"This is the peer reviewed version of the following article: Adv. Synth. Catal. 2015, 357, 2849 –2854 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/adsc.201500635/abstract]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving ."     Aluminium  Catalysed  Oxazolidinone  Synthesis  and  their  Conversion  into  Functional  Non-­‐Symmetrical  Ureas   Victor  Laserna,a  Wusheng  Guoa  and  Arjan  W.  Kleija,b*   a   Institute  of  Chemical  Research  of  Catalonia  (ICIQ),  Av.  Països  Catalans  16,  43007  –  Tarragona,  Spain   Fax;  (+34)-­‐977920823;  Tel.:  (+34)-­‐977920247;  E-­‐mail:  akleij@iciq.es   b   Catalan  Institute  of  Research  and  Advanced  Studies  (ICREA),  Pg.  Lluís  Companys  23,  08010  –   Barcelona,  Spain   Received:  ((will  be  filled  in  by  the  editorial  staff))   Supporting  information  for  this  article  is  available.   Abstract.  An  efficient  and  practical  aluminium-­‐ catalysed  approach  towards  a  range  of  functional   oxazolidinones  is  reported.  The  method  is  based  on   cheap  and  readily  available  starting  materials  including   terminal  and  internal  (bicyclic)  epoxides  and   phenylcarbamate.  The  oxazolidinones  serve  as  highly   useful  synthons  for  the  high  yield  preparation  of   nonsymmetrical  ureas  by  nucleophilic  ring-­‐opening   affor-­‐   ding  the  targeted  urea  compounds  with  excellent   functional  group  diversity,  and  high  regio-­‐selectivity   and  isolated  yields  up  to  >99%.     Keywords:  aluminium;  N,O−ligands;  homogeneous   catalysis;  oxazolidinones;  ureas     Introduction   Organic  ureas  are  ubiquitous  structures  in  organic   chemistry  and  their  re-­‐emerged  application  potential   in  various  areas  of  chemistry  has  been  recently   highlighted.[1]  Prominent  fields  where  ureas  have   gained  importance  include  (asymmetric)   organocatalysis[2,3]  and  supramolecular  chemistry.[4]   Organocatalytic  activation  of  organic  substrates  by   means  of  hydrogen-­‐bonding  patterns  that  comprise   of  the  two  urea  NH  groups  has  been  recognized  as  a   powerful  tool  to  orientate  carbonyl  fragments  in   order  to  increase  the  efficiency  of  various  organic   conversions.  Asymmetric  ureas  have  also  been   developed  successfully  and  applied  as  enantio-­‐ controlling  mediators  in,  for  instance,  the   asymmetric  Strecker  reaction.[5]  In  the  context  of   supramolecular  applications,  N,N´-­‐disubstituted  urea   derivatives  have  proven  to  be  versatile  building   blocks  for  the  preparation  of  hydrogen-­‐bonded   supramolecular  polymers,[6,7]  helical  type   foldamers[8]  and  anion  transporting  molecules.[9]   There  exist  various  synthetic  methods  towards   nonsymmetrical  ureas  although  in  most  cases   reactive  species  such  as  carbonylimidazolide[10]  or  (in   situ  prepared)  isocyanate  reagents[11-­‐13]  are  required   together  with  air-­‐sensitive/toxic  additives[14,15]   and/or  expensive  metal  catalysts/ligands.[12]   Therefore,  we  set  out  to  explore  a  practical  synthesis   of  nonsymmetrical  ureas  from  readily  available  and   cheap  starting  materials  combined  with  a  highly   modular  nature  of  the  reaction  partners  (see  Scheme   1).  