181,159 research outputs found
Site-selective C-H Functionalization using Directing Group Strategy via C-H Bond Activation
No full textThe thesis entitled “Site-selective C-H Functionalization using Directing Group Strategy via C-H Bond Activation” is divided into two sections. Section A, is presented in four chapters, comprising the work on the aromatic ortho-C-H addition to maleimide, mechanistic studies with DFT, ortho-C-H oxidative Heck reaction with maleimides, and ortho-C-H addition to maleimide with a deciduous/traceless directing group. Section B describes a formal oxidative [2+2+2] benzannulation of indoles with alkynes via a directing group strategy.
Publications:
1. Ru (II)-Catalyzed C–H Activation: Ketone-Directed Novel 1, 4-Addition of Ortho C–H Bond to Maleimides KR Bettadapur, V Lanke, KR Prabhu; Org. Lett., 2015, 17, 4658-4661
2. A Deciduous Directing Group Approach for the Addition of Aryl and Vinyl nucleophiles to Maleimides KR Bettadapur, V Lanke, KR Prabhu; Chem. Comm., 2017, 53, 6251-6254
3. Weak Directing Group Steered Formal [2+2+2]- Oxidative Cycloaddition for Selective Benzannulation of Indoles KR Bettadapur, R Kapanaiah, V Lanke and KR Prabhu; J. Org. Chem., DOI: 10.1021/acs.joc.7b0271
An introduction to granular flow / K. Kesava Rao, Prabhu R. Nott.
No full textengineering bookfair2015Includes bibliographical references (p. 463-482) and index.xxi, 490 pages :This book describes theories for granular flow based on continuum models and alternative discrete models
Design and Development of Metal-free Cross Dehydrogenative Coupling Reactions for the Construction of C-S, C-O and C-C bonds
No full textThe thesis entitled “Design and Development of Metal-Free Cross Dehydrogenative Coupling Reactions for the construction of C-S, C-O and C-C bonds” is divided into three Chapters. Chapter 1 is presented in five parts, which reveals the cross dehydrogenative coupling (CDC) strategies for the C–S bond forming reactions through C–H functionalization strategy using heterocyclic thiols and thiones. Chapter 2 presents tetrabutyl ammonium iodide (TBAI) catalyzed chemoselective α-aminoxylation of ketones with N-hydroxyimidates using TBHP as oxidant under cross dehydrogenative coupling (CDC) strategy. Chapter 3 describes a transition metal-free Minisci reaction for the acylation of isoquinolines, quinolines, and quinoxaline.
Chapter 1
Iodine Promoted C-S Bond Forming Reactions using Dimethyl Sulfoxide as an Oxidant
Chapter 1 reveals the utility of cross dehydrogenative coupling (CDC) reactions for the formation of C–S bonds by employing C–H functionalization strategies.1 The direct functionalization of C–H bonds to form C–C and C–X (N, O, S and P) bonds using metal-free reaction conditions is an interesting research topic in recent years.2 Use of dimethyl sulfoxide as an oxidant is emerging as one of the research topics of great interest and utility.3 Heterocyclic thiols and thiones are important precursors for synthesizing a variety of pharmaceuticals and biologically active compounds.4 Therefore it is useful to develop CDC reactions using heterocyclic thiols and thiones as precursors. In this chapter, we describe CDC reactions of heterocyclic thiols and thiones for the sulfenylation of ketones, aldehydes, α, β unsaturated methyl ketone derivatives, pyrazolones, enaminones and imidazoheterocycles using DMSO as an oxidant
Chapter 1: Part 1
Iodine Promoted Regioselective α-Sulfenylation of Carbonyl Compounds using Dimethyl Sulfoxide as an Oxidant: In this chapter, a rare regioselective C–H sulfenylation of carbonyl compounds with heterocyclic thiones and thiols have been described using iodine and dimethyl sulfoxide as reagents. Thus, dimethyl sulfoxide (as an oxidant) and stoichiometric amount of iodine have been used for the sulfenylation of ketones using heterocyclic thiones. Whereas the sulfenylation of ketones with heterocyclic thiols required catalytic amount of iodine. This protocol offers a rare regioselective sulfenylation of (i) methyl ketones in the presence of more reactive α-CH2 or α-CH groups, and (ii) aldehydes under CDC method. A few representative examples are highlighted in Scheme 1.5 The application of this methodology has been demonstrated by synthesizing a few precursors for Julia-Kocienski olefination intermediates.
