Regio- and Stereoselective Heck α-Arylation of Cinnamyl Alcohols

Abstract

The Heck reaction of cinnamyl alcohols with aryl iodides has been investigated using n-Bu₄NOAc as the base in toluene. Under these conditions, the reaction affords regio- and stereoselectively (Z)-2,3-diarylallylic alcohols in moderate to good yields. Experimental evidence suggests that the observed selectivity in formation of the vinylic substitution products is kinetic in origin under these conditions and that both the base and the solvent play a key role.

Key words

palladium - arylation - cinnamyl alcohols - Heck reaction

References and Notes

• 1 For a recent review, see: Muzart J. Tetrahedron  2005,  61:  4179 
• 2 Melpolder JB. Heck RF. J. Org. Chem.  1976,  41:  265 
• 3 Chalk AJ. Magennis SA. J. Org. Chem.  1976,  41:  273 
• 4 Bagnell L. Kreher U. Strauss CR. Chem. Commun.  2001,  29 
• 5 Bouquillon S. Ganchegui B. Estrine B. Hénin F. Muzart J. J. Organomet. Chem.  2001,  634:  153 
• 6 Yonehara K. Mori K. Hashizume T. Chung K.-G. Ohe K. Uemura S. J. Organomet. Chem.  2000,  603:  40 
• 7 Calò V. Nacci A. Monopoli A. Ferola V. J. Org. Chem.  2007,  72:  2596 
• 8 Amorese A. Arcadi A. Bernocchi E. Cacchi S. Cerrini S. Fedeli W. Ortar G. Tetrahedron  1989,  45:  813 
• 9 Battistuzzi G. Cacchi S. Fabrizi G. Synlett  2002,  439 
• 10a Battistuzzi G. Cacchi S. Fabrizi G. Org. Lett.  2003,  5:  777 
• 10b Battistuzzi G. Cacchi S. Fabrizi G. Bernini R. Synlett  2003,  1133 
• 11 Ambrogio I. Fabrizi G. Cacchi S. Henriksen ST. Fristrup P. Tanner D. Norrby P.-O. Organometallics  2008,  27:  3187 
• 12a Battistuzzi G. Cacchi S. De Salve I. Fabrizi G. Parisi LM. Adv. Synth. Catal.  2005,  347:  308 
• 12b Battistuzzi G. Bernini R. Cacchi S. De Salve I. Fabrizi G. Adv. Synth. Catal.  2007,  349:  297 
• 14a Jeffery T. J. Chem. Soc., Chem. Commun.  1984,  1287 
• 14b Jeffery T. Tetrahedron Lett.  1985,  26:  2667 
• For recent reviews on the palladium-catalyzed oxidation of alcohols, see:
• 15a Muzart J. Tetrahedron  2003,  59:  5789 
• 15b Stoltz BM. Chem. Lett.  2004,  33:  362 
• 15c Sigman MS. Jensen DR. Acc. Chem. Res.  2006,  39:  221 
• 16 Tamaru Y. Yamada Y. Inoue K. Yamamoto Y. Yoshida Z.-I. J. Org. Chem.  1983,  48:  1286 
• 17 Blackburn TF. Shwartz J. J. Chem. Soc., Chem. Commun.  1977,  157 
• 18 Rao VS. Perlin AS. J. Org. Chem.  1982,  47:  367 
• 20 Cacchi S. Ciattini PG. Morera E. Ortar G. Tetrahedron Lett.  1992,  33:  3073 
• 21 (Z)-3-Phenyl-2-propen-1-ol was prepared via selective hydrogenation of 3-phenyl-2-propyn-1-ol according to the method described by: Denis J.-N. Greene AE. Serra AA. Luche M.-J. J. Org. Chem.  1986,  51:  46 
• 22 Netherton M. Fu GC. Org. Lett.  2001,  3:  4295 

