Indium(III) Acetate-Catalyzed 1,4-Reduction and Reductive Aldol Reactions of α-Enones with Phenylsilane

Abstract

A catalytic amount of In(OAc)₃ smoothly promoted 1,4-reduction of certain α-enones with PhSiH₃ in ethanol at ambient temperature. The intermediary enolates could be used for inter- and intramolecular aldol reactions and intramolecular Michael addition.

Key words

indium - reductions - enones - silicon - aldol reactions

References

• 1,4-Hydrosilylation:
• 1a Speier JL. Webster JA. Barnes GH. J. Am. Chem. Soc.  1957,  79:  974 
• 1b Bourhis R. Frainnet E. Moulines F. J. Organomet. Chem.  1977,  141:  157 
• 1c Barlow AP. Boag NM. Stone GA. J. Organomet. Chem.  1980,  191:  39 
• 1d Kogure T. Ojima I. Organometallics  1982,  1:  1390 
• 1e Mahoney WS. Stryker JM. J. Am. Chem. Soc.  1989,  111:  8818 
• 1f Hilty TK. Revis A. J. Org. Chem.  1990,  55:  2972 
• 1g Chan TH. Zheng GZ. Tetrahedron Lett.  1993,  34:  3095 
• 1h Johnson CR. Raheja RK. J. Org. Chem.  1994,  59:  2287 
• 1i Lipshutz BH. Keith J. Papa P. Vivian R. Tetrahedron Lett.  1998,  39:  4627 
• 1j Appella DH. Moritani Y. Shintani R. Ferreira EM. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  9473 
• 1k Lipshutz BH. Chrisman W. Noson K. Papa P. Sclafani JA. Vivian RW. Keith JM. Tetrahedron  2000,  56:  2779 
• 2 1,4-Hydroboration: Evans DA. Fu GC. J. Org. Chem.  1990,  55:  5678 
• 1,4-Hydroalumination:
• 3a Tsuda T. Hayashi T. Satomi H. Kawamoto T. Saegusa T. J. Org. Chem.  1986,  51:  537 
• 3b Ikeno T. Kimura T. Ohtsuka Y. Yamada T. Synlett  1999,  96 
• 1,4-Hydrostannylation:
• 4a Four P. Guibe P. Tetrahedron Lett.  1982,  23:  1825 
• 4b Keinan E. Gleize PA. Tetrahedron Lett.  1982,  23:  477 
• 5 Huddleston RR. Krische MJ. Synlett  2003,  12 
• 6a Revis A. Hilty TK. Tetrahedron Lett.  1987,  28:  4809 
• 6b Isayama S. Mukaiyama T. Chem. Lett.  1989,  2005 
• 6c Matsuda I. Takahashi K. Sato S. Tetrahedron Lett.  1990,  31:  5331 
• 6d Kiyooka S. Shimizu A. Torii S. Tetrahedron Lett.  1998,  39:  5237 
• 6e Taylor SJ. Morken JP. J. Am. Chem. Soc.  1999,  121:  12202 
• 6f Ooi T. Doda K. Sakai D. Maruoka K. Tetrahedron Lett.  1999,  40:  2133 
• 6g Taylor SJ. Duffey MO. Morken JP. J. Am. Chem. Soc.  2000,  122:  4528 
• 6h Zhao C.-X. Duffey MO. Taylor SJ. Morken JP. Org. Lett.  2001,  3:  1829 
• 7a Baik T.-G. Luis AL. Wang L.-C. Krische MJ. J. Am. Chem. Soc.  2001,  123:  5112 
• 7b Wang L.-C. Jang H.-Y. Roh Y. Lynch V. Schultz AJ. Wang X. Krische MJ. J. Am. Chem. Soc.  2002,  124:  9448 
• 7c Jang H.-Y. Huddleston RR. Krische MJ. J. Am. Chem. Soc.  2002,  124:  15156 
• 7d Huddleston RR. Krische MJ. Org. Lett.  2003,  5:  1143 
• Ranu et al. have reported the InCl₃-catalyzed 1,4-reduction of electron-deficient alkenes with NaBH₄. See:
• 8a Ranu BC. Samanta S. Tetrahedron Lett.  2002,  43:  7405 
• 8b Ranu BC. Samanta S. J. Org. Chem.  2003,  68:  7130 
• 9 Quite recently, Baba et al. have reported a similar catalytic system for reductive aldol reaction, in which InBr₃ and Et₃SiH are used as catalyst and reducing agent, respectively. See: Shibata I. Kato H. Ishida T. Yasuda M. Baba A. Angew. Chem. Int. Ed.  2004,  43:  711 
• 13 Abernethy CD. Cole ML. Jones C. Organometallics  2000,  19:  4852 
• 15a Inoue K. Sawada A. Shibata I. Baba A. J. Am. Chem. Soc.  2002,  124:  906 
• 15b Inoue K. Sawada A. Shibata I. Baba A. Tetrahedron Lett.  2001,  42:  4661 
• 15c Takami K. Mikami S. Yorimitsu H. Shinokubo H. Oshima K. Tetrahedron  2003,  59:  6627 
• According to the method reported by Montgomery et al., 8 and 14a were prepared by ozonolysis of cyclopentene and the subsequent Wittig olefination with Ph₃PCHC(O)Ph. This method was used also for the preparation of 12a, 12b, and 14b from 1-methylcyclopentene, 1,5-dimethyl-1,5-cyclooctadiene, and 1,5-cyclooctadiene, respectively. See:
• 21a Montgomery J. Savchenko AV. Zhao Y. J. Org. Chem.  1995,  60:  5699 
• 21b See also the following paper for the preparation of 12a and 12b: Huddleston RR. Cauble DF. Krische MJ. J. Org. Chem.  2003,  68:  11 

10

The use of In(acac)₃ (acac = acetylacetonate) instead of In(OAc)₃ gave 2a and 3a in 34% and 65% yields, respectively. InCl₃ also promoted the reaction of 1a with PhSiH₃ in Et₂O at r.t. (2a, 29%; 3a, 49%).

11

The use of other hydrosilanes [Et₃SiH, PhMe₂SiH, poly(methylhydrosiloxane)] instead of PhSiH₃ resulted in no reduction under the same conditions.

12

The use of a half amount of PhSiH₃ lowered the yield to 62%.

14

General Procedure for the In(OAc) ₃ -Catalyzed 1,4-Reduction of α-Enones with PhSiH ₃ : Under N₂, α-enone 1 (0.50 mmol) and PhSiH₃ (54 mg, 0.50 mmol) were added to a suspension of In(OAc)₃ (15 mg, 0.05 mmol) in EtOH (1.0 mL). The mixture was stirred at r.t. for 1.5 h and quenched with sat. aq NaHCO₃. The extract with t-BuOMe was dried over Na₂SO₄ and evaporated. The residual oil was purified by silica gel column chromatography.

16

As shown here, the reductive aldol reaction is much slower than the 1,4-reduction. This observation is attributable to slow regeneration of the indium hydride species from the indium aldolate intermediate.

17

The In(OAc)₃-catalyzed reduction of 6a with PhSiH₃ (r.t., 1.5 h) gave 1-naphthylmethanol in 82% yield.

18

As proposed by Baba et al. (ref. [9] ), the syn-selectivity can be attributed by the formation of Z-4b by a concerted hydroindation and the subsequent aldol addition via a cyclic transition state. However, we have no evidence of the selective formation of Z-4b.

19

Typical Procedure for the In(OAc) ₃ -Catalyzed Reductive Aldol Reaction of α-Enones with Aldehydes: Under N₂, α-enone 1b (73 mg, 0.50 mmol), 6a (102 mg, 0.65 mmol), and PhSiH₃ (54 mg, 0.50 mmol) were added to a suspension of In(OAc)₃ (15 mg, 0.05 mmol) in EtOH (0.25 mL). The mixture was stirred at 0 °C for 36 h. The work-up and purification were performed by the procedure described in ref. [14] . Compound 7ba (syn:anti = 92:8): IR (neat): 3540 (br s, OH), 1680 (C=O) cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 0.69 (t, J = 7.6 Hz, 2.76 H), 0.86 (t, J = 7.6 Hz, 0.24 H), 1.63-1.79 (m, 1 H), 1.89-2.08 (m, 1 H), 3.52 (d, J = 5.9 Hz, 0.08 H), 3.80 (d, J = 1.7 Hz, 0.92 H), 3.96 (ddd, J = 9.1, 3.8, 3.6 Hz, 0.92 H), 4.11 (ddd, J = 8.2, 6.2, 5.9 Hz, 0.08 H), 5.82 (dd, J = 6.2, 5.9 Hz, 0.08 H), 5.85 (br s, 0.92 H), 7.31-7.96 (m, 12 H). ¹³C NMR (68 MHz, CDCl₃) for the major isomer: δ = 12.25 (CH₃), 20.17 (CH₂), 51.62 (CH), 70.12 (CH), 122.49 (CH), 124.51 (CH), 125.28 (CH), 125.34 (CH), 126.04 (CH), 127.94 (CH), 128.38 (CH × 2), 128.75 (CH × 2), 129.14 (CH), 129.86 (C), 133.63 (CH), 133.73 (C), 136.69 (C), 137.22 (C), 206.37 (C). For the minor isomer (only well-resolved peaks): δ = 11.88 (CH₃), 24.18 (CH₂), 53.14 (CH), 72.85 (CH), 123.01 (CH), 124.37 (CH), 125.48 (CH), 126.17 (CH), 128.07 (CH), 128.43 (CH), 129.03 (CH), 130.53 (C), 133.16 (CH), 138.15 (C), 206.08 (C).

20

The reaction of 1b with octanal was carried out in THF containing an equimolar amount of EtOH at 70 °C. However, both the yield of 7 and the syn-selectivity dropped to 52% and 56% syn, respectively.

22

For the stereochemical assignment of 9, 15a, and 15b, see ref. [7a] . The relative configurations of 13a and 13b were determined by their NMR data reported in ref. [21b] .

23

Krische et al. have reported cis-selective reductive aldol reactions of 8 and 12a, and trans-selective reductive Michael reaction of 14. See ref. [7] and ref. [21b]