Functionalization of C-H Bonds: The Baran Synthesis of Dihydroxyeudesmane

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Columbia University ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Du Bois ◽  
Rh Catalyst ◽  
Hydride Abstraction ◽  
Mcgill University ◽  
Radical Removal ◽  
The University ◽  
Useful Yield

Arumugam Sudalai of the National Chemical Laboratory, Pune reported (Tetrahedron Lett. 2008, 49, 6401) a procedure for hydrocarbon iodination. With straight chain hydrocarbons, only secondary iodination was observed. Chao-Jun Li of McGill University uncovered (Adv. Synth. Cat. 2009, 351, 353) a procedure for direct hydrocarbon amination, converting cyclohexane 1 into the amine 3. Justin Du Bois of Stanford University established (Angew. Chem. Int. Ed. 2009, 48, 4513) a procedure for alkane hydroxylation, converting 4 selectively into the alcohol 6. The oxirane 8 usually also preferentially ozidizes methines, hydroxylating steroids at the C-14 position. Ruggero Curci of the University of Bari found (Tetrahedron Lett. 2008, 49, 5614) that the substrate 7 showed some C-14 hydroxylation, but also a useful yield of the ketone 9. The authors suggested that the C-7 acetoxy group may be deactivating the C-14 C-H. C-H bonds can also be converted directly to carbon-carbon bonds. Mark E. Wood of the University of Exeter found (Tetrahedron Lett. 2009, 50, 3400) that free-radical removal of iodine from 10 followed by intramolecular H-atom abstraction in the presence of the trapping agent 11 delivered 12 with good diastereo control. Professor Li observed (Angew. Chem. Int. Ed. 2008, 47, 6278) that under Ru catalysis, hydrocarbons such as 13 could be directly arylated. He also established (Tetrahedron Lett. 2008, 49, 5601) conditions for the direct aminoalkylation of hydrocarbons such as 13, to give 17. Huw M. L. Davies of Emory University converted (Synlett 2009, 151) the ester 4 to the homologated diester 19 in preparatively useful yield using the diazo ester 18, the precursor to a selective, push-pull stabilized carbene. Intramolecular bond formation to an unactivated C-H can be even more selective. Guoshen Liu of the Shanghai Institute of Organic Chemistry developed (Organic Lett. 2009, 11, 2707) an oxidative Pd system that cyclized 20 to the seven-membered ring lactam 21 . Professor Du Bois devised (J. Am. Chem. Soc. 2008 , 130, 9220) a Rh catalyst that effected allylic amination of 22, to give 23 with substantial enantiocontrol. Dalibor Sames of Columbia University designed (J. Am. Chem. Soc. 2009, 131, 402) a remarkable cascade approach to C-H functionalization. Exposure of 24 to Lewis acid led to intramolecular hydride abstraction. Cyclization of the resulting stabilized carbocation delivered the tetrahydropyan 25 with remarkable diastereocontrol.

Diels–Alder Cycloaddition: Pancratistatin (Cho), Nootkatone (Reddy), Platensimycin (Zhang/Lee), Scabronine G (Nakada), Isoglaziovianol (Trauner)

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Aldol Condensation ◽  
Diels Alder ◽  
Cancer Center ◽  
Columbia University ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Intramolecular Cycloaddition ◽  
Enantiomerically Pure ◽  
Peking University ◽  
The University

