Synlett 2012; 23(12): 1821-1823
DOI: 10.1055/s-0031-1291158
letter
© Georg Thieme Verlag Stuttgart · New York

Development of a Dual Fries–Claisen Rearrangement Strategy

Liam J. Duffy
a  Research Institute for the Environment, Physical Sciences and Mathematics, Keele University, Keele ST5 5BG, UK
,
Jason Garcia-Torres
b  Chemistry Department, Loughborough University, Loughborough, Leics LE11 3TU, UK
,
Raymond C. F. Jones
b  Chemistry Department, Loughborough University, Loughborough, Leics LE11 3TU, UK
,
Steven M. Allin*
c  School of Science & Technology, Nottingham Trent University, Clifton, Nottingham NG11 8NS, UK, Fax: +44(115)8486352   Email: steve.allin@ntu.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 28 March 2012

Accepted: 09 April 2012

Publication Date:
22 June 2012 (online)


Abstract

In this paper we describe the development and application of a sequential Fries–Claisen rearrangement strategy as a new route for annelation on an aromatic ring. We demonstrate the potential utility of this protocol through the synthesis of a pyranonaphthoquinone target.

 
  • References and Notes


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  • 7 General Procedure for the Fries–Claisen Rearrangements: Claisen Rearrangement of 8 4-(Allyloxy)-8-(benzyloxy)naphthalen-1-yl dimethyl carbamate (8, 1.0 g, 2.65 mmol) was heated under reflux in mesitylene (10 mL) for 24 h. The solvent was removed under reduced pressure to yield a tarry brown solid. The crude solid was dissolved in hexanes (30 mL) and placed under reduced pressure in order to azeotropically remove any residual mesitylene. The resulting solid was filter-washed with cold hexane (30 mL) to yield 9 as a dark brown solid (793 mg, 79%); mp 89–91 °C. IR (thin film, CH2Cl2): 3416, 1634, 1262 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.58, 2.75, 3.26 (2 H, d, J = 6.4 Hz), 5.10 (2 H, s), 5.11–5.12 (1 H, m), 5.15 (1 H, q, J = 2.0 Hz), 5.90–5.97 (1 H, m), 6.14 (1 H, s), 6.74 (1 H, s), 6.82 (1 H, d, J = 7.6 Hz), 7.20 (1 H, t, J = 8.4 Hz), 7.36–7.49 (5 H, m), 7.65 (1 H, d, J = 8.4 Hz). 13C NMR (100 MHz, CDCl3): δ = 34.3, 35.7, 36.4, 70.7, 106.5, 115.0, 116.2, 119.1, 120.1, 121.5, 125.0, 126.9, 128.0, 128.2, 128.5 (2 C), 129.2, 136.2, 137.0, 139.6, 147.0, 154.4, 156.3. HRMS–FAB: m/z calcd for C23H23NO4: 377.1627; found: 377.1621 [M+].Fries Rearrangement of 12 4-(Allyloxy)-8-(benzyloxy)-1-methoxy-N,N-dimethyl-2-naphthamide (12, 1.68 g, 4.30 mmol) was heated to 160 °C in mesitylene, and the reaction was monitored by 1H NMR analysis. After 3 h the mesitylene was removed by eva-poration under reduced pressure. The crude tarry brown solid was dissolved in hexanes and placed under reduced pressure in order to azeotropically remove any residual mesitylene. This process was repeated three times to give a light brown solid which was chromatographed on silica gel, eluting with light PE–EtOAc (1:1), to give 13 as a white solid (1.28 g, 76%); mp 169–170 °C. IR (ATR): 1594, 1570, 1261, 1058 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.82 (3 H, s), 3.16 (3 H, s), 3.24 (1 H, dd, J = 7.2, 16.2 Hz), 3.37 (1 H, dt, J = 1.8, 16.2 Hz), 3.73 (3 H, s), 5.12–5.18 (2 H, m), 5.22 (2 H, q, J = 12.0 Hz), 5.87–5.99 (1 H, m), 6.22 (1 H, s), 6.92 (1 H, d, J = 7.8 Hz), 7.31–7.43 (4 H, m), 7.54 (2 H, d, J = 6.9 Hz), 7.81 (1 H, dd, J = 0.6, 8.4 Hz). 13C NMR (100 MHz, CDCl3): δ = 32.3, 34.6, 38.5, 63.7, 71.3, 108.2, 115.2, 116.2, 117.1, 119.7, 126.0, 127.5 (2 C), 127.8, 128.5 (2 C), 128.7, 129.0, 135.6, 137.0, 145.8, 146.8, 155.0, 169.4. HRMS (EI, CI): m/z calcd for C24H25NO4: 392.1856; found: 392.1853 [MH+]
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