Synthesis of γ- and δ-Lactones from Alkynols

Abstract

The reaction of alkynyl phenyl selenides with p-toluenesulfonic acid gives rise to a proton-induced ring-closure reaction ­affording γ- and δ-lactones.

alkynes - lactone-cyclization reactions - organoselenium reagents - regiospecificity

References and Notes

1a Ohloff G. Progress in the Chemistry of Organic Natural Products   Vol. 35:  Zechmeister L. Springer Verlag; Wien: 1978.  p.431 

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2b Mulzer J. In Comprehensive Organic Synthesis   Vol. 6:  Trost BM. Fleming I. Pergamon; New York: 1991.  p.323 

2c Ogliarusco MA. Wolfe JF. Synthesis of Lactones and Lactams   Patai S. Rappoport Z. Wiley; Chichester: 1993. and references therein

2d Collins I. J. Chem. Soc., Perkin. Trans. 1  1999,  1377 

3 Liang L. Ramaseshan M. MaGee DI. Tetrahedron  1993,  49:  2159 

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9

All new compounds were fully characterized by MS, ¹H NMR and ¹³C NMR spectroscopy and by combustion analysis. Compounds 1b,c, [8] 1e [16] and 1h,i [8] were prepared as described in the literature from the corresponding epoxides whereas compound 1f was obtained by reduction of the corresponding aldehyde with NaBH₄. Alkynol 1a was obtained by reaction of a propargyl organometallic reagent with the proper carbonyl compound. [5] Compound 1d was prepared by reduction of the corresponding ketone [17] with NaBH₄. Hydroxy ester 1g was obtained by reduction of the corresponding oxoester, which was synthesized by alkylation of the dianion [18] of (-)-endo-borneyl 3-oxo-butanoate. [19] Physical, spectral and analytical data of selected compounds are reported below.
(2 S ,3 R )-2-(Dibenzylamino)-1-phenylhex-5-yn-3-ol ( 1c). Oil, 72% yield. ¹H NMR (200 MHz, CDCl₃): δ = 7.38-7.06 (m, 15 H), 4.05-3.90 (m, 1 H), 3.80-3.50 (m, 4 H), 3.16-2.58 (m, 3 H), 2.58 (ddd, 1 H, J = 16.7, 3.7, 2.7 Hz), 2.23 (ddd, 1 H, J = 16.7, 8.3, 2.7 Hz), 2.08 (d, 1 H, J = 4.7 Hz), 1.94 (t, 1 H, J = 2.7 Hz). ¹³C NMR (50 MHz, CDCl₃): δ = 140.9, 139.5 (2 C), 129.5 (2 C), 128.8 (3 C), 128.3 (4 C), 128.2 (3 C), 126.9 (2 C), 125.9, 81.3, 70.9, 70.6, 62.8, 54.7, 54.2, 32.1, 25.7. Anal. Calcd for C₂₆H₂₇NO: C, 84.51; H, 7.37; N, 3.79. Found: C, 84.18; H, 7.67; N, 3.62.
(3 R )-1-(Benzyloxy)hept-6-yn-3-ol ( 1i). Oil, 73% yield. [α]_D ²³ +24.6 (c 1.75, CHCl₃). ¹H NMR (200 MHz, CDCl₃): δ = 7.45-7.20 (m, 5 H), 4.51 (s, 2 H), 3.94 (quint, 1 H, J = 5.7 Hz), 3.79-3.57 (m, 2 H), 3.07 (br s, 1 H), 2.32 (dt, 2 H, J = 5.0, 2.6 Hz), 1.95 (t, 1 H, J = 2.6 Hz), 1.82-1.58 (m, 4 H). ¹³C NMR (50 MHz, CDCl₃): δ = 137.7, 128.4 (2 C), 127.7 (2 C), 127.6, 84.2, 73.2 (2 C), 69.8, 68.9, 68.4, 36.2, 35.7. MS: m/z (relative intensity) = 218 (18), 159 (11), 109 (64), 91 (100), 83 (10), 65 (12). Anal. Calcd for C₁₄H₁₈O₂: C, 77.03; H, 8.31. Found: C, 77.29; H, 8.65.

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10b Tingoli M. Tiecco M. Testaferri L. Balducci R. Synlett  1993,  211 

11

Ring-Closure Reaction. General Procedure.
To a solution of the alkynyl phenyl selenide 8 (1 mmol) in CH₂Cl₂ (15 mL) powdered p-toluenesulfonic acid monohydrate (4 mmol) was added at r.t. and the reaction mixture was stirred at 60 °C. The progress of the reaction was monitored by TLC. Reaction times ranged from 1-9 h. Solid K₂CO₃ and CH₂Cl₂ were added and the mixture was filtered. The filtrate was dried and evaporated. After chromatography on silica gel column, compounds 12 and 13 were obtained in a pure form. Compounds 12a and 13c are commercial products whereas lactones 12c, [20] 13a [21] and 13b [22] have physical and spectral data identical to those reported in the literature. Physical and spectral data of 12b, 13e and 13f are reported below.
(5 S )-5-[(Benzyloxy)methyl]dihydrofuran-2(3 H )-one ( 12b). [23] Oil, 71% yield. [α]_D ²⁴ +21.0 (c 1.45, EtOH) {Lit. [23] [α]_D ¹⁵ +18.1 (c 2.7, EtOH)}. ¹³C NMR (50 MHz, CDCl₃): δ = 177.2, 137.6, 128.4 (2 C), 127.7, 127.5 (2 C), 78.9, 73.4, 71.5, 28.3, 24.0. MS: m/z (%) = 206 (2), 105 (22), 91 (100), 85 (78), 65 (19).
(6 S )-6-[(Benzyloxy)methyl]tetrahydro-2 H -pyran-2-one [24] (13e).
Oil, 61% yield. [α]_D ²² +9.1 (c 2.88, CHCl₃). ¹³C NMR (50 MHz, CDCl₃): δ = 171.1, 137.7, 128.4 (2 C), 127.7, 127.6 (2 C), 79.0, 73.5, 71.8, 29.6, 24.5, 18.2. MS: m/z (%) = 129 (1) [M - 91], 114 (58), 99 (35), 91 (100), 71 (45), 55 (23).
(6 R )-6-[2-(Benzyloxy)ethyl]tetrahydro-2 H -pyran-2-one [25] (13f).
Oil, 59% yield. [α]_D ²⁸ +55.0 (c 2.01, CHCl₃). ¹³C NMR (50 MHz, CDCl₃): δ = 171.8, 138.1, 128.3 (2 C), 127.9 (2 C), 127.6, 77.5, 73.1, 65.7, 36.0, 29.6, 27.9, 18.3. MS: m/z (%) = 234 (16), 206 (8), 107 (44), 91 (100), 79 (14), 68 (30), 55 (12).

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25

The possible use of the presently described method for the synthesis of medium-sized lactones was suggested by a referee.