Directed ortho-Metalation of N,N-Dialkyl O-Aryl Carbamates. Methodology, Anionic ortho Fries Rearrangement, and Lateral Metalation

Described is the directed ortho-lithiation reaction of N,N-dialkyl O-aryl carbamates, N,N-dialkyl O-naphthyl-1 and N,N-dialkyl O-naphthyl-2 carbamates with sec-butyllithium/TMEDA followed by quenching with various electrophiles to afford a range of polysubstituted aromatic compounds (Tables 1 and 2, Schemes 2 and 3). Warming solutions of the ortho-lithiated O-carbamates to room temperature without external quench with electrophiles leads to the formation of salicylamide and 1- and 2-hydroxynaphthamide derivatives by an anionic ortho-Fries rearrangements (Scheme 4). The relative stability and reactivity of different N,N-dialkyl O-carbamates has been investigated. Lateral metalation of 2-tolyl O-carbamate with LDA provides a synthesis of benzo[b]furan-2(3H)-ones (Scheme 2). Using reported results, a comparison of seven O-based directed metalation groups in reaction with several electrophiles is made. The described methodology is useful for the preparation of highly, 1,2,3-substituted, aromatic compounds

[1]  V. Snieckus,et al.  Directed ortho‐Metalation of Aryl Amides, O‐Carbamates, and Methoxymethoxy Systems: Directed Metalation Group Competition and Cooperation , 2018 .

[2]  Claudia Feberero,et al.  ortho‐Lithiation Reactions of O‐(3,n‐Dihalophenyl) N,N‐Diethylcarbamates: Synthesis of Dihalosalicylamides and 2,3,n‐Trihalophenol Derivatives , 2016 .

[3]  Chien‐Chi Hsiao,et al.  Nickel-Catalyzed Csp2–Csp3 Cross-Coupling via C–O Bond Activation , 2016 .

[4]  M. Adler,et al.  One-Pot Synthesis of O-Aryl Carbamates , 2015 .

[5]  V. Snieckus,et al.  Directed Metalation-Suzuki-Miyaura Cross-Coupling Strategies: Regioselective Synthesis of Hydroxylated 1-Methyl-phenanthrenes. , 2015, The Journal of organic chemistry.

[6]  T. Kimachi,et al.  Highly enantioselective (-)-sparteine-mediated lateral metalation-functionalization of remote silyl protected ortho-ethyl N,N-dialkyl aryl O-carbamates. , 2015, The Journal of organic chemistry.

[7]  L. Tietze,et al.  A domino approach to the enantioselective total syntheses of blennolide C and gonytolide C. , 2014, Chemistry.

[8]  V. Snieckus,et al.  Directed ortho metalation strategies. Effective regioselective routes to 1,2-, 2,3-, and 1,2,3-substituted naphthalenes. , 2014, Organic letters.

[9]  B. Jursic,et al.  Preparation of substituted semicarbazides from corresponding amines and hydrazines via phenyl carbamates , 2014 .

[10]  V. Snieckus,et al.  A practical in situ generation of the Schwartz reagent. Reduction of tertiary amides to aldehydes and hydrozirconation. , 2014, Organic letters.

[11]  M. Suckow,et al.  O-phenyl carbamate and phenyl urea thiiranes as selective matrix metalloproteinase-2 inhibitors that cross the blood-brain barrier. , 2013, Journal of medicinal chemistry.

[12]  Johnathan Board,et al.  The Directed ortho Metallation-Cross- Coupling Fusion: Development and Application in Synthesis , 2013 .

[13]  M. Putala,et al.  Highly sterically hindered binaphthalene-based monophosphane ligands: synthesis and application in stereoselective Suzuki–Miyaura reactions , 2013 .

[14]  V. Snieckus,et al.  Reductive cleavage of aryl O-carbamates to phenols by the Schwartz reagent. Expedient link to the directed ortho metalation strategy. , 2013, Organic letters.

