Arrays of Stereogenic Centers: The Shin/Chandrasekhar Synthesis of (+)-Lactacystin

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Major Product ◽  
South Florida ◽  
Allylic Alcohol ◽  
Israel Institute ◽  
University Of Illinois ◽  
Enantiomerically Pure ◽  
Boston College ◽  
Stereogenic Centers ◽  
Institute Of Technology ◽  
The University

Kami L. Hull of the University of Illinois established (J. Am. Chem. Soc. 2014, 136, 11256) conditions for the diastereoselective hydroamination of 1 with 2 to give 3. Jon C. Antilla of the University of South Florida employed (Org. Lett. 2014, 16, 5548) an enantiomerically-pure Li phosphate to direct the opening of the prochiral epoxide 4 to 5. Jordi Bujons and Pere Clapés of IQAC-CSIC engineered (Chem. Eur. J. 2014, 20, 12572) an enzyme that mediated the enantioselective addition of glycolaldehyde 7 to an aldehyde 6, leading to 8. Takahiro Nishimura of Kyoto University set (J. Am. Chem. Soc. 2014, 136, 9284) the two stereogenic centers of 11 by adding 10 to the diene 9. Amir H. Hoveyda of Boston College added (J. Am. Chem. Soc. 2014, 136, 11304) the propargylic anion derived from 13 to the aldehyde 12 to give, after oxida­tion, the diol 14. Yujiro Hayashi of Tohoku University constructed (Adv. Synth. Catal. 2014, 356, 3106) 17 by the combination of 15 with 16. Yitzhak Apeloig and Ilan Marek of Technion-Israel Institute of Technology prepared (J. Org. Chem. 2014, 79, 12122) the bromo diol 20 by rearranging the adduct between the alkyne 19 and the acyl silane 18. James P. Morken, also of Boston College, effected (J. Am. Chem. Soc. 2014, 136, 17918) enantioselective coupling of 22 with the bis-borane 21. The prod­uct allyl borane added to benzaldehyde to give the alcohol 23. Sentaro Okamoto of Kanagawa University reduced (Org. Lett. 2014, 16, 6278) the aryl oxetane 24 to an intermediate that coupled with allyl bromide to give the alco­hol 25. In the presence of catalytic CuCN, the alternative diastereomer was the major product. Erick M. Carreira of ETH Zürich used (Angew. Chem. Int. Ed. 2014, 53, 13898) a combination of an Ir catalyst and an organocatalyst to couple the aldehyde 27 with the allylic alcohol 26. The four possible combinations of enantiomerically pure catalysts worked equally well, enabling the preparation of each of the four enan­tiomerically pure diastereomers of 28.

Functional Group Transformations

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Gold Catalyst ◽  
Sulfonyl Chloride ◽  
Allylic Alcohol ◽  
West Virginia University ◽  
Israel Institute ◽  
University Of Texas ◽  
Amino Amide ◽  
Cu Catalyst ◽  
Institute Of Technology ◽  
The University

