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Synthesis 2009(4): 627-635  
DOI: 10.1055/s-0028-1083351
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Practical Synthesis of α-Substituted tert-Butyl Acrylates from Meldrum’s Acid and Aldehydes

Christopher G. Frost*a, Stephen D. Penrosea, Robert Gleaveb
a Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
Fax: +44(1225)386231; e-Mail: c.g.frost@bath.ac.uk;
b Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK

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Publication History

Received 29 August 2008
Publication Date:
02 February 2009 (online)

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Abstract

An expeditious synthesis of α-substituted tert-butyl acryl­ates from commercially available aldehydes and Meldrum’s acid has been established. The method benefits from a telescoped condensation-reduction sequence to afford 5-monosubstituted Meldrum’s acid derivatives followed by a Mannich-type reaction triggered by a rapid cycloreversion of the dioxinone ring on heating with tert-butyl alcohol.

Key words

alkenes - Mannich bases - acrylate derivatives - tandem reactions - aldehydes

Functionalised α-substituted acrylic acid esters are of increasing importance in the design and synthesis of new polymer-based materials for a wide variety of applications in different areas of chemistry, biotechnology, nanotechnology, and material science. [¹] Furthermore, they are valuable intermediates for the 1,4-addition reaction of nucleophiles in both biological systems and for organic synthesis. [²] Consequently, a number of methods have been developed to allow access to structurally diverse α-substituted acrylates, and some of the reported approaches are illustrated in Scheme  [¹] .

Scheme 1

The classical method for acrylate synthesis involves a Mannich reaction of α-monosubstituted malonic half esters (Scheme  [¹] ). [³] This route can be problematic, with difficulties in the selective formation of the monosubstituted malonate diester. Furthermore, it is not possible to obtain the α-substituted tert-butyl acrylate by this method, due to difficulties with the hydrolysis of the corresponding diester. The α-functionalisation of acrylates employing the Baylis-Hillman reaction (Scheme  [¹] ) or aza variant is well documented, but limited to α-hydroxy- or α-amino-substituted products. [4] The methylenation of functionalised phosphonates via a Wittig-Horner reaction using paraformaldehyde (Scheme  [¹] ) allows convenient access to α-methylene adipate derivatives, although, surprisingly, this route is rarely utilised. [5] Palladium and nickel complexes have been studied in the catalytic synthesis of α-aryl-α,β-unsaturated carbonyl compounds by the cross-coupling of α-organometallics with aryl halides or the complementary combination of an α-halocarbonyl compound and an sp²-carbon-derived organometallic compound (Scheme  [¹] ). [6] However, in the context of preparing α-substituted acrylates, there are few reported examples, and mixtures of products are often isolated. [7]

Herein, we report a practical and scalable synthesis of a wide range of α-substituted tert-butyl acrylates 4 from commercially available aldehydes 2 and Meldrum’s acid (1) (Scheme  [²] ); this approach is complementary to established routes from carboxylic acids. [8] The method entails a telescoped condensation-reduction sequence to afford 5-monosubstituted Meldrum’s acid derivatives 3, followed by a Mannich-type reaction triggered by a rapid cycloreversion of the dioxinone ring on heating (Scheme  [²] ). [9]

Scheme 2

A number of methods for the synthesis of α,β-unsaturated Meldrum’s acid derivatives has been reported, including the use of strong base and N,N-dimethylformamide as a solvent, [¹0] neat aldehyde, [¹¹] zinc dust, [¹²] and, more recently, pyridinium acetate. [¹³] A remarkably expedient method is the uncatalysed Knoevenagel condensation of aldehydes and 1 in water, reported by Bigi et al. [¹4] This protocol offers significant advantages over existing methods for the preparation of α-substituted tert-butyl acrylates, as it circumvents the use of expensive coupling reagents and the generation of side products. Thus, the Knoevenagel condensation of thiophene-2-carbaldehyde (2a) and 1 in water afforded a bright-yellow, solid condensation product after two hours at 75 ˚C (Scheme  [³] ). The compound was isolated by simple filtration, and washed with water and hexane to give the desired α,β-unsaturated Meldrum’s acid derivative 5a. The crude product could be used in the next step without further purification. Consequently, 5a was cooled to 0 ˚C and dissolved in dichloromethane, and acetic acid was introduced. After the reaction mixture had stirred for 15 minutes, sodium borohydride was added in small portions over one hour. A rapid colour change occurred in 15 minutes, corresponding to the loss in conjugation and completion of the reaction. After a simple aqueous workup, the 5-monosubstituted Meldrum’s acid derivative 3a was obtained in high yield (Scheme  [³] ).

Scheme 3

This two-step route proved to be effective for a range of aldehydes, notably those that are liquids at room temperature. [¹5] However, problems arose when solid aldehydes with poor solubility in water were used or when the intermediate α,β-unsaturated Meldrum’s acid derivatives were not easily isolated as crystalline solids. This was rectified by telescoping the two operations by a simple extraction with dichloromethane. The improved procedure is illustrated for vanillin (2b) (Scheme  [4] ). In this case, separation of the Knoevenagel condensation product 5b from the starting aldehyde proved difficult and resulted in low yields of isolated product.

Scheme 4

Table 1 Synthesis of 5-Substituted Derivatives of Meldrum’s Acid

Product R Yielda (%)
3a 2-thienyl 88
3b 3-MeO-4-HOC6H3 87
3c 3-thienyl 88
3d 3-methyl-2-thienyl 91
3e PMP 87
3f 2-MeOC6H4 94
3g 1,3-benzodioxol-4-yl 73
3h 1,3-benzodioxol-5-yl 76
3i 2,3,4-(MeO)3C6H2 64
3j 2-F-4-MeOC6H3 82
3k 3-Cl-4-MeOC6H3 63
3l 4-FC6H4 61
3m 2,6-F2C6H3 98
3n 4-MeSC6H4 89
3o Tol 95
3p 2,6-Me2C6H3 92
3q 1-naphthyl 97
3r i-Pr 92
a Isolated yield.

The telescoped procedure involved taking the dichloromethane extracts from the Knoevenagel condensation and drying them over magnesium sulfate before they were cooled to 0 ˚C for the conjugate reduction step (Scheme  [4] ). This afforded product 3b in 87% yield after a single recrystallisation from hot ethyl acetate. Using this telescoped method, 20 compounds were synthesised in good to excellent yields (Table  [¹] ). The products isolated were air and moisture stable, making them suitable for large-scale synthesis. The method was not suitable for certain heteroaromatic aldehydes such as furan and pyrrole, due to sensitivity to acid and light, respectively. Other problematic aldehydes are straight-chain aliphatics, which tended to react with a second equivalent of Meldrum­’s acid to afford an insoluble solid.