[15]  M. Vincent,et al.  Lithium choreography: intramolecular arylations of carbamate-stabilised carbanions and their mechanisms probed by in situ IR spectroscopy and DFT calculations. , 2012, Chemistry.

[16]  J. Magolan,et al.  Directed remote aromatic metalations: mechanisms and driving forces. , 2012, Chemistry.

[17]  M. Luo,et al.  Diversity Oriented Design of Various Benzophenone Derivatives and Their in Vitro Antifungal and Antibacterial Activities , 2011, Molecules.

[18]  K. Houk,et al.  Suzuki-Miyaura cross-coupling of aryl carbamates and sulfamates: experimental and computational studies. , 2011, Journal of the American Chemical Society.

[19]  Timothy E. Hurst,et al.  Iridium-catalyzed C-H activation versus directed ortho metalation: complementary borylation of aromatics and heteroaromatics. , 2010, Chemistry.

[20]  V. Snieckus,et al.  Combined directed ortho metalation-halogen dance (HD) synthetic strategies. HD-anionic ortho fries rearrangement and double HD sequences. , 2010, Organic letters.

[21]  Zhangjie Shi,et al.  Nickel-catalyzed efficient and practical Suzuki-Miyaura coupling of alkenyl and aryl carbamates with aryl boroxines. , 2010, Organic letters.

[22]  V. Snieckus,et al.  N,N-diethyl O-carbamate: directed metalation group and orthogonal Suzuki-Miyaura cross-coupling partner. , 2009, Journal of the American Chemical Society.

[23]  N. Garg,et al.  Suzuki-Miyaura coupling of aryl carbamates, carbonates, and sulfamates. , 2009, Journal of the American Chemical Society.

[24]  G. El‐Hiti,et al.  Unexpected variations in sites of lithiation of N-(2-methoxybenzyl)- pivalamide , 2009 .

[25]  Daniel J. Tetlow,et al.  N to C aryl migration in lithiated carbamates: alpha-arylation of benzylic alcohols. , 2009, Journal of the American Chemical Society.

[26]  K. Singh,et al.  Autocatalysis in lithium diisopropylamide-mediated ortholithiations. , 2008, Journal of the American Chemical Society.

[27]  K. Singh,et al.  Anionic Snieckus-Fries rearrangement: solvent effects and role of mixed aggregates. , 2008, Journal of the American Chemical Society.

[28]  V. Snieckus,et al.  Combined Metalation–Cross Coupling Strategies: A Synthesis of Schumanniophytine by a Key Biaryl O‐Carbamate Remote Anionic Fries Rearrangement , 2008 .

[29]  S. Webber,et al.  Syntheses of novel myxopyronin B analogs as potential inhibitors of bacterial RNA polymerase. , 2007, Bioorganic & medicinal chemistry letters.

[30]  M. Lobera,et al.  Synthesis of the alkenyl-substituted tetracyclic core of the bisabosquals. , 2007, Tetrahedron.

[31]  L. Eltis,et al.  Combined directed ortho Metalation/Suzuki-Miyaura cross-coupling strategies. Regiospecific synthesis of chlorodihydroxybiphenyls and polychlorinated biphenyls. , 2007, The Journal of organic chemistry.

[32]  M. A. Peña,et al.  Palladium-catalyzed aryl-aryl cross-coupling reaction using ortho-substituted arylindium reagents. , 2007, The Journal of organic chemistry.

[33]  K. Singh,et al.  Lithium diisopropylamide-mediated ortholithiation and anionic fries rearrangement of aryl carbamates: role of aggregates and mixed aggregates. , 2006, Journal of the American Chemical Society.

[34]  V. Snieckus,et al.  Substitution of hydroxybiaryls via directed ortho-lithiation of N-silylated O-aryl N-isopropylcarbamates. , 2005, The Journal of organic chemistry.

[35]  V. Snieckus,et al.  Directed ortho metalation methodology. The N,N-dialkyl aryl O-sulfamate as a new directed metalation group and cross-coupling partner for Grignard reagents. , 2005, Organic letters.

