Academic literature on the topic '2-Amino alcohol'

Cancheng Guo of Hunan University devised (J. Org. Chem. 2014, 79, 2709) con­ditions for the oxidative cleavage of an alkyne 1 to the esters 2 and 3. Hirokazu Arimoto of Tohoku University found (Chem. Commun. 2014, 50, 2758) that IBX oxidized a primary alcohol 4 to the acid 5 one carbon shorter. David Milstein of the Weizmann Institute of Science uncovered (J. Am. Chem. Soc. 2014, 136, 2998) condi­tions for the direct oxidation of the cyclic amine 6 to the lactam 7, with concomitant evolution of H₂. Cyclic ene sulfonamides such as 9 are versatile synthetic intermediates. Henri Doucet of the Université de Rennes reported (Adv. Synth. Catal. 2014, 356, 119) the regioselective conversion of 8 to 9. In this case, the oxidizing agent was the organo-PdBr intermediate. There have been many reports of the functionalization of the oxygenated carbons of cyclic ethers, as exemplified by the conversion of 10 to 11, observed (J. Org. Chem. 2014, 79, 3847) by Jianlin Han of Nanjing University. If these methods were regiose­lective with an acyclic benzyl ether, this could be a new method for the removal of that common protecting group. Jianliang Xiao of the University of Liverpool described (J. Am. Chem. Soc. 2014, 136, 8350) a selective benzylic ether oxidation that converted 12 to 13. Baris Temelli of Hacettepe University effected (Synthesis 2014, 46, 1407) the conversion of a primary nitro compound 14 into the corresponding nitrile 15. Jean- Michel Vatèle of Université Lyon 1 oxidized (Synlett 2014, 25, 1275) the primary alcohol 16 to the nitrile 17. Many methods have been put forward for the oxidation of primary alcohols to alde­hydes and secondary alcohols to ketones. Piperidinium oxy radicals such as TEMPO are widely used to catalyze this transformation. Yoshikazu Kimura of Iharanikkei Chemical Industry Co. Ltd. established (Synlett 2014, 25, 596) a manufacturing proc­ess for crystalline NaOCl•5H₂O that served as the bulk oxidant for the conversion of 18 to 19. Neither a ketone nor an aldehyde was chlorinated under the reaction condi­tions. Yoshiharu Iwabuchi of Tohoku University showed (Angew. Chem. Int. Ed. 2014, 53, 3236) that with his piperidinium oxy radical AZADO and Cu catalysis, air could be the bulk oxidant for the otherwise difficult conversion of the amino alcohol 20 to the amino ketone 21.

The Am aryllidaceae alkaloid gracilamine 3 was isolated in 2005 from the Turkish plant Galanthus gracilis. The supply of the natural product was not sufficient to assess the biological activity. Dawei Ma of the Shanghai Institute of Organic Chemistry envisioned (Angew. Chem. Int. Ed. 2012, 51, 10141) that the pentacyclic skeleton of 3 could be assembled by intramolecular dipolar cycloaddition, converting 1 to 2. The successful completion of the synthesis also enabled the full establishment of the relative configuration of 3. The immediate precursor to the ylide 1 was the aldehyde 9. The preparation of 9 began with the reductive amination of piperonal 4 with tyramine 5. The crude product was formylated to give the amide 6. Oxidative cyclization converted 6 to 7, which was reduced to a 1:1 mixture of diastereomers, only one of which (illustrated) could be carried onto the natural product. The undesired diastereomer was oxidized and recycled. Further reduction gave the amine, which was protected to give 8. With 8 in hand, the stage was set for regioselective von Braun degradation. Exposure to Troc-Cl gave a benzylic chloride that was hydrolyzed with AgNO3 to the benzylic alcohol. Dess-Martin oxidation completed the preparation of the aldehyde 9. Condensation of 9 with leucine ethyl ester 10 gave an imine, which on heating cyclized to racemic 2 with 5:1 diastereocontrol. Other diastereomers were possible, but the constraints of the fused 5/5 system ensured that the alternative transition states were significantly higher in energy. On exposure of the amino alcohol from deprotection of 2 to modified Pfitzner-Moffatt conditions, the amine was again protected and the alcohol was oxidized to the ketone to give 11. On deprotection, the amine added in a conjugate sense to give a ketone that was reduced to gracilamine 3 The diene 9 is prochiral, so there is the possibility that chiral catalysis could set the absolute configuration of 2 and so of 3. Attempts by the authors to catalyze the intramolecular dipolar cycloaddition were, however, so far not successful.

