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Application of Organic Azides for the Synthesis of Nitrogen-Containing Molecules

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Application of Organic Azides for the Synthesis of Nitrogen-Containing Molecules ACCOUNT 21 Application of Organic Azides for the Synthesis of Nitrogen-Containing Molecules Shunsuke Chiba* Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore Fax +6567911961; E-mail: [email protected] Received 31 May 2012 Organic azides possess diverse chemical reactivities.4 Abstract: In this account, recent advances made on the reactions of several types of organic azides, such as vinyl azides, cyclic 2-azido Owing to their 1,3-dipole character, they undergo [3+2] alcohols, a-azido carbonyl compounds, towards the synthesis of cycloaddition with unsaturated bonds, such as those in nitrogen-containing molecules are described. alkynes and alkenes as well as carbonitriles (Scheme 1, part a).5 Organic azides can also be regarded as nitrene 1 Introduction equivalents (Scheme 1, part b).6 Accordingly, their reac- 2 Chemistry of Vinyl Azides tions with nucleophilic anions, electrophilic cations, and 2.1 Thermal [3+2]-Annulation of Vinyl Azides with 1,3-Dicar- radicals can formally provide the corresponding nitrogen bonyl Compounds 2.2 Manganese(III)-Catalyzed Formal [3+2]-Annulation with anions, cations, and radicals, respectively, forming a new 1,3-Dicarbonyl Compounds bond with the internal azido nitrogen and releasing molec- 2.3 Manganese(III)-Mediated/Catalyzed Formal [3+3]-Annu- ular nitrogen. Moreover, the generation of anions, cations, lation with Cyclopropanols and radicals at the a-position to the azido moiety can re- 2.4 Synthesis of Isoquinolines from a-Aryl-Substituted Vinyl sult in rapid denitrogenation to deliver the corresponding Azides and Internal Alkynes by Rhodium–Copper Bimetal- iminyl species, which can be used in further synthetic lic Cooperation transformations (i.e., carbon–nitrogen bond formation). 3 Chemistry of Cyclic 2-Azido Alcohols 3.1 Manganese(III)-Catalyzed Ring Expansion of 2-Azido- cyclobutanols (a) 1,3-Dipoles N R 3.2 Palladium(II)-Catalyzed Ring Expansion of Cyclic 2-Azido N N N alkenes R N N CC Alcohols N CC R N triazolines N + 4 Chemistry of a-Azido Carbonyl Compounds CC alkynes CC N triazoles 4.1 Orthogonal Synthesis of Isoindole and Isoquinoline Deriv- R N CN nitriles N R NNN atives CN 4.2 Generation of Iminylcopper Species and Their Catalytic tetrazoles Carbon–Carbon Bond Cleavage under an Oxygen Atmo- (b) Nitrene equivalents + sphere N R N N R N N 2 4.3 Copper(II)-Catalyzed Aerobic Synthesis of Azaspirocyclo- nitrenes hexadienones 5 Conclusion with carbanions or other nucleophiles – + + R N N N R N X 2 Key words: azides, nitrogen-containing heterocycles, radical reac- N X with carbocations tions, redox reactions, oxygenations + Downloaded by: University of Oxford. Copyrighted material. + + R N N N R N C N C 2 with carbon radicals + R N N + R N N C N C 2 1 Introduction chemistry of α-azido anions, cations, and radicals N N + C N N The chemistry of organic azides commenced with the syn- C N 2 N N 1 + C N N thesis of phenyl azide by Griess in 1864 and the discov- C N 2 N N + ery of the rearrangement of acyl compounds with C N N C N 2 2 hydrogen azide (HN3) by Curtius in 1890. Since 1950, various synthetic organic reactions have been developed Scheme 1 using acyl, aryl, and alkyl azides, which have been exten- sively applied for the synthesis of nitrogen-containing We have been interested in the intriguing chemical reac- azaheterocycles as well as peptides.3 tivity of organic azides, such as vinyl azides, cyclic 2-azi- do alcohols, and a-azido carbonyl compounds (Scheme 2). In this account, we describe recent advances made on the reactions of these organic azides towards the SYNLETT 2012, 23, 21–44 xx.xx.2011 synthesis of nitrogen-containing molecules which have Advanced online publication: 09.12.2011 been developed in our research group. DOI: 10.1055/s-0031-1290108; Art ID: A59911ST © Georg Thieme Verlag Stuttgart · New York 22 S. Chiba ACCOUNT N inyl species serve for the formation of carbon–nitrogen N N R N bonds. In this section, we present the synthesis of azahet- N N N HO R' erocycles from vinyl azides via several types of reaction R N O N mode based on the above chemical reactivities. -azido carbonyl cyclic 2-azido a vinyl azides compounds alcohols Scheme 2 2.1 Thermal [3+2]-Annulation of Vinyl Azides with 1,3-Dicarbonyl Compounds During the course of our study on the chemistry of 2H- 2 Chemistry of Vinyl Azides azirine derivatives,11 it was found that the reaction of azir- ine 1 with acetylacetone (2) in 1,2-dichloroethane at room Intermolecular annulation