The  approach  uses  oxazolidinones  (cyclic   carbamates)  as  intermediates  that  allow  for   nucleophilic  ring-­‐opening  by  suitable  amines.  Such   an  approach  is  not  completely  without   precedence,[16,17]    however  so  far  oxazolidinone  type   intermediates  have  been  rarely  used  for  the   preparation  of  nonsymmetrical  ureas  with  wide   1 scope[18-­‐20]  and  thus  a  more  general  methodology   based  on  these  precursors  derived  from  readily   available,  cheap  epoxides  and  phenylcarbamate   (Scheme  1)  would  provide  an  attractive  and  simple   route  towards  highly  functional  ureas.       Scheme  1.  A  modular  approach  towards  non-­‐ symmetrical  ureas  through  oxazolidinone   intermediates.   Jacobsen  et  al.  recently  disclosed  a  method  for  the   formation  of  chiral  amino-­‐alcohols  through  a   Co(salen)  mediated  enantio-­‐selective  conversion  of   meso-­‐cyclic  epoxides  in  the  presence  of   phenylcarbamate  as  nucleophile.[21]  This  approach   demonstrated  the  use  of  phenylcarbamate  as  a   cheap  and  readily  available  reagent  in  the  formal   transfer  of    an  “amide”  unit  to  an  epoxide  giving   enantio-­‐enriched  oxazolidinones  as  intermediates   towards  the  synthesis  of  chiral  amino-­‐alcohols.   However,  the  reported  method  was  restricted  to  a   limited  number  of  cyclic  epoxides.  In  order  to  be  able   to  develop  a  more  general  method  towards   oxazolidinone  precursors  en  route  to   nonsymmetrical  ureas,  we  envisioned  that  our   previously  reported  Lewis  acidic   Al(aminotriphenolate)  catalysts  would  present  an   alternative  catalyst  for  oxazolidinone  formation   (Scheme  1).  Recently  we  showed  that  both  internal   as  well  as  terminal  epoxides  are  easily  activated   towards  nucleophilic  ring-­‐opening  by  these  catalyst   systems  to  form  highly  functional  cyclic  carbonates   in  the  presence  of  carbon  dioxide.[22-­‐24]  In  this  work   we  will  show  that  these  Al-­‐catalysts  provide  easy   access  to  a  wide  range  of  oxazolidinone  precursors   useful  for  a  modular  approach  towards  highly   functionalized  ureas  that  are  generally  obtained  in   excellent  yield  and  regio-­‐selectivity.   Results  and  Discussion   We  first  set  out  to  test  a  small  series  of   Al(aminotriphenolate)  complexes  A-­‐C  (Figure  1)  in   the  synthesis  of  oxazolidinone  1  under  various   conditions  (Table  1)  using  the  coupling  of   cyclohexene  oxide  (CHO)  and  phenylcarbamate  as  a   benchmark  reaction.  The  reaction  without  the   addition  of  catalyst  does  not  proceed  at  50ºC  (entry   1),  and  at  70ºC  only  low  conversion  of  the   phenylcarbamate  reagent  is  noted.  In  general  we   found  that  those  reactions  that  were  carried  out  at   this  latter  temperature  (entries  2,  5−8  and  14−15)   caused  (partial)  decomposition  of  the  carbamate   reagent  and  the  white  precipitates  noted  could  be   isolated  and  assigned  to  the  formation  of  1,3,5-­‐ triazine-­‐2,4,6(1H,  3H,  5H)-­‐trione,  a  cyclic  structure   supported  by  1H,  15N,  13C  NMR  and  IR  analysis  (see   Supporting  Information).     