Scheme 1. Iodine promoted rare regioselective α-sulfenylation of ketones and aldehydes
Siddaraj , Y.; Prabhu, K. R. Org. Lett. 2016, 18, 6090
Chapter 1: Part 2
Regioselective Sulfenylation of α’-CH3 or α’-CH2 Groups of α, β Unsaturated Ketones using
Dimethyl Sulfoxide as an Oxidant: In this chapter, an interesting regioselective sulfenylation of α’-CH3 or α’-CH2 groups of α, β unsaturated ketones using dimethyl sulfoxide as an oxidant and catalytic amount of aq. HI (20 mol %) as an additive has been described. This eco-friendly method uses readily available, inexpensive I2 or HI and DMSO. This methodology exhibits a high regioselectivity without forming Michael addition product in the presence of strong acid such as aq. HI or iodine, which is difficult to achieve under cross dehydrogenative coupling (CDC) conditions. Current methodology exhibits a broad substrate scope. A few examples are shown in Scheme 2.6
Scheme 2. HI and DMSO promoted α’-sulfenylation of α, β unsaturated ketones
Siddaraju, Y.; Prabhu, K. R. (Manuscript submitted)
Chapter 1: Part 3
Iodine Catalyzed Sulfenylation of Pyrazolones using Dimethyl Sulfoxide as an Oxidant: In this chapter, a sustainable and efficient strategy for the sulfenylation of pyrazolones has been described using metal-free conditions by employing DMSO as an oxidant and iodine as a catalyst. A variety of heterocyclic thiols, heterocyclic thiones and disulfides undergo C–H functionalization reaction with pyrazolone derivatives furnishing the corresponding sulfenylated products in short time. Most of the products are isolated in pure form without column purification. A few examples are presented in Scheme 3.7
Scheme 3. Iodine promoted sulfenylation of pyrazolones
Siddaraju, Y.; Prabhu, K. R. Org. Biomol. Chem. 2017, 15, 5191
Chapter 1: Part 4
Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: Sulfenylation of Enaminones using Dimethyl Sulfoxide as an Oxidant: In this chapter, synthesis of poly functionalized aminothioalkenes has been described using substoichiometric amount of iodine and DMSO as an oxidant. This metal-free methodology enables a facile sulfenylation of enaminones with heterocyclic thiols and thiones. This methodology is one of the simple approaches for the sulfenylation of enaminones under cross dehydrogenative coupling method. A few examples are highlighted in Scheme 4.8
Scheme 4. Cross-dehydrogenative coupling approach for sulfenylation of enaminones
Siddaraju, Y.; Prabhu, K. R. J. Org. Chem. 2017, 82, 3084
Chapter 1: Part 5
Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: A Regioselective Sulfenylation of Imidazoheterocycles using DMSO as an Oxidant: In this chapter, a simple synthetic approach for the regioselective sulfenylation of imidazoheterocycles using iodine as a catalyst and DMSO as an oxidant under cross dehydrogenative coupling (CDC) reaction conditions has been demonstrated. This protocol provides an efficient, mild and inexpensive method for coupling heterocyclic thiols and heterocyclic thiones with imidazoheterocycles. This is the first report on sulfenylation of imidazoheterocycles with heterocyclic thiols and heterocyclic thiones under metal-free conditions. A few examples are shown in Scheme 5.9
Scheme 5. Cross-dehydrogenative coupling approach for sulfenylation of imidazoheterocycles
Siddaraju, Y.; Prabhu, K. R. J. Org. Chem. 2016, 81, 7838
Chapter 2
Chemoselective α-Aminoxylation of Aryl Ketones: Cross Dehydrogenative Coupling Reactions Catalyzed by Tetrabutyl Ammonium Iodide: In this chapter, chemoselective α-aminoxylation of ketones with N-hydroxyimidates catalyzed by tetrabutyl ammonium iodide (TBAI) has been presented. The coupling reaction of a variety of ketones with N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI), N-hydroxybenzotriazole (HOBt) or 1-hydroxy-7-azabenzotriazole (HOAt) using TBHP as oxidant has been investigated. This α-aminoxylation of ketones is chemoselective as aryl methyl ketones, aliphatic ketones as well as benzylic position are inactive under the reaction condition. A few examples are highlighted in Scheme 6.10 The application of this method has been demonstrated by transforming a few coupled products into synthetically useful vinyl phosphates.
