CBS Oxazaborolidines - Versatile Catalysts for Asymmetric Synthesis

Biographical Sketches

René T. Stemmler was born in Frankfurt/Main, Germany, in 1976. He studied chemistry at the University of Freiburg, Germany and the University of North Carolina at Chapel Hill, NC, USA. ­Currently, he is pursuing his PhD under the supervision of Professor Carsten Bolm at the RWTH Aachen University, Germany. His ­research is focused on the design and synthesis of novel, chiral ­organometallic catalysts and the development of new reactions for asymmetric catalysis.

Introduction

CBS Oxazaborolidines 1a-c are well-established catalysts, which mediate the enantio- and diastereoselective reduction of highly functionalized ketones. [1] [2] Recently, the substrate scope has been extended to include oxime ethers [3] and ketimines. [4] Accordingly, these reagents have been extensively applied in natural product synthesis, for instance in the recently published total syntheses of (-)-laulimalide, [5] brevetoxin-B, [6] (+)-tanikolide, [7] and bistramide A. [8] Additionally, oxazaborolidines 1 were used in the kinetic resolution [9] and the dynamic kinetic ­resolution of atropoisomeric lactones. [9b] [10]

More recently, the protonated oxazaborolidinium salts 2a and 2b were used as chiral Lewis acids [11] in catalytic enantioselective Diels-Alder reactions, [12] the cyanosilylation of aldehydes, [13] Michael additions, [14] and a vinylogous ­Mukaiyama aldol reaction. [15]

Compound 1a is typically generated in situ by reaction of (S)- or (R)-2,2-diphenylhydroxymethylpyrrolidine with BH₃·THF, [2] while oxazaborolidines 1b,c may be prepared using the corresponding boronic acids. [1c] [16] In a similar fashion, reaction of the same chiral pyrrolidine substrate with o-tolylboroxine furnishes o-tolyl-CBS-oxazaborolidine, [16] which, when protonated with triflic acid or trif­limide, affords the oxazaborolidinium salts 2a and 2b, respectively. [12b] [d] The facile preparation and modification of the oxazaborolidines, along with their high reactivity and selectivity, render members of this class of molecules as important candidates for future applications in asymmetric catalysis.

Abstracts

(A) One representative example of the value of the CBS reagents of type 1 in natural product synthesis was recently demonstrated in the total synthesis of (-)-laulimalide A by Uenishi, in which a highly functionalized and complex 1,2-enone was diastereoselectively reduced to the corresponding allylic alcohol in high yield. A single isomer was obtained. [5]
(B) Demir et al. described the stereospecific reduction of benzyl oxime ethers to the corresponding free amines. In the presence of oxazaborolidine (S)-1a the E-isomer was reduced to the S-enantio­mer, whereas reduction of the Z-isomer with the same reagent leads to the R-isomer with high enantioselectivity. Ozonolysis of the furan ring of each isomer allowed enantioselective access to the corresponding amino acids in high yields. [3a]
(C) The total syntheses of the odorants georgyone, arborone, and structural congeners were reported by Corey and co-workers. The key steps in each synthesis involved an intermolecular Diels-Alder reaction catalyzed by the oxazaborolidinium salt (S)-2b. For instance, the intermediate in the synthesis of (-)-georgyone, which is shown here, was prepared with 96% ee and a diastereomeric ratio of 6:1. [12a]
(D) A catalytic, enantioselective Michael addition using 20 mol% of catalyst (R)-2b was recently accomplished by Corey, in which, for instance, the reaction of a silyl ketene acetal with cyclo­hexenone furnished the 1,4-addition product in 91% yield with 90% ee. [14]
(E) Very recently, Boeckman et al. reported the first application of chiral oxazaborolidinium salts in an asymmetric vinylogous ­Mukaiyama aldol reaction. The assembly of a butenolide was accomplished with good diastereoselectivity by the addition of tri­methylsiloxyfuran to an aldehyde in the presence of catalyst (R)-2a. Additional methyl substituents on the diphenyl moiety of the oxazaborolidinium salt improved the diastereoselectivity to 95:5 (threo/erythro), with a diastereomeric ratio (threo) of >95:5. [15]