With the 5-monosubstituted Meldrum’s acid derivatives 3a-r in hand, the Mannich-type reaction with N,N-di­methylmethyleneiminium iodide (6) to install the exo-methylene­ could be explored. [¹6] Initially, the reaction of 3a with tert-butyl alcohol and 6 was optimised as shown in Table  [²] . The reaction proceeds by rapid cycloreversion of the dioxinone ring to establish the tert-butyl ester and trigger the Mannich-type reaction. A significant advantage of this method is that the reaction byproducts (acetone, carbon dioxide, and dimethylamine) are volatile, resulting in clean conversion to product. Using neat tert-butyl alcohol as a solvent led to incomplete dissolution of 6 and lower yields (Table  [²] , entries 1 and 2). The quantity of 6 was also critical, with 1.1 equivalents giving poor yields, while the use of an excess, 2.6-3.5 equivalents, afforded excellent yields of product 4a (Table  [²] , entries 3-6).

Table 2 Optimisation of the Reaction of 3a with tert-Butyl Alcohol and 6

Entry 6
(equiv) 		Ratio
t-BuOH/THF 		Temp
(˚C) 		Yielda (%)
of 4a
1 1.1 1:0 65 28
2 2.0 1:0 65 73
3 2.6 1:0 70 81
4 2.6 1:1 70 89
5 2.6 1:1 reflux 68
6 3.5 1:1 70 91
a Isolated yield.

The scope of the method was investigated with 5-monosubstituted Meldrum’s acid derivatives 3a-r (Table  [³] ). When substrate 3 and reagent 6 were dissolved in a mixture of anhydrous tetrahydrofuran and tert-butyl alcohol for optimum solubility, and the mixture was heated to 70 ˚C overnight, the desired product was obtained in >95% purity after aqueous workup. Simple purification by short flash column chromatography afforded analytically pure materials. Pleasingly, α-substituted tert-butyl acrylates 4a-r were all formed in good to excellent yields (Table  [³] ), and all products were stable to air and moisture with no isomerisation to the tert-butyl 2-methyl-3-phenyl­acrylate species.

Table 3 Synthesis of α-Substituted tert-Butyl Acrylates 4 from 5-Substituted Derivatives 3 of Meldrum’s Acid

Product R Yielda (%)
4a 2-thienyl 92
4b 3-MeO-4-HOC6H3 57
4c 3-thienyl 82
4d 3-methyl-2-thienyl 78
4e PMP 95
4f 2-MeOC6H4 94
4g 1,3-benzodioxol-4-yl 90
4h 1,3-benzodioxol-5-yl 87
4i 2,3,4-(MeO)3C6H2 88
4j 2-F-4-MeOC6H3 83
4k 3-Cl-4-MeOC6H3 91
4l 4-FC6H4 84
4m 2,6-F2C6H3 84
4n 4-MeSC6H4 98
4o Tol 82
4p 2,6-Me2C6H3 85
4q 1-naphthyl 92
4r i-Pr 98
a Isolated yield.

In conclusion, a practical synthesis of α-substituted tert-butyl acrylates from commercially available aldehydes and Meldrum’s acid is presented. The reaction conditions are mild and tolerate many functional groups commonly used in organic synthesis. The method complements existing routes to α-substituted acrylates and is anticipated to be of particular utility for applications that require the tert-butyl ester.

Commercially available solvents and reagents were obtained from Sigma-Aldrich Company Ltd, Lancaster Synthesis Ltd and Fisher Scientific Ltd and were used without further purification, with the exception of Meldrum’s acid which was recrystallised from EtOH. CH2Cl2 and THF were dried and degassed under an argon atmosphere over activated alumina columns using an Innovative Technology Solvent Purification System (SPS). Melting points were determined on a Buchi 235 melting point apparatus. IR spectra were recorded on a Nicolet Nexus FTIR spectrometer, over the range 4000-200 cm-¹ and averaged over 32 scans, using KBr discs or NaCl plates. 1H NMR (300 MHz) and ¹³C NMR (75.5 MHz) spectroscopic measurements were carried out on Bruker AV300 or AVANCE 400 spectrometers. MS determinations were obtained on Fisons VG autospec Finnigan MAT 8340 (EI/CI MS) and Bruker micrOTOF-Q (CI-HRMS) instruments. Elemental analyses were carried out at the University of Bath using an Exeter Analytical CE 440 elemental analyser.

5-Monosubstituted Meldrum’s Acid Derivatives 3a-r; General Procedure

2,2-Dimethyl-1,3-dioxane-4,6-dione (1; 1.5 g, 10.5 mmol) was added portionwise to a stirred suspension of aldehyde 2 (10.0 mmol) in H2O (25 mL) at 23 ˚C. A reflux condenser was attached and the mixture was stirred at 75 ˚C for 2 h. After cooling of the mixture to r.t., the precipitated solid was dissolved in CH2Cl2 (100 mL), and the soln was passed through a hydrophobic frit into a second round-bottomed flask. The crude arylidene 5 was subsequently cooled to 0 ˚C (NaCl/ice), and AcOH (5 mL) was added with stirring of the mixture for 5 min under N2. NaBH4 (4 equiv) was added portionwise over 1 h or until the soln turned colourless. The reaction mixture was quenched with H2O (50 mL) and extracted with CH2Cl2 (50 mL). The combined organic extracts were washed with brine (2 × 75 mL) and H2O (2 × 75 mL) and dried (MgSO4), yielding the title compound, which could be used without further purification. Recrystallisation from hot EtOAc-hexanes afforded analytically pure compounds.

2,2-Dimethyl-5-(2-thienylmethyl)-1,3-dioxane-4,6-dione (3a)

Cream solid; yield: 98%; mp 128 ˚C (EtOAc).

IR (KBr): 3100, 3014, 2936 (C-H), 1778, 1744 (C=O), 1298 (C-S) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.03 (dd, J = 5.0, 1.3 Hz, 1 H, CH Ar), 7.10-7.02 (m, 1 H, CH Ar), 6.94-6.90 (m, 1 H, CH Ar), 3.76 (t, J = 4.6 Hz, 1 H, CH), 3.72 (d, J = 4.6 Hz, 2 H, CH 2), 1.76 (s, 3 H, CCH 3), 1.59 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 164.9, 138.1, 127.9, 126.8, 125.0, 105.3, 48.2, 28.3, 27.1, 26.4.