Figure  1.  Al-­‐catalysts  A−C  used  in  this  work.   Therefore,  we  decided  to  optimize  further  the   catalysis  conditions  at  50ºC  using  various  catalysts,   catalyst  loadings  and  amount  of  the  epoxide  (CHO).   Al-­‐catalyst  A  performs  much  better  than  B  (cf.,   entries  5-­‐8)  but  its  use  results  in  moderate  substrate   conversion  levels  at  50ºC  (entries  3  and  4).  Much   better  activity  was  noted  for  the  chloride-­‐substituted   Al-­‐complex  C  for  which  a  loading  of  2.5  mol%  and  an   equimolar  amount  of  epoxide  (entry  11)  already   provided  81%  conversion.  Further  increasing  the   epoxide/carbamate  ratio  to  2  led  to  nearly  full   conversion  (95%)  with  a  high  isolated  yield  (89%)  for   the  oxazolidinone  product  (entry  9).  Therefore,  the   reaction  conditions  of  this  latter  entry  seem  to  be   rather  ideal  for  the  synthesis  of  oxazolidinone  1.     2   Table  1.  Screening  of  catalyst  structures  A-­‐C  and   reaction  conditions  in  the  synthesis  of  oxazolidinone   1  from  cyclohexene  oxide  and  phenylcarbamate.[a]   Entry   Cat.   Amount   CHO   T   Conv.[b]     [mol%]   [mmol]   [ºC]   [%]   1   −   −   1.0   50   0   2   −   −   1.0   70   17[c]   3   A   2.5   1.0   50   41   4   A   5.0   1.0   50   47   5   A   2.5   1.0   70   94[c]   6   A   5.0   1.0   70   99[c]   7   B   2.5   1.0   70   10[c]   8   B   5.0   1.0   70   15[c]   9   C   2.5   1.0   50   95(89)[d]   10   C   5.0   1.0   50   99   11   C   2.5   0.5   50   81   12   C   2.5   0.75   50   84   13   C   2.5   2.0   50   99   14   C   1.0   1.0   70   99[c]   15   C   2.5   1.0   70   general,  this  Al-­‐mediated  synthesis  allows  for  a  wide   range  of  (functional)  groups  to  be  present  in  the   epoxide  substrate  including  alkene  (2  and  4),  alkyl   halide  (5),  arylbromide  (9),  epoxidic  (8),  alkyne  (13)   and  ether  (10  and  13-­‐15)  groups.  Of  further  note  are   the  syntheses  of  oxazolidinones  11  and  16  and   compounds  1−3  that  comprise  of  an  (a)cyclic  dialkyl-­‐ substituted  pattern.  The  alternative  formation  of   acyclic  and  cyclic  4,5−  and  5,5´−disubstituted   oxazolidinone  regio-­‐isomers  from  aziridenes/CO2[25-­‐ 27] ,  epoxide/isocyanate[28,29]  or  propargylic   amine/CO2[30]  substrate  combinations  typically   require  harsher  reaction  conditions,  a  higher  loading   of  catalyst  and/or  the  use  of   stoichiometric/expensive  additives  and  more   elaborative  procedures.  The  method  disclosed  here   towards  oxazolidinones  1−16  is  operationally  simple   and  allows  for  high  conversion  under  attractive   reaction  conditions  (50ºC,  2  mol%  of  catalyst).  The   majority  of  the  oxazolidinone  compounds  could  be   isolated  in  good  yields  (up  to  91%)  and  high  regio-­‐ selectivity  for  the  5−isomer  was  noted  with  some   exceptions  (cf.,  the  synthesis  of  9,  12  and  16).  