Samuel J. Danishefsky of Columbia University and the Memorial Sloan-Kettering Cancer Center made (Proc. Natl. Acad. Sci. 2013, 110, 10904) the unexpected obser­vation that methylation of the enolate derived from conjugate addition to the readily-prepared 1 followed by intramolecular alkene metathesis led to the trans fused ketone 2. This can be contrasted to the diastereo- and regioisomer 3, the product from Diels-Alder cycloaddition of 2-methylcyclohexenone to isoprene. The trans ring fusion of 2 is particularly significant because ozonolysis followed by aldol condensation would deliver the angularly-methylated trans-fused 6/5 C–D ring system of the steroids and related natural products. Cheon-Gyu Cho of Hanyang University added (Org. Lett. 2013, 15, 5806) the activated dienophile 4 to the dienyl lactone to give, after oxidation, the dibro­mide 5. Debromination followed by oxidation led to the antineoplastic lactam pancratistatin 6. D. Srinivasa Reddy of CSIR-National Chemical Laboratory Pune devised (J. Org. Chem. 2013, 78, 8149) a cascade protocol of Diels-Alder cycloaddition of 8 to the diene 7, followed by intramolecular aldol condensation, to give the enone 9. Oxidative manipulation followed by methylenation completed the synthesis of the commercially important grapefruit flavor nootkatone 10. Xinhao Zhang and Chi-Sing Lee of the Peking University Shenzen Graduate School uncovered (J. Org. Chem. 2013, 78, 7912) another cascade transformation, intermolecular addition of 11 to 12 followed by intramolecular Conia-ene cyclization, to give the tricyclic 13. Further manipulation led to an established intermediate for the total synthesis of platensimycin 14. Masahisa Nakada of Waseda University prepared (Angew. Chem. Int. Ed. 2013, 52, 7569) the enantiomerically-pure allene 15. Oxidation of the phenol to the monoketal of the cyclohexadienone set the stage for intramolecular cycloaddition to give 16. Oxidative cleavage followed by intramolecular alkene metathesis led to (+)-scabronine G 17. Dirk Trauner of the University of Munich assembled (Org. Lett. 2013, 15, 4324) the enantiomerically-pure alcohol 18. Oxidation gave the quinone, leading to intra­molecular Diels–Alder cycloaddition. The free alcohol then added to the exocyclic alkene of that product, to give, after further oxidation, the ether 19. Deprotection fol­lowed by reduction then completed the synthesis of (−)-isoglaziovianol 20.

Organic Functional Group Conversion

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Hong Kong ◽  
Allylic Alcohol ◽  
Primary Alcohols ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
University Of Texas ◽  
University Of Wisconsin ◽  
Pan American ◽  
Acetate Formation ◽  
The University

Pradeep Kumar of the National Chemical Laboratory, Pune, developed (Tetrahedron Lett. 2010, 51, 744) a new procedure for the conversion of an alcohol 1 to the inverted chloride 3. Michel Couturier of OmegaChem devised (J. Org. Chem. 2010, 75, 3401) a new reagent for the conversion of an alcohol 4 to the inverted fluoride 6. For both reagents, primary alcohols worked as well. Patrick H. Toy of the University of Hong Kong showed (Synlett 2010, 1115) that diethyl-lazodicarboxylate (DEAD) could be used catalytically in the Mitsunobu coupling of 7. Employment of 8 minimized competing acetate formation. In another application of hyper-valent iodine chemistry, Jaume Vilarrasa of the Universitat de Barcelona observed (Tetrahedron Lett. 2010, 51, 1863) that the Dess-Martin reagent effected the smooth elimination of a pyridyl selenide 10. Ken-ichi Fujita and Ryohei Yamaguchi of Kyoto University extended (Org. Lett. 2010, 12, 1336) the “borrowed hydrogen” approach to effect conversion of an alcohol 12 to the sulfonamide 13. Dan Yang, also of the University of Hong Kong, developed (Org. Lett. 2010, 12, 1068, not illustrated) a protocol for the conversion of an allylic alcohol to the allylically rearranged sulfonamide. Shu-Li You of the Shanghai Institute of Organic Chemistry used (Org. Lett. 2010, 12, 800) an Ir catalyst to effect rearrangement of an allylic sulfinate 14 to the sulfone. Base-mediated conjugation then delivered 15. K. Rama Rao of the Indian Institute of Chemical Technology, Hyderabad, devised (Tetrahedron Lett. 2010, 51, 293) a La catalyst for the conversion of an iodoalkene 16 to the alkenyl sulfide 17. Alkenyl selenides could also be prepared. James M. Cook of the University of Wisconsin, Milwaukee, described (Org. Lett. 2010, 12, 464, not illustrated) a procedure for coupling alkenyl iodides and bromides with N-H heterocycles and phenols. Hansjörg Streicher of the University of Sussex showed (Tetrahedron Lett. 2010, 51, 2717) that under free radical conditions, the carboxylic acid derivative 18 could be decarboxylated to the alkenyl iodide 19. Bimal K. Banik of the University of Texas–Pan American found (Synth. Commun. 2010, 40, 1730) that water was an effective solvent for the microwave-mediated addition of a secondary amine 21 to a Michael acceptor 20.

