Synthesis 2017; 49(03): 484-503
DOI: 10.1055/s-0036-1588888
short review
© Georg Thieme Verlag Stuttgart · New York

Substrate-Controlled Aldol Reactions from Chiral α-Hydroxy Ketones

Gabriel Aullón
b  Departament de Química Inorgànica i Orgànica, Secció de Química Inorgànica, Universitat de Barcelona, Carrer Martí i Franqués 1-11, 08028 Barcelona, Catalonia, Spain   Email: [email protected]   Email: [email protected]
,
Pedro Romea*
a  Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Universitat de Barcelona, Carrer Martí i Franqués 1-11, 08028 Barcelona, Catalonia, Spain
,
Fèlix Urpí*
a  Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Universitat de Barcelona, Carrer Martí i Franqués 1-11, 08028 Barcelona, Catalonia, Spain
› Author Affiliations
Further Information

Publication History

Received: 26 July 2016

Accepted after revision: 02 September 2016

Publication Date:
12 October 2016 (online)


Dedicated to Professor Clayton H. Heathcock on the occasion of his 80th birthday

Abstract

Chiral α-hydroxy ketones are valuable platforms from which highly stereoselective substrate-controlled aldol reactions may be performed. The suitable choice of the hydroxyl protecting group and the enolization conditions produce aldol adducts that can be easily manipulated to give a variety of enantiomerically pure compounds. Moreover, such aldol reactions often play a crucial role in the coupling of elaborate fragments in advanced steps of the synthesis of natural products. Together, these features confer to the α-hydroxy ketones a prominent position among the chiral substrates that are capable of providing highly asymmetric transformations.

1 Introduction

2 Pioneering Contributions

3 Boron-Mediated Aldol Reactions from α-Hydroxy Ethyl Ketones

4 Titanium-Mediated Aldol Reactions from α-Hydroxy Ethyl Ketones

5 Other Aldol Reactions from α-Hydroxy Ethyl Ketones

6 Aldol Reactions from α-Hydroxy Methyl Ketones

7 Conclusions

 
  • References

  • 2 For a classical review on substrate-controlled reactions, see: Hoveyda AH, Evans DA, Fu GC. Chem. Rev. 1993; 93: 1307
  • 3 Catalysts can promote substrate-controlled reactions. For a recent review on substrate-controlled natural product biosynthesis catalyzed by enzimes, see: Ding W, Li Y, Zhang Q. ACS Chem. Biol. 2015; 10: 1590
  • 4 Modern Methods in Stereoselective Aldol Reactions. Mahrwald R. Wiley-VCH; Weinheim: 2013
  • 5 For a classic overview on the reactivity of boron enolates, see: Cowden CJ, Paterson I. Org. React. 1997; 51: 1
  • 6 For a recent overview on the titanium(IV) enolate chemistry, see: Ciez D, Palasz A, Trzewik B. Eur. J. Org. Chem. 2016; 1476
    • 7a Buse CT, Heathcock CH. J. Am. Chem. Soc. 1977; 99: 8109
    • 7b Heathcock CH, White CT. J. Am. Chem. Soc. 1979; 101: 7076
  • 8 Heathcock CH, Pirrung MC, Buse CT, Hagen JP, Young SD, Sohn JE. J. Am. Chem. Soc. 1979; 101: 7077
  • 9 Masamune S, Choy W, Kerdesky FA. J, Imperiali B. J. Am. Chem. Soc. 1981; 103: 1566
  • 10 For related studies on lithium enolates, see: Masamune S, Ali SA, Snitman DL, Garvey DS. Angew. Chem., Int. Ed. Engl. 1980; 19: 557
  • 11 Masamune S, Hirama M, Mori S, Ali SA, Garvey DS. J. Am. Chem. Soc. 1981; 103: 1568
  • 12 Van Draanen NA, Arseniyadis S, Crimmins MT, Heathcock CH. J. Org. Chem. 1991; 56: 2499
    • 13a Brown HC, Dhar RK, Bakshi RK, Pandiarajan PK, Singaram B. J. Am. Chem. Soc. 1989; 111: 3441
    • 13b Brown HC, Dhar RK, Ganesan K, Singaram B. J. Org. Chem. 1992; 57: 499
    • 13c Brown HC, Dhar RK, Ganesan K, Singaram B. J. Org. Chem. 1992; 57: 2716
    • 13d Ganesan K, Brown HC. J. Org. Chem. 1993; 58: 7162
  • 14 Paterson I, Wallace DJ, Velázquez SM. Tetrahedron Lett. 1994; 35: 9083

