2-二烷基膦基-2′,4′,6′-三异丙基-3,6-二甲氧基-1,1′-联苯的合成工艺
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摘要
以1,4-二甲氧基-2-氟苯和2,4,6-三异丙基溴苯为原料合成2-碘-3,6-二甲氧基-2′,4′,6′-三异丙基-1,1′-联苯.在四氢呋喃和甲苯混合溶液中将联基碘代物制成格式试剂,在溴化亚铜和溴化锂的催化下,与二环己基氯化膦或二叔丁基氯化膦进行反应,分别以82%和75%的产率生成2-二环己基膦基-2′,4′,6′-三异丙基-3,6-二甲氧基-1,1′-联苯和2-二叔丁基膦基-2′,4′,6′-三异丙基-3,6-二甲氧基-1,1′-联苯,并对其结构进行了表征.
2-(di-alkylphosphino)-2′,4′,6′-triisopropyl-3,6-dimethoxy-1,1′-biphenyl was synthesized with 1,4-dimethoxy-2-fluorobenzene and 2,4,6-triisopropylbromobenzene as the raw materials. The biphenyl iodide was then tranfered into the grignard reagent in tetrahydrofuran and toluene solution. After the reaction with dicyclichexylphosphine chloride or ditertbutylphosphine chloride under the catalysis of copper bromide and lithium bromide,the title product were got with the yield of 82% and 75%,and their structures were also characterized.
2-(di-alkylphosphino)-2′,4′,6′-triisopropyl-3,6-dimethoxy-1,1′-biphenyl was synthesized with 1,4-dimethoxy-2-fluorobenzene and 2,4,6-triisopropylbromobenzene as the raw materials. The biphenyl iodide was then tranfered into the grignard reagent in tetrahydrofuran and toluene solution. After the reaction with dicyclichexylphosphine chloride or ditertbutylphosphine chloride under the catalysis of copper bromide and lithium bromide,the title product were got with the yield of 82% and 75%,and their structures were also characterized.
引文
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[3] FLECKENSTEIN C A,PLENIO H. Sterically demanding trialkylphosphines for palladium-catalyzed cross coupling reactionsalternatives to Pt-Bu3[J]. Chemical Society Reviews,2010,39:694-711.
[4] WOLFE J P,BUCHWALD S L. Cheminform abstract:scope and limitations of the Pd/BINAP-catalyzed amination of aryl bromides[J]. Cheminform,2000,65(4):1144-1157.
[5] YIN J,ZHAO M M,HUFFMAN M A,et al. Pd-catalyzed N-arylation of heteroarylamines[J]. Organic Letters,2002,4(20):3481-3484.
[6] ZHAO M,YIN J,HUFFMAN M A,et al. A very concise synthesis of a potent N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitor[J]. Tetrahedron,2006,62(6):1110-1115.
[7] BONALA R,TORRES M C,AND C R I,et al. Synthesis of the PhIP adduct of 2′-deoxyguanosine and its incorporation into oligomeric DNA[J]. Chemical Research in Toxicology,2006,19(6):734-738.
[8] SHEN Z,HONG Y,HE X,et al. Switching the chemoselectivity in the amination of 4-chloroquinazolines with aminopyrazoles[J].Organic Letters,2010,41(26):552-553.
[9] SURRY D S,BUCHWALD S L. Dialkylbiaryl phosphines in Pd-catalyzed amination:a user’s guide[J]. Chemical Science,2011,2:27-50.
[10] MARTIN R,BUCHWALD S L. Palladium-catalyzed Suzuki-miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands[J]. Accounts of Chemical Research,2008,41(11):1461-1473.
[11] BUSACCA C A,FANDRICK D R,SONG J J,et al. The growing impact of catalysis in the pharmaceutical industry[J]. Advanced Synthesis and Catalysis,2011,353(11-12):1825-1864.
[12] TORBORG C,BELLER M. Recent applications of palladium-catalyzed coupling reactions in the pharmaceutical,agrochemical,and fine chemical industries[J]. Advanced Synthesis and Catalysis,2010,351(18):3027-3043.
[13] WATSON D A,SU M,TEVEROVSKIY G,et al. Formation of ArF from LPdAr(F):catalytic conversion of aryl triflates to aryl fluorides[J]. Science,2009,325:1661-1664.
[14] MAITI D,FORS B P,HENDERSON J L,et al. Palladium-catalyzed coupling of functionalized primary and secondary amines with aryl and heteroaryl halides:two ligands suffice in most cases[J]. Chemical Science,2010,2(1):57-68.
[15] FORS B P,BUCHWALD S L. A multiligand based Pd catalyst for C-N cross-coupling reactions[J]. Journal of the American Chemical Society,2011,2011(2):15914-15917.
[16] FORS B P,WATSON D A,BISCOE M R,et al. A highly active catalyst for Pd-catalyzed amination reactions:cross-coupling reactions using aryl mesylates and the highly selective monoarylation of primary amines using aryl chlorides[J]. Journal of the American Chemical Society,2010,40(7):13552-13554.
[17] HENDERSON J L,MCDERMOTT S M,BUCHWALD S L. Palladium-catalyzed amination of unprotected halo-7-azaindoles[J].Organic Letters,2011,2011(3):4438-4441.
[18] FORS B P,DOOLEWEERDT K D,ZENG Q,et al. An efficient system for the Pd-catalyzed cross-coupling of amides and aryl chlorides[J]. Tetrahedron,2009,65:6576.
[19] HOSHIYA N,BUCHWALD S L. An improved synthesis of Brett Phos and Rock Phos-type biarylphosphine ligands[J]. Advanced Synthesis and Catalysis,2012,354(10):2031-2037.