13

Typical Procedure for the Preparation of Cinnamyl Alcohols - Preparation of 1b
A Carousel Reaction Tube (Radley Discovery), equipped with a magnetic stirrer, was charged with 1-(trifluoro-methyl)-3-iodobenzene (1.0 g, 3,68 mmol), methyl acrylate (993 µL, 11,02 mmol), Et₃N (1.53 mL, 11.02 mmol), and Pd(OAc)₂ (24.8 mg, 0.11 mmol) in DMF (4 mL). The reaction mixture was warmed at 80 ˚C and stirred at the same temperature for 1.5 h under argon. After cooling, the reaction mixture was diluted with EtOAc, washed twice with a NaCl solution, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was dissolved in toluene (4 mL), the resultant solution was cooled at -78 ˚C, DIBAL-H (1 M in hexane, 8 mL, 8.08 mmol) was added, and the reaction mixture was stirred at this temperature for 2 h under argon. After this time the reaction mixture was warmed at r.t., diluted with EtOAc, washed twice with a NaCl solution, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by chromatography on SiO₂ (n-hexane-EtOAc, 60:40) to afford 522 mg (70% yield) of 1b as oil. IR (neat): 3343, 2925, 1440, 1332, 1124 cm^-¹; ^¹H NMR (400.13 MHz, CDCl₃): δ = 7.63 (s, 1 H), 7.55 (d, J = 7.6 Hz, 1 H), 7.50 (d, J = 7.7 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 1 H), 6.67 (d, J = 16.0 Hz, 1 H), 6.45 (dt, J ₁ = 16.0 Hz, J ₂ = 5.4 Hz, 1 H), 4.37 (t, J = 4.3 Hz, 2 H), 1.61 (br s, 1 H). ^¹³C NMR (100.6 MHz, CDCl₃): δ = 137.6, 131.1 (q, J = 33.0 Hz), 130.7, 129.6, 129.4, 129.1, 124.20 (q, J = 3.7 Hz), 124.2 (q, J = 272.3 Hz), 123.19 (q, J = 3.8 Hz), 63.4. ^¹9F NMR (376.5 MHz, CDCl₃): δ = -62.8. MS: m/e (rel. int.) = 202 (3) [M⁺], 133 (12), 69 (100), 57 (21), 51 (18).

19

One of the referees suggested that the alcohols 3 and 5 are probably partly present as alkoxides (formed via deprotonation by the acetate anions) that can either react with HPdOAc or HPdI formed in the Heck reaction to generate HPdOCH₂R. β-Hydride elimination generates the corresponding aldehyde and HPdH.

23

Typical Procedure for the Preparation of ( Z )- α -Aryl-cinnamyl Alcohols - Preparation of 3c
A Carousel Reaction Tube (Radley Discovery), equipped with a magnetic stirrer, was charged with 1b (60 mg, 0.297 mmol), 4-iodanisole (104 mg, 0.445 mmol), Pd(OAc)₂ (2 mg, 0.009 mmol), and n-Bu₄NOAc (179 mg, 0.594 mmol) in toluene (1 mL). The reaction mixture was warmed to 90 ˚C and stirred at the same temperature for 24 h under argon. After this time the reaction mixture was diluted with EtOAc, washed twice with a NaCl solution, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by chromatography on SiO₂ (n-hexane-EtOAc, 85:15) to afford 72 mg (79% yield) of 3c. Mp 80-82 ˚C. IR (KBr): 3297, 2923, 1606, 1513, 1330 cm^-¹. ^¹H NMR (400.13 MHz, CDCl₃): δ = 7.68 (s, 1 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.56-7.54 (m, 4 H), 6.68 (d, J = 12.0 Hz, 2 H), 6.92 (s, 1 H), 4.67 (s, 2 H), 3.86 (s, 3 H), 1.58 (br s, 1 H). ^¹³C NMR (100.6 MHz,CDCl₃): δ = 159.6, 141.0, 137.8, 132.3, 132.0, 130.7 (q, J = 32.0 Hz), 128.7, 128.1, 127.7, 125.6 (q, J = 3.8 Hz), 124.0 (q, J = 272.6 Hz), 123.7 (q, J = 3.8 Hz), 114.1, 60.1, 55.2. ^¹9F (376.5 MHz, CDCl₃): δ = -62.6. MS: m/e (rel. int.): 308 (4) [M⁺], 145 (4), 89 (12), 77 (16), 59 (100), 51 (26).