Stereoselectivity of Intramolecular Diels-Alder Reaction of Hydroxamate-Tethered 1,3,9-Decatrienes under Thermal and Microwave Heating

Abstract

Intramolecular Diels-Alder (IMDA) reaction of the hydroxamate-tethered 1,3,9-decatrienes has been investigated under both thermal and microwave heating, and the stereoselectivity has been revisited. It was found that a temperature-dependent rearrangement of (2E,4E)-hexadien-1-yl N-benzylhydroxamates into the corresponding (2E,4)-1-methylpentadien-1-yl derivatives took place prior to IMDA reaction upon heating, and up to four cycloadducts were identified by analysis of the crude reaction mixtures. The IMDA reaction could be accelerated with microwave irradiation at 180 ˚C in MeCN. Stereoselectivity of the microwave-assisted IMDA reaction has been examined by using the substituents appended at C1, C5, and C10 of the hydroxamate-tethered 1,3,9-decatrienes.

Key words

1,3,9-decatriene - Diels-Alder reaction - hydroxamate - microwave - stereoselectivity

References and Notes

• For selected reviews on microwave-assisted organic synthesis, see:
• 1a Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 
• 1b Kappe CO. Dallinger D. Mol. Diversity  2009,  13:  71 
• 1c Caddick S. Fitzmaurice R. Tetrahedron  2009,  65:  3325 
• 1d Dai W.-M. Shi J. Comb. Chem. High Throughput Screening  2007,  10:  837 
• For selected reviews on IMDA reaction, see:
• 2a Taber DF. Intramolecular Diels-Alder and Alder Ene Reactions   Springer; Berlin: 1984. 
• 2b Fallis AG. Can. J. Chem.  1984,  62:  183 
• 2c Ciganek E. Org. React.  1984,  32:  1 
• 2d Craig D. Chem. Soc. Rev.  1987,  187 
• 2e Roush WR. In Advances in Cycloaddition   Vol. 2:  Curran DP. JAI; Greenwich / CT: 1990.  p.91 
• 2f Roush WR. In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Paquette LA. Pergamon; Oxford: 1991.  p.513 
• 2g Craig D. Stereoselective Synthesis, In Methods of Organic Chemistry (Houben-Weyl)   4th ed., Vol. E21c:  Helmchen G. Hoffmann RW. Mulzer J. Schumann E. Thieme; Stuttgart: 1995.  p.2872 
• 2h Bear B. Sparks SM. Shea KJ. Angew. Chem. Int. Ed.  2001,  40:  820 
• 2i Stocking EM. Williams RM. Angew. Chem. Int. Ed.  2003,  42:  3078 
• 3 Wu J. Sun L. Dai W.-M. Tetrahedron  2006,  62:  8360 ; and references cited therein
• 4 Wu J. Yu H. Wang Y. Xing X. Dai W.-M. Tetrahedron Lett.  2007,  48:  6543 
• 5 Boechkman RK. Demko DM. J. Org. Chem.  1982,  47:  1789 
• 6 Ishikawa T. Senzaki M. Kadoya R. Morimoto T. Miyake N. Izawa M. Saito S. J. Am. Chem. Soc.  2001,  123:  4607 
• 7 The parent ester- and amide-tethered 1,3,9-decatrienes formed the IMDA adducts as an ca. 90:10 mixture of cis- and trans-bicyclic lactone and lactam, respectively, see: Martin SF. Williamsoon SA. Gist RP. Smith KM. J. Org. Chem.  1983,  48:  5170 
• 8 Taguchi T. Saito A. Yanai H. Chem. Rec.  2007,  7:  167 
• 11 Formation of trans-bicyclic adducts from both normal and inverse electron-demand IMDA reactions of imidazole-substituted hydroxamate-tethered 1,3,9-decatrienes was reported, see: Sivappa R. Hernandez NM. He Y. Lovely CJ. Org. Lett.  2007,  9:  3861 
• For reviews on synthesis of 1,2-oxazines, see:
• 12a Tsoungas PG. Heterocycles  2002,  57:  1149 
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Representative Procedure for Microwave-Assisted IMDA Reaction
