THAT ARE NOT LOUILLOTTIUS009850268B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 ,850 , 268 B2 Hoveyda et al. ( 45 ) Date of Patent: Dec . 26 , 2017 ( 54 ) METATHESIS CATALYSTS AND METHODS 17/ 269 (2013 . 01 ) ; C07C 17 /275 ( 2013. 01 ) ; THEREOF C07C 17 / 278 ( 2013 . 01 ) ; C07C 17361 ( 2013 .01 ) ; C07C 37 /62 ( 2013 .01 ) ; C07C 41/ 30 (71 ) Applicants :Massachusetts Institute of ( 2013 . 01 ) ; C07C 45 /63 ( 2013 . 01 ) ; C07C Technology , Cambridge , MA (US ) ; 67 /307 ( 2013 .01 ) ; C07C 67 /333 (2013 .01 ) ; Trustees of Boston College, Chestnut C07D 209 / 10 ( 2013 . 01 ) ; C07D 209 /48 Hill , MA (US ) ( 2013 .01 ) ; C070 333 /54 ( 2013 . 01) ; COFF 5 / 025 ( 2013 .01 ) ; CO7F 7 / 1844 ( 2013 .01 ) ; (72 ) Inventors : Amir H . Hoveyda , Lincoln , MA (US ) ; CO7F 7 / 1852 ( 2013 .01 ) ; C07 ) 9 /00 ( 2013 .01 ) ; Hanmo Zhang , Chestnut Hill, MA C07 ) 51/ 00 ( 2013 .01 ) ; B01J 2231/ 543 (US ) ; Ming Joo Koh , Chestnut Hill , ( 2013 . 01 ) ; B01 ) 2531 / 64 ( 2013 .01 ) ; B01J MA (US ) ; Richard Royce Schrock , 2531/ 66 ( 2013. 01 ); C07C 2601/ 14 ( 2017 .05 ) ; Winchester , MA (US ) C07C 2603/ 26 ( 2017 .05 ) (58 ) Field of Classification Search (73 ) Assignees : Trustees of Boston College , Chestnut CPC .. C07C 17 / 275 ; C07C 45/ 63 ; C07C 37 /62 ; Hill , MA (US ) ; Massachusetts B01J 2231/ 543 ; B01J 2531 /64 ; B01J Institute of Technology , Cambridge, 2531/ 66 ; B01J 31/ 2265 MA (US ) USPC .. .. 548 /402 ; 514 / 408 , 184 ( * ) Notice: Subject to any disclaimer , the term of this See application file for complete search history . patent is extended or adjusted under 35 U . S . C . 154 ( b ) by 0 days . ( 56 ) References Cited ( 21) Appl . No. : 14 /933 , 741 U . S . PATENT DOCUMENTS 2012/ 0323000 Al 12 / 2012 Hoveyda et al . ( 22 ) Filed : Nov . 5 , 2015 2014 /0309388 Al 10 /2014 Schrock et al. (65 ) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2016 /0194343 A1 Jul . 7 , 2016 EP 0585887 3 / 1994 WO WO 2011008258 A2 * 1 / 2011 . .. .. B01J 31/ 1805 Related U . S . Application Data Wo 2011097642 8 / 2011 (60 ) Provisional application No .62 / 075 ,315 , filed on Nov . (Continued ) 5 , 2014 . OTHER PUBLICATIONS (51 ) Int. Ci. C07C 17 /275 ( 2006 .01 ) Dobereiner , et al ., " Catalytic Synthesis of n - Alkyl Arenes Through C07C 45 /63 ( 2006 . 01 ) Alkyl Group Cross -Metathesis ” , JACS , 135 , 2013 , 12572 -12575 . C07C 37 /62 ( 2006 .01 ) (Continued ) B01J 31 / 22 ( 2006 .01 ) CO7F 11 / 00 ( 2006 . 01 ) CO7D 333/ 54 ( 2006 . 01 ) Primary Examiner — Matthew Coughlin C07D 209 / 10 ( 2006 . 01 ) Assistant Examiner — Sagar Patel C07D 209 /48 ( 2006 .01 ) ( 74 ) Attorney, Agent, or Firm — Stoel Rives LLP CO7F 5 /02 ( 2006 .01 ) CO7F 7 / 18 ( 2006 . 01 ) ( 57 ) ABSTRACT C07C 17 / 266 ( 2006 .01 ) C07C 17 / 269 ( 2006 .01 ) The present application provides , among other things, com C07C 17 / 278 ( 2006 .01 ) pounds and methods for metathesis reactions . In some C07C 17 / 10 ( 2006 . 01 ) embodiments , the present disclosure provides methods for C07C 17 / 14 ( 2006 . 01 ) preparing alkenyl halide with regioselectivity and / or stereo C07C 171361 ( 2006 .01 ) selectivity . In some embodiments , the present disclosure CO7B 37 / 04 ( 2006 . 