Jeffrey C. Pelletier of Wyeth Research, Collegeville, PA has developed (Tetrahedron Lett. 2007, 48, 7745) a easy work-up Mitsunobu procedure for the conversion of a primary alcohol such as 1 to the corresponding primary amine 2. Shlomo Rozen of Tel-Aviv University has taken advantage (J. Org. Chem. 2007, 72, 6500) of his own method for oxidation of a primary amine to the nitro compound to effect net conversion of an amino ester 3 to the alkylated amino ester 5. Note that the free amine of 3 or 5 would react immediately with methyl iodide. Keith A. Woerpel of the University of California, Irvine has uncovered (J. Am. Chem. Soc. 2007, 129, 12602) a Cu catalyst that, with 7, effected direct conversion of silyl ethers such as 6 to the allyl silane 8. An Ag catalyst gave 9, which also shows arllyl silane reactivity. Biswanath Das of the Indian Institute of Chemical Technology, Hyderabad has established (Tetrahedron Lett. 2007, 48, 6681) a compact procedure for the direct conversion of an aromatic aldehyde such as 10 to the benzylic halide 11. This will be especially useful for directly generating benzylic halides that are particularly reactive. α-Sulfinylation of ketones often requires intial generation of the enolate. J. S. Yadav, also of the Indian Institute of Chemical Technology, Hyderabad, has devised (Tetrahedron Lett. 2007, 48, 5243) an oxidative protocol for installing sulfur adjacent to a ketone. In a related development, Richard S. Grainger of the University of Birmingham has established (Angew. Chem. Int. Ed. 2007, 46, 5377) a simple procedure for the conversion of thio esters such as 14 to the corresponding ketone 16. Yoshiya Fukumoto of Osaka University has shown (J. Am. Chem. Soc. 2007, 129, 13792) that a terminal alkyne 17 can be directly converted into the enamine 18 by Rh-catalyzed addition of a secondary amine. Lukas Hintermann and Carsten Bolm of RWTH Aachen have found (J. Org. Chem. 2007, 72, 5704) that inclusion of water gave the aldehyde, which could be oxidized with the residual Ru catalyst to the acid.

Erick M. Carreira at ETH Zürich reported (Science 2013, 340, 1065) the enantiose­lective α-allylation of aldehyde 1 with alcohol 2 to produce 3 using a dual catalytic system involving a chiral iridium complex and amine 5. This stereodivergent method allows access to all of the possible stereoisomers of 3. In a conceptually related proc­ess, John F. Hartwig at the University of California, Berkeley reported (J. Am. Chem. Soc. 2013, 135, 2068) the highly stereoselective allylic alkylation of azlactone 6 with allylic carbonate 7 catalyzed by a combination of Ir(cod)Cl₂, ligand 9, and racemic silver phosphate 10. An enantioselective three-component Mannich-type reaction of tert-butyl diazo­acetate, aniline, and imine 11 to produce α,β-bis(arylamino) acid derivative 13 under dual catalysis with Rh₂(OAc)₄ and acid 12 was developed (Synthesis 2013, 45, 452) by Wenhao Hu at the Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development. Keiji Maruoka at Kyoto University reported (Chem. Commun. 2013, 49, 1118) a one-pot cross double-Mannich reaction of acetylalde­hyde 14, and imines 16 and 17 using axially chiral amino sulfonamide 15 to obtain densely functionalized 1,3-diamine 18 as a single stereoisomer. Jeffrey S. Johnson at the University of North Carolina at Chapel Hill reported (Org. Lett. 2013, 15, 2446) the asymmetric synthesis of enantioenriched anti-α-hydroxy-β-amino acid derivative 21 from 19 by treatment with oxone followed by catalytic hydrogenation using Ru(II) complex 20. Naoya Kumagai and Masakatsu Shibasaki at the Institute of Microbial Chemistry found (Org. Lett. 2013, 15, 2632) that a sil­ver complex of bisphosphine 24 effected a syn-selective and highly enantioselective Mannich-type reaction of aldimine 22 and α-sulfanyl lactone 23 to furnish the stereo­diad 25 with very high ee. The enantioselective homocrotylation of octanal 26 with cyclopropylcarbinylbo­ronate 27 to produce alcohol 28 with high ee was disclosed (J. Am. Chem. Soc. 2013, 135, 82) by Isaac J. Krauss at Brandeis University with computational studies pro­vided by Kendall N. Houk at UCLA. Benjamin List at the Max-Planck-Institut für Kohlenforschung reported (J. Am. Chem. Soc. 2013, 135, 6677) the enantioselective epoxidation of cyclohexenone 29 utilizing cinchona alkaloid- derived catalyst 30.

