The Head-to-Head Reductive Coupling of Homoallylic Alcohols Promoted by Titanium(II)-Olefin Complexes

Abstract

Reaction of homoallylic alcohols 1a-e with i-PrMgBr in the presence of Ti(i-PrO)₄ leads to the unbranched saturated diols 2a-e as the main products in moderate to good yields. The head-to-head regioselectivity in reductive coupling of 4-penten-1-ol and 5-hexen-2-ol was also observed. Coupling of 2-methyl-5-hexen-2-ol, as well as unsaturated alcohols in which vinyl and hydroxyl groups are more distant from one another, proceeded with head-to-tail or tail-to-tail regioselectivity. It is supposed, that the unusual head-to-head regioselectivity in reductive coupling of homoallylic alcohols 1a-e is due to the formation of the key titanacyclopentane intermediates F and G having two fused oxatitanacyclopentane rings.

Key words

titanium alkoxides - Grignard reagents - homoallylic alcohols - reductive coupling

References

• 1a Kulinkovich OG. Sviridov SV. Vasilevskii DA. Pritytskaya TS. Zh. Org. Khim.  1989,  25:  2244 
• 1b Kulinkovich OG. Sviridov SV. Vasilevskii DA. Synthesis  1991,  234 
• 2a Kulinkovich OG. Savchenko AI. Sviridov SV. Vasilevskii DA. Mendeleev Commun.  1993,  230 
• 2b Epstein OL. Savchenko AI. Kulinkovich OG. Tetrahedron Lett.  1999,  40:  5935 
• 3a Kulinkovich OG. Sviridov SV. Vasilevskii DA. Savchenko AI. Zh. Org. Khim.  1991,  27:  294 
• 3b Kulinkovich OG. Sviridov SV. Vasilevskii DA. Savchenko AI. Zh. Org. Khim.  1991,  27:  1428 
• 4a Kasatkin A. Sato F. Tetrahedron Lett.  1995,  36:  6079 
• 4b Lee J. Kim H. Cha JK. J. Am. Chem. Soc.  1996,  119:  4198 
• 4c Lee J. Kim YG. Bae JG. Cha JK. J. Org. Chem.  1996,  61:  4878 
• 4d Lee J. Kang CH. Kim H. Cha JK. J. Am. Chem. Soc.  1996,  119:  291 
• 5a Kulinkovich OG. de Meijere A. Chem. Rev.  2000,  100:  2789 
• 5b Sato F. Urabe H. Okamoto S. Chem. Rev.  2000,  100:  2835 
• 6 Epstein OL. Kulinkovich OG. Tetrahedron Lett.  2001,  42:  3757 
• 8a Gibson DH. De Puy CH. Chem. Rev.  1974,  74:  605 
• 8b

  Kulinkovich, O. G. Chem. Rev. 2003, 103, in press.

• 9a Savchenko AI. Kulinkovich OG. Russ. J. Org. Chem. (Engl. Transl.)  1997,  33:  846 
• 9b Chevtchouk TA. Kulinkovich OG. Russ. J. Org. Chem. (Engl. Transl.)  2000,  36:  1124 
• 10a Kulinkovich OG. Savchenko AI. Shevchuk TA. Russ. J. Org. Chem. (Engl. Transl.)  1999,  35:  225 
• 10b Chevtchouk TA. Isakov VE. Kulinkovich OG. Tetrahedron  1999,  55:  13205 
• 11 Quan LG. Kim S.-H. Lee JC. Cha JK. Angew. Chem. Int. Ed.  2002,  41:  2160 
• 12 The Fe- catalyzed ‘head-to-head’ coupling of alkenes has been disclosed recently: Small BL. Marcucci AJ. Organometallics  2001,  20:  5738 ; and references therein
• 14 Kulinkovich OG. Epstein OL. Isakov VE. Khmel’nitskaya EA. Synlett  2001,  49 
• 17 Epstein OL. Savchenko AI. Kulinkovich OG. Russ. Chem. Bull.  2000,  278 
• 18 Kulinkovich OG. Pure Appl. Chem.  2000,  72:  1715 
• 19 Wright WG. Warren FL. J. Chem. Soc., C  1967,  284 

7

In some cases, diisopropoxytitanacyclopropane is more smoothly involved in olefin-exchange reactions than 2-substituted titanacyclopropane reagents (see ref. [6] ).