Since   these  reactions  occur  with  inversion  of  configuration   at  the  carbon  centre  at  the  initial  stage  of  the   reaction  (i.e.,  nucleophilic  attack  of  the  carbamate   reagent  onto  the  epoxide-­‐Al  complex),  those   reactions  that  involve  cis-­‐configured  carbon  centres   in  the  oxirane  unit  give  rise  to  oxazolidinones  with  a   trans  disposition  (cf.,  syntheses  of  1-­‐3  and  11a).  Thus   these  conversions  proceed  with  formal  inversion   unlike  the  reactions  between  isocyanates  and   epoxides.[29]     99(71)[c,d]   [a]  General  conditions:  0.5  mmol  phenylcarbamate,   catalyst  A-­‐C  (0−5  mol%),  18  h,  CH3CN.  [b]  Conversion   determined  by  1H  NMR  (CDCl3)  based  on  phenol   formation.  [c]  White  precipitate  noted.  [d]  Isolated   yield  of  oxazolidinone  product  in  brackets.   Once  discovered  the  best  conditions  for  the   conversion  of  CHO  into  product  1  using  the  most   effective  Al  catalyst  (i.e.,  C),  we  then  started  to   investigate  the  scope  of  this  process  (Scheme  2).  In   3 phenoxide  as  a  leaving  group.[31]  The  formation  of   phenol,  as  a  result  of  the  phenoxide  abstracting  a   proton,  is  easily  recognized  in  the  reaction  mixture   and  thus  allows  for  following  the  course  of  the   process  (see  Table  1,  Scheme  3).     Scheme  3.  Proposed  mechanism  leading  to  formal   inversion  in  cis-­‐2,3-­‐dimethyloxirane.       Scheme  2.  Synthesis  of  oxazolidinones  1−16  from   various  epoxides  and  phenylcarbamate  catalysed  by   Al-­‐aminotriphenolate  complex  C  (2  mol%).  Reported   here  are  isolated  yields  after  column  purification;   selectivities  refer  to  regio-­‐isomers  formed  in  the   case  of  terminal  epoxide  conversion  (note:  only  the   major  isomer  is  shown).   This  inversion  pathway  was  further  substantiated  by   the  synthesis  of  11b  (cis  diastereoisomer  of  11a;  dr  >   99%)  that  was  prepared  from  the  trans-­‐epoxide.   The  envisioned  mechanism  involves  a  nucleophilic   attack  of  the  phenyl  carbamate  on  the  coordinated   epoxide  producing  a  reactive  alkoxide  which  is   stabilized  by  the  Al  complex  (Scheme  3)  displaying   dual  character:  the  aminotriphenolate  ligand  acts   here  as  a  proton  relay  mediator  increasing  the   nucleophilic  character  of  the  alkoxide  which  allows  a   more  efficient  ring-­‐closing  to  occur  releasing  the   final  (configurationally  inverted)  product  and  a   The  oxazolidinones  1-­‐16  serve  as  useful  precursors   towards  the  formation  of  highly  functional,   nonsymmetrical  ureas  as  shown  in  Scheme  4.   Treatment  of  the  respective  oxazolidinone  precursor   with  a  suitable  amine  (1.2−4  equiv)  allows  for   isolation  of  the  urea  product  in  high  yield  and   chemo-­‐selectivity.  The  aminolysis  of  the   oxazolidinone  occurs  with  exclusive  preference  for   scission  of  the  NH−C=O  bond.  The  formation  of  ureas   17-­‐24,  27  and  28  from  bicyclic  oxazolidinones   proceeds  generally  under  mild  reaction  conditions  in   the  presence  of  a  small  excess  of  amine  reagent  in   CH3CN  solvent.  