[36]  V. Snieckus,et al.  Directed ortho Metalation reaction of aryl O-carbamates on solid support. , 2005, Organic letters.

[37]  Marna C. Whisler,et al.  Jenseits thermodynamischer Acidität: der Komplex‐induzierte Näherungseffekt (CIPE) bei Deprotonierungen , 2004 .

[38]  V. Snieckus,et al.  Beyond thermodynamic acidity: a perspective on the complex-induced proximity effect (CIPE) in deprotonation reactions. , 2004, Angewandte Chemie.

[39]  M. Schlosser,et al.  Regioflexibility in the Functionalization of Multiply Halogenated Quinolines , 2004 .

[40]  V. Snieckus,et al.  The Directed ortho Metalation Reaction – A Point of Departure for New Synthetic Aromatic Chemistry , 2004 .

[41]  I. Kozhevnikov.  Friedel–Crafts acylation and related reactions catalysed by heteropoly acids , 2003 .

[42]  V. I. Rozenberg,et al.  Efficient Synthesis of Enantiomerically and Diastereomerically Pure [2.2]Paracyclophane‐Based N,O‐Ligands , 2003 .

[43]  B. Wibbeling,et al.  Stereoselective intermolecular carbolithiation of open-chain and cyclic 1-Aryl-1-alkenyl N, N-diisopropylcarbamates coupled with electrophilic substitution. Observation of p-carboxylation in a benzyllithium derivative , 2002 .

[44]  D. Hoppe,et al.  Synthesis of substituted phenols by directed ortho-lithiation of in situ N-silyl-protected O-aryl N-monoalkylcarbamates , 2001 .

[45]  S. Danishefsky,et al.  Total synthesis and determination of the absolute configuration of frondosin B. , 2001, Journal of the American Chemical Society.

[46]  H. Geneste,et al.  2-Substituted 4-(Trifluoromethyl)phenols by Directed ortho-Lithiation , 2001 .

[47]  V. Snieckus,et al.  N-Cumyl Benzamide, Sulfonamide, and Aryl O-Carbamate Directed Metalation Groups. Mild Hydrolytic Lability for Facile Manipulation of Directed Ortho Metalation Derived Aromatics , 1999 .

[48]  T. Hense,et al.  Enantioselective Synthesis with Lithium/(−)‐Sparteine Carbanion Pairs , 1997 .

[49]  Lawrence Jones,et al.  Synthesis of tritium, deuterium, and carbon-14 labeled (S)-N-ethyl-N-methyl-3-[1-(dimethylamino)ethyl]carbamic acid phenyl ester, (L)-2,3-dihydroxybutanedioic acid salt (SDZ ENA 713 hta), an investigational drug for the treatment of alzheimer's disease , 1997 .

[50]  M. Kerr,et al.  Anionic Homologous Fries Rearrangement of O-(2-Methylaryl)carbamates. A Regiospecific Route to Benzo[b]furan-2(3H)-ones including an Unnamed Metabolite from Helenium Species , 1997 .

[51]  Taeyoung Yoon,et al.  The Total Synthesis of Dynemicin A Leading to Development of a Fully Contained Bioreductively Activated Enediyne Prodrug , 1996 .

[52]  V. Snieckus,et al.  Nickel(0)-catalyzed cross coupling of aryl O-carbamates and aryl triflates with Grignard reagents. Directed ortho metalation-aligned synthetic methods for polysubstituted aromatics via a 1,2-dipole equivalent , 1992 .

[53]  V. Snieckus,et al.  Remote directed metalation of biaryl o-carbamates. Ring to ring carbamoyl transfer route to biaryls, dibenzo[b,d]pyranones, and the natural fluorenone dengibsin , 1992 .

[54]  Ramesh Krishnamurti,et al.  1.8 – Friedel–Crafts Alkylations , 1991 .