reactions can allow for the temperature gave tetrasubstituted pyrrole 3 in quantitative straightforward and selective construction of complex cy- yield after 33 hours (Scheme 4). clic molecular structures in a one-pot manner from rela- EtO C 2 tively simple building blocks, one of the most ideal COMe Cl 7 Cl O O CO Et processes in organic synthesis from an atom- and step- 2 Me + N 8 N Me economical point of view. Inspired by this perspective, Me H DCE Cl Cl r.t., 33 h (1.2 equiv) 2 we have recently been interested in the application of vi- 1 quant nyl azides as a three-atom unit including one nitrogen for 3 various types of annulation reactions to prepare azahet- Scheme 4 erocycles. One of the attractive chemical properties of vinyl azides is While the reaction of azirine 1 with acetylacetone (2) in their ability to undergo thermal decomposition to give tetrahydrofuran (THF) has been reported, the yield of pyr- highly strained three-membered cyclic imines, 2H-azir- role 3 was low.12 The generation of 3 in high yield in the ines, via vinylnitrene intermediates following denitroge- above reaction (Scheme 4) led us to further investigate the nation (Scheme 3, part a).9 Moreover, the carbon–carbon pyrrole formation. double bond of vinyl azides can be used for the formation The reaction may proceed through the addition of acetyl- of new carbon–carbon bonds with appropriate organome- acetone (2) to the imino carbon of azirine 1,13 followed by tallic compounds (R′–[M]) or radical species (R¢) which nucleophilic attack of the nitrogen in the resulting aziri- results in the generation of iminyl metals or iminyl radi- dine to a carbonyl group with concurrent ring opening of cals, respectively (Scheme 3, parts b and c).10 These im- the strained three-membered ring.14 However, the insta- bility and poor accessibility of the 2H-azirines prevented R us using this strategy as a synthetic method for pyrroles. R R N Δ (a) Accordingly, we planned to use vinyl azides as precursors N – N N N 2 15 H -azirines 2 N of 2H-azirines which can be easily synthesized and han- vinylnitrenes dled (Scheme 5). R R R R' As proposed in Scheme 5, simple heating of a mixture of R' R'–[M] [M] N N (b) N ethyl 2-azido-3-(2,6-dichlorophenyl)acrylate (4) and N N – N 2 [M] N N acetylacetone (2) in toluene at 100 °C provided pyrrole 5 16 in 86% yield (Table 1, entry 1). Various 2-azido-substi- Downloaded by: University of Oxford. Copyrighted material. R R R' tuted cinnamates possessing electron-donating and -with- R' R N N (c) R' N N – N drawing groups on the phenyl group (entries 2–8), as well 2 N N N as a derivative containing a pyridyl moiety (entry 9), re- Scheme 3 acted with acetylacetone (2) to give the corresponding 2- Biographical Sketch Shunsuke Chiba was born University of Tokyo (work- Nanyang Technological in Zushi, Kanagawa, Japan, ing under Professor Koichi University, Singapore, as an in 1978. He obtained his Narasaka). He was appoint- assistant professor. His re- B.Eng. from Waseda Uni- ed as a research associate at search focus is methodology versity in 2001 and received the University of Tokyo in development in the area of his Ph.D. in 2006 from the 2005. In 2007, he moved to synthetic organic chemistry. Synlett 2012, 23, 21–44 © Thieme Stuttgart · New York ACCOUNT Applications of Organic Azides for the Synthesis of Nitrogen-Containing Molecules 23 17,18 2 2 R COMe R indoles via intramolecular C–H amination. It is note- 1 R O O Δ + N 1 worthy that the above intermolecular reactions of 2-azido- – N R Me 2 Me Me N N 2 – H O H 2 2 substituted cinnamate derivatives with acetylacetone (2) gave pyrroles exclusively without any indole formation. – N – H O 2 2 As b-substituents (R1) of azidoacrylates, ethoxycarbonyl 2 Me R 2 2 1 1 R R COMe R R Me O and alkyl groups could be introduced, giving the corre- N O H N Me H 1 H O R sponding pyrroles in good yields (entries 12 and 13). Sim- OH N Me O H Me ple azidoacrylate 30 also reacted smoothly (entry 14). B A Using a-aryl-substituted vinyl azides, not only phenyl Scheme 5 groups, but also naphthyl, indolyl, pyrrolyl, and ben- zothiophenyl moieties could be installed at the 3-position of the resulting trisubstituted pyrroles (entries 15–26). a- arylpyrroles in good yields. Vinyl azides 22 and 24 bear- Alkyl-substituted vinyl azide 56 reacted smoothly to give ing acetyl and (dimethylamino)carbonyl moieties instead the corresponding pyrrole 57 in 82% yield (entry 27). An of an a-ethoxycarbonyl group could be employed to give E,Z-mixture of 2-phenylvinyl azide (58) could also be the corresponding pyrroles 23 and 25 (entries 10 and 11, used to prepare trisubstituted pyrrole 59 in 85% yield (en- respectively).
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