01 ) provides methods for preparing alkenyl halide with regiose C07C 17 / 02 ( 2006 . 01 ) lectivity and Z - selectivity . In some embodiments , the pres C07J 9 / 00 ( 2006 .01 ) ent disclosure provides methods for preparing alkenyl halide C07 ) 51/ 00 ( 2006 . 01 ) with regioselectivity and E - selectivity . In some embodi C07C 671307 ( 2006 .01 ) ments , provided technologies are particularly useful for C07C 671333 ( 2006 .01 ) preparing alkenyl fluorides . In some embodiments , a pro C07C 41/ 30 (2006 . 01) vided compound useful for metathesis reactions has the ( 52 ) U . S . CI. structure of formula II - a . In some embodiments , a provided CPC . .. .. .. .. C07F 11/ 00 (2013 .01 ) ; B01J 31 /2265 compound useful for metathesis reactions has the structure ( 2013 . 01 ) ; CO7B 37 /04 (2013 . 01 ) ; C07C 17 / 02 of formula II - b . ( 2013 .01 ) ; C07C 17 / 10 ( 2013 .01 ) ; C07C 17 / 14 ( 2013 .01 ) ; C07C 17/ 266 ( 2013 .01 ); C07C 16 Claims, No Drawings US 9 ,850 ,268 B2 Page 2 ( 56 ) References Cited FOREIGN PATENT DOCUMENTS wo 2014172534 10 / 2014 WO 2015136093 9 / 2015 OTHER PUBLICATIONS Fomine , et al. , “ Metathesis of Fluorinated Olefins by Ruthenium Alkylidene Catalysts . Fluorine Substituent Effects on a Ru -Carbene ( Alkylidene ) Complex Stability : A Computational Study ” , Applied Catalysis A : General, 355 , 2009 , 148 - 155 . MacNaughtan , et al. , “ Cross -Metathesis of Vinyl Halides . Scope and Limitations of Ruthenium - Based Catalysts ” , Organometallics , 28 , 2009 , 2880 - 2887 . PCT/ US2015 / 059286 , International Search Report and Written Opinion , dated Mar. 14 , 2016 , 15 pages . Zhang , et al. , “ Preparation of Macrocyclic Z - Enoates and ( E , Z ) - or ( Z , E ) - Dienoates Through Catalytic Stereoselective Ring - Closing Metathesis ” , JACS , 136 , 2014 , 16493 - 16496 . * cited by examiner US 9 ,850 ,268 B2 METATHESIS CATALYSTS AND METHODS wherein : THEREOF M is molybdenum or tungsten ; R ! is an optionally substituted group selected from C1- 20 aliphatic , C1- 20 heteroaliphatic having 1 - 3 heteroatoms CROSS -REFERENCE TO RELATED independently selected from nitrogen , oxygen , or sulfur, APPLICATIONS phenyl, a 3 - 7 membered saturated or partially unsaturated carbocyclic ring , an 8 - 10 membered bicyclic saturated , The present application claims priority to the U . S . Pro partially unsaturated or aryl ring , a 5 - 6 membered mono visional Application No . 62 /075 ,315 , filed Nov. 5 , 2014 , the cyclic heteroaryl ring having 1 - 4 heteroatoms indepen entirety of which is incorporated herein by reference . dently selected from nitrogen , oxygen , or sulfur, a 4 - 7 10 membered saturated or partially unsaturated heterocyclic STATEMENT REGARDING FEDERALLY ring having 1 - 3 heteroatoms independently selected from nitrogen , oxygen , or sulfur, a 7 - 10 membered bicyclic SPONSORED RESEARCH OR DEVELOPMENT saturated or partially unsaturated heterocyclic ring having This invention was made with government support under 1 - 5 heteroatoms independently selected from nitrogen , Grant No . GM59426 awarded by the National Institute of oxygen , or sulfur , or an 8 - 10 membered bicyclic het Health and Grant No . CHE - 1362763 awarded by the eroaryl ring having 1 - 5 heteroatoms independently National Science Foundation . The U . S . government has selected from nitrogen , oxygen , or sulfur; or R is option certain rights in the invention . ally substituted 20 FIELD OF THE INVENTION (RX )p The present invention generally relates to metathesis reactions . 