    • For theoretical studies on the aldol reaction from Z-borinates, see:
    • 15a Bernardi A, Capelli AM, Comotti A, Gennari C, Gardner M, Goodman JM, Paterson I. Tetrahedron 1991; 47: 3471
    • 15b Bernardi A, Gennari C, Goodman JM, Paterson I. Tetrahedron: Asymmetry 1995; 6: 2613

      For theoretical studies on the enolization of ketones by L2BCl, see:
    • 16a Goodman JM. Tetrahedron Lett. 1992; 33: 7219
    • 16b Goodman JM, Paterson I. Tetrahedron Lett. 1992; 33: 7223
    • 16c Murga J, Falomir E, Carda M, Marco JA. Tetrahedron 2001; 57: 6239
  • 17 Paterson I. Synthesis 1998; 639

    • For theoretical studies on the aldol reaction from E-borinates, see:
    • 18a Vulpetti A, Bernardi A, Gennari C, Goodman JM, Paterson I. Tetrahedron 1993; 49: 685
    • 18b See Ref. 15b.

      For key interactions with the aldehyde proton, see:
    • 19a Corey EJ, Rohde JJ, Fischer A, Azimioara MD. Tetrahedron Lett. 1997; 38: 33
    • 19b Corey EJ, Rohde JJ. Tetrahedron Lett. 1997; 38: 37
  • 20 Galobardes M, Gascón M, Mena M, Romea P, Urpí F, Vilarrasa J. Org. Lett. 2000; 2: 2599
    • 21a Carda M, Murga J, Falomir E, González F, Marco JA. Tetrahedron 2000; 56: 677
    • 21b Murga J, Falomir E, González F, Carda M, Marco JA. Tetrahedron 2002; 58: 9697
    • 21c Murga J, Ruiz P, Falomir E, Carda M, Peris G, Marco JA. J. Org. Chem. 2004; 69: 1987
  • 22 Interestingly, other attempts based on the enolization with LDA, Bu2BOTf/DIPEA, TiCl4/DIPEA, or Sn(OTf)2/DIPEA failed.
    • 23a Marco JA, Carda M, Díaz-Oltra S, Murga J, Falomir E, Roeper H. J. Org. Chem. 2003; 68: 8577
    • 23b Díaz-Oltra S, Ruiz P, Falomir E, Murga J, Carda M, Marco JA. Org. Biomol. Chem. 2012; 10: 6937
  • 24 Paterson I, Wallace DJ. Tetrahedron Lett. 1994; 35: 9087
  • 25 Li P, Li J, Arikan F, Ahlbrecht W, Dieckmann M, Menche D. J. Org. Chem. 2010; 75: 2429
  • 26 Zhang Z, Chen Y, Adu-Ampratwum D, Okumu AA, Kenton NT, Forsyth CJ. Org. Lett. 2016; 18: 1824
  • 27 Cheng B, Trauner D. J. Am. Chem. Soc. 2015; 137: 13800
  • 28 Díaz-Oltra S, Murga J, Falomir E, Carda M, Peris G, Marco JA. J. Org. Chem. 2005; 70: 8130
  • 29 Paterson I, Chen DY.-K, Coster MJ, Aceña JL, Bach J, Gibson KR, Keown LE, Oballa RM, Trieselmann T, Wallace DJ, Hodgson AP, Norcross RD. Angew. Chem. Int. Ed. 2001; 40: 4055
  • 30 Crimmins reported a similar boron-mediated aldol reaction from an α-OBn methyl ketone, see: Crimmins MT, Katz JD, McAtee LC, Tabet EA, Kirincich SJ. Org. Lett. 2001; 3: 949
  • 31 Interestingly, the parallel lithium-mediated aldol reaction turned out to be nonstereoselective. See, for instance: Anderson JC, McDermott BP, Griffin EJ. Tetrahedron 2000; 56: 8747