Mark Gandelman of the Technion–Israel Institute of Technology devised (Adv. Synth. Catal. 2011, 353, 1438) a protocol for the decarboxylative conversion of an acid 1 to the iodide 3. Doug E. Frantz of the University of Texas, San Antonio effected (Angew. Chem. Int. Ed. 2011, 50, 6128) conversion of a β-keto ester 4 to the diene 5 by way of the vinyl triflate. Pei Nian Liu of the East China University of Science and Technology and Chak Po Lau of the Hong Kong Polytechnic University (Adv. Synth. Catal. 2011, 353, 275) and Robert G. Bergman and Kenneth N. Raymond of the University of California, Berkeley (J. Am. Chem. Soc. 2011, 133, 11964) described new Ru catalysts for the isomerization of an allylic alcohol 6 to the ketone 7. Xiaodong Shi of West Virginia University optimized (Adv. Synth. Catal. 2011, 353, 2584) a gold catalyst for the rearrangement of a propargylic ester 8 to the enone 9. Xue-Yuan Liu of Lanzhou University used (Adv. Synth. Catal. 2011, 353, 3157) a Cu catalyst to add the chloramine 11 to the alkyne 10 to give 12. Kasi Pitchumani of Madurai Kamaraj University converted (Org. Lett. 2011, 13, 5728) the alkyne 13 into the α-amino amide 15 by reaction with the nitrone 14. Katsuhiko Tomooka of Kyushu University effected (J. Am. Chem. Soc. 2011, 133, 20712) hydrosilylation of the propargylic ether 16 to the alcohol 17. Matthew J. Cook of Queen’s University Belfast (Chem. Commun. 2011, 47, 11104) and Anna M. Costa and Jaume Vilarrasa of the Universitat de Barcelona (Org. Lett. 2011, 13, 4934) improved the conversion of an alkenyl silane 18 to the iodide 19. Vinay Girijavallabhan of Merck/Kenilworth developed (J. Org. Chem. 2011, 76, 6442) a Co catalyst for the Markovnikov addition of sulfide to an alkene 20. Hojat Veisi of Payame Noor University oxidized (Synlett 2011, 2315) the thiol 22 directly to the sulfonyl chloride 23. Nicholas M. Leonard of Abbott Laboratories prepared (J. Org. Chem. 2011, 76, 9169) the chromatography-stable O-Su ester 25 from the corresponding acid 24.

Preparation of Benzene Derivatives

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Aryl Halide ◽  
Allylic Alcohol ◽  
Chemical Technology ◽  
University Of Pennsylvania ◽  
Benzene Derivatives ◽  
Aryl Iodide ◽  
University Of Illinois ◽  
Institute Of Technology ◽  
The University ◽  
Optimized Conditions

Several new methods have been put forward for the functionalization of benzene derivatives. J. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad has devised (Chem. Lett. 2008, 37, 652) a procedure for direct thiocyanation, converting 1 into 2. Sukbok Chang of KAIST has established (Chem. Commun. 2008, 3052) that both NH4Cl and aqueous NH3 could be used to directly aminate an aryl iodide such as 3. John F. Hartwig of the University of Illinois has developed (J. Am. Chem. Soc. 2008, 130, 7534) a protocol for the directed borylation of anilines such as 5 and of phenols, based on a transient silylation. Karsten Menzel of Merck West Point (Tetrahedron Lett. 2008, 49, 415) has observed selective exchange of tribromobenzene derivatives such as 7, with the direction of the selectivity being controlled by the fourth substituent on the benzene. Gary A. Molander of the University of Pennsylvania has extensively developed the stable, readily prepared trifluoroborates, exemplified by 10 (J. Org. Chem. 2008, 73, 2052) and 14 (Organic Lett. 2008, 10, 1795) as partners for Suzuki-Miyaura coupling. The conversion of 9 to 10 is complementary to aminocarbonylation, exemplified by the conversion of 12 to 13 reported (Tetrahedron Lett. 2008, 49, 2221) by Bhalchandra M. Bhanage of the Institute of Chemical Technology, University of Mumbai. The coupling of 9 with 14 is complementary to the long-known Heck coupling of an aryl halide such as 16 with an allylic alcohol, as illustrated by the preparation of 18 described (Tetrahedron Lett. 2008, 49, 3279) by Martin E. Maier of the Universität Tübingen. Professor Hartwig has also (Organic Lett. 2008, 10, 1545, 1549) optimized conditions for the Pd-catalyzed arylation of ester enolates such as 19. Gang Zhou of Schering-Plough, Kenilworth, NJ has developed (Organic Lett. 2008, 10, 2517) a related transformation, the arylation of deprotonated sulfonamides. Peter Somfai of the Royal Institute of Technology, Stockholm has established (Angew. Chem. Int. Ed. 2008, 47, 1907) a complementary procedure, base-mediated elimination of t -butoxide from 24, followed by 1,2-addition of an aryl or heteroaryl Grignard reagent.