Diels-Alder Cycloaddition: (+)-Armillarivin (Banwell), Gelsemiol (Gademann), (+)-Frullanolide (Liao), Myceliothermophin A (Uchiro), Peribysin E (Reddy), Caribenol A (Li/Yang)

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Elevated Pressure ◽  
Diels Alder ◽  
Cope Rearrangement ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
Peking University ◽  
National University ◽  
Diastereoselective Addition ◽  
The University

Martin G. Banwell of the Australian National University prepared (Org. Lett. 2013, 15, 1934) the enantiomerically pure diol 1 by fermentation of the aromatic precursor. Diels-Alder addition of cyclopentenone 2 proceeded well at elevated pressure to give 3, the precursor to (+)-armillarivin 4. Karl Gademann of the University of Basel found (Chem. Eur. J. 2013, 19, 2589) that the Diels-Alder addition of 6 to 5 proceeded best without solvent and with Cu catalysis to give 7. Reduction under free radical conditions led to gelsemiol 8. Chun-Chen Liao of the National TsingHua University carried out (Org. Lett. 2013, 15, 1584) the diastereoselective addition of 10 to 9. A later oxy-Cope rearrangement established the octalin skeleton of (+)-frullanolide 12. D. Srinivasa Reddy of CSIR-National Chemical Laboratory devised (Org. Lett. 2013, 15, 1894) a strategy for the construction of the angularly substituted cis-fused aldehyde 15 based on Diels-Alder cycloaddition of 14 to the diene 13. Further transformation led to racemic peribysin-E 16. An effective enantioselective catalyst for dienophiles such as 14 has not yet been developed. Hiromi Uchiro of the Tokyo University of Science prepared (Tetrahedron Lett. 2012, 53, 5167) the bicyclic core of myceliothermophin A 19 by BF3•Et2O-promoted cyclization of the tetraene 17. The single ternary center of 17 mediated the formation of the three new stereogenic centers of 18, including the angular substitution. En route to caribenol A 22, Chuang-Chuang Li and Zhen Yang of the Peking University Shenzen Graduate School assembled (J. Org. Chem. 2013, 78, 5492) the triene 20 from two enantiomerically pure precursors. Inclusion of the radical inhibitor BHT sufficed to suppress competing polymerization, allowing clean cyclization to 21. Methylene blue has also been used (J. Am. Chem. Soc. 1980, 102, 5088) for this purpose.

Organocatalyzed C–C Ring Construction: The Mihovilovic Synthesis of Piperenol B

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
State University ◽  
Air Oxidation ◽  
Microbial Oxidation ◽  
Max Planck ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Northwestern University ◽  
National University ◽  
The University ◽  
Oregon State University

M. Kevin Brown of Indiana University prepared (J. Am. Chem. Soc. 2015, 137, 3482) the cyclobutane 3 by the organocatalyzed addition of 2 to the alkene 1. Karl Anker Jørgensen of Aarhus University assembled (J. Am. Chem. Soc. 2015, 137, 1685) the complex cyclobutane 7 by the addition of 5 to the acceptor 4, followed by conden­sation with the phosphorane 6. Zhi Li of the National University of Singapore balanced (ACS Catal. 2015, 5, 51) three enzymes to effect enantioselective opening of the epoxide 8 followed by air oxidation to 9. Gang Zhao of the Shanghai Institute of Organic Chemistry and Zhong Li of the East China University of Science and Technology added (Org. Lett. 2015, 17, 688) 10 to 11 to give 12 in high ee. Akkattu T. Biju of the National Chemical Laboratory combined (Chem. Commun. 2015, 51, 9559) 13 with 14 to give the β-lactone 15. Paul Ha-Yeon Cheong of Oregon State University and Karl A. Scheidt of Northwestern University reported (Chem. Commun. 2015, 51, 2690) related results. Dieter Enders of RWTH Aachen University constructed (Chem. Eur. J. 2015, 21, 1004) the complex cyclopentane 20 by the controlled com­bination of 16, 17, and 18, followed by addition of the phosphorane 19. Derek R. Boyd and Paul J. Stevenson of Queen’s University Belfast showed (J. Org. Chem. 2015, 80, 3429) that the product from the microbial oxidation of 21 could be protected as the acetonide 22. Ignacio Carrera of the Universidad de la República described (Org. Lett. 2015, 17, 684) the related oxidation of benzyl azide (not illustrated). Manfred T. Reetz of the Max-Planck-Institut für Kohlenforschung and the Philipps-Universität Marburg found (Angew. Chem. Int. Ed. 2014, 53, 8659) that cytochrome P450 could oxidize the cyclohexane 23 to the cyclohexanol 24. F. Dean Toste of the University of California, Berkeley aminated (J. Am. Chem. Soc. 2015, 137, 3205) the ketone 25 with 26 to give 27. Benjamin List, also of the Max-Planck-Institut für Kohlenforschung, reported (Synlett 2015, 26, 1413) a parallel investigation. Philip Kraft of Givaudan Schweiz AG and Professor List added (Angew. Chem. Int. Ed. 2015, 54, 1960) 28 to 29 to give 30 in high ee.

