Stereocontrolled Construction of Arrays of Stereogenic Centers

Chemical Laboratory ◽

Enantiomerically Pure ◽

Stereogenic Centers ◽

Diastereoselective Addition ◽

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.

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

Organic Synthesis ◽

10.1093/oso/9780190200794.003.0081 ◽

2015 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Elevated Pressure ◽

Diels Alder ◽

Cope Rearrangement ◽

Chemical Laboratory ◽

Enantiomerically Pure ◽

Peking University ◽

National University ◽

Diastereoselective Addition ◽

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.

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

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0077 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Aldol Condensation ◽

Diels Alder ◽

Cancer Center ◽

Columbia University ◽

Chemical Laboratory ◽

Intramolecular Cycloaddition ◽

Enantiomerically Pure ◽

Peking 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.

Metal-Mediated C–C Ring Construction: The Lei Synthesis of (−)-Huperzine Q

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0076 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Organic Chemistry ◽

Conjugate Addition ◽

Harvard University ◽

Unsaturated Ester ◽

Pd Catalyst ◽

Enantiomerically Pure ◽

Shanghai Institute ◽

Diastereoselective Addition ◽

University Of Bristol ◽

Following the Szymoniak protocol, Morwenna S. M. Pearson-Long and Philippe Bertus of the Université du Maine added (Synthesis 2015, 47, 992) the Grignard reagent 2 to the nitrile 1 to give the cyclopropyl amine 3. Chen-Guo Feng of the Shanghai Institute of Organic Chemistry prepared (Chem. Commun. 2015, 51, 8773) the cyclobutane 6 by enantioselective conjugate addition of 5 to the unsaturated ester 4. Martin Kotora of Charles University showed (Eur. J. Org. Chem. 2015, 2868) that the zirconacycle from the eneyne 7 reacted with the aldehyde 8 to give, after iodination, the alcohol 9. Xiaoming Feng of Sichuan University used (Angew. Chem. Int. Ed. 2015, 54, 1608) a scandium catalyst to effect the intramolecular Roskamp cyclization of 10 to 11. Celia Dominguez of CHDI observed (Org. Lett. 2015, 17, 1401) that the double alkylation of the ester 12 with the dibromide 13 proceeded with high diastereoselectivity, to give 14. Hirokazu Tsukamoto of Tohoku University cyclized (Chem. Commun. 2015, 51, 8027) 15 to 16 in high ee. Daniel J. Weix of the University of Rochester found (J. Am. Chem. Soc. 2015, 137, 3237) that under the influence of an enantiomerically-pure Ti catalyst, the organonickel species derived from 18 opened the prochiral epoxide 17 to give 19 in high ee. John F. Bower of the University of Bristol optimized (J. Am. Chem. Soc. 2015, 137, 463) conditions for the highly diastereoselective Rh-mediated cyclocarbonylation of 20 to 21. Margaret A. Brimble of the University of Auckland initiated (J. Org. Chem. 2015, 80, 2231) the construction of the cyclohexenone 24 by the diastereoselective addition of 23 to the unsaturated ester 22. Olivier Baslé and Marc Maduit of ENSC Rennes devised (Chem. Eur. J. 2015, 21, 993) conditions for the preparation of 26 by enantioselective conjugate addition to the cyclohexenone 25. Yoshito Kishi of Harvard University demonstrated (Tetrahedron Lett. 2015, 56, 3220) that the carbenoid generated from the epoxide 27 cyclized to 28 with high diastereoselectivity. Wenjun Tang, also of the Shanghai Institute of Organic Chemistry, developed (Angew. Chem. Int. Ed. 2015, 54, 3033) a Pd catalyst for the diastereoselective (because it is enantioselective) cyclization of 29 to 30.

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

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0071 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

San Antonio ◽

Bond Formation ◽

Bryn Mawr ◽

Chemical Laboratory ◽

Enantiomerically Pure ◽

University Of Texas ◽

National University ◽

Institute Of Technology ◽

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.

The Paterson Synthesis of (−)-Leiodermatolide

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0096 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Aldol Condensation ◽

Oxidative Cleavage ◽

Magnesium Bromide ◽

Silyl Ether ◽

Enantiomerically Pure ◽

University Of Cambridge ◽

Mukaiyama Aldol ◽

Hydride Elimination ◽

Reduced Toxicity ◽

(−)-Leiodermatolide 4, isolated from the lithistid sponge Leiodermatium sp., showed 5.0-nM activity against PANC-1 pancreatic carcinoma cells, and reduced toxicity toward normal cells. Ian Paterson of the University of Cambridge established (Angew. Chem. Int. Ed. 2014, 53, 2692) a synthetic route to 4 based on sp2–sp2 coupling, as exemplified by the combination of 1 with 2 to give 3. Addition of the boron enolate of the enantiomerically-pure benzoate 5 to the iodoaldehyde 6 gave 7, that was silylated, reduced, and deprotected to give 1. Addition of the boron enolate of ent-5 to propanal gave 8. The α-acyloxy ketone of 8 served as a masked acylating agent. The addition of allyl magnesium bromide followed by oxidative cleavage led to the ketone 9. The preparation of 2 was completed by diastereoselective Mukaiyama aldol condensation of 9 with the ketene silyl acetal 10. The intramolecular Heck coupling of 1 with 2 presumably proceeded by way of the organo-Pd intermediate 11. β-Hydride elimination could have given one or more of four possible dienes, but in fact the E,E product 3 dominated, as expected. The allylic H’s are activated for elimination, while the H’s β to the silyl ether are deactivated both electronically and sterically. The third component of 4 was the stannane 17. Applying the same strategy, the addition of ent-5 to the aldehyde 12 gave 13, that was protected and condensed with 14 to deliver, after oxidative cleavage, the alkynyl ketone 15. Conjugate addition of iodide proceeded with good geometric control to give 16, that was protected and stannylated to complete the preparation of 17. The diol 3 was oxidatively cleaved, and the resulting aldehyde was carried on to the iodide 18. This was coupled with the stannane 17 to give the diene 19. A sequence of deprotection, oxidation, and further deprotection yielded a tetraol, that was lactonized with high selectivity to give the 16-membered ring of (−)-leiodermatolide 4.

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

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0016 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Columbia University ◽

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.

Organic Functional Group Conversion

Organic Synthesis ◽

10.1093/oso/9780199965724.003.0005 ◽

2013 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Hong Kong ◽

Allylic Alcohol ◽

Primary Alcohols ◽

Chemical Laboratory ◽

University Of Texas ◽

University Of Wisconsin ◽

Pan American ◽

Acetate Formation ◽

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.

The Fürstner Synthesis of Amphidinolide F

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0090 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Amino Alcohol ◽

Aldol Condensation ◽

Free Acid ◽

The Other ◽

Unsaturated Ester ◽

Alkyne Metathesis ◽

Max Planck ◽

Ring Closing Metathesis ◽

Enantiomerically Pure ◽

Metathesis Catalyst

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.

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

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0072 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

State University ◽

Air Oxidation ◽

Microbial Oxidation ◽

Max Planck ◽

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.

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

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0037 ◽

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 ◽

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.