13

Typical procedure: To a solution of homoallylic alcohol 1b (0.86 g, 10 mmol) in Et₂O (15 mL) Ti(i-PrO)₄ (1.5 mL, 5 mmol) and i-PrMgBr (20 mmol of 1.2-1.5 M solution in Et₂O) were added consequently dropwise in 30 min at room temperature, and the mixture was stirred for an additional 30 min. After acidic work up (20 mL of 10% aq. H₂SO₄) and extraction with ethyl acetate, organic layers were washed with saturated NaHCO₃ and brine, dried over MgSO₄ and evaporated. 2,9-Decanediol 2b (containing near 10% of 4-methyl-2,8-nonanediol 3b by NMR and GC-MS-analysis) (0.61 g, 70%) was isolated by column chromatography on silica gel (eluent: cyclohexane-ethyl acetate). After two crystallisations (petroleum ether-benzene) 0.38 g of crystalline 2,9-decanediol 2b was obtained: mp 32-33 °C. (lit. [19] mp 33 °C); ¹H NMR (400 MHz, CDCl₃): δ = 1.17 (d, 6 H, J = 6.4 Hz), 1.20-1.48 (m, 12 H), 2.07 (br s, 2 H), 3.68-3.78 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃) δ = 23.33, 25.57, 29.48, 39.18, 67.89; MS (70 eV) 29, 45 (100%), 55, 69, 81, 96, 112, 123, 141, 155; IR (CCl₄, cm^-1) 3600.

15

Selected NMR data of the reductive coupling products: 1-[6-(1-Hydroxycyclopentyl)hexyl]-1-cyclopentanol ( 2d): ¹³C NMR (100 MHz, CDCl₃): δ = 23.79, 24.59, 30.18, 39.64, 41.47, 82.51. (2 E , 12 E )-2,12-Tetradecadiene-4,11-diol ( 2e): ¹H NMR (400 MHz, CDCl₃): δ = 1.20-1.38 (m, 8 H), 1.38-1.56 (m, 4 H), 1.67 (d, 6 H, J = 6.4 Hz), 1.72 (br s, 2 H), 3.98 (q, 2 H, J = 6.6 Hz), 5.40-5.48 (m, 2 H), 5.56-5.68 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ = 17.56, 25.32, 29.42, 37.20, 73.00, 126.52, 134.38. 2,9-Dimethyl-2,9-decanediol ( 2c): ¹H NMR (400 MHz, CDCl₃): δ = 1.12-1.20 (m, 12 H), 1.24-1.36 (m, 4 H), 1.36-1.46 (m, 4 H), 1.50 (br s, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ = 24.22, 29.14, 30.09, 43.89, 70.90. 1,10-Decanediol ( 2g): ¹H NMR (400 MHz, CDCl₃): δ = 1.22-1.44 (m, 12 H), 1.48-1.64 (m, 4 H), 2.05 (br s, 2 H), 3.61 (t, 4 H, J = 6.6 Hz); ¹³C NMR (100 MHz, CDCl₃): δ = 25.66, 29.31, 29.43, 32.67, 62.85. 2,11-Dodecanediol ( 2h): ¹H NMR (400 MHz, CDCl₃): δ = 1.17 (d, 6 H, J = 6.4 Hz), 1.24-1.50 (m, 16 H), 1.94 (br s, 2 H), 3.71-3.84 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ = 23.34, 25.65, 29.44, 29.53, 39.25, 67.95.

16

After acidic hydrolysis of the reaction products, diols 3b and 4,5-dimethyl-2,7-octanediol were obtained in 29% yield as an nearly equimolar mixture (GC-MS).