This  procedure  is  attractive,  practical   and  proceeds  with  full  conversion  of  the  starting   materials.  In  the  case  where  oxazolidinones  derived   from  terminal  epoxides  are  used  as  starting   materials  (i.e.,  25,  26  and  29-­‐32),  the  aminolysis   reaction  required  generally  higher  temperature,   longer  reaction  times  and  a  larger  excess  of  amine   reagent  (4  equiv)  under  solvent-­‐free  conditions.  In   the  latter  cases,  somewhat  lower  isolated  yields  are   noted  (up  to  73%).   The  scope  demonstrated  in  Scheme  3  illustrates  that   highly  functionalized  ureas  can  be  prepared   including  those  incorporating  pyrrolidine  (17),  alkene   (19,  23,  25  and  29),  alkyne  (20  and  31),  heterocyclic   4 (17,  24,  25,  27,  31  and  32),  alkyl  amine  (28)  and   vicinal  diol  (26)  groups.  Note  that  urea  26  is  derived   from  the  oxazolidinone  5  which  is  based  on  the   initial  use  of  epichlorohydrin.  The  longer  reaction   time  needed  to  convert  5  into  26  resulted  in   effective  hydrolysis  of  the  alkyl  chloride  fragment   which  is  in  line  with  the  recorded  NMR  data  and   mass  spectrometric  analysis  (see  Supporting   Information).   Both  primary  as  well  as  secondary  amines  (cf.,   syntheses  of  17,  22,  27  and  32)  react  smoothly  with   the  oxazolidinone  precursors  further  amplifying  the   potential  scope  of  this  urea  formation  reaction.  The   molecular  structure  of  urea  27  (Figure  2)  was   determined  by  X-­‐ray  diffraction.  Compound  27  was   derived  from  oxazolidinone  1.  Thus,  the  relative   configuration  of  the  urea  and  the  free  alcohol  groups   (trans)  is  further  testament  of  the  proposed   inversion  mechanism  as  depicted  in  Scheme  3.       Figure  2.  X-­‐ray  molecular  structure  determined  for   urea  27.  Selected  interatomic  distances  (Å)  and   angles  (º)  with  esd´s  in  parentheses:  N(1A)-­‐C(1A)  =   1.366(5),  N(2A)-­‐C(1A)  =  1.356(5),  C(1A)-­‐O(1A)  =   1.248(5),  N(2A)-­‐C(6A)  =  1.449(5);  N(1A)-­‐C(1A)-­‐N(2A)   =  117.8(4),  N(1A)-­‐C(1A)-­‐O(1A)  =  120.4(4),  N(2A)-­‐ C(1A)-­‐O(1A)  =  121.8(4).     Scheme  4.  Synthesis  of  nonsymmetrical  ureas  17−32   from  oxazolidinone  precurcors  and   primary/secondary  amines.  Reported  yields  are   isolated  ones  after  column   purification/crystallization.   The  diversity  of  functional  groups  in  the  presented   scope  of  urea  products  has  potential  in  post-­‐ synthetic  modifications  as  shown  in  Scheme  5.  To   demonstrate  further  use  of  these  scaffolds,  urea  13   was  subjected  to  “click”  chemistry  conditions  using   benzyl  azide  as  coupling  partner:  this  afforded  the   triazole  34  smoothly  in  91%  yield.[32]  The  use  of  click   reactions  to  functionalize  polymer  supports  or  other   macromolecular  structures  is  interesting  for   catalytic[33]  and  supramolecular  applications[34,35]  and   therefore  this  chemistry  combined  with  suitable  urea   synthons  opens  up  new  opportunities  in   aforementioned  areas.       5   Scheme  5.  Synthetic  potential  of  urea  13.   