Scheme 6. Chemoselective α-aminoxylation of ketones with N-hydroxyimidates
Siddaraju, Y.; Prabhu, K. R. Org. Biomol. Chem. 2015, 13, 11651
Chapter 3
A Transition Metal-Free Minisci Reaction: Acylation of Isoquinolines, Quinolines, and Quinoxaline: In this chapter, transition metal-free acylation of isoquinoline, quinoline and quinoxaline derivatives with aldehydes has been described by employing TBAB (tetrabutyl ammonium bromide, 30 mol %) and K2S2O8 as an oxidant under cross dehydrogenative coupling (CDC) reaction. This intermolecular acylation of electron-deficient heteroarenes provides an easy access and a novel acylation method of heterocyclic compounds. The application of this CDC strategy has been illustrated by synthesizing isoquinoline-derived natural products. A few representative examples are shown in Scheme 7.11
Scheme 7. CDC reactions of heteroarenes with aldehydes
Siddaraju, Y.; Lamani, M.; Prabhu, K. R. J. Org. Chem. 2014, 79, 385
A narrow QRS tachycardia with changing rate: What is the mechanism(s)?
No full textAbstract not availableMukund A. Prabhu, Geoffrey R. Wong, Robert D. Anderson, Jonathan M. Kalma
Raorchestes leucolatus Vijayakumar, Dinesh, Prabhu & Shanker, 2014, sp. nov.
No full text8. Raorchestes leucolatus sp. nov. (Figures 2, 3 & 12; Tables 2 & 3) Holotype: ZSI/ WGRC /V/A/ 879 (CESF 1146), an adult male (SVL 16.9 mm), collected by S.P. Vijayakumar, Mrugank V. Prabhu and and Mayavan in July 2010 from a wet evergreen forest site (10.9731 N, 76.6289 E), Elivalmalai Massif (Fig 1), Peninsular India. Paratype: ZSI/ WGRC /V/A/ 880 (CESF 1147), an adult male (SVL 17.1 mm), collected by S.P. Vijayakumar, Mrugank V. Prabhu and Mayavan in July 2010 from a wet evergreen forest site (10.9731 N, 76.6289 E), Elivalmalai Massif (Fig 1), Western Ghats, Peninsular India. Lineage diagnosis. Raorchestes leucolatus sp. nov. can be diagnosed by its phylogenetic position within the Bombayensis clade (Fig 3) and exhibits moderate levels (16 S— 2.9 %) of divergence from its closest relative R. tuberohumerus. It also shows strong differences in morphology (Fig 12 a,d,e,f). The lineage is diagnosed based on its phylogenetic position, genetic divergence and morphological distinctness. Field diagnosis. Morphology. Raorchestes leucolatus sp. nov. could be morphologically confused with its close relative R. tuberohumerus. However, it can be distinguished from R. tuberohumerus on many aspects of morphology. Raorchestes leucolatus sp. nov. can be distinguished by its smaller size (males) 16.9 mm (16.2–17.1, n= 4) (vs. 18.4 mm (17.7 –19.0, n= 6) in R. tuberohumerus); head width, HW/SVL= 0.38 (0.37–0.39, n= 4) greater than head length, HL/SVL= 0.29 (0.28–0.31, n= 4) (vs. HW/SVL= 0.35 (0.33–0.36, n= 6) almost equal to head length (HL/SVL= 0.37 (0.36–0.40, n= 6) in R. tuberohumerus); shorter thigh length, TL/SVL= 0.45 (0.43–0.46, n= 4) (vs. TL/SVL= 0.50 (0.46–0.52, n= 6) in R. tuberohumerus); shorter foot length, FOL/SVL= 0.36 (0.35–0.36, n= 4) (vs. FOL/SVL= 0.40 (0.37–0.43) in R. tuberohumerus); groin region with white blotches (vs. groin region with yellow blotches in R. tuberohumerus; disc colour orange (vs. disc colour grey to brown in R. tuberohumerus). Geography. Found to be restricted to the mid-elevations of Elivalmalai Massif (see natural history and distribution for details). Ecology. Found to be an understory forest species (n= 4) and was observed in short grasses and shrubs along the forest edges. Description of holotype (all measurements in mm). A small sized bush frog (SVL = 16.9 mm), width of head sub equal to head length (HW = 6.2 mm; HL = 5.2 mm), flat dorsally; snout acutely pointed in total profile, slightly protruding beyond mouth. Snout length is sub equal to diameter of eye (SL = 2.2 mm, EL = 2.3 mm). Canthus rostralis angular, loreal region flat. Interorbital space (IUE = 2.1 mm) flat and sub equal to upper eyelid (UEW = 1.5 mm). Interorbital space between posterior margins of the eyes 1.7 times that of anterior margins (IFE = 3.5, IBE = 5.8 mm). Nostrils oval, nearer to tip of snout. Weak symphysial knob. Eyes small, pupil horizontal. Tympanum indistinct, rounded, barely visible behind the eye. Tongue bifid, granular without papilla. Supratympanic fold from behind eye to shoulder. Relative length of fingers I<II<IV<III. Finger tips with well developed small disks (fd 3 = 0.8 mm; fw 3 = 0.5) with distinct circum–marginal grooves, fingers with dermal fringes on both sides. Webbing on palm absent, subarticular tubercles moderate and pre-pollex moderate. Supernumerary tubercles absent. Hind limb long, heels touch when folded at right angles to the body. Thigh/Femur (TL = 7.8 mm), sub equal to Shank/Tibia (ShL = 7.5 mm); longer than foot (FOL = 6.1 mm) and less than heel to tip of fourth toe (TFOL = 10.2 mm). Relative toe length I<II<III<V<IV, webbing poor; web formula (I 1 - 1 II 1- 2 III 1- 2 IV 2 - 1 V). Tibiotarsal articulation reaches posterior corner of eye. Outer metatarsal tubercle, supernumerary tubercles and tarsal tubercle absent. Color in life. Dorsum maroon with a pair of distinct orange patch on the shoulder. An orange coloured horizontal broken band between the upper eyelids. Groin with distinct white blotches, ventrally varying shades of brown with irregular white spots on the belly. Throat darker towards lips, disks on finger and toes distinctly orange. Iris coarsely speckled with varying shades of golden brown, overlaid on an irregular brown markings. Distinct rufous edged speckles around the pupil (Fig 12 (b)). Etymology. The species is named after one of its distinct characteristics, the ‘white patch’ on the groin (Greek: leukos = white). Natural history and distribution. The species was discovered in the mid elevations (894–958 m, n= 2) and was observed at forested sites in the Elivalmalai Massif (Fig 1 & 2) situated north of Palghat Gap. Currently there are no reports of any allied species from north of its range. The southern most range of R. tuberohumerus, its geographically closest relative, appears to be Wayanad plateau (Fig 1). Further surveys are needed to verify the occurrence of this species or any close relatives in the lower elevations of Nilgiri Massif.Published as part of Vijayakumar, S. P., Dinesh, K. P., Prabhu, Mrugank V. & Shanker, Kartik, 2014, Lineage delimitation and description of nine new species of bush frogs (Anura: Raorchestes, Rhacophoridae) from the Western Ghats Escarpment, pp. 451-488 in Zootaxa 3893 (4) on pages 477-479, DOI: 10.11646/zootaxa.3893.4.1, http://zenodo.org/record/28757
Regioselective Functionalization of Indoles using Directing Group Strategy : An Efficient Transition Metal Catalysis
No full textThe thesis entitled “Regioselective Functionalization of Indoles using Directing Group Strategy: An Efficient Transition Metal Catalysis” is divided into two sections. Section A, which is presented in three chapters, describes the regioselective alkenylation of indoles using directing group strategy. Whereas, Section B, which is divided in to two chapters, narrates the synthesis of 4-amino indoles using directing group strategy and site selective addition of maleimide to indole at C2-position.