    • For other examples, see:
    • 32a Paterson I, Wallace DJ. Tetrahedron Lett. 1994; 35: 9477
    • 32b Paterson I, Doughty VA. Tetrahedron Lett. 1999; 40: 393
    • 32c Paterson I, Florence GJ, Gerlach K, Scott JP, Sereinig N. J. Am. Chem. Soc. 2001; 123: 9535
    • 32d Hoffmann RW, Mas G, Brandl T. Eur. J. Org. Chem. 2002; 3455
    • 32e Paterson I, Di Francesco ME, Kuehn T. Org. Lett. 2003; 5: 599
    • 32f Díaz-Oltra S, Murga J, Falomir E, Carda M, Marco JA. Tetrahedron 2004; 60: 2979
    • 32g Galobardes M, Gascón M, Romea P, Urpí F. Lett. Org. Chem. 2005; 2: 312
    • 32h Crossman JS, Perkins MV. J. Org. Chem. 2006; 71: 117
    • 32i Lister T, Perkins MV. Org. Lett. 2006; 8: 1827
    • 32j Wender PA, Bi FC, Buschmann N, Gosselin F, Kan C, Kee J.-M, Ohmura H. Org. Lett. 2006; 8: 5373
    • 32k Paterson I, Anderson EA, Findlay AD, Knappy CS. Tetrahedron 2008; 64: 4768
    • 32l Paterson I, Ashton K, Britton R, Cecere G, Chouraqui G, Florence GJ, Knust H, Stafford J. Chem. Asian J. 2008; 3: 367
    • 32m Fleury E, Lannou M.-I, Bistri O, Sautel F, Massiot G, Pancrazi A, Ardisson J. J. Org. Chem. 2009; 74: 7034
    • 32n Paterson I, Britton R, Delgado O, Gardner NM, Meyer A, Naylor GJ, Poullennec KG. Tetrahedron 2010; 66: 6534
    • 32o Paterson I, Steadman VA, McLeod MD, Trieselman T. Tetrahedron 2011; 67: 10119
    • 32p Paterson I, Ng KK.-H, Williams S, Millican DC, Dalby SM. Angew. Chem. Int. Ed. 2014; 53: 2692
    • 32q Van der Peet PL, Gunawan C, Torigoe S, Yamasaki S, Williams SJ. Chem. Commun. 2015; 51: 5100
    • 33a Siegel C, Thornton ER. Tetrahedron Lett. 1986; 27: 457
    • 33b Siegel C, Thornton ER. J. Am. Chem. Soc. 1989; 111: 5722
  • 34 Choudhury A, Thornton ER. Tetrahedron 1992; 27: 5701
  • 35 Evans DA, Clark JS, Metternich R, Novack VJ, Sheppard GS. J. Am. Chem. Soc. 1990; 112: 866
  • 36 Evans DA, Urpí F, Somers TC, Clark JS, Bilodeau MT. J. Am. Chem. Soc. 1990; 112: 8215
  • 37 Evans DA, Rieger DL, Bilodeau MT, Urpí F. J. Am. Chem. Soc. 1991; 113: 1047
    • 38a Martín R, Pascual O, Romea P, Rovira R, Urpí F, Vilarrasa J. Tetrahedron Lett. 1997; 38: 1633
    • 38b Ferreró M, Galobardes M, Martín R, Montes T, Romea P, Rovira R, Urpí F, Vilarrasa J. Synthesis 2000; 1608
  • 39 Figueras S, Martín R, Romea P, Urpí F, Vilarrasa J. Tetrahedron Lett. 1997; 38: 1637
  • 40 Actually, the lower diastereoselectivity (dr 91:9) was obtained with the non-sterically hindered acetaldehyde.
  • 41 Nebot J, Figueras S, Romea P, Urpí F, Ji Y. Tetrahedron 2006; 62: 11090
  • 42 Esteve J, Jiménez C, Nebot J, Velasco J, Romea P, Urpí F. Tetrahedron 2011; 67: 6045
    • 43a Esteve C, Ferreró M, Romea P, Urpí F, Vilarrasa J. Tetrahedron Lett. 1999; 40: 5079
    • 43b Esteve C, Ferreró M, Romea P, Urpí F, Vilarrasa J. Tetrahedron Lett. 1999; 40: 5083
  • 44 Larrosa I, Romea P, Urpí F. Org. Lett. 2006; 8: 527

