Suzuki cross-coupling of unactivated secondary alkyl chlorides. Angew Chem Int Ed 49:6676–6678
Lundin PM, Fu GC (2010) Asymmetric Suzuki cross-couplings of activated secondary alkyl electrophiles: arylations of racemic α-chloroamides. J Am Chem Soc 132:11027–11029
Owston NA, Fu GC (2010) Asymmetric alkyl–alkyl cross-coupling of unactivated secondary alkyl electrophiles: stereoconvergent Suzuki reactions of racemic acylated halohydrins. J Am Chem Soc 132:11908–11909
Lu Z, Wisily A, Fu GC (2011) Stereoconvergent amine-directed alkyl–alkyl Suzuki reactions of unactivated secondary alkyl chlorides. J Am Chem Soc 133:8154–8155
He A, Falk JR (2010) Stereospecific Suzuki cross-coupling of alkyl α-cyanohydrin triflates. J Am Chem Soc 132:2524–2525
Hatakeyama T, Hashimoto T, Kondo Y, Fujiwara Y, Seike H, Takaya H, Tamada Y, Ono T, Nakamura M (2010) Iron-catalyzed Suzuki–Miyaura coupling of alkyl halides. J Am Chem Soc 132:10674–10676
Nishihara Y, Okada Y, Jiao J, Suetsugu M, Lan M-T, Kinoshita M, Iwasaki M, Takagi K (2011) Highly regio- and stereoselective synthesis of multialkylated olefins through carbozirconation of alkynylboronates and sequential Negishi and Suzuki–Miyaura coupling reactions. Angew Chem Int Ed 50:8660–8664
Lee J-Y, Fu GC (2003) Room-temperature Hiyama cross-couplings of arylsilanes with alkyl bromides and iodides. J Am Chem Soc 125:5616–5617
Powell DA, Fu GC (2004) Nickel-catalyzed cross-couplings of organosilicon reagents with unactivated secondary alkyl bromides. J Am Chem Soc 126:7788–7789
Strotman NA, Sommer S, Fu GC (2007) Hiyama reactions of activated and unactivated secondary alkyl halides catalyzed by a nickel/norephedrine complex. Angew Chem Int Ed 46:3556–3558
Dai X, Strotman NA, Fu GC (2008) Catalytic asymmetric Hiyama cross-couplings of racemic α-bromo ester. J Am Chem Soc 130:3302–3303
Eckhardt M, Fu GC (2003) The first applications of carbene ligands in cross-couplings of alkyl electrophilics: Sonogashira reactions of unactivated alkyl bromides and iodides. J Am Chem Soc 125:13642–13643
Altenhoff G, Wurtz S, Glorius F (2006) The first palladium-catalyzed Sonogashira coupling of unactivated secondary alkyl bromides. Tetrahedron Lett 47:2925–2928
Vechorkin O, Barmaz D, Proust V, Hu X (2009) Ni-catalyzed Sonogashira coupling of nonactivated alkyl halides: orthogonal functionalization of alkyl iodides, bromides, and chlorides. J Am Chem Soc 131:12078–12079
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Yamamoto, A., Nishimura, Y., Nishihara, Y. (2013). Recent Advances in Cross-Coupling Reactions with Alkyl Halides. In: Nishihara, Y. (eds) Applied Cross-Coupling Reactions. Lecture Notes in Chemistry, vol 80. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-32368-3_8
Download citation
DOI: https://doi.org/10.1007/978-3-642-32368-3_8
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-32367-6
Online ISBN: 978-3-642-32368-3
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)