Organocatalyzed C–C Ring Construction: The Bradshaw/Bonjoch Synthesis of (−)-Cermizine B

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
San Antonio ◽  
Bond Formation ◽  
Bryn Mawr ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
University Of Texas ◽  
National University ◽  
Institute Of Technology ◽  
The University

In a continuation of his studies (OHL20141229, OHL20140811) of organocatalyzed 2+2 photocycloaddition, Thorsten Bach of the Technische Universität München assembled (Angew. Chem. Int. Ed. 2014, 53, 7661) 3 by adding 2 to 1. Li-Xin Wang of the Chengdu Institute of Organic Chemistry also used (Org. Lett. 2014, 16, 6436) an organocatalyst to effect the addition of 5 to 4 to give 6. Shuichi Nakamura of the Nagoya Institute of Technology devised (Org. Lett. 2014, 16, 4452) an organocatalyst that mediated the enantioselective opening of the aziridine 7 to 8. Zhi Li of the National University of Singapore cloned (Chem. Commun. 2014, 50, 9729) an enzyme from Acinetobacter sp. RS1 that reduced 9 to 10. Gregory C. Fu of Caltech developed (Angew. Chem. Int. Ed. 2014, 53, 13183) a phosphine catalyst that directed the addition of 12 to 11 to give 13. Armido Studer of the Westfälische Wilhelms-Universität Münster showed (Angew. Chem. Int. Ed. 2014, 53, 9622) that 15 could be added to 14 to give 16 in high ee. Akkattu T. Biju of CSIR-National Chemical Laboratory described (Chem. Commun. 2014, 50, 14539) related results. The photostimulated enantioselective ketone alkylation developed (Chem. Sci. 2014, 5, 2438) by Paolo Melchiorre of ICIQ was powerful enough to enable the alkyl­ation of 17 with 18 to give 19, overcoming the stereoelectronic preference for axial bond formation. David W. Lupton of Monash University established (J. Am. Chem. Soc. 2014, 136, 14397) the organocatalyzed transformation of the dienyl ester 20 to 21. James McNulty of McMaster University added (Angew. Chem. Int. Ed. 2014, 53, 8450) azido acetone 23 to 22 to give 24 in high ee. There are sixteen enantiomerically-pure diastereomers of the product 27. John C.-G. Zhao of the University of Texas at San Antonio showed (Angew. Chem. Int. Ed. 2014, 53, 7619) that with the proper choice of organocatalyst, with or without subsequent epimerization, it was possible to selectively prepare any one of eight of those diastereomers by the addition of 26 to 25. William P. Malachowski of Bryn Mawr College showed (Tetrahedron Lett. 2014, 55, 4616) that 28, readily prepared by a Birch reduction protocol, was converted by heating followed by exposure to catalytic Me3P to the angularly-substituted octalone 29.

C–N Ring Construction: The Hattori Synthesis of (+)-Spectaline

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Gold Catalyst ◽  
Ring Expansion ◽  
Homoserine Lactone ◽  
Amide Bond ◽  
State University ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Colorado State University ◽  
Schwartz Reagent ◽  
Rh Catalyst