Stereocontrolled C-O Ring Construction: The Fuwa/Sasaki Synthesis of Attenol A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Gold Catalysis ◽  
Membered Ring ◽  
Allylic Alcohol ◽  
State University ◽  
Prins Cyclization ◽  
University Of Florida ◽  
University Of Pittsburgh ◽  
Colorado State University ◽  
Institute Of Technology ◽  
The University

Since five-membered ring ethers often do not show good selectivity on equilibration, single diastereomers are best formed under kinetic control. Aaron Aponick of the University of Florida demonstrated (Organic Lett. 2008, 10, 669) that under gold catalysis, the allylic alcohol 1 cyclized to 2 with remarkable diastereocontrol. Six-membered rings also formed with high cis stereocontrol. Ian Cumpstey of Stockholm University showed (Chem. Commun. 2008, 1246) that with protic acid, allylic acetates such as 3 cyclized with clean inversion at the allylic center, and concomitant debenzylation. J. Stephen Clark of the University of Glasgow found (J. Org. Chem. 2008, 73, 1040) that Rh catalyzed cyclization of 5 proceeded with high selectivity for insertion into Ha, leading to the alcohol 6. Saumen Hajra of the Indian Institute of Technology, Kharagpur took advantage (J. Org. Chem. 2008, 73, 3935) of the reactivity of the aldehyde of 7, effecting selective addition of 7 to 8, to deliver, after reduction, the lactone 9. Tomislav Rovis of Colorado State University observed (J. Org. Chem. 2008, 73, 612) that 10 could be cyclized selectively to either 11 or 12. Nadège Lubin-Germain, Jacques Uziel and Jacques Augé of the University of Cergy- Pontoise devised (Organic Lett. 2008, 10, 725) conditions for the indium-mediated coupling of glycosyl fluorides such as 13 with iodoalkynes such as 14 to give the axial C-glycoside 15. Katsukiyo Miura and Akira Hosomi of the University of Tsukuba employed (Chemistry Lett. 2008, 37, 270) Pt catalysis to effect in situ equilibration of the alkene 16 to the more stable regioisomer. Subsequent condensation with the aldehyde 17 led via Prins cyclization to the ether 18. Paul E. Floreancig of the University of Pittsburgh showed (Angew. Chem. Int. Ed. 2008, 47, 4184) that Prins cyclization could be also be initiated by oxidation of the benzyl ether 19 to the corresponding carbocation. Chan-Mo Yu of Sungkyunkwan University developed (Organic Lett. 2008, 10, 265) a stereocontrolled route to seven-membered ring ethers, by Pd-mediated stannylation of allenes such as 21, followed by condensation with an aldehyde.

Metal-Mediated Carbocyclic Construction: The Simpkins Synthesis of Ialibinones A and B

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Gold Catalyst ◽  
Conjugate Addition ◽  
South Florida ◽  
Pt Catalyst ◽  
General Strategy ◽  
Ru Catalyst ◽  
University Of Technology ◽  
Rh Catalyst ◽  
Institute Of Technology ◽  
The University