25 BACKGROUND each of R2 and R3 is independently R ', _ OR ', SR ', - N ( R ' ) 2 , OC ( O ) R ', - SOR ', — SO , R ', SO N ( R ') 2 , CO ) N ( R ') 2 , NR ' C (O ) R ', or - NR ' SO , R ', provided Catalytic metathesis has transformed chemical synthesis that R2 and R3 are not simultaneously hydrogen ; and offers exceptionally efficient pathways for the synthesis* 30 R * is R ' , or an optionally substituted group selected from of many commercially important chemicals including bio - 30 - Ar, C1- 20 aliphatic , C1- 20 heteroaliphatic having 1 - 3 logically active molecules , oleochemicals , renewables , fine heteroatoms independently selected from nitrogen , oxy chemicals , and polymeric materials . There remains an unmet gen , or sulfur , phenyl, a 3 - 7 membered saturated or neneed for improved methods and catalysts for metathesis partially unsaturated carbocyclic ring , an 8 - 10 membered reactions, for example , in terms of better catalyst stability bicyclic saturated , partially unsaturated or aryl ring , a 5 - 6 and / or activity , efficiency and stereoselectivity . membered monocyclic heteroaryl ring having 1 - 4 het eroatoms independently selected from nitrogen , oxygen , SUMMARY or sulfur , a 4 - 7 membered saturated or partially unsatu rated heterocyclic ring having 1 - 3 heteroatoms indepen Among other things, the present disclosure recognizes 40 dently selected from nitrogen , oxygen , or sulfur, a 7 - 10 that it is particularly challenging to use alkenyl halides as membered bicyclic saturated or partially unsaturated het metathesis substrates to provide alkenyl halides efficiently erocyclic ring having 1 - 5 heteroatoms independently and selectively . The present disclosure , among other things , selected from nitrogen , oxygen , or sulfur, or an 8 - 14 provides technologies, e . g . , compounds, compositions, membered bicyclic or tricyclic heteroaryl ring having 1 - 5 methods, etc . for preparing alkenyl halides through metath - 45 heteroatoms independently selected from nitrogen , oxy esis reactions with high efficiency , high regioselectivity and gen , or sulfur ; high Z - or E - selectivity . Ar is of the following formula : DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS 50 maan ( R ) to D ( R ) 1 . General Description of Certain Embodiments of YBY the Invention In some embodiments , a provided catalyst or metal com - 55 (R * ) m plex is of formula II -a : wherein : m is 0 - 3 ; Il- a Ring B is an optionally substituted group selected from 60 phenyl or a 5 - 6 membered monocyclic heteroaryl ring having 1 - 4 heteroatoms independently selected from Z=2– nitrogen , oxygen , or sulfur ; p and q are independently 0 - 6 ; each of Ring C and Ring D is independently optionally R3 substituted groups selected from phenyl , a 3 - 7 mem bered saturated or partially unsaturated carbocyclic ring,