MS (EI/CI): m/z (%) = 258 (45) [M + NH4 +], 240 (5) [M + H+], 173 (50) [C8H10OS + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C11H16O4NS: 258.0795; found: 258.0791.

Anal. Calcd for C11H12O4S: C, 55.0; H, 5.03. Found: C, 54.2; H, 4.96.

5-(4-Hydroxy-3-methoxybenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3b)

Cream solid; yield: 66%; mp 133 ˚C (EtOAc).

IR (KBr): 3400 (O-H), 2831 (C-O-CH3), 1778, 1754 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.85 (br s, 1 H, CH Ar), 6.81-6.79 (m, 2 H, CH Ar), 5.56 (s, 1 H, OH), 3.82 (s, 3 H, OCH 3), 3.72 (t, J = 4.9 Hz, 1 H, CH), 3.42 (d, J = 4.9 Hz, 2 H, CH 2), 1.72 (s, 3 H, CCH 3), 1.47 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.5, 146.2, 144.7, 128.8, 122.5, 114.3, 112.6, 105.2, 55.9, 48.3, 31.9, 28.4, 27.3.

ESI-HRMS: m/z [M + Na+] calcd for C14H16Na1O6: 303.0845; found: 303.0822.

Anal. Calcd for C14H16O6: C, 60.0; H, 5.75. Found: C, 60.8; H, 5.81.

2,2-Dimethyl-5-(3-thienylmethyl)-1,3-dioxane-4,6-dione (3c)

Cream solid; yield: 91%; mp 81-83 ˚C (EtOAc).

IR (KBr): 3102, 3014, 2936 (C-H), 1774, 1744 (C=O), 1298 (C-S) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.22 (dd, J = 4.9, 3.0 Hz, 1 H, CH Ar), 7.18-7.72 (m, 1 H, CH Ar), 7.02 (dd, J = 4.90, 1.13 Hz, 1 H, CH Ar), 3.74 (t, J = 4.6 Hz, 1 H, CH), 3.50 (d, J = 4.6 Hz, 2 H, CH 2), 1.73 (s, 3 H, CCH 3), 1.51 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.2, 136.7, 129.2, 125.4, 123.9, 105.1, 47.5, 28.2, 27.1, 26.5.

MS (EI/CI): m/z (%) = 258 (55) [M + NH4 +], 240 (5) [MH+], 173 (45) [C8H10OS + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C11H16O4NS: 258.0795; found: 258.0789.

Anal. Calcd for C11H12O4S: C, 55.0; H, 5.03. Found: C, 54.4; H, 4.98.

2,2-Dimethyl-5-[(3-methyl-2-thienyl)methyl]-1,3-dioxane-4,6-dione (3d)

Cream solid; yield: 83%; mp 78-80 ˚C (EtOAc).

IR (KBr): 3108, 3007, 2987 (C-H), 1785, 1741 (C=O), 1298 (C-S) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.98 (d, J = 4.9 Hz, 1 H, Ar), 6.64 (d, J = 4.9 Hz, 1 H, Ar), 3.78 (t, J = 4.6 Hz, 1 H, CH), 3.53 (d, J = 4.6 Hz, 2 H, CH 2), 2.18 (s, 3 H, CH 3), 1.69 (s, 3 H, CCH 3), 1.54 (s, 3 H, CCH 3.

¹³C NMR (75.5 MHz, CDCl3): δ = 165.5, 136.2, 132.8, 130.6, 123.5, 105.7, 48.6, 48.5, 28.8, 27.5, 25.0, 16.0.

HRMS (CI): m/z [M + NH4 +] calcd for C12H18O4NS: 272.0957; found: 272.0924

Anal. Calcd for C12H14O4S: C, 56.7; H, 5.55. Found: C, 56.2; H, 5.49.

5-(4-Methoxybenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3e) [¹7]

White solid; yield: 98%; mp 82-85 ˚C (EtOAc) (Lit. [¹7]  85-86 ˚C).

IR (KBr): 3006, 2961, 2915 (C-H), 1787, 1746 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.24 (d, J = 8.7 Hz, 2 H, CH Ar), 6.81 (d, J = 8.7 Hz, 2 H, CH Ar), 3.77 (s, 3 H, OCH 3), 3.72 (t, J = 4.9 Hz, 1 H, CH), 3.44 (d, J = 4.9 Hz, 2 H, CH 2), 1.72 (s, 3 H, CCH 3), 1.48 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.3, 158.6, 130.8, 129.0, 113.8, 105.1, 55.1, 48.1, 31.3, 28.3, 27.1.

MS (EI/CI): m/z (%) = 282 (45) [M + NH4 +], 265 (5) [M + H+], 198 (50) (C10H12O3 + NH4).

HRMS (CI): m/z [M + NH4 +] calcd for C14H20NO5: 282.3118; found: 282.3114.

Anal. Calcd for C14H16O5: C, 63.6; H, 6.10. Found: C, 63.1; H, 6.06.

5-(2-Methoxybenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3f)

Cream solid; yield: 92%; mp 97-100 ˚C (EtOAc).

IR (KBr): 3000, 2940, 2886 (C-H), 1772, 1751 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.36 (dd, J = 7.5, 1.9 Hz, 1 H, CH Ar), 7.25 (td, J = 7.9, 1.9 Hz, 1 H, CH Ar), 6.93 (td, J = 7.5, 1.1 Hz, 1 H, CH Ar), 6.85 (d, J = 7.9 Hz, 1 H, CH Ar), 4.03 (t, J = 6.0 Hz, 1 H, CH), 3.83 (s, 3 H, OCH 3), 3.40 (d, J = 6.0 Hz, 2 H, CH 2), 1.77 (s, 3 H, CCH 3), 1.73 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 170.4, 164.9, 156.7, 131.1, 127.8, 125.3, 120.0, 110.0, 104.4, 59.8, 54.7, 45.5, 28.0, 27.3, 25.8, 20.4, 13.7.

MS (EI/CI): m/z (%) = 282 (40) [M + NH4 +], 265 (10) [M + H+], 198 (50) (C10H12O3 + NH4).

HRMS (CI): m/z [M + NH4 +] calcd for C14H20NO5: 282.3118; found: 282.3112.

Anal. Calcd for C14H16O5: C, 63.6; H, 6.10. Found: C, 62.8; H, 6.01.