The enantioselective epoxidation of a terminal alkene 1 has been a long-sought goal of organic synthesis. Albrecht Berkessel of the University of Cologne devised (Angew. Chem. Int. Ed. 2013, 52, 8467) a Ti catalyst that mediated the conversion of 1 to 2. Zhi Li of the National University of Singapore described (Chem. Commun. 2013, 49, 11572) a cell-based system that effected the enantioselective epoxidation of 3 to 4. Antonio Mezzetti of ETH Zürich and Francesco Santoro of Firmenich SA car­ried out (Angew. Chem. Int. Ed. 2013, 52, 10352) the enantioselective hydrogena­tion of 5 to the allylic alcohol 6. Elena Fernández of the Universitat Rovira i Virgilli and Andrew Whiting of Durham University devised (Org. Lett. 2013, 15, 4810) a protocol for the enantioselective conjugate borylation of the imine derived from 7, leading to the secondary alcohol 8. Benjamin List of the Max-Planck-Institute für Kohlenforschung, Mülheim and Choong Eui Song of Sungkyunkwan University con­densed (Angew. Chem. Int. Ed. 2013, 52, 12143) the thioester 10 with the aldehyde 9 to give the alcohol 11. Toshiro Harada of the Kyoto Institute of Technology developed (Org. Lett. 2013, 15, 4198) a general procedure for the enantioselective addition of a terminal alkene 12 to an aldehyde 9. As illustrated by the preparation of 13, this appears to be tolerant of a variety of organic functional groups. Professor Harada also established (Chem. Eur. J. 2013, 19, 17707) a protocol for the enantioselective addition of an alkyne 14 to an aldehyde to give the branched product 15. Chun-Jiang Wang and Xumu Zhang of Wuhan University hydrogenated (Angew. Chem. Int. Ed. 2013, 52, 8416) the alkyne 16 to the protected allylic amine 17. Keiji Maruoka of Kyoto University effected (J. Am. Chem. Soc. 2013, 135, 18036) the enantioselective α-amination of an aldehyde 18, to give 19. David W. C. MacMillan of Princeton University described (J. Am. Chem. Soc. 2013, 135, 11521) a comple­mentary approach, not illustrated. David J. Fox of the University of Warwick reduced (Chem. Commun. 2013, 49, 10022) the ketone 20, then rearranged the resulting sec­ondary alcohol to the α-amino amide 21.

( + )-Pinnatoxin A 3, isolated from the shellfish Pinna muricata, is thought to be a calcium channel activator. A key transformation in the synthesis of 3 reported (J. Am. Chem. Soc . 2008, 130, 3774) by Armen Zakarian, now at the University of California, Santa Barbara, was the diastereoselective Claisen rearrangement of 1 to 2. The alcohol portion of ester 1 was derived from the aldehyde 4, prepared from D-ribose. The absolute configuration of the secondary allylic alcohol was established by chiral amino alcohol catalyzed addition of diethyl zinc to the unsaturated aldehyde 5. The acid portion of the ester 1 was prepared from (S)-citronellic acid, by way of the Evans imide 7. Methylation proceeded with high diasterocontrol, to give 8. Functional group manipulation provided the imide 9. Alkylation then led to 10, again with high diastereocontrol. In each case, care had to be taken in the further processing of the α-chiral acyl oxazolidinones. Direct NaBH4 reduction of 8 delivered the primary alcohol. To prepare the acid 10, the alkylated acyl oxazolidinone was hydrolyzed with alkaline hydrogen peroxide. On exposure of the ester 1 to the enantiomerically-pure base 11, rearrangement proceeded with high diastereocontrol, to give the acid 2. This outcome suggests that deprotonation proceeded to give the single geometric form of the enolate, that was then trapped to give specifically the ketene silyl acetal 12. This elegant approach is dependent on both the ester 1 and the base 11 being enantiomerically pure. The carbocyclic ring of pinnatoxin A 3 was assembled by intramolecular aldol condensation of the dialdehyde 11. This outcome was remarkable, in that 11 is readily epimerizable, and might also be susceptible to β-elimination. Note that the while the diol corresponding to 11 could be readily oxidized to 11 under Swern conditions, attempts to oxidize the corresponding hydroxy aldehyde were not fruitful.