Adriaan J. Minnaard and Ben L. Feringa of the University of Groningen devised (J. Am. Chem. Soc. 2010, 132, 14349) what promises to be a general strategy for the construction of enantiomerically pure cyclopropanes, based on conjugate addition to acceptors such as 1 . X. Peter Zhang of the University of South Florida developed (J. Am. Chem. Soc. 2010, 132, 12796) a Co catalyst for the enantioselective cyclopropanation of α-olefins such as 3. Seiji Iwasa of Toyohashi University of Technology designed (Angew. Chem. Int. Ed. 2010, 49, 8439) a resin-bound Ru catalyst that could be used repeatedly for the enantioselective cyclization of the ester 6. Rai-Shung Lin of National Tsing-Hua University showed (Angew. Chem. Int. Ed. 2010, 49, 9891) that a gold catalyst could expand the alkyne 8 to the cyclobutene 9. Takao Ikariya of the Tokyo Institute of Technology reported (J. Am. Chem. Soc. 2010, 132, 16637) a detailed study of the enantioselective conjugate addition of malonate 11 to cyclopentenone 10. Vladimir A. D’yakonov of the Russian Academy of Sciences, Ufa, showed (Tetrahedron Lett. 2010, 51, 5886) that a cyclic alkyne 13 could be annulated to the cyclopentenone 14. Shunichi Hashimoto of Hokkaido University also designed (Angew. Chem. Int. Ed. 2010, 49, 6979) a resin-bound Rh catalyst that could also be used repeatedly for the enantioselective cyclization of the ester 15. Tushar Kanti Chakraborty of the Central Drug Research Institute used (Tetrahedron Lett. 2010, 51, 4425) Ti(III) to mediate the diastereoselective cyclization of 17 to 18. Alexandre Alexakis of the University of Geneva extended (Synlett 2010, 1694) enantioselective conjugate addition of isopropenyl to the more difficult enone 19. Joseph P. A. Harrity of the University of Sheffield showed (Org. Lett. 2010, 12, 4832) that Pd could catalyze the rearrangement of 21 to 22. Strategies for the controlled construction of polycyclic ring systems are also important. Günter Helmchen of the Universität Heidelberg showed (J. Org. Chem. 2010, 75, 7917) that 23 was efficiently cyclized to the diene with Pt catalyst. The reaction could be carried out in the presence of the dienophile 24 to give 25 directly.

Establishing Arrays of Stereogenic Centers: The Sato/Chida Synthesis of (-)-Kainic Acid

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Catalyst System ◽  
Allylic Alcohol ◽  
University Of Pennsylvania ◽  
Ni Catalyst ◽  
Max Planck ◽  
Stereogenic Centers ◽  
University College London ◽  
Enantioselective Addition ◽  
La Jolla ◽  
The University

Benjamin List of the Max-Planck-Institut, Mülheim, devised (J. Am. Chem. Soc. 2010, 132, 10227) a catalyst system for the stereocontrolled epoxidation of a trisubstituted alkenyl aldehyde 1. Takashi Ooi of Nagoya University effected (Angew. Chem. Int. Ed. 2010, 49, 7562; see also Org. Lett. 2010, 12, 4070) enantioselective Henry addition to an alkynyl aldehyde 3. Madeleine M. Joullié of the University of Pennsylvania showed (Org. Lett. 2010, 12, 4244) that an amine 7 added selectively to an alkynyl aziridine 6. Yutaka Ukaji and Katsuhiko Inomata of Kanazawa University developed (Chem. Lett. 2010, 39, 1036) the enantioselective dipolar cycloaddition of 9 with 10. K. C. Nicolaou of Scripps/La Jolla observed (Angew. Chem. Int. Ed. 2010, 49, 5875; see also J. Org. Chem. 2010, 75, 8658) that the allylic alcohol from enantioselective reduction of 12 could be hydrogenated with high diastereocontrol. Masamichi Ogasawara and Tamotsu Takahashi of Hokkaido University added (Org. Lett. 2010, 12, 5736) the allene 14 to the acetal 15 with substantial stereocontrol. Helen C. Hailes of University College London investigated (Chem. Comm. 2010, 46, 7608) the enzyme-mediated addition of 18 to racemic 17. Dawei Ma of the Shanghai Institute of Organic Chemistry, in the course of a synthesis of oseltamivir (Tamiflu), accomplished (Angew. Chem. Int. Ed. 2010, 49, 4656) the enantioselective addition of 21 to 20. Shigeki Matsunaga of the University of Tokyo and Masakatsu Shibasaki of the Institute of Microbial Chemistry developed (Org. Lett. 2010, 12, 3246) a Ni catalyst for the enantioselective addition of 23 to 24. Juthanat Kaeobamrung and Jeffrey W. Bode of ETH-Zurich and Marisa C. Kozlowski of the University of Pennsylvania devised (Proc. Natl. Acad. Sci. 2010, 107, 20661) an organocatalyst for the enantioselective addition of 27 to 26. Yihua Zhang of China Pharmaceutical University and Professor Ma effected (Tetrahedron Lett. 2010, 51, 3827) the related addition of 27 to 29. There have been scattered reports on the stereochemical course of the coupling of cyclic secondary organometallics. In a detailed study, Paul Knochel of Ludwig-Maximilians- Universität München showed (Nat. Chem. 2020, 2, 125) that equatorial bond formation dominated, exemplified by the conversion of 31 to 33.