5-(1,3-Benzodioxol-4-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3g)

Cream solid; yield: 73%; mp 127-128 ˚C (EtOAc).

IR (KBr): 1755, 1725 (C=O), 1276 (O-C-O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.81 (d, J = 2.3 Hz, 1 H, Ar), 6.77 (d, J = 6.8 Hz, 1 H, Ar), 6.72 (dd, J = 6.8 Hz, 1 H, 2.3 Hz, Ar), 5.93 (s, 2 H, OCH 2O), 3.99 (t, J = 5.7 Hz, 1 H, CH), 3.42 (d, J = 5.7 Hz, 2 H, CH 2), 1.80 (s, 3 H, CCH 3), 1.72 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 147.5, 145.6, 123.6, 122.2, 119.4, 107.8, 105.4, 101.0, 46.4, 29.0, 27.0, 26.7.

ESI-HRMS: m/z [M + Na+] calcd for C14H14O6Na1: 301.0688; found: 301.0671.

Anal. Calcd for C14H12O6: C, 60.9; H, 4.40. Found: C, 59.9; H, 4.30.

5-(1,3-Benzodioxol-5-ylmethyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3h)

Cream solid; yield: 76%; mp 114-116 ˚C (EtOAc).

IR (KBr): 1772, 1751 (C=O), 1256 (O-C-O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.31 (s, 1 H, CH Ar), 8.06 (d, J = 1.9 Hz, 1 H, CH Ar), 7.54 (dd, J = 8.3, 1.9 Hz, 1 H, CH Ar), 6.09 (s, 2 H, OCH 2O), 4.12 (t, J = 6.1 Hz, 1 H, CH), 3.40 (d, J = 6.1 Hz, 2 H, CH 2), 1.76 (s, 3 H, CCH 3), 1.71 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 164.3, 160.7, 153.6, 148.7, 134.6, 126.8, 111.7, 108.9, 104.7, 102.8, 54.1, 32.7.

HRMS (EI/CI): m/z [M + Na+] calcd for C14H12O6Na1: 301.0688; found: 301.0692.

Anal. Calcd for C14H12O6: C, 60.9; H, 4.40. Found: C, 60.2; H, 4.37.

2,2-Dimethyl-5-(2,3,4-trimethoxybenzyl)-1,3-dioxane-4,6-dione (3i)

Cream solid; yield: 79%; mp 91-94 ˚C (EtOAc).

IR (KBr): 2895, 2845, 2828 (C-O-CH3), 1775, 1742 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.02 (d, J = 8.7 Hz, 1 H, CH Ar), 6.61 (d, J = 8.7 Hz, 1 H, CH Ar), 4.03 (t, J = 5.7 Hz, 1 H, CH), 3.91 (s, 3 H, OCH 3), 3.85 (s, 3 H, OCH 3), 3.83 (s, 3 H, OCH 3), 3.31 (d, J = 5.7 Hz, 2 H, CCH 2), 1.77 (s, 3 H, CH 3), 1.71 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.2, 152.9, 151.6, 141.8, 125.4, 123.4, 107.0, 104.8, 60.7, 60.6, 55.8, 47.0, 28.5, 27.2, 26.4.

HRMS (EI): m/z [M + Na+] calcd for C16H20O7Na: 347.1107; found: 347.1100.

Anal. Calcd for C16H20O7: C, 59.3; H, 6.22. Found: C, 58.8; H, 6.17.

5-(2-Fluoro-4-methoxybenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3j)

Cream solid; yield: 82%; mp 128-130 ˚C (EtOAc).

IR (KBr): 2840 (C-O-CH3), 1786, 1744 (C=O), 1514 (C-F) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.23 (t, J = 8.67 Hz, 1 H, CH Ar), 6.59 (dd, J = 8.67, 2.64 Hz, 1 H, CH Ar), 6.53 (dd, J = 12.1, 2.64 Hz, 1 H, CH Ar), 3.72 (t, J = 6.03 Hz, 1 H, CH), 3.71 (s, 3 H, OCH 3), 3.32 (d, J = 6.03 Hz, 2 H, CH 2), 1.72 (s, 3 H, CCH 3), 1.64 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 164.9, 163.1, 160.1, 159.9, 159.8, 132.3, 132.2, 116.2, 109.8, 109.8, 105.1, 101.7, 101.4, 55.5, 46.9, 46.9, 28.6, 26.6, 25.2, 25.2.

ESI-HRMS: m/z [M + Na+] calcd for C14H15O5F1Na1: 305.0801; found: 305.0810.

Anal. Calcd for C16H20O7: C, 59.6; H, 5.36. Found: C, 59.1; H, 5.32.

5-(3-Chloro-4-methoxybenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3k)

Cream solid; yield: 63%; mp 142 ˚C (EtOAc).

IR (KBr): 2837 (C-O-CH3), 1784, 1741 (C=O), 7584 (C-Cl) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.35 (s, 1 H, CH Ar), 7.21 (d, J = 8.3 Hz, 1 H, CH Ar), 6.84 (d, J = 8.3 Hz, 1 H, CH Ar), 3.87 (s, 3 H, OCH 3), 3.71 (t, J = 4.9 Hz, 1 H, CH), 3.40 (d, J = 4.9 Hz, 2 H, CH 2), 1.75 (s, 3 H, CCH 3), 1.58 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.0, 154.1, 131.5, 130.1, 129.3, 122.2, 111.9, 105.2, 56.1, 48.1, 30.8, 28.4, 27.1.

ESI-HRMS: m/z [M + Na+] calcd for C14H15Cl1O5Na1: 321.0506; found: 321.0503.

Anal. Calcd for C14H15Cl1O5: C, 56.3; H, 5.06. Found: C, 56.0; H, 4.94.

5-(4-Fluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3l) [¹8]

White solid; yield: 97%; mp 107-110 ˚C (EtOAc).

IR (KBr): 3014, 2954, 2893 (C-H), 1786, 1744 (C=O), 1514 (C-F) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.33-7.27 (m, 2 H, CH Ar), 6.97 (t, J = 8.7 Hz, 2 H, CH Ar), 3.73 (t, J = 4.9 Hz, 1 H, CH), 3.46 (d, J = 4.9 Hz, 2 H, CH 2), 1.79 (s, 3 H, CCH 3), 1.74 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 173.9, 165.1, 163.5, 160.3, 132.6, 132.6, 131.5, 131.4, 130.2, 115.4, 115.3, 115.1, 105.2, 48.0, 31.1, 28.3, 27.1.