Magnus Rueping of RWTH Aachen University found (Chem. Commun. 2015, 51, 2111) that under Fe catalysis, a Grignard reagent would couple with the iodoazetidine 1 to give the substituted azetidine 2. Timothy F. Jamison of MIT established (Chem. Eur. J. 2015, 21, 7379) a protocol for converting 3, readily available from commercial homoserine lactone, to the alkylated azetidine 4. Long-Wu Ye of Xiamen University used (Chem. Commun. 2015, 51, 2126) a gold catalyst to cyclize 5, readily prepared in high ee, to the versatile ene sulfonamide 6. Chang- Hua Ding and Xue-Long Hou of the Shanghai Institute of Organic Chemistry added (Angew. Chem. Int. Ed. 2015, 54, 1604) the racemic aziridine 7 to the enone 8 to give the pyrrolidine 9 in high ee. Arumugam Sudalai of the National Chemical Laboratory employed (J. Org. Chem. 2015, 80, 2024) proline as an organocatalyst to mediate the addition of 11 to 10, leading to the pyrrolidine 12. Aaron D. Sadow of Iowa State University developed (J. Am. Chem. Soc. 2015, 137, 425) a Zr catalyst for the enantioselective cyclization of the prochiral 13 to 14. Masahiro Murakami of Kyoto University devised (Angew. Chem. Int. Ed. 2015, 54, 7418) a Rh catalyst for the enantioselective ring expansion of the photocycliza­tion product of 15 to the enamine 16. Sebastian Stecko and Bartlomiej Furman of the Polish Academy of Sciences reduced (J. Org. Chem. 2015, 80, 3621) the carbohydrate-derived lactam 17 with the Schwartz reagent to give an intermediate that could be coupled with an isonitrile, leading to the amide 18. Lei Liu of Shandong University oxidized (Angew. Chem. Int. Ed. 2015, 54, 6012) the alkene 19 in the presence of 20 to give 21. Tomislav Rovis of Colorado State University optimized (J. Am. Chem. Soc. 2015, 137, 4445) a Zn catalyst for the addition of 22 to the nitro alkene 23, leading, after reduction, to the piperidine 24. Carlos del Pozo and Santos Fustero of the Universidad de Valencia used (Org. Lett. 2015, 17, 960) a chiral auxiliary to direct the cyclization of 25 to the bicyclic amine 26. In another illustration of the use of microwave irradiation to activate amide bond rotation, G. Maayan of Technion showed (Org. Lett. 2015, 17, 2110) that 27 could be cyclized efficiently to the medium ring lactam 28.

Functional Group Protection: The Pohl Synthesis of β-1,4-Mannuronate Oligomers

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Iron Catalyst ◽  
Gold Catalyst ◽  
State University ◽  
Allyl Ester ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Benzyl Ethers ◽  
Institute Of Technology ◽  
Tokyo Medical ◽  
The University

D. Srinivasa Reddy of the National Chemical Laboratory converted (Org. Lett. 2015, 17, 2090) the selenide 1 to the alkene 2 under ozonolysis conditions. Takamitsu Hosoya of the Tokyo Medical and Dental University found (Chem. Commun. 2015, 51, 8745) that even highly strained alkynes such as 4 can be generated from a sulfinyl vinyl triflate 3. An alkyne can be protected as the dicobalt hexacarbonyl complex. Joe B. Gilroy and Mark S. Workentin of the University of Western Ontario found (Chem. Commun. 2015, 51, 6647) that following click chemistry on a non-protected distal alkyne, deprotection of 5 to 6 could be effected by exposure to TMNO. Stefan Bräse of the Karlsruhe Institute of Technology and Irina A. Balova of Saint Petersburg State University showed (J. Org. Chem. 2015, 80, 5546) that the bend of the Co complex of 7 enabled ring-closing metathesis, leading after deprotection to 8. Morten Meldal of the University of Copenhagen devised (Eur. J. Org. Chem. 2015, 1433) 9, the base-labile protected form of the aldehyde 10. Nicholas Gathergood of Dublin City University and Stephen J. Connon of the University of Dublin developed (Eur. J. Org. Chem. 2015, 188) an imidazolium catalyst for the exchange deprotection of 11 to 13, with the inexpensive aldehyde 12 as the acceptor. Peter J. Lindsay-Scott of Eli Lilly demonstrated (Org. Lett. 2015, 17, 476) that on exposure to KF, the isoxa­zole 14 unraveled to the nitrile 15. Masato Kitamura of Nagoya University observed (Tetrahedron 2015, 71, 6559) that the allyl ester of 16 could be removed to give 17, with the other alkene not affected. Benzyl ethers are among the most common of alcohol protecting groups. Yongxiang Liu and Maosheng Cheng of Shenyang Pharmaceutical University showed (Adv. Synth. Catal. 2015, 357, 1029) that 18 could be converted to 19 simply by expo­sure to benzyl alcohol in the presence of a gold catalyst. Reko Leino of Åbo Akademi University developed (Synthesis 2015, 47, 1749) an iron catalyst for the reductive benzylation of 20 to 21. Related results (not illustrated) were reported (Org. Lett. 2015, 17, 1778) by Chae S. Yi of Marquette University.