References and Notes

• For reviews, see:
• 1a Cho BT. Tetrahedron  2006,  62:  7621 
• 1b Cho BT. Aldrichimica Acta  2002,  35:  3 
• 1c Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1986;   Angew. Chem.  1998,  110:  2092 
• 1d Itsuno S. Org. React.  1998,  52:  395 
• CBS represents the initials of the researchers who discovered the reagents 1a-c, namely Corey, Bakshi, and Shibata:
• 2a Corey EJ. Bakshi RK. Shibata S. J. Am. Chem. Soc.  1987,  109:  5551 
• 2b Corey EJ. Bakshi RK. Shibata S. Chen C.-P. Singh VK. J. Am. Chem. Soc.  1987,  109:  7925 
• 3a Demir AS. Sesenoglu Ö. Ülkü D. Arici C. Helv. Chim. Acta  2003,  86:  91 
• 3b Demir AS. Sesenoglu Ö. Aksoy-Cam H. Kaya H. Aydogan K. Tetrahedron: Asymmetry  2003,  14:  1335 
• 3c Demir AS. Sesenoglu Ö. Gerçek-Arkin Z. Tetrahedron: Asymmetry  2001,  12:  2309 
• 4a Gosselin F. O’Shea PD. Roy S. Reamer RA. Chen C.-y. Volante RP. Org. Lett.  2005,  7:  355 
• 4b Kirton EHM. Tughan G. Morris RE. Field RA. Tetrahedron Lett.  2004,  45:  853 
• 5 Uenishi J. Ohmi M. Angew. Chem. Int. Ed.  2005,  44:  2756 ; Angew. Chem.  2005,  117:  2816 
• 6 Matsuo G. Kawamura K. Hori N. Matsukura H. Nakata T. J. Am. Chem. Soc.  2004,  126:  14374 
• 7 Kita Y. Matsuda S. Fujii E. Horai M. Hata K. Fujioka H. Angew. Chem. Int. Ed.  2005,  44:  5857 ; Angew. Chem.  2005,  117:  6007 
• 8 Crimmins MT. DeBaillie AC. J. Am. Chem. Soc.  2006,  128:  4936 
• 9a Molander GA. George KM. Monovich LG. J. Org. Chem.  2003,  68:  9533 
• 9b Bringmann G. Pabst T. Henschel P. Kraus J. Peters K. Peters E.-M. Rycroft DS. Connolly JD. J. Am. Chem. Soc.  2000,  122:  9127 
• 10a Abe H. Takeda S. Fujita T. Nishioka K. Takeuchi Y. Harayama T. Tetrahedron Lett.  2004,  45:  2327 
• 10b Bringmann G. Menche D. Kraus J. Mühlbacher J. Peters K. Peters E.-M. Brun R. Bezabih M. Abegaz BM. J. Org. Chem.  2002,  67:  5595 
• 10c Bringmann G. Ochse M. Götz R. J. Org. Chem.  2000,  65:  2069 
• 11 For a review, see: Bolm C. Rantanen T. Schiffers I. Zani L. Angew. Chem. Int. Ed.  2005,  44:  1758 ; Angew. Chem.  2005,  117:  1788 
• 12a Hong S. Corey EJ. J. Am. Chem. Soc.  2006,  128:  1346 
• 12b Ryu DH. Corey EJ. J. Am. Chem. Soc.  2003,  125:  6388 
• 12c Zhou G. Hu Q.-Y. Corey EJ. Org. Lett.  2003,  5:  3979 
• 12d Corey EJ. Shibata T. Lee TW. J. Am. Chem. Soc.  2002,  124:  3808 
• 12e Ryu DH. Lee TW. Corey EJ. J. Am. Chem. Soc.  2002,  124:  9992 
• 13 Ryu DH. Corey EJ. J. Am. Chem. Soc.  2004,  126:  8106 
• 14 Liu D. Hong S. Corey EJ. J. Am. Chem. Soc.  2006,  128:  8160 
• 15 Boeckman RK. Pero JE. Boehmler DJ. J. Am. Chem. Soc.  2006,  128:  11032 
• 16 Compounds (S)-1b, (R)-1b, and (S)-o-tolyl-CBS-oxaza-borolidine are commercially available