[55]  Victor Snieckus,et al.  Directed ortho metalation. Tertiary amide and O-carbamate directors in synthetic strategies for polysubstituted aromatics , 1990 .

[56]  V. Snieckus,et al.  The 2-(trimethylsilyl)ethoxymethoxy (OSEM) directed ortho metalation group. New regiospecific synthetic routes to substituted benzenes and pyridines , 1990 .

[57]  M. Tsukazaki,et al.  Ortho-lithiation of phenols using the bis(dimethylamino)phosphoryl group as a directing group. , 1989 .

[58]  W. Bailey,et al.  The mechanism of the lithium-halogen interchange reaction: a review of the literature , 1988 .

[59]  Joseph A. Miller.  Metal-promoted Fries rearrangement , 1987 .

[60]  D. Redmore,et al.  Metalation-induced double migration of phosphorus from oxygen to carbon. Convenient preparation of bis(2-hydroxyaryl)phosphinic acids , 1986 .

[61]  J. Näsman,et al.  Tetramethyldiamido phosphate directed β-lithiation of a π-excessive heterocycle; d2-synthon to 2-substituted butenolides , 1986 .

[62]  A. Wada,et al.  ortho-Directed lithiation of (2-methoxy)ethoxy- and (2-dimethylamino)ethoxy-arenes , 1985 .

[63]  V. Snieckus,et al.  The directed ortho lithiation of O-aryl carbamates. An anionic equivalent of the Fries rearrangement , 1983 .

[64]  R. Ronald,et al.  Regioselective metalation reactions of some substituted (methoxymethoxy)arenes , 1982 .

[65]  E. E. Tamelen,et al.  Biogenetic-type total synthesis of (.+-.)-triptonide and (.+-.)-triptolide , 1982 .

[66]  P. Beak,et al.  The tertiary amide as an effective director of ortho lithiation , 1982 .

[67]  H. Brezenoff,et al.  Cardiovascular control by cholinergic mechanisms in the central nervous system. , 1982, Annual review of pharmacology and toxicology.

[68]  C. Townsend,et al.  Studies of methoxymethyl-directed metalation , 1982 .

[69]  C. P. Lewis,et al.  Methoxymethyl-directed aryl metalation. Total synthesis of (.+-.)-averufin , 1981 .

[70]  L. Melvin.  An efficient synthesis of 2-hydroxyphenylphosphonates , 1982 .

[71]  N. S. Narasimhan,et al.  Synthetic Application of Lithiation Reactions; Part XIII. Synthesis of 3-Phenylcoumarins and Their Benzo Derivatives , 1979 .

[72]  J. B. Stothers,et al.  Unprecedented 1,3-acyl shift from alkyl to aryl carbon via a phenyl anion , 1979 .

[73]  R. Ronald.  A new stereoselective synthesis of (+)-debromoaplysin and (+)-aplysin , 1976 .

[74]  H. Christensen.  Preparation of Salicylaldehydes via the Ortho-Lithio Derivatives of Methoxymethyl-Protected Phenols , 1975 .

[75]  F. N. Kotsonis,et al.  Complexation as a factor in metalation reactions. Metalation of 1-methoxy-2-phenoxyethane , 1973 .

[76]  R. Stern,et al.  Electron Exchange Polymers. X. A General Method for the Preparation of Phenolic Polystyrenes1a , 1957 .

[77]  W. Parham,et al.  The protection of hydroxyl groups. , 1948, Journal of the American Chemical Society.

[78]  G. Wittig,et al.  Über das Verhalten der halogenierten Anisole gegen Phenyl‐lithium (V. Mitteil. über die Reaktionsweise des Phenyl‐lithiums) , 1940 .

[79]  H. Gilman,et al.  Relative Reactivities of Organometallic Compounds. XX.* Metalation , 1939 .

[80]  G. Wittig,et al.  Über die Austauschbarkeit von aromatisch gebundenem Wasserstoff gegen Lithium mittels Phenyl-lithiums , 1938 .