Conclusion   We  here  disclose  a  simple  but  effective  two-­‐step   method  for  the  formation  of  highly  functional,   nonsymmetrical  ureas  from  easy  to  prepare   oxazolidinones.  The  cyclic  carbamates  are  derived   from  cheap  and  readily  available  epoxides  and   phenylcarbamate  mediated  through  Al-­‐catalysis.  The   method  is  further  characterized  by  its  operational   simplicity  and  wide  scope  in  ureas  that  can  be   attained.  Further  to  this,  these  functional  ureas  may   serve  as  suitable  scaffolds  in  organic  synthesis  which   can  be  post-­‐modified  using  “click”  type  reactions  as   demonstrated  herein.   Experimental  Section   Oxazolidinone  Synthesis   Typically,  phenyl  carbamate  (1  mmol),  the  epoxide  (2   mmol),  the  aluminium  catalyst  (2  mol%)  and   acetonitrile  (2  mL)  were  introduced  into  a  glass  vial   (5  ml)  equipped  with  a  stirring  bar.  The  vial  was   closed  and  introduced  into  a  silicon  oil  bath   preheated  at  the  desired  reaction  temperature   (50−70ºC)  and  stirred  for  18  h.  Once  the  reaction   mixture  had  cooled  down  to  r.t.  the  product  was   purified  by  flash-­‐column  chromatography  following   analysis.  Full  characterization  data  and  copies  of   relevant  spectra  are  provided  in  the  Supporting   Information.   Urea  Synthesis   Typically,  the  oxazolidinone  (0.5  mmol)  was   introduced  into  an  HPLC  vial  equipped  with  a  stirring   bar.  For  the  oxazolidinones  based  on  bicyclic   scaffolds,  the  amine  reagents  were  introduced   (usually  1.2  equiv  but  was  risen  to  1.8  equiv  when   dealing  with  volatile  amines)  with  addition  of   acetonitrile  (0.2  mL)  and  heated  to  the  desired   temperature  (50ºC)  for  18  h.  Once  the  reaction   mixture  had  cooled  down  to  r.t.  the  pure  product   was  isolated  by  evaporation  of  the  excess  of  amine,   and  the  crude  ureas  recrystallized  from   dichloromethane  (ureas  20,  21,  23,  24,  27  and  28)  or   purified  by  flash  column  chromatography.  The   oxazolidinones  with  monocyclic  scaffolds  were   treated  with  the  respective  amine  reagent  (4  equiv)   under  neat  conditions  and  heated  to  70ºC  for  66  h.   The  products  were  then  isolated  by  recrystallization   from  dichloromethane  (for  urea  29)  or  purified  by   flash  column  chromatography.  Full  characterization   data  and  copies  of  relevant  spectra  are  provided  in   the  Supporting  Information.   Crystallographic  Studies   The  measured  crystal  was  stable  under  atmospheric   conditions;  nevertheless  it  was  treated  under  inert   conditions  immersed  in  perfluoro-­‐polyether  as   protecting  oil  for  manipulation.  Data  Collection:   measurements  were  made  on  a  Bruker-­‐Nonius   diffractometer  equipped  with  an  APPEX  II  4K  CCD   area  detector,  a  FR591  rotating  anode  with  Mo  Kα   radiation,  Montel  mirrors  and  a  Kryoflex  low   temperature  device  (T  =  −173  °C).  Full-­‐sphere  data   collection  was  used  with  ω  and  φ  scans.  