Functional Group Transformation: The Castle Synthesis of Celogentin C

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Allylic Alcohol ◽  
Efficient Reduction ◽  
Simple Protocol ◽  
Peking University ◽  
Celogentin C ◽  
Purdue University ◽  
Institute Of Technology ◽  
Tertiary Amides ◽  
The University ◽  
Functional Group Transformation

Mark Cushman of Purdue University found (J. Org. Chem. 2010, 75, 3507) that a benzylic methyl ether 1 could be converted to the aldehyde 2 by N -bromosuccinimide. Two equivalents of NBS gave the methyl ester. Ning Jiao of Peking University used (Organic Lett. 2010, 12, 2888) NaN3 followed by DDQ to oxidize a benzylic halide 3 to the nitrile 4. Hugues Miel of Almac Sciences oxidized (Tetrahedron Lett. 2010, 51, 3216) the ketone 5 to the nitro derivative 6. The oxidative conversion of the nitro compound 7 to the ketone 8 described (Tetrahedron Lett. 2009, 50, 6389) by Vera L. Patrocinio Pereira of the Universidade Federal do Rio de Janeiro proceeded without epimerization. Sundarababu Baskaran of the Indian Institute of Technology Madras established (Angew. Chem. Int. Ed. 2010, 49, 804) that oxidative cleavage of the benzylidene acetal 9 delivered 10 with high regioselectivity. The intramolecular alkene dihydroxylation of 11 originated (Angew. Chem. Int. Ed. 2010, 49, 4491) by Erik J. Alexanian of the University of North Carolina gave 12 with high diastereocontrol. Ruimao Hua of Tsinghua University took advantage (J. Org. Chem. 2010, 75, 2966) of the H-donor properties of DMF to develop an efficient reduction of the alkyne 13 to the alkyne 14 . Alejandro F. Barrero of the University of Granada developed (J. Am. Chem. Soc. 2010, 132, 254) Ti (III) conditions for the reduction of the allylic alcohol 15 to the terminal alkene 16. Isolated alkenes were stable to these conditions. P. Veeraraghavan Ramachandran, also of Purdue University, effected (Tetrahedron Lett. 2010, 51, 3167) reductive amination of 17 to 18 using the now readily available NH3 - BH3 . Bin Ma and Wen-Cherng Lee of BiogenIdec developed (Tetrahedron Lett. 2010, 51, 385) a simple protocol for the conversion of an acid 19 to the free amine 20. Marc Lemaire of Université Lyons 1 established (Tetrahedron Lett. 2010, 51, 2092) that the silane 22 reduced primary, secondary, and tertiary amides to the aldehydes.