ESI-HRMS: m/z [M + Na+] calcd for C13H13F1O6 Na1: 275.0696; found: 275.0690

Anal. Calcd for C13H13F1O4: C, 61.9; H, 5.19; found: C, 61.8; H, 5.16.

5-(2,6-Difluorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3m)

White solid; yield: 98%; mp 125-127 ˚C (EtOAc).

IR (KBr): 3004, 2954, 2909 (C-H), 1782, 1748 (C=O), 1625, 1593 (C-F) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.26-7.14 (m, 1 H, Ar), 6.97 (t, J = 8.3 Hz, 2 H, CH Ar), 3.98 (t, J = 6.9 Hz, 1 H, CH), 3.43 (d, J = 6.9 Hz, 2 H, CH 2), 1.81 (s, 3 H, CCH 3), 1.77 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 164.4, 163.0, 159.7, 128.5, 113.4, 111.4, 111.1, 105.1, 45,1, 28.5, 26.4, 19.8.

HRMS (EI/CI): m/z [M + NH4 +] calcd for C13H16F2O4N: 288.1047; found: 288.1042.

Anal. Calcd for C13H12F2O4: C, 57.8; H, 4.48; found: C, 57.9; H, 4.45.

5-[4-(Methylsulfanyl)benzyl]-2,2-dimethyl-1,3-dioxane-4,6-dione (3n)

Cream solid; yield: 89%; mp 96-98 ˚C (EtOAc).

IR (KBr): 2996, 2945, 2897, 2875 (C-H), 1789, 1747 (C=O), 1498 (S-CH3) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.25 (d, J = 6.4 Hz, 2 H, CH Ar), 7.17 (d, J = 6.4 Hz, 2 H, CH Ar), 3.73 (t, J = 4.9 Hz, 1 H, CH), 3.44 (s, 3 H, SCH 3), 3.44 (d, J = 4.9 Hz, 2 H, CH 2), 1.73 (s, 3 H, CCH 3), 1.54 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.1, 137.3, 133.8, 130.3, 126.7, 105.1, 48.1, 31.5, 28.4, 27.2, 15.8.

HRMS (CI): m/z [M + Na+] calcd for C14H16O4Na1S: 303.0662; found: 303.0651.

Anal. Calcd for C14H16O4S: C, 59.9; H, 5.75; found: C, 59.9; H, 5.72%

2,2-Dimethyl-5-(4-methylbenzyl)-1,3-dioxane-4,6-dione (3o) [¹9]

White solid; yield: 95%; mp 110-112 ˚C (EtOAc) (Lit. [¹9] 112-113 ˚C).

IR (KBr): 3004, 2942, 2896 (C-H), 1786, 1751 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.19 (d, J = 7.9 Hz, 2 H, CH Ar), 7.08 (d, J = 7.9 Hz, 2 H, CH Ar), 3.78 (t, J = 4.9 Hz, 1 H, CH), 3.60 (d, J = 4.9 Hz, 2 H, CH 2), 2.29 (s, 3 H, CH 3), 1.72 (s, 3 H, CCH 3), 1.50 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.2, 162.8, 136.5, 134.0, 129.4, 129.0, 106.0, 105.0, 47.9, 35.9, 31.4, 28.2, 27.3, 26.9, 20.8.

5-(2,6-Dimethylbenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3p)

White solid; yield: 92%; mp 112-115 ˚C (EtOAc).

IR (KBr): 3000, 2960, 2867 (C-H), 1776, 1739 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.13-7.01 (m, 3 H, CH Ar), 3.70 (t, J = 6.0 Hz, 1 H, CH), 3.50 (d, J = 6.0 Hz, 2 H, CH 2), 2.42 (s, 6 H, CH 3), 1.79 (s, 3 H, CCH 3), 1.77 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.0, 137.0, 134.9, 128.6, 126.8, 104.9, 47.0, 28.7, 26.6, 26.4, 20.2.

HRMS (CI): m/z [M + Na+] calcd for C15H18O4Na1: 285.1097; found: 285.1091.

Anal. Calcd for C15H18O4: C, 68.6; H, 6.92; found: C, 68.4; H, 6.88%

2,2-Dimethyl-5-(1-naphthylmethyl)-1,3-dioxane-4,6-dione (3q) [²0]

Cream solid; yield: 97%; mp 135-137 ˚C (EtOAc).

IR (KBr): 3057, 3000, 2869 (C-H), 1781, 1750 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.08 (d, J = 8.3 Hz, 1 H, CH Ar), 7.90 (d, J = 8.3 Hz, 1 H, CH Ar), 7.79 (d, J = 8.3 Hz, 1 H, CH Ar), 7.65 (d, J = 7.2 Hz, 1 H, CH Ar), 7.61-7.47 (m, 2 H, CH Ar), 7.44 (t, J = 7.2 Hz, 1 H, CH Ar), 3.93 (d, J = 5.3 Hz, 2 H, CH 2), 3.81 (t, J = 5.3 Hz, 1 H, CH), 1.70 (s, 3 H, CCH 3), 1.69 (s, 3 H, CCH 3).

¹³C NMR (75.5 MHz, CDCl3): δ = 165.3, 134.0, 133.9, 131.2, 129.2, 128.4, 127.8, 126.7, 125.7, 125.5, 122.7, 105.1, 47.7, 28.7, 28.6, 26.4.

5-Isobutyl-2,2-dimethyl-1,3-dioxane-4,6-dione (3r) [²0]

White solid; yield: 92%; mp 119-120 ˚C (EtOAc) (Lit. [²0] 120 ˚C).

IR (KBr): 3003, 2893, 2861 (C-H), 1797, 1748 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 3.43 (t, J = 5.7 Hz, 1 H, CH), 1.8-2.15 [m, 3 H, CH(CH3)2, CH 2 overlap], 1.77 (s, 3 H, CH 3), 1.72 (s, 3 H, CH 3), 0.85 [d, J = 6.0 Hz, 6 H, CH(CH 3)2].

¹³C NMR (75.5 MHz, CDCl3): δ = δ 165.9, 104.8, 44.1, 35.2, 28.5, 26.7, 25.8, 22.0.