Programs   used:  Data  collection  Apex2  V2011.3  (Bruker-­‐Nonius   2008),  data  reduction  Saint+Version  7.60A  (Bruker   AXS  2008)  and  absorption  correction  SADABS  V.   2008−1  (2008).  Structure  Solution:  SHELXTL  Version   6.10  (Sheldrick,  2000)  was  used.[36]  Structure   Refinement:  SHELXTL-­‐97-­‐UNIX  VERSION.  Crystal  data   for  27:  C11H20N2O3,  Mr  =  228.29,  triclinic,  P-­‐1,  a  =   6.4520(13)  Å,  b  =  9.1250(18)  Å,  c  =  20.031(4)  Å,  a  =   92.00º,  b  =  92.90º,  g  =  90.06º,  V  =  1177.1(4)  Å3,  Z  =   4,  ρ  =  1.288  mg·∙M−3,  m  =  0.094  mm−1,  l  =  0.71073  Å,  T   =  100(2)  K,  F(000)  =  496,  crystal  size  =  0.15  ×  0.04  ×   0.01  mm,  θ(min)  =  1.018°,  θ(max)  =  27.67°,  5421   reflections  collected,  5421  reflections  unique,  GoF  =   1.061,  R1  =  0.0812  and  wR2  =  0.1951  [I  >  2σ(I)],  R1  =   0.1438  and  wR2  =  0.2367  (all  indices),  min/max   6 residual  density  =  −0.716/0.718  [e·∙Å−3].   Completeness  to  θ(27.67°)  =  98.9%.  CCDC  number   1405849.   [10]   K.  J.  Padiya,  S.  Gavade,  B.  Kardile,  M.  Tiwari,   S.  Bajare,  M.  Mane,  V.  Gaware,  S.  Varghese,  D.  Harel,   S.  Kurhade,  Org.  Lett.  2012,  14,  2814-­‐2817.   Acknowledgements   [11]   E.  V.  Vinogradova,  B.  P.  Fors,  S.  L.  Buchwald,   J.  Am.  Chem.  Soc.  2012,  134,  11132-­‐11135.   We  thank  ICIQ,  ICREA  and  the  Spanish  Ministerio  de   Economía  y  Competitividad  (MINECO)  through   Severo  Ochoa  Excellence  Accreditation  2014-­‐2018   (SEV-­‐2013-­‐0319)  and  project  CTQ2014-­‐60419-­‐R  for   support.  W.G.  thanks  the  CELLEX  foundation  for   financial  support  and  V.L.  wishes  to  acknowledge  the   Generalitat  de  Catalunya  for  an  FI  fellowship.   Eduardo  C.  Escudero-­‐Adán  and  Dr.  Eddy  Martin  are   thanked  for  the  X-­‐ray  crystallographic  analysis.   References   [1]   N.  Volz,  J.  Clayden,  Angew.  Chem.  Int.  Ed.   2011,  50,  12148-­‐12155.   [2]   S.  J.  Connon,  Chem.  Commun.  2008,  2499-­‐ 2510.   [3]   Y.  Takemoto,  Org.  Biomol.  Chem.  2005,  3,   4299-­‐4306.   [4]   S.  Dawn,  M.  B.  Dewal,  D.  Sobransingh,  M.  C.   Paderes,  A.  C.  Wibowo,  M.  D.  Smith,  J.  A.  Krause,  P.  J.   Pellechia,  L.  S.  Shimizu,  J.  Am.  Chem.  Soc.  2011,  133,   7025-­‐7032.   [5]   J.  T.  Su,  P.  Vachal,  E.  N.  Jacobsen,  Adv.  Synth.   Catal.  2001,  343,  197-­‐200.   [6]   For  an  example  see:  J.  J.  van  Gorp,  J.  A.  J.   Vekemans,  E.W.  Meijer,  J.  Am.  Chem.  Soc.  2002,  124,   14759-­‐14769.   [12]   H.  V.  Le,  B.  Ganem,  Org.  Lett.  2011,  13,  2584-­‐ 2585.   [13]  H.  Lebel,  O.  Leogane,  Org.  Lett.  2006,  8,  5717-­‐ 5720.   [14]   J.  A.  Fritz,  J.  S.  Nakhla,  J.  P.  Wolfe,  Org.  Lett.   2006,  8,  2531-­‐2534.   [15]   M.  B.  Bertrand,  J.  P.  Wolfe,  Tetrahedron   2005,  61,  6447-­‐6459.   [16]   For  use  of  this  aminolysis  reaction  in  the   preparation  of  urea-­‐tethered  neoglycoconjugates:  Y.   Ichikawa,  Y.  Matsukawa,  M.  Isobe,  J.  Am.  Chem.  Soc.   2006,  128,  3934-­‐3938.   [17]   T.  Yoshimitsu,  T.  Ino,  T.  Tanaka,  Org.  Lett.   2008,  10,  5457-­‐5460.   [18]   E.  Bon,  R.  Réau,  G.  Bertrand,  Tetrahedron   Lett.  1996,  37,  1217-­‐1220.   [19]   G.  Chen,  P.  Pan,  Y.  Yao,  Y.  Chen,  X.  