Synlett 2016; 27(06): 961-964
DOI: 10.1055/s-0035-1561318
letter
© Georg Thieme Verlag Stuttgart · New York

Convenient Access to meso Benzylic Bisalkynes

Philip C. Bulman Page*
a  School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK   Email: p.page@uea.ac.uk
,
G. Richard Stephenson*
a  School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK   Email: p.page@uea.ac.uk
,
James Harvey
a  School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK   Email: p.page@uea.ac.uk
,
Annie-Claude Gaumont
b  Laboratoire de Chimie Moléculaire et Thio-organique, UMR CNRS 6507, INC3M, FR308, ENSICAEN & Université de Caen-Normandie, 6 Bvd Maréchal Juin, 14050 Caen, France
,
Carole Alayrac
b  Laboratoire de Chimie Moléculaire et Thio-organique, UMR CNRS 6507, INC3M, FR308, ENSICAEN & Université de Caen-Normandie, 6 Bvd Maréchal Juin, 14050 Caen, France
,
Alexandra M. Z. Slawin
c  School of Chemistry, University of St Andrews, Purdie Building, St. Andrews, Fife KY16 9ST, Scotland, UK
› Author Affiliations
Further Information

Publication History

Received: 06 October 2015

Accepted after revision: 13 December 2015

Publication Date:
11 January 2016 (online)


Abstract

meso-Bisalkynes and alkenes have potential as substrates for desymmetrization processes. The preparation of several meso-bis(1′-hydroxy-2′-propynyl)benzenes and their derivatives from phthalaldehydes using inexpensive and readily available reagents is described.

Supporting Information

 
  • References and Notes

  • 1 For an example, see: Breuilles P, Schmittberger T, Uguen D. Tetrahedron Lett. 1993; 34: 4205
  • 2 For a review of examples employing enzymes, see: García-Urdiales E, Alfonso I, Gotor V. Chem. Rev. 2011; 111: 110
  • 3 For a review of examples employing asymmetric epoxidation reactions, see: Katsuki T. Curr. Org. Chem. 2001; 5: 663
    • 4a Meng J, Fokin VV, Finn MG. Tetrahedron Lett. 2005; 46: 4543
    • 4b Zhou F, Tan C, Tang J, Zhang Y.-Y, Gao W.-M, Wu H.-H, Yu Y.-H, Zhou J. J. Am. Chem. Soc. 2013; 135: 10994
    • 4c Stephenson GR, Buttress JP, Deschamps D, Lancelot M, Martin JP, Sheldon AI. G, Alayrac C, Gaumont A.-C, Bulman Page PC. Synlett 2013; 24: 2723
    • 4d Osako T, Uozumi Y. Org. Lett. 2014; 16: 5866
    • 4e Song T, Li L, Zhou W, Zheng Z.-J, Deng Y, Xu Z, Xu L.-W. Chem. Eur. J. 2015; 21: 554
    • 4f Brittain WD. G, Buckley BR, Fossey JS. Chem. Commun. 2015; 51: 17217
    • 4g Osaka T, Uozumi Y. Synlett 2015; 26: 1474
  • 5 Page PC. B, Appleby LF, Chan Y, Day DP, Buckley BR, Slawin AM. Z, Allin SM, McKenzie MJ. J. Org. Chem. 2013; 78: 8074
  • 6 For the general concept of ‘click’ chemistry, see: Kolb HC, Finn MG, Sharpless KB. Angew. Chem. Int. Ed. 2001; 40: 2004
    • 7a For a recent review, see: Liang L, Astruc D. Coord. Chem. Rev. 2011; 255: 2933

    • See also:
    • 7b Use of copper: Tornoe CW, Christensen C, Medal M. J. Org. Chem. 2002; 67: 3057
    • 7c Alkyne–azide cycloaddition: Huisgen R. Angew. Chem. Int. Ed. Engl. 1963; 2: 565
    • 8a Pellico D, Gómez-Gallego M, Ramírez-López P, Mancheño MJ, Sierra MA, Torres MR. Chem. Eur. J. 2010; 16: 1592
    • 8b Melikyan GG, Spencer R, Abedi E. J. Org. Chem. 2009; 74: 8541
  • 9 Neuhaus P, Cnossen A, Gong JQ, Herz LM, Anderson HL. Angew. Chem. Int. Ed. 2015; 54: 7344
  • 10 Tang N, Su W, Krein DM, Mclean DG, Brant MC, Fleitz PA, Brandelik DM, Sutherland RL, Cooper TM. Mater. Res. Soc. Symp. Proc. 1997; 479: 47
  • 11 1,2-Bis(prop-2-yn-1-ol)benzene 1a,b Ethynylmagnesium bromide solution (0.5 M in THF, 66 mL, 32.80 mmol) was added to a solution of o-phthalaldehyde (2.00 g, 14.93 mmol) in THF (75 mL). The mixture was heated to reflux with stirring for 4 h, and allowed to cool to room temperature. The reaction was quenched with sat. aq NH4Cl (300 mL) and extracted with Et2O (3 × 30 mL). The organic layers were combined and dried over MgSO4, filtered, and the solvents removed under reduced pressure. The crude product was purified using column chromatography, eluting with EtOAc–PE (1:1) and using a vanillin dip to visualize the spots on TLC. A mixture of diastereoisomers was isolated as a yellow oil (2.47 g, 89%). The HNMR spectrum showed a mixture of isomers in a ratio of 2.1:1. The meso isomer was precipitated from the product mixture using CH2Cl2–PE, and was separated by filtration of the crystalline meso isomer and washing with PE. The (±)-isomer remained in the filtrate. Several precipitations were required to achieve almost complete separation. meso-(1S,1′R)-1,2-Bis-(prop-2-yn-1-ol)benzene (1a) Large colourless crystals (1.67 g, 60%), mp 98–99 °C. IR (neat): 3276, 3264, 2116 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.92–7.77 (m, 2 H), 7.49–7.35 (m, 2 H), 5.91 (dd, J = 4.7, 2.2 Hz, 2 H), 2.95 (d, J = 4.7 Hz, 2 H), 2.74 (d, J = 2.2 Hz, 2 H). 13C NMR (126 MHz, CDCl3): δ = 134.7, 129.7, 129.1, 80.3, 75.8, 62.7. Crystal data: C12H10O2, M = 186.21, triclinic, a = 9.7265(12) Å, b = 10.6455(11) Å, c = 11.2471(7) Å, V = 980.67(19) Å3, T = 173 K, space group P-1 (no. 2), Z = 4, 13495 reflections measured, 3562 unique (R int = 0.0564), which were used in all calculations. The final wR2 was 0.1219 (all data). (±)-1,2-Bis-(prop-2-yn-1-ol)benzene (1b) Thick orange oil (0.79 g, 29%). IR (neat): 3414, 3287, 2117 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.73–7.63 (m, 2 H), 7.41–7.37 (m, 2 H), 6.03 (d, J = 2.3 Hz, 2 H), 2.73 (d, J = 2.3 Hz, 2 H). 13C NMR (126 MHz, CDCl3): δ = 137.7, 129.5, 129.3, 82.8, 75.8, 63.4.
  • 12 Dale JA, Dull DL, Mosher HS. J. Org. Chem. 1969; 34: 2543