α-Substituted tert -Butyl Acrylates 4a-r from 5-Monosubstituted Meldrum’s Acid Derivatives 3a-r; General Procedure

An oven-dried 50-mL round-bottomed flask was charged under N2 with the appropriate 3 (2.08 mmol) and 6 (1.00 g, 5.41 mmol). The solids were dissolved in THF (12 mL) and anhyd t-BuOH (12 mL). The reaction mixture was then heated to 70 ˚C and stirred at that temperature for 18 h. Upon cooling of the mixture to r.t., the solvent was removed in vacuo, and the yellow residue was taken up in Et2O (25 mL), extracted with a sat. NaHCO3 soln (20 mL), 10% aq KHSO4 (20 mL), and a sat. NaCl soln (20 mL), and dried (MgSO4). The solvent was removed in vacuo and the resulting oils were purified by flash column chromatography [silica gel, petrol (40-60) CH2Cl2, 2:1]; this gave the corresponding product 4.

tert -Butyl 2-(2-Thienylmethyl)acrylate (4a)

Acrylate 4a was prepared by the general procedure described above, from Meldrum’s acid derivative 3a (0.50 g, 2.08 mmol) and 6 (1.24 g, 6.69 mmol).

Colourless oil; yield: 0.43 g (92%); R f = 0.55 (petrol-CH2Cl2, 2:1).

IR (neat): 2979, 2931 (C=CH2), 1711 (C=O), 1368 (C-S) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.0 (dd, J = 5.3, 1.1 Hz, 1 H, Ar), 7.0 (dd, J = 3.4, 5.3 Hz, 1 H, Ar), 6.82 (dd, J = 3.4, 1.1 Hz, 1 H, Ar), 6.16 (s, 1 H, CHH), 5.50 (s, 1 H, CHH), 3.79 (s, 2 H, CH 2), 1.47 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.8, 141.6, 141.1, 126.8, 125.5, 126.8, 123.8, 80.9, 32.3, 28.8, 28.0.

MS (EI/CI): m/z (%) = 242 (25) [M + NH4 +], 225 (25) [M + H+], 186 (50) [C8H7O2S + NH4 +].

HRMS (CI): m/z [M + H+] calcd for C12H17O2S: 225.0944; found: 225.0943.

tert -Butyl 2-2-(4-Hydroxy-3-methoxybenzyl)acrylate (4b)

Acrylate 4b was prepared by the general procedure described above, from Meldrum’s acid derivative 3b (0.50 g, 1.79 mmol) and 6 (0.875 g, 4.73 mmol).

White semisolid; yield: 0.27 g (57%); R f = 0.20 (petrol-CH2Cl2, 2:1); mp 41-43 ˚C (hexanes).

IR (neat): 2979 (C=CH2), 1711 (C=O), 1493 (O-CH3) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.84 (dd, J = 7.2, 1.1 Hz, 1 H, CH Ar), 6.70 (s, 1 H, CH Ar), 6.68 (dd, J = 7.2, 1.9 Hz, 1 H, CH Ar), 6.12 (dd, J = 1.5, 0.75 Hz, 1 H, C=CH2), 5.37 (dd, J = 3.0, 1.5 Hz, 1 H, C=CH2), 3.85 (s, 3 H, OCH 3), 3.53 (s, 2 H, CH 2), 1.46 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 166.2, 146.3, 143.9, 142.0, 130.8, 124.7, 121.6, 114.1, 111.4, 80.6, 55.7, 37.7, 27.9.

MS (EI/CI): m/z (%) = 282 (35) [M + NH4 +], 264 (15) [M + H+], 208 (50) [C11H12O4 + NH4 +].

ESI-HRMS: m/z [M + Na+] calcd for C15H20O4Na1: 287.1259; found: 287.1258

tert -Butyl 2-(3-Thienylmethyl)acrylate (4c)

Acrylate 4c was prepared by the general procedure described above, from Meldrum’s acid derivative 3c (0.50 g, 2.08 mmol) and 6 (1.24 g, 6.69 mmol).

Colourless oil; yield: 0.41 g (82%); R f = 0.55 (petrol-CH2Cl2, 2:1).

IR (neat): 2976, 2934 (C=CH2), 1709 (C=O), 1366 (C-S) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.23 (dd, J = 5.0, 3.0 Hz, 1 H, Ar), 6.97 (s, 1 H, Ar), 6.91 (dd, J = 5.0, 1.1 Hz, 1 H, Ar), 6.12 (s, 1 H, CHH), 5.39 (s, 1 H, CHH), 3.60 (s, 2 H, CH 2), 1.44 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 166.1, 141.2, 139.3, 128.4, 125.2, 124.7, 121.4, 80.6, 65.7, 32.6, 15.2, 27.9.

MS (EI/CI): m/z (%) = 242 (20) [M + NH4 +], 225 (20) [M + H+], 186 (60) [C8H7O2S + NH4 +].

HRMS (CI): m/z [M + H+] calcd for C12H17O2S: 225.0944; found: 225.0943.

tert -Butyl 2-[(3-Methyl-2-thienyl)methyl]acrylate (4d)

Acrylate 4d was prepared by the general procedure described above, from Meldrum’s acid derivative 3d (0.50 g, 1.97 mmol) and 6 (1.05 g, 5.91 mmol).

Colourless oil; yield: 0.38 g (78%); R f = 0.5 (petrol-CH2Cl2, 2:1).

IR (neat): 2977, 2929 (C=CH2), 1712 (C=O), 1392 (C-S) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.06 (d, J = 4.9 Hz, 1 H, Ar), 6.81 (d, J = 4.9 Hz, 1 H, Ar), 6.15 (s, 1 H, CHH), 5.33 (s, 1 H, CHH), 3.69 (s, 3 H, CH 2), 2.14 (s, 3 H, CH 3), 1.50 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.8, 140.4, 134.1, 133.9, 129.9, 124.8, 122.0, 80.8, 29.8, 27.9, 13.5, 53.3.

MS (EI/CI): m/z (%) = 256 (10) [M + NH4 +], 239 (20) [M + H+], 200 (80) [C9H10O2S + NH4 +].

HRMS (CI): m/z [M + H+] calcd for C13H18O2S: 239.1100; found: 239.1099

tert -Butyl 2-(4-Methoxybenzyl)acrylate (4e)

Acrylate 4e was prepared by the general procedure described above, from Meldrum’s acid derivative 3e (0.50 g, 1.89 mmol) and 6 (1.05 g, 5.68 mmol).

Colourless oil; yield: 0.45 g (95%); R f = 0.35 (petrol-CH2Cl2, 2:1).