C–O Natural Products: (–)-Hybridalactone (Fürstner), (+)-Anthecotulide (Hodgson), (–)-Kumausallene (Tang), (±)-Communiol E (Kobayashi), (–)-Exiguolide (Scheidt), Cyanolide A (Rychnovsky)

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Max Planck ◽  
Enantiomerically Pure ◽  
University Of Oxford ◽  
University Of Wisconsin ◽  
Favorskii Rearrangement ◽  
Alternative Approach ◽  
Ether Oxygen ◽  
Institute Of Technology ◽  
The University ◽  
Complementary Strategy

Control of the absolute configuration of adjacent alkylated stereogenic centers is a classic challenge in organic synthesis. In the course of the synthesis of (–)-hybridalactone 4, Alois Fürstner of the Max-Planck-Institut Mülheim effected (J. Am. Chem. Soc. 2011, 133, 13471) catalytic enantioselective conjugate addition to the simple acceptor 1. The initial adduct, formed in 80% ee, could readily be recrystallized to high ee. In an alternative approach to high ee 2,3-dialkyl γ-lactones, David M. Hodgson of the University of Oxford cyclized (Org. Lett. 2011, 13, 5751) the alkyne 5 to an aldehyde, which was condensed with 6 to give 7. Coupling with 8 then delivered (+)-anthecotulide 9. The enantiomerically pure diol 10 is readily available from acetylacetone. Weiping Tang of the University of Wisconsin dissolved (Org. Lett. 2011, 13, 3664) the symmetry of 10 by Pd-mediated cyclocarbonylation. The conversion of the lactone 11 to (–)-kumausallene 12 was enabled by an elegant intramolecular bromoetherification. Shoji Kobayshi of the Osaka Institute of Technology developed (J. Org. Chem. 2011, 76, 7096) a powerful oxy-Favorskii rearrangement that enabled the preparation of both four-and five-membered rings with good diastereocontrol, as exemplified by the conversion of 13 to 14. With the electron-withdrawing ether oxygen adjacent to the ester carbonyl, Dibal reduction of 14 proceeded cleanly to the aldehyde. Addition of ethyl lithium followed by deprotection completed the synthesis of (±)-communiol E. En route to (–)-exiguolide 18, Karl A. Scheidt of Northwestern University showed (Angew. Chem. Int. Ed. 2011, 50, 9112) that 16 could be cyclized efficiently to 17. The cyclization may be assisted by a scaffolding effect from the dioxinone ring. Dimeric macrolides such as cyanolide A 21 are usually prepared by lactonization of the corresponding hydroxy acid. Scott D. Rychnovsky of the University of California Irvine devised (J. Am. Chem. Soc. 2011, 133, 9727) a complementary strategy, the double Sakurai dimerization of the silyl acetal 19 to 20.

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.

Alkylated Stereogenic Centers: The Jia Synthesis of (−)-Goniomitine

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Chemistry ◽  
Bimetallic Catalyst ◽  
The Other ◽  
Wild Type Enzyme ◽  
Enantiomerically Pure ◽  
Unsaturated Lactone ◽  
University Of Oxford ◽  
Stereogenic Centers ◽  
The University

