Frustrated Lewis Pairs (FLP’s):

Catalysis with Focus on Hydrogena;on

LONG LIT: 6/29/17

VAN TRAN

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Intro

!  LP’sfirstdescribedbyGilbertN.Lewis–1923!  Electronpairdonor&electronpairacceptorinterac?on

!  1942:H.C.Brown–sterics

!  1959:G.WiGg/1966:Tochtermann–specialreac?vity

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Hydrogen Ac;va;on Beginnings !  DouglasStephan

!  Reversible,intramolecular(2006)

!  Irreversible,intermolecular(2007)

!  Erker&Stephan(2007)

*DFTcalculated

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Cataly;c Hydrogena;on

!  GoodforbulkyN!  GoodforbasicN

!  GoodforbulkyN!  Protona?onfirstforbasicN!  ForregularN,needLAaddi?ve

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Cataly;c Hydrogena;on 1 !  Bulky(N)imines

!  SubstrateasLB(imines&aziridines)

!  Enamines&imines

LA-LBadductpreventsproductinhibi?onBulkynitrogenprevents

productinhibi?on

Iminesw/electronpoornitrogenrequirePMes3

addi?veasLB(e.g.protectednitriles)

!  Protectedimines&nitriles

Reduc?onofenamines&bulkierimines.

Reduc?onofenamines&iminesatambienttemperature.

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Cataly;c Hydrogena;on 2 !  N-Heterocycles–Stephan

!  Metallocenes(enamines)–Erker

ActsasFLPcatalystforhydrogena?onofimines&silyl

enolethers.

!  Silylenolethers–Erker

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Cataly;c Hydrogena;on 3 !  Olefins

WeakLBcreatesstrongH+source.

Intermediateswithstabilizedca?ons.

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Cataly;c Hydrogena;on 4 !  Olefins

!  Carbonylstoalcohols

!  Alkynestocisalkenes

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Cataly;c Hydrogena;on 5 !  Transferhydrogena?on

!  ammoniaborane

!  diisopropylamine

Concerted2Htransfer.

Stepwisehydrobora?onthenH+transfer.

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General Principles !  H2spli)ngac.vityisbasedonmatchinginterac?onb/wLA&LB

!  Sterics:encountercomplex!  Electronics:differenceinLewisacidity/basicity!  Condi?ons:temperature&pressuredependent

!  Mechanismissubstratedependent!  Protona.onfirst:

!  Basicsubstrates(unprotectedimines)!  BasicityofLBisimportant(rela?vetosubstrate)

!  WeakLBforolefins(stabilizedca?onintermediate)!  Hydridetransferfirst:

!  Polarizedpibonds!  Pre-coordinatedtoaddedLA!  Conjugatedolefins

!  Hydrobora.onfirst:!  Reac?vepibonds(alkynes)!  Non-polarizedpibonds

!  Concerted2Htransfer:!  Notcommon,ohenforBH3NH3transferhydrogena?on

!  Bulkierand/orweakerLA"beierFGtolerance

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Cataly;c Asymmetric Hydrogena;on

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Cataly;c Asymmetric Hydrogena;on

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!  Chiralboranes/borates–Klankermayer(2008-2010)

!  Phosphoniumhydridoborates–Klankermayer(2012)

!  Chiralphosphines–Stephan(2011)!  Lessthan25%eewith20%(S,S)-diop

Cataly;c Asymmetric Hydrogena;on 1

Loweree(≤76%)thanchiralborates,butmorestablereagent.

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!  Ansa-ammoniumborates–Repo(2011)

Cataly;c Asymmetric Hydrogena;on 2

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!  Ansa-ammoniumborates–Repo(2011)

Cataly;c Asymmetric Hydrogena;on 2

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!  Ansa-ammoniumborates–Repo(2011)

!  Lowerbasicity!  ReleasesH2faster&atlowertemp.!  Moreac?vecatalystforbasicsubstrates.

!  Impliesprotona?onisratedeterminingforbasic&bulkysubstrates.

!  Fornon-bulkysubstrates,dissocia?onofprdfromLAisratedetermining.

Cataly;c Asymmetric Hydrogena;on 2

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!  Ansa-ammoniumborates–Repo(2011)

!  Axiallychiralammoniumboronate–Repo(2015)

!  Chiralsulfonamide–Du(2016)

Cataly;c Asymmetric Hydrogena;on 3

Racemizesunderreac?oncondi?ons.

≤37%ee≤17%ee

Imines:34-92%yield32-83%ee

Enamines:42-95%yield47-99%ee

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!  Axiallychiraldienesasprecursors–Du(2013-2016)

Cataly;c Asymmetric Hydrogena;on 4

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!  Carbonyls–Piers(1996)

!  Iminesasymmetric–Mewald&Klankermayer(2011-2012)

!  Heterocycles

Cataly;c Hydrosilyla;on !  Imines–Piers(2000)

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!  Cataly?cC-Hac?va?onboryla?on–Fontaine(2015)

!  Carbon-basedLA–Stephan(2013)

!  Perfluoroalkyla?on

Miscellaneous

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!  Reduc?veetherifica?on–Soos(2017)

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Thank You!

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