Functional Group Protection

2015 ◽  
Author(s):  
Tristan H. Lambert
Keyword(s):  
Practical Method ◽  
Rna Aptamers ◽  
Advanced Materials ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Amberlyst 15 ◽  
Selective Protection ◽  
Classic Problem ◽  
Aldehydes And Ketones ◽  
The University

Martin D. Burke at the University of Illinois at Urbana-Champaign reported (Nature Chem. 2012, 4, 996) that the amphotericin B derivative 1 could be site-selectively acylated at the C15, C4′, or C2′ hydroxyls by electronic tuning of the acylating agent (e.g., 2 leading to 3). Another impressive example of selective protection was disclosed (Nature Chem. 2012, 4, 789) by Andreas Herrmann at the Zernike Institute for Advanced Materials, who found that RNA aptamers such as 5 selectively bind to neomycin 4, leaving only one of the amino groups exposed for acylation to selectively furnish, for example, 7. A convenient new benzylating reagent called TriBOT (9) was introduced (Org. Lett. 2012, 14, 5026) by Munetaka Kunishima at Kanazawa University and was shown to be useful for the benzylation of alcohols such as 8. Subhash P. Chavan at the National Chemical Laboratory in India reported (Tetrahedron Lett. 2012, 53, 4683) a very practical method for PMB protection of alcohols including 11 using simply p-anisyl alcohol and Amberlyst-15. For PMB deprotection, Aurélien Blanc and Patrick Pale at the University of Strasbourg reported (J. Org. Chem. 2012, 77, 9227) that use of catalytic AgSbF6 and trimethoxybenzene (14) is a mild and effective method, even in the context of potentially sensitive substrates such as 13. The deprotection of tosylated amines is a classic problem in synthesis. Now Katsuhiko Tomooka at Kyushu University has developed (J. Am. Chem. Soc. 2012, 134, 19358) a unique strategy involving nucleophilic attack at nitrogen by phosphide anion, a process that readily lends itself to the conversion of substrates such as 16 to (for example) carbamate 17. Propylphosphonic anhydride (T3P) was found (Tetrahedron Lett. 2012, 53, 5030) by John Kallikat Augustine and Pujari Vijaykumar at Syngene International Ltd. in India to catalyze the acetalization of aldehydes such as 18 under essentially neutral conditions. Interestingly, acetalization of aldehydes and ketones, including 20, under basic conditions using N-hydroxybenzenesulfonimide was reported (Synlett 2012, 23, 2773) by Alfred Hassner at Bar-Ilan University in Israel.

C–H Functionalization: The Maimone Synthesis of Podophyllotoxin

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
University Of California ◽  
University Of Illinois ◽  
Methyl Group ◽  
Du Bois ◽  
Princeton University ◽  
University Of Cambridge ◽  
Rh Catalyst ◽  
Institute Of Technology ◽  
La Jolla ◽  
The University

