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Synlett 2006(4): 0587-0590  
DOI: 10.1055/s-2006-932477
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of γ- and δ-Lactones from Alkynols

Marcello Tiecco*, Lorenzo Testaferri, Andrea Temperini, Raffaella Terlizzi, Luana Bagnoli, Francesca Marini, Claudio Santi
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Università di Perugia, 06123 Perugia, Italy
Fax: +39(075)5855116; e-Mail: tiecco@unipg.it;
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Publication History

Received 22 December 2005
Publication Date:
20 February 2006 (online)

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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.

Key words

alkynes - lactone-cyclization reactions - organoselenium reagents - regiospecificity

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