IR (neat): 2979 (C=CH2), 1710 (C=O), 1512 (O-CH3) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.10 (d, J = 6.8 Hz, 2 H, CH Ar), 6.82 (d, J = 6.8 Hz, 2 H, CH Ar), 6.11 (dd, J = 1.5, 0.75 Hz, 1 H, C=CH2), 5.40 (dd, J = 3.4, 1.5 Hz, 1 H, C=CH2), 3.79 (s, 3 H, OCH 3), 3.53 (s, 2 H, CH 2), 1.44 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 158.0, 142.1, 131.1, 129.9, 124.8, 113.7, 80.6, 55.2, 37.3, 28.0.

MS (EI/CI): m/z (%) = 282 (30) [M + NH4 +], 266 (80) [M + H+], 210 (50) [C11H12O3 + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C15H24O3N: 266.1751; found: 266.1750.

tert -Butyl 2-(2-Methoxybenzyl)acrylate (4f)

Acrylate 4f was prepared by the general procedure described above, from Meldrum’s acid derivative 3f (0.50 g, 1.89 mmol) and 6 (0.875 g, 4.73 mmol).

Colourless oil; yield: 0.43 g (94%); R f = 0.35 (petrol-CH2Cl2, 2:1).

IR (neat): 2979 (C=CH2), 1711 (C=O), 1493 (O-CH3) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.21 (td, J = 7.9, 1.5 Hz, 1 H, CH Ar), 7.12 (dd, J = 7.5, 1.5 Hz, 1 H, CH Ar), 6.89 (td, J = 7.5, 1.1 Hz, 1 H, CH Ar), 6.86 (d, J = 7.9 Hz, 1 H, CH Ar), 6.10 (dd, J = 2.6, 1.1 Hz, 1 H, C=CH2), 5.26 (dd, J = 3.4, 1.5 Hz, 1 H, C=CH2), 3.80 (s, 3 H, OCH 3), 3.59 (s, 2 H, CH 2), 1.47 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 208.5, 192.0, 181.5, 178.6, 175.6, 171.4, 161.4, 131.5, 106.4, 82.9, 79.0.

MS (EI/CI): m/z (%) = 282 (10) [M + NH4 +], 266 (80) [M + H+], 210 (50) [C11H12O3 + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C15H24O3N: 266.1751; found: 266.1749.

tert -Butyl 2-(1,3-Benzodioxol-4-ylmethyl)acrylate (4g)

Acrylate 4g was prepared by the general procedure described above, from Meldrum’s acid derivative 3g (0.51 g, 1.83 mmol) and 6 (0.961 g, 5.20 mmol).

Colourless oil; yield: 0.43 g (90%); R f = 0.35 (petrol-CH2Cl2, 1:1).

IR (neat): 1712 (C=O), 1247 (O-C-O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.81 (s, 1 H, CH Ar), 6.72 (dd, J = 7.5, 1.9 Hz, 1 H, CH Ar), 6.61 (dd, J = 8.3, 1.9 Hz, 1 H, CH Ar), 6.19 (dd, J = 2.6, 1.1 Hz, 1 H, C=CH2), 5.87 (s, 2 H, OCH 2O), 5.43 (dd, J = 2.6, 1.1 Hz, 1 H, C=CH2), 3.54 (s, 2 H, CH 2), 1.45 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.9, 148.7, 145.8, 139.8, 130.8 125.0, 122.4, 120.4, 115.2, 114.1 106.7, 100.4, 80.5, 31.4, 27.9.

MS (EI/CI): m/z (%) = 280 (15) [M + NH4 +], 262 (25) [M + H+], 224 (60) [C11H10O4 + NH4 +].

ESI-HRMS: m/z [M + Na+] calcd for C15H18O4Na1: 285.1103; found: 285.1101

tert -Butyl 2-(1,3-Benzodioxol-5-ylmethyl)acrylate (4h)

Acrylate 4h was prepared by the general procedure described above, from Meldrum’s acid derivative 3h (0.51 g, 1.83 mmol) and 6 (0.961 g, 5.20 mmol).

Colourless oil; yield: 0.41 g (87%); R f = 0.35 (petrol-CH2Cl2, 1:1).

IR (neat): 1708 (C=O), 1251 (O-C-O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.74 (dd, J = 15.1, 7.5 Hz, 1 H, CH Ar), 6.70 (dd, J = 7.5, 1.5 Hz, 1 H, CH Ar), 6.66 (dd, J = 7.5, 1.5 Hz, 1 H, CH Ar), 6.16 (dd, J = 2.6, 1.1 Hz, 1 H, C=CH2), 5.91 (s, 2 H, OCH 2O), 5.39 (dd, J = 2.6, 1.1 Hz, 1 H, C=CH2), 3.56 (s, 2 H, CH 2), 1.46 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.9, 147.0, 145.5, 139.8, 125.0, 122.8, 121.2, 120.4, 106.7, 100.4, 80.5, 31.4, 27.9.

MS (EI/CI): m/z (%) = 280 (15) [M + NH4 +], 262 (25) [M + H+], 224 (60) [C11H10O4 + NH4 +].

ESI-HRMS: m/z [M + Na+] calcd for C15H18O4Na1: 285.1103; found: 285.1091

tert -Butyl 2-(2,3,4-Trimethoxybenzyl)acrylate (4i)

Acrylate 4i was prepared by the general procedure described above, from Meldrum’s acid derivative 3i (0.50 g, 1.54 mmol) and 6 (0.856 g, 4.62 mmol).

Yellow oil; yield: 0.42 g (88%); R f = 0.3 (CH2Cl2).

IR (neat): 2976, 2937 (C=CH2), 1712 (C=O) 1627, 1618 (O-CH3) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.80 (d, J = 8.7 Hz, 1 H, CH Ar), 6.60 (H, d, J = 8.7 Hz, CH Ar), 6.14 (dd, J = 2.6, 1.1 Hz, 1 H, C=CH2), 5.38 (dd, J = 3.4, 1.5 Hz, 1 H, C=CH2), 3.86 (s, 3 H, OCH 3), 3.84 (s, 3 H, OCH 3), 3.83 (s, 3 H, OCH 3), 3.53 (s, 2 H, CH 2), 1.46 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 166.3, 152.3, 151.9, 142.2, 141.6, 125.0, 124.5, 124.4, 107.0, 80.5, 60.8, 60.6, 55.9, 31.6, 28.7, 28.0.

MS (EI/CI): m/z (%) = 326 (10) [M + NH4 +], 309 (10) [M + H+], 210 (80) [C13H16O5 + NH4 +].