Matthias Beller of the Universität Rostock developed (Angew. Chem. Int. Ed. 2014, 53, 6477) a Rh catalyst for the acceptorless dehydrogenation of an alkane 1 to the alkene 2. Bhisma K. Patel of the Indian Institute of Technology Guwahati effected (Org. Lett. 2014, 16, 3086) oxidation of cyclohexane 3 and 4 to form the allylic benzoate 5. Justin Du Bois of Stanford University devised (Chem. Sci. 2014, 5, 656) an organocatalyst that mediated the hydroxylation of 6 to 7. Vladimir Gevorgyan of the University of Illinois, Chicago hydrosilylated (Nature Chem. 2014, 6, 122) 8 to give an intermediate that, after Ir-catalyzed intramolecular C–H functionalization followed by oxidation, was converted to the diacetate 9. Sukbok Chang of KAIST used (J. Am. Chem. Soc. 2014, 136, 4141) the methoxime of 10 to direct selective amination of the adjacent methyl group, leading to 11. John F. Hartwig of the University of California, Berkeley effected (J. Am. Chem. Soc. 2014, 136, 2555) diastereoselective Cu-catalyzed amination of 12 with 13 to make 14. David W. C. MacMillan of Princeton University accomplished (J. Am. Chem. Soc. 2014, 136, 6858) β-alkylation of the aldehyde 15 with acrylonitrile 16 to give 17. Yunyang Wei of the Nanjing University of Science and Technology alkenylated (Chem. Sci. 2014, 5, 2379) cyclohexane 3 with the styrene 18, leading to 19. Bin Wu of the Kunming Institute of Botany described (Org. Lett. 2014, 16, 480) the Pd-mediated cyclization of 20 to 21. Similar results using Cu catalysis were reported (Angew. Chem. Int. Ed. 2014, 53, 3496, 3706) by Yoichiro Kuninobu and Motomu Kanai of the University of Tokyo and by Haibo Ge of IUPUI. Jin-Quan Yu of Scripps La Jolla constructed (J. Am. Chem. Soc. 2014, 136, 5267) the lactam 24 by γ-alkenyl­ation of the amide 22 with 23, followed by cyclization. Philippe Dauban of CNRS Gif-sur-Yvette prepared (Eur. J. Org. Chem. 2014, 66) the useful crystalline chiron 27 by asymmetric amination of the enol triflate 26 with 25. Matthew J. Gaunt of the University of Cambridge showed (J. Am. Chem. Soc. 2014, 136, 8851) that the phenylative cyclization of 28 with 29 to 30 proceeded with near-perfect retention of absolute configuration.

Stereocontrolled Construction of Arrays of Stereogenic Centers

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Aldol Condensation ◽  
Simple Procedure ◽  
Unsaturated Ester ◽  
Magnesium Bromide ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
Stereogenic Centers ◽  
Diastereoselective Addition ◽  
The University

Complex natural products and even some complex pharmaceuticals contain arrays of stereogenic centers. Sometimes, the desired array is readily available from a natural product, but usually, such arrays of multiple stereogenic centers must be assembled. Armando Córdova of Stockholm University has reported (Angew. Chem. Int. Ed. 2007, 46, 778) a simple procedure for the organocatalyst-mediated addition of the nitrene equivalent 2 to an α, β-unsaturated aldehyde to give the protected aziridine 4 in high ee. Organocatalysis was also used (Organic Lett. 2007, 9, 1001) by Arumugam Sudalai of the National Chemical Laboratory, Pune, to effect coupling of the aldehyde 5 with dibenzylazodicarboxylate 6 to give, following the List procedure, the intermediate aldehyde 7. Osmylation of the derived unsaturated ester 8 proceeded with high diastereocontrol, to give 9. Products 4 and 9 have adjacent stereogenic centers. Hisashi Yamamoto of the University of Chicago has introduced (J. Am. Chem. Soc. 2007, 129, 2762) the linchpin reagent acetaldehyde “super”silyl enol ether 11. Diastereoselective addition of 11 to the enantiomerically-pure aldehyde 10, with concomitant silyl transfer, followed by the addition of allyl magnesium bromide delivered the protected triol 12 in high de and ee. Arrays that combine alkylated and oxygenated or aminated centers are also important. Akio Kamimura of Yamaguchi University took (J. Org. Chem. 2007, 72, 3569) a Baylis- Hillman like approach, adding thiophenoxide to t -butyl acrylate in the presence of an enantiomerically-pure aldehyde N-sulfinimine such as 13 to give the adduct 14 with high diastereocontrol. Keiji Maruoka of Kyoto University has designed (Angew. Chem. Int. Ed. 2007, 46, 1738) the chiral amine 17, that catalyzed the condensation of an aldehyde with ethyl glyoxylate 16 with high enantiocontrol. In a very thoughtful approach, Liu-Zhu Gong of the University of Science and Technology of China in Hefei extended (Chem. Commun. 2007, 736) the now-classic aldol condensation of cyclohexanone to 4-substituted cyclohexanones such as 19. The product 21 could be carried in many directions, including to the Bayer-Villiger product 22. Arrays of alkylated and polyalkylated centers have been among the most challenging to prepare.

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