Meng,  Z.   Li,  Tetrahedron  2008,  64,  9078-­‐9087.   [20]   I.  Maya,  O.  López,  J.  G.  Fernández-­‐Bolaños,  I.   Robina,  J.  Fuentes,  Tetrahedron  Lett.  2001,  42,  5413-­‐ 5416.   [21]   J.  A.  Birrell,  E.  N.  Jacobsen,  Org.  Lett.  2013,   15,  2895-­‐2897.   [7]   R.  P.  Sijbesma,  F.  H.  Beijer,  L.  Brunsveld,  B.  J.   B.  Folmer,  J.  H.  K.  K.  Hirschberg,  R.  F.  M.  Lange,  J.  K.   L.  Lowe,  E.  W.  Meijer,  Science  1997,  278,  1601-­‐1604.   [22]   C.  J.  Whiteoak,  E.  Martin,  E.  C.  Escudero-­‐ Adán  A.  W.  Kleij,  Adv.  Synth.  Catal.  2013,  355,  2233-­‐ 2239.   [8]   One  example:  J.  M.  Rodriguez,  A.  D.   Hamilton,  Angew.  Chem.  Int.  Ed.  2007,  46,  8614-­‐ 8617.   [23]   C.  J.  Whiteoak,  N.  Kielland,  V.  Laserna,  E.  C.   Escudero-­‐Adán,  E.  Martin,  A.  W.  Kleij,  J.  Am.  Chem.   Soc.  2013,  135,  1228-­‐1231.   [9]   S.  Hussain,  P.  R.  Brotherhood,  L.W.  Judd,  A.   P.  Davis,  J.  Am.  Chem.  Soc.  2011,  133,  1614-­‐1617.   [24]   V.  Laserna,  G.  Fiorani,  C.  J.  Whiteoak,  E.   Martin,  E.  Escudero-­‐Adán,  A.  W.  Kleij,  Angew.  Chem.   Int.  Ed.  2014,  53,  10416-­‐10419.   7 [25]   M.  T.  Hancock,  A.  R.  Pinhas,  Tetrahedron   Lett.  2003,  44,  5457-­‐5460.   [26]   J.  Seayad,  A.  M.  Seayad,  J.  K.  P.  Ng,  C.  L.  L.   Chai,  ChemCatChem  2012,  4,  774-­‐777.   [27]   F.  Fontana,  C.  C.  Chen,  V.  K.  Aggarwal,  Org.   Lett.  2011,  13,  3454-­‐3457.   [28]   P.  Wang,  J.  Qin,  D.  Yuan,  Y.  Wang,  Y.  Yao,   ChemCatChem  2015,  7,  1145-­‐1151.   [29]   T.  Baronsky,  C.  Beattie,  R.  W.  Harrington,  R.   Irfan,  M.  North,  J.  G.  Osende,  C.  Young,  ACS  Catal.   2013,  3,  790-­‐797.   [30]   M.  Shi,  Y.-­‐M.  Shen,  J.  Org.  Chem.  2002,  67,   16-­‐21.   [31]   We  have  monitored  the  reaction  between   cyclohexene  oxide  and  phenyl  carbamate  by  13C   NMR  spectroscopy  and  resonances  of  the  product,   the  released  phenol,  phenyl  carbamate  and  an   additional  species  were  noted.  The  latter  may  be   assigned  to  an  open  carbamate  structure  prior  to   ring-­‐closure  leading  to  the  cyclic  carbamate,  see  the   Supporting  Information  for  details.   [32]   F.  Himo,  T.  Lovell,  R.  Hilgraf,  V.  V.  Rostovtsev,   L.  Noodleman,  K.  B.  Sharpless,  V.  V.  Fokin,  J.  Am.   Chem.  Soc.  2005,  127,  210.   [33]   C.  J.  Whiteoak,  A.  H.  Henseler,  C.  Ayats,  A.   W.  Kleij,  M.  A.  Pericàs,  Green  Chem.  2014,  16,  1552.   [34]   S.  Dawn,  M.  B.  Dewal,  D.  Sobransingh,  M.  C.   Paderes,  A.  C.  Wibowo,  M.  D.  Smith,  J.  A.  Krause,  P.  J.   Pellechia,  L.  S.  Shimizu,  J.  Am.  Chem.  Soc.  2011,  133,   7025.   [35]   J.  M.  Roberts,  B.  M.  Fini,  A.  A.  Sarjeant,  O.  K.   Farha,  J.  T.  Hupp,  K.  A.  Scheidt,  J.  Am.  Chem.  Soc.   2012,  134,  3334.   [36]   G.  M.  Sheldrick,  SHELXTL  Crystallographic   System,  version  6.10;  Bruker  AXS,  Inc.:  Madison,  WI,   2000.         8 FULL  PAPER     Expedient  Synthesis  of  Functionalized  Non-­‐ Symmetrical  Ureas  from  Oxazolidinone  Precursors         Adv.  Synth.  Catal.  2015,  357,  Page  –  Page   Victor  Laserna,  Wusheng  Guo,  Arjan  W.  Kleij*         9