HRMS (CI): m/z [M + H+] calcd for C17H25O3N: 309.1697; found: 309.1698.

tert -Butyl 2-(2-Fluoro-4-methoxybenzyl)acrylate (4j)

Acrylate 4j was prepared by the general procedure described above, from Meldrum’s acid derivative 3j (0.50 g, 1.77 mmol) and 6 (0.875 g, 4.73 mmol).

Pale yellow oil; yield: 0.39 g (83%); R f = 0.35 (petrol-CH2Cl2, 2:1).

IR (neat): 2978 (C=CH2), 1708 (C=O), 1627 (O-CH3), 1509 (C-F) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.06 (t, J = 8.7 Hz, 1 H, CH Ar), 6.60 (dd, J = 8.7, 2.6 Hz, 1 H, CH Ar), 6.51 (s, 1 H, CH Ar), 6.12 (dd, J = 2.6, 1.1 Hz, 1 H, C=CH2), 5.32 (dd, J = 1.5, 0.74 Hz, 1 H, C=CH2), 3.76 (s, 3 H, OCH 3), 3.53 (s, 2 H, CH 2), 1.45 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.9, 163.0, 159.5, 159.4, 140.4, 131.3, 131.2, 124.8, 117.5, 109.5, 101.5, 80.6, 55.3, 30.3, 27.9.

MS (EI/CI): m/z (%) = 284 (10) [M + NH4 +], 266 (20) [M + H+], 228 (70) [C11H11F1O3 + NH4 +].

ESI-HRMS: m/z [M + Na+] calcd for C15H19O3F1Na1: 289.1216; found: 289.1204

tert -Butyl 2-(3-Chloro-4-methoxybenzyl)acrylate (4k)

Acrylate 4k was prepared by the general procedure described above, from Meldrum’s acid derivative 3k (0.50 g, 1.67 mmol) and 6 (0.875 g, 4.73 mmol).

Yellow oil; yield: 0.43 g (91%); R f = 0.30 (petrol-CH2Cl2, 2:1).

IR (neat): 2979 (C=CH2), 1711 (C=O), 1590 (O-CH3) 756 (C-Cl) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.17 (d, J = 2.3 Hz, 1 H, CH Ar), 7.02 (dd, J = 8.3, 2.3 Hz, 1 H, CH Ar), 6.82 (d, J = 8.3 Hz, 1 H, CH Ar), 6.12 (dd, J = 1.5, 0.75 Hz, 1 H, C=CH2), 5.37 (dd, J = 3.0, 1.5 Hz, 1 H, C=CH2), 3.84 (s, 3 H, OCH 3), 3.48 (s, 2 H, CH 2), 1.42 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.8, 153.3, 141.3, 132.1, 130.5, 128.0, 125.1, 121.9, 111.8, 80.6, 55.9, 37.0, 27.8.

MS (EI/CI): m/z (%) = 300 (10) [M + NH4 +], 282 (10) [M + H+], 244 (80) [C11H11Cl1O3 + NH4 +].

ESI-HRMS: m/z [M + Na+] calcd for C15H19Cl1O3Na1: 305.0920; found: 305.0919

tert -Butyl 2-(4-Fluorobenzyl)acrylate (4l)

Acrylate 4l was prepared by the general procedure described above, from Meldrum’s acid derivative 3l (0.52 g, 2.20 mmol) and 6 (0.925 g, 5.00 mmol).

Colourless oil; yield: 0.46 g (84%); R f = 0.55 (petrol-CH2Cl2, 2:1).

IR (neat): 2983, 3052 (C=CH2), 1712 (C=O), 1510 (C-F) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.14 (dd, J = 8.7, 5.7 Hz, 2 H, CH Ar), 6.97 (t, J = 8.7 Hz, 2 H, CH Ar), 6.14 (dd, J = 1.5, 0.75 Hz, 1 H, C=CH2), 5.37 (dd, J = 3.0, 1.5 Hz, 1 H, C=CH2), 3.56 (s, 2 H, CH 2), 1.35 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.9, 163.0, 159.8, 141.5, 134.6, 130.3, 130.2, 125.2, 115.1, 114.9, 80.7, 37.4, 27.9.

MS (EI/CI): m/z (%) = 254 (34) [M + NH4 +], 237 (15) [M + H+], 198 (50) [C10H9F1O2 + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C14H21O2F1N: 254.1551; found: 254.1551

tert -Butyl 2-(2,6-Difluorobenzyl)acrylate (4m)

Acrylate 4m was prepared by the general procedure described above, from Meldrum’s acid derivative 3m (0.52 g, 2.20 mmol) and 6 (0.925 g, 5.00 mmol).

Colourless oil; yield: 0.46 g (84%); R f = 0.6 (petrol-CH2Cl2, 2:1).

IR (neat): 2980, 2934 (C=CH2), 1712 (C=O), 1594, 1470 (C-F) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.26-7.14 (m, 1 H, Ar), 6.97 (t, J = 7.6 Hz, 2 H, CH Ar), 6.12 (d, J = 1.1 Hz, 1 H, C=CH2), 5.19 (d, J = 0.75 Hz, 1 H, C=CH2), 3.64 (s, 2 H, CH 2), 1.49 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 165.7, 163.2, 159.9, 138.8, 128.3, 124.3, 114.8, 111.0, 80.9, 27.9, 24.5.

MS (EI/CI): m/z (%) = 272 (30) [M + NH4 +], 255 (10) [M + H+], 216 (60) [C10H8F2O2 + NH4 +].

HRMS (CI): m/z calcd for C14H20O2F2N [M + NH4 +]: 272.1457; found: 272.1459.

tert -Butyl 2-[4-(Methylsulfanyl)benzyl]acrylate (4n)

Acrylate 4n was prepared by the general procedure described above, from Meldrum’s acid derivative 3n (0.50 g, 1.78 mmol) and 6 (1.01 g, 5.35 mmol).

Yellow oil; yield: 0.46 g (98%); R f = 0.4 (petrol-CH2Cl2, 2:1).

IR (neat): 2978, 2934 (C=CH2), 1712 (C=O), 1137 (C-S) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.20 (d, J = 8.3 Hz, 2 H, CH Ar), 6.11 (d, J = 8.3 Hz, 2 H, CH Ar), 6.14 (d, J = 1.5, 0.75 Hz, 1 H, C=CH2), 5.38 (dd, J = 3.0, 1.5 Hz, 1 H, C=