Peter Wipf at the University of Pittsburgh utilized (J. Org. Chem. 2013, 78, 167) an alkynol-furan Diels-Alder reaction to convert 1 into the hydroxyindole 2. An intramolecular Larock indole synthesis was employed (Angew. Chem. Int. Ed. 2013, 52, 4902) by Yanxing Jia at Peking University for the conversion of aniline 3 to tricyclic indole 4. The reaction of boronodiene 5 with nitrosobenzene to produce pyrrole 6 was reported (Chem. Commun. 2013, 49, 5414) by Bertrand Carboni at CNRS University of Rennes and Andrew Whiting at Durham University. The merger of imine 7 with propargyl amine 8 in the presence of a strong base, leading to pyrrole 9, was disclosed (Org. Lett. 2013, 15, 3146) by Boshun Wan at the Chinese Academy of Sciences. Bin Li and Baiquan Wang at Nankai University found (Org. Lett. 2013, 15, 136) that pyrrole 12 could be prepared by the oxidative annulation of enamide 10 with alkyne 11 via ruthenium catalysis in the presence of copper(II). Naohiko Yoshikai at Nanyang Technological University demonstrated (Org. Lett. 2013, 15, 1966) that N-allyl imine 13 could be cyclized to pyrrole 14 via dehydrogenative intramolecular Heck cyclization. Rhett Kempe at the University of Bayreuth developed (Nature Chem. 2013, 5, 140) a “sustainable” pyrrole synthesis in which iridium complex 17 catalyzed the dehydrogenative coupling of alcohol 15 and phenylalaninol (16) to produce pyrrole 18. In a related process, David Milstein at the Weizmann Institute of Science found (Angew. Chem. Int. Ed. 2013, 52, 4012) that the ruthenium complex 20 effected the transformation of 2-octanol (19) and 16 to furnish pyrrole 21. An alternative ruthenium-catalyzed pyrrole synthesis from readily available components was developed (Angew. Chem. Int. Ed. 2013, 52, 597) by Matthias Beller, allowing for the preparation of 25 from ketone 22, diol 23, and amine 24. Meanwhile, with a bit of hetero-aromatic alchemy, Huw M.L. Davies at Emory University converted (J. Am. Chem. Soc. 2013, 135, 4716) the furan 26 to pyrrole 28 by reaction with triazole 27 under rhodium catalysis. Professor Kempe also developed (Angew. Chem. Int. Ed. 2013, 52, 6326) a method for the synthesis of pyridine 30 from amino alcohol 29 and propanol using an iridium catalyst closely related to 17.