Section A
Chapter 1. C2-Alkenylation of indoles
The indole ring system is one of the most abundant heterocycles present in nature. The synthesis and functionalization of indoles is one of the major areas of focus for synthetic organic chemists.1 Alkenylation of indole at C2-position is a challenging task due to the electrophilic nature of the reaction. For this reason, the functionalization of indole at C2-position is less addressed. In this chapter, a highly regioselective alkenylation of indole at the C2-position has been described by using the Ru(II) catalyst and employing a directing group (DG) strategy.2 This directing group strategy offers rare selectivity for the alkenylation of N-benzoylindole at the C2-position in the presence of the more reactive C3-position. A variety of N-benzoylindole derivatives are shown to undergo alkenylation at C2-positon. Deprotection of the benzoyl group has also been demonstrated, and the resulting products serve as a useful synthon for synthesizing a variety of natural products. A few representative examples are highlighted in Scheme 1.3
1 (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873.
(b) Karamyan, K. A. J.; Hamann, M. T. Chem. Rev. 2010, 110, 4489.
2 (a) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(b) Engle, K. M.; Mei, T.-S.; Wasa, M.; J.-Q. Yu, Acc. Chem. Res. 2012, 45, 788.
(c) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45, 936.
(d) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879.
3 Lanke, V.; Prabhu, K. R. Org. Lett. 2013, 15, 2818.
Scheme 1: C2- Alkenylation of indoles
Chapter 2 describes a highly regioselective alkenylation of indoles at the C4-position by employing aldehyde functional group as a directing group, and Ru as a catalyst, under a mild reaction conditions. This approach leads to a short synthetic route for C4-alkenylated indoles, which serve as precursors for ergot alkaloids and related heterocyclic compounds.4 Further The potential of the present strategy has been demonstrated by performing (i) scale up reaction, (ii) selective reduction of olefin double bond and (iii) synthesizing substituted 1,3,4,5-tetrahydrobenzo[cd] in two steps with an overall yield of 68%. 1,3,4,5-Tetrahydrobenzo[cd] is one of the key intermediates for synthesizing ergot alkaloids. A few examples are highlighted in Scheme 2.5
4 (a) Horwell, D. C. Tetrahedron 1980, 36, 3123.
(b) Kozikowski, A. P.; Ishida, H. J. Am. Chem. Soc. 1980, 102, 4265.
(c) Oppolzer, W.; Grayson, J. I.; Wegmann, H.; Urrea, M. Tetrahedron 1983, 39, 3695.
(d) Hatanaka, N.; Ozaki, O.; Matsumoto, M. Tetrahedron Lett. 1986, 27, 3169.
(e) Horwell, D. C.; Verge, J. P. Phytochemistry 1979, 18, 519.
5 anke, V.; Prabhu, K. R. Org. Lett. 2013, 15, 6262.
Scheme 2: C4- Alkenylation of indoles
Chapter 3 of Section A, presents a novel mode of selective alkenylation of indoles using Ru and Rh catalyst. In these alkenylation reactions, selectivity between C2- and C4-positions of indole framework has been achieved by altering the property of directing group. Methyl ketone, as directing group, furnishes exclusively C2-alkenylated product, whereas trifluoromethyl ketone as a directing group changes the selectivity to C4, indicating that electronic nature of the directing group controls the choice between a 5-membered and 6-membered metallacycle. Developing such divergent and selective C-H functionalizations, between C2- and C4-positions, on the indole framework can lead to easy and short synthetic routes for natural, unnatural and biologically-active compounds.6 Further screening of other carbonyl derived directing groups revealed that strong and weak directing groups exhibit opposite selectivity. Experimental
6 (a) Bronner, S. M.; Goetz, A. E.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 3832.
(b) Nathel, N. F. F.; Shah, T. K.; Bronner, S. M.; Garg, N. K. Chem. Sci., 2014, 5, 2184.
(c) A Beilstein/Crossfire search shows that more than 600 C4- substituted indole-containing natural products exist and nearly 10,000 bioactive C4-substituted indoles have been reported. controls, deuteration experiments and preliminary DFT calculations lend support to the proposed mechanism. A few representative examples are highlighted in Scheme 3.7
Scheme 3: C4- vs C2-Alkenylation of ndoles
Deuterium Labeling studies were carried out to shed light on the site of metallacycle formation and hence the origin of selectivity. Both COCF3 and COCH3 substrates were independently subjected to both standard conditions A and B, along with either D2O or AcOD as deuterium sources (Scheme 4).
7 Lanke, V.; Bettadapur, K. R.; Prabhu, K. R. Manuscript submitted.
Scheme 4: Deuterium labeling studies
The Section B is divided into 2 chapters.
Chapter 1 presents a method for synthesizing of 3-(indol-2-yl) succinimide derivatives by using a directing group strategy. Selective functionalization at C2-position of indole in the presence of highly reactive C3-position has been achieved. A conjugate addition, instead of Heck-type reaction, has been achieved by careful selection of the alkene partner (maleimides and maleate esters). This selectivity has been achieved by avoiding β-hydride elimination. Succinimide derivatives are structural motifs that are found in many natural products and drug molecules. Moreover, succinimides can be easily reduced into 5-membered pyrrolidine rings, γ-lactams and lactims, which are part of structural scaffolds of useful natural products.8 Further the application of the protocol has been showcased by performing reduction to obtain pyrrolidine and 1,4 diols. A few representative examples are highlighted in Scheme5.9 8 (a)Crider, A. M.; Kolczynski, T. M.; Yates, K. M. J. Med. Chem. 1980, 23, 324.
(b) Isaka, M.; Rugseree, N.; Maithip, P.; Kongsaeree, P.; Prabpai, S.; Thebtaranonth, Y. Tetrahedron 2005, 61, 5577.
(c) Uddin, J.; Ueda, K.; Siwu, E. R. O.; Kita, M.; Uemura, D. Bioorg. Med. Chem. 2006, 14, 6954. (d) Hubert, J. C.; Wijnberg, J. B. P. A.; Speckamp, W. N. Tetrahedron 1975, 31, 1437.
(e) Wijnberg, J. B. P. A.; Schoemaker, H. E.; Speckamp, W. N. Tetrahedron 1978, 34, 179.
9 Lanke, V.; Bettadapur, K. R.; Prabhu, K. R. Org. Lett. 2015, 17, 4662.
Scheme 5: Addition of Maleimide to Indole at C2-position
Chapter 2 describes a highly regioselective amidation of unprotected indoles at the C4-position by employing aldehyde functional group as a directing group. This reaction has been performed using Ir(III) catalyst, under mild reaction conditions. Thus, an efficient, simple, short synthetic route for C4-amido indoles has been achieved. C4-Amido indoles are privileged molecules, which serve as precursors for indolactum V,10 teleocidin and related heterocyclic compounds.11 To the best our knowledge, this is the first report of using aldehyde as a directing group for amidation reactions. The potential of the present strategy has been demonstrated by performing scaling up reaction, and deprotection of tosyl group to obtain corresponding amines. A few representative examples are highlighted in Scheme 6.12
10 Garg, N. K. et al., J. Am. Chem. Soc. 2011, 133, 3832
11 Kehler, J. J. Med. Chem. 2014, 57, 5823
12 Lanke, V.; Prabhu, K. R. (Manuscript submitted).
Scheme 6: C4- amidation of indoles
Characterisation of an anionic antimicrobial peptide isolated from green coconut water
No full textHarris, F., Prabhu, S., Dennison, S. R., Radek, I., Lea, R. and Snape, T. (2011). . . University of Durham
- …