John W. Wong of Pfizer and Kurt Faber of the University of Graz used (Adv. Synth. Catal. 2014, 356, 1878) a wild-type enzyme to reduce the nitrile 1 to 2 in high ee. Takafumi Yamagami of Mitsubishi Tanabe Pharma described (Org. Process Res. Dev. 2014, 18, 437) the practical diastereoselective coupling of the racemic acid 3 with the inexpensive pantolactone 4 to give, via the ketene, the ester 5 in high de. Takeshi Ohkuma of Hokkaido University devised (Org. Lett. 2014, 16, 808) a Ru/Li catalyst for the enantioselective addition of in situ generated HCN to an N-acyl pyrrole 6 to give 7 in high ee. Yujiro Hayashi of Tohoku University found (Chem. Lett. 2014, 43, 556) that an aldehyde 8 could be condensed with formalin, leading in high ee to the masked aldehyde 9. Stephen P. Fletcher of the University of Oxford prepared (Org. Lett. 2014, 16, 3288) the lactone 12 in high ee by adding an alkyl zirconocene, prepared from the alkene 11, to the unsaturated lactone 10. In a remarkable display of catalyst control, Masakatsu Shibasaki of the Institute of Microbial Chemistry and Shigeki Matsunaga of the University of Tokyo opened (J. Am. Chem. Soc. 2014, 136, 9190) the racemic aziridine 13 with malonate 14 using a bimetallic catalyst. One enantiomer of the aziridine was converted specifically to the branched product 15 in high ee. The other enantiomer of the aziridine was converted to the regioisomeric opening product. Kimberly S. Peterson of the University of North Carolina at Greensboro used (J. Org. Chem. 2014, 79, 2303) an enantiomerically-pure organophosphate to selec­tively deprotect the bis ester 16, leading to 17. Chunling Fu of Zhejiang University and Shengming Ma of the Shanghai Institute of Organic Chemistry showed (Chem. Commun. 2014, 50, 4445) that an organocatalyst could mediate the brominative oxi­dation of 18 to 19. The ee of the product was easily improved via selective crystalliza­tion of the derived dinitrophenylhydrazone. James P. Morken of Boston College developed (Org. Lett. 2014, 16, 2096) condi­tions for the allylation of an allylic acetate such as 20 with 21, to deliver the coupled product 22 with high maintenance of ee.

The Castle Synthesis of (-)-Acutumine

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Sigmatropic Rearrangement ◽  
Allylic Alcohol ◽  
Cope Rearrangement ◽  
Enantiomerically Pure ◽  
Quaternary Centers ◽  
Brigham Young University ◽  
Weinreb Amide ◽  
Facial Selectivity ◽  
Stereogenic Centers ◽  
Diastereoselective Reduction

The complex tetracyclic alkaloid (-)-acutumine 3, isolated from the Asian vine Menispermum dauricum, shows selective T-cell toxicity. The two adjacent cyclic all-carbon quaternary centers of 3 offered a particular challenge. Steven L. Castle of Brigham Young University solved (J. Am. Chem. Soc. 2009, 131, 6674) this problem by effecting net enantioselective conjugate allylation of the enantiomerically pure substrate 1 to give 2 with high diastereocontrol. The starting coupling partners ( Organic Lett . 2006, 8, 3757; Organic Lett. 2007, 9, 4033) for the synthesis were the Weinreb amide 4, prepared over several steps from 2,3- dimethoxyphenol, and the diastereomerically- and enantiomerically-pure cyclopentenyl iodide 5, prepared by singlet oxygenation of cyclopentadiene followed by enzymatic hydrolysis. Transmetalation of 5 by the Knochel protocol, addition of the resulting organometallic to 4 and enantioselective (and therefore diastereoselective) reduction of the resulting ketone delivered the alcohol 6. Methods for installing cyclic halogenated stereogenic centers are not well developed. Exposure of the allylic alcohol to mesyl chloride gave the chloride 7 with inversion of absolute configuration. Remarkably, this chlorinated center was carried through the rest of the synthesis without being disturbed. A central step in the synthesis of 3 was the spirocyclization of 7 to 8. Initially, iodine atom abstraction generated the aryl radical. The diastereoselectivity of the radical addition to the cyclopentene was set by the adjacent silyloxy group. The α-keto radical so generated reacted with the Et3Al to give a species that was oxidized by the oxaziridine to the α-keto alcohol, again with remarkable diastereocontrol. Conjugate addition to the cyclohexenone 1 failed, so an alternative strategy was developed, diastereoselective 1,2-allylation of the ketone followed by oxy-Cope rearrangement. The stereogenic centers of 1 are remote from the cyclohexenone carbonyl, so could not be used to control the facial selectivity of the addition. Fortunately, the stoichiometric enantiomerically-pure Nakamura reagent delivered the allyl group preferentially to one face of the ketone 1, to give 9. The subsequent sigmatropic rearrangement to establish the very congested second quaternary center of 2 then proceeded with remarkable facility, at 0°C for one hour.

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