Several remarkable one-carbon homologations have recently appeared. André B. Charette of the Université de Montréal reported (J. Org. Chem. 2008, 73, 8097) the alkylation of diiodomethane with alkyl iodides such as 1, to give the diiodoalkane 2. Carlo Punta and the late Ombretta Porta of the Politecnico di Milano effected (Organic Lett. 2008, 10, 5063) reductive condensation of an amine 3 with an aldehyde 4 in the presence of methanol, to give the amino alcohol 5. Timothy S. Snowden of the University of Alabama showed (Organic Lett. 2008, 10, 3853) that NaBH4 reduced the carbinol 7, easily prepared from the aldehyde 6, to the acid 8. Ram N. Ram of the Indian Institute of Technology, Delhi found (J. Org. Chem. 2008, 73, 5633) that CuCl reduced 7 to the chloro ketone 9. Kálmán J. Szabó of Stockholm University extended (Chem. Commun. 2008, 3420) his elegant work on in situ borinate formation, coupling, in one pot, the allylic alcohol 10 with the acetal 11 (hydrolysed in situ) to deliver the alcohol 12 as a single diastereomer. Samir Z. Zard of the Ecole Polytechnique developed (J. Am. Chem. Soc. 2008, 130, 8898) the 6-fluoropyridyloxy ether of 13 as an effective radical leaving group, enabling efficient coupling with 14, activated by dilauroyl peroxide, to give 15. Shu Kobayashi of the University of Tokyo established (Chem. Commun. 2008, 6354) that the anion of the sulfonyl imidate 17 participated in direct Pd-mediated allylic coupling with the carbonate 16. The product sulfonyl imidate 18 is itself of medicinal interest. It is also easily converted to other functional groups, including the aldehyde 19. Jianliang Xiao of the University of Liverpool found (J. Am. Chem. Soc. 2008, 130, 10510) that Pd-mediated coupling of an aldehyde 21 in the presence of pyrrolidine led to the ketone 22. The reaction is probably proceeding via Heck coupling of the aryl halide with the in situ generated enamine. Alois Fürstner of the Max Planck Institut, Mülheim observed (J. Am. Chem. Soc. 2008, 130, 8773) that in the presence of the simple catalyst Fe(acac)3 a Grignard reagent 24 coupled smoothly with an aryl halide 23 to give 25.

The amphidinolides, having zero, one, or (as exemplified by amphidinolide F 3) two tetrahydrofuran rings, have shown interesting antineoplastic activity. It is a tribute to his development of robust Mo catalysts for alkyne metathesis that Alois Fürstner of the Max-Planck-Institut für Kohlenforschung Mülheim could with confidence design (Angew. Chem. Int. Ed. 2013, 52, 9534) a route to 3 that relied on the ring-closing metathesis of 1 to 2 very late in the synthesis. Three components were prepared for the assembly of 1. Julia had already reported (J. Organomet. Chem. 1989, 379, 201) the preparation of the E bromodiene 5 from the sulfone 4. The alcohol 7 was available by the opening of the enantiomerically-pure epoxide 6 with propynyl lithium, followed by oxidation following the Pagenkopf pro­tocol. Amino alcohol-directed addition of the organozinc derived from 5 to the alde­hyde from oxidation of 7 completed the assembly of 8. Addition of the enantiomer 10 of the Marshall butynyl reagent to 9 followed by protection, oxidation to 11, and addition of, conveniently, the other Marshall enan­tiomer 12 led to the protected diol 13. Silylcupration–methylation of the free alkyne set the stage for selective desilylation and methylation of the other alkyne. Iodination then completed the trisubstituted alkene of 14. Methylation of the crystalline lactone 15, readily prepared from D-glutamic acid, led to a mixture of diastereomers. Deprotonation of that product followed by an aque­ous quench delivered 16. Reduction followed by reaction with the phosphorane 17 gave the unsaturated ester, that cyclized with TBAF to the crystalline 18. The last ste­reogenic center of 22 was established by proline-mediated aldol condensation of the aldehyde 19 with the ketone 20. To assemble the three fragments, the ketone of 21 was converted to the enol triflate and thence to the alkenyl stannane. Saponification gave the free acid 22, that was acti­vated, then esterified with the alcohol 18. Coupling of the stannane with the iodide 14 followed by removal of the TES group led to the desired diyne 1. It is noteworthy that the Mo metathesis catalyst is stable enough to tolerate the free alcohol of 1 in the cyclization to 2.

Propranolol, ((R,S)-1-iso-propylamino-3-(1-naphthoxy)-2-propanol), is a β-adrenergic antagonist and is commercially available as a racemic mixture. Only the S-enantiomer has the desired therapeutic effect. Therefore, many researchers have been working on strategies to obtain S-propranolol with high enantiomeric purity. One approach to carry out the acetylation of (R,S)-Propranolol using Candida antarctica lipase B, CalB. This reaction leads to an enantiomeric purity of 96% at a relatively low conversion rate of 30 %. In our research group, we have been studying this reaction. The CalB active s