    • For other examples, see:
    • 45a Chakraborty TK, Goswami RK. Tetrahedron Lett. 2006; 47: 4917
    • 45b Chakraborty TK, Goswami RK. Tetrahedron Lett. 2007; 48: 6463
  • 46 Evans DA, Chapman KT, Carreira EM. J. Am. Chem. Soc. 1988; 110: 3568
    • 47a Narasaka K, Pai F.-C. Tetrahedron 1984; 40: 2233
    • 47b Chen K.-M, Hardtmann GE, Prasad K, Repic O, Shapiro MJ. Tetrahedron Lett. 1987; 28: 155
  • 48 Paterson I, Perkins MV. Tetrahedron 1996; 52: 1811
    • 49a Galobardes M, Mena M, Romea P, Urpí F, Vilarrasa J. Tetrahedron Lett. 2002; 43: 6145
    • 49b Esteve J, Matas S, Pellicena M, Velasco J, Romea P, Urpí F, Font-Bardia M. Eur. J. Org. Chem. 2010; 3146
  • 50 Nebot J, Romea P, Urpí F. J. Org. Chem. 2009; 74: 7518
  • 51 Nebot J, Romea P, Urpí F. Org. Biomol. Chem. 2012; 10: 6395
  • 52 Esteve J, Lorente A, Romea P, Urpí F, Ríos-Luci C, Padrón JM. Eur. J. Org. Chem. 2011; 960
  • 53 Solsona JG, Romea P, Urpí F, Vilarrasa J. Org. Lett. 2003; 5: 519
  • 54 Solsona JG, Romea P, Urpí F. Tetrahedron Lett. 2004; 45: 5379
  • 55 For double stereodifferentiating titanium-mediated aldol reactions based on ketone 11, see: Solsona JG, Nebot J, Romea P, Urpí F. Synlett 2004; 2127
  • 56 For the influence of additives on the stereochemical outcome of these reactions, see: Rodríguez-Cisterna V, Villar C, Romea P, Urpí F. J. Org. Chem. 2007; 72: 6631
  • 57 Jung ME, Yoo D. Org. Lett. 2007; 9: 3543
  • 58 Solsona JG, Romea P, Urpí F. Org. Lett. 2003; 5: 4681
  • 59 Pellicena M, Krämer K, Romea P, Urpí F. Org. Lett. 2011; 13: 5350
  • 60 For a related strategy, see ref. 55.
  • 61 Alcoberro S, Gómez-Palomino A, Solà R, Romea P, Urpí F, Font-Bardia M. Org. Lett. 2014; 16: 584
  • 62 Wu B, Liu Q, Sulikowski GA. Angew. Chem. Int. Ed. 2004; 43: 6673
  • 63 Peng Z.-H, Woerpel KA. J. Am. Chem. Soc. 2003; 125: 6018
    • 64a Denmark SE, Pham SM. Org. Lett. 2001; 3: 2201
    • 64b Denmark SE, Fujimori S, Pham SM. J. Org. Chem. 2005; 70: 10823
  • 65 Ariza X, Garcia J, Romea P, Urpí F. Synthesis 2011; 2175
  • 66 For an insightful analysis of the transition states involved in the boron-mediated aldol reactions of methyl ketones, see: Goodman JM, Paton RS. Chem. Commun. 2007; 2124
  • 67 Evans DA, Carter PH, Carreira EM, Charette AB, Prunet JA, Lautens M. J. Am. Chem. Soc. 1999; 121: 7540
  • 68 Paterson I, Findlay AD, Noti C. Chem. Asian J. 2009; 4: 594
  • 69 For a related application, see: Fürstner A, Kattnig E, Lepage O. J. Am. Chem. Soc. 2006; 128: 9194
  • 70 Lorenz M, Bluhm N, Kalesse M. Synthesis 2009; 3061
  • 71 Trost BM, Urabe H. J. Org. Chem. 1990; 55: 3982

    • For some reviews on the impact of Mukaiyama aldol reaction in the synthesis of natural products, see:
    • 72a Brodmann T, Lorenz M, Schäckel R, Simsek S, Kalesse M. Synlett 2009; 174
    • 72b Kan SB. J, Ng KK.-H, Paterson I. Angew. Chem. Int. Ed. 2013; 52: 9097
    • 72c Kalesse M, Cordes M, Symkenberg G, Lu H.-H. Nat. Prod. Rep. 2014; 31: 563
  • 73 Lorenz M, Kalesse M. Org. Lett. 2008; 10: 4371
  • 74 Guérinot A, Lepesqueux G, Sablé S, Reymond S, Cossy J. J. Org. Chem. 2010; 75: 5151
    • 75a Gregg C, Perkins MV. Tetrahedron 2013; 69: 387
    • 75b Gregg C, Perkins MV. Tetrahedron 2013; 69: 6845
  • 76 Hara A, Morimoto R, Iwasaki Y, Saitoh T, Ishikawa Y, Nishiyama S. Angew. Chem. Int. Ed. 2012; 51: 9877

    • For other lithium-mediated aldol reactions from α,β-dihydroxy methyl ketones for the synthesis of amphidinolides, see:
    • 77a Chakraborty TK, Thippeswamy D, Suresh VR, Jayaprakash S. Chem. Lett. 1997; 563
    • 77b Chakraborty TK, Suresh VR. Tetrahedron Lett. 1998; 39: 7775
    • 77c Ishiyama H, Takemura T, Tsuda M, Kobayashi J. J. Chem. Soc., Perkin Trans. 1 1999; 1163
    • 77d Cid MB, Pattenden G. Tetrahedron Lett. 2000; 41: 7373
    • 77e Zhang W, Carter RG. Org. Lett. 2005; 7: 4209
    • 77f Liesener FP, Jannsen U, Kalesse M. Synthesis 2006; 2590
    • 77g Deng L, Ma Z, Zhao G. Synlett 2008; 728
    • 77h Lu L, Zhang W, Carter RG. J. Am. Chem. Soc. 2008; 130: 7253
    • 77i Fürstner A, Bouchez LC, Morency L, Funel J.-A, Liepins V, Porée F.-H, Gilmour R, Laurich D, Beaufils F, Tamiya M. Chem. Eur. J. 2009; 15: 3983
    • 77j Lu L, Zhang W, Nam S, Horne DA, Jove R, Carter RG. J. Org. Chem. 2013; 78: 2213
  • 78 For a precedent, see the reaction reported by Heathcock in Scheme 4, eq. 3.
    • 79a Palomo C, González A, García JM, Landa C, Oiarbide M, Rodríguez S, Linden A. Angew. Chem. Int. Ed. 1998; 37: 180
    • 79b Palomo C, Oiarbide M, Aizpurua JM, González A, García JM, Landa C, Odriozola I, Linden A. J. Org. Chem. 1999; 64: 8193
    • 80a Lorente A, Pellicena M, Romea P, Urpí F. Tetrahedron Lett. 2010; 51: 942
    • 80b Lorente A, Pellicena M, Romea P, Urpí F. Tetrahedron 2015; 71: 1023
    • 81a Pellicena M, Solsona JG, Romea P, Urpí F. Tetrahedron Lett. 2008; 49: 5265
    • 81b Pellicena M, Solsona JG, Romea P, Urpí F. Tetrahedron 2012; 68: 10338
    • 82a Denmark SE, Stavenger RA. J. Org. Chem. 1998; 63: 9524
    • 82b Denmark SE, Stavenger RA. J. Am. Chem. Soc. 2000; 122: 8837