To a 10 mL pressurized process vial were added the 1,3,9-decatriene 5a ⁶ (110.0 mg, 0.43 mmol) and MeCN (5 mL). The loaded vial was then sealed with a cap containing a silicon septum, and put into the microwave cavity and heated at 180 ˚C for 30 min (the holding time) with the temperature measured by an IR sensor. After cooling to r.t., the reaction mixture was concentrated under reduced pressure, and the residue was analyzed by ^¹H NMR spectroscopy for estimating the dr given in entry 2 of Table  [¹] . The crude reaction mixture was then purified by column chromatography (silica gel, 9% EtOAc in PE) to give the adducts 7a (87.0 mg, 79%), 8a (8.0 mg, 7%), and 9a (11.0 mg, 10%). The results of other IMDA reactions are given in Table  [¹] .
Characterization Data for Compound 7a ⁶
A colorless oil. R _f  = 0.51 (25% EtOAc in hexane). IR (film): 2956, 2924, 2868, 1641, 1454, 1217, 1017 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.33-7.26 (m, 5 H), 5.72 (dd, J = 10.4, 1.6 Hz, 1 H), 5.42 (ddd, J = 10.0, 4.4, 2.8 Hz, 1 H), 4.92 and 4.69 (ABq, J = 14.8 Hz, 2 H), 3.98 (dd, J = 11.2, 5.2 Hz, 1 H), 3.68 (dd, J = 11.2, 9.2 Hz, 1 H), 2.83-2.70 (m, 2 H), 2.32-2.23 (m, 2 H), 1.36-1.26 (m, 1 H), 1.01 (d, J = 6.8 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 170.1, 136.9, 136.1, 128.5 (2×), 128.1 (2×), 127.6, 122.8, 71.7, 50.1, 39.0, 34.3, 32.7, 30.2, 21.2.
Characterization Data for Compound 8a
A colorless oil. R _f  = 0.63 (25% EtOAc in hexane). IR (film): 2956, 2926, 2872, 1681, 1455, 1217 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.34-7.26 (m, 5 H), 5.66 (br d, J = 10.0 Hz, 1 H), 5.42 (ddd, J = 10.0, 1.2, 1.2 Hz, 1 H), 4.91 and 4.60 (ABq, J = 15.2 Hz, 2 H), 4.14 (dd, J = 9.6, 9.2 Hz, 1 H), 3.59 (dd, J = 9.6, 8.4 Hz, 1 H), 2.60-2.42 (m, 3 H), 2.05 (ddd, J = 13.6, 1.2, 1.2 Hz, 1 H), 1.80 (ddd, J = 13.6, 13.6, 6.4 Hz, 1 H), 1.05 (d, J = 7.6 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 175.0, 136.4, 134.0, 128.5 (2×), 128.3 (2×), 127.7, 124.5, 73.9, 49.6, 38.5, 34.9, 29.0, 27.6, 21.0. MS (+ESI): m/z (%) = 280 (100) [M + Na⁺], 258 (3) [M + H⁺]. HRMS (+ESI): m/z calcd for C₁₆H₁₉NO₂Na [M + Na⁺]: 280.1308; found: 280.1305.
Characterization Data for Compound 9a
A colorless oil. R _f  = 0.58 (25% EtOAc in hexane). IR (film): 2970, 2923, 1670, 1437, 1233 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.36-7.26 (m, 5 H), 5.88-5.81 (m, 1 H), 5.38 (ddd, J = 10.0, 4.8, 1.6 Hz, 1 H), 4.87 and 4.67 (ABq, J = 14.8 Hz, 2 H), 3.60 (dq, J = 8.4, 6.4 Hz, 1 H), 2.81 (ddd, J = 7.6, 7.6, 3.6 Hz, 1 H), 2.65-2.56 (m, 1 H), 2.35-2.23 (m, 1 H), 2.11-1.98 (m, 2 H), 1.91-1.83 (m, 1 H), 1.24 (d, J = 6.4 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 171.1, 136.3, 129.4, 128.4 (2×), 128.4 (2×), 127.5, 124.8, 80.7, 49.9, 42.1, 36.6, 22.7, 22.2, 18.0. MS (+ESI): m/z (%) = 280 (100) [M + Na⁺], 258 (4) [M + H⁺]. HRMS (+ESI): m/z calcd for C₁₆H₁₉NO₂Na [M + Na⁺]: 280.1308; found: 280.1302.

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The X-ray crystal data of 9b and 13b have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no CCDC 738480 and CCDC 738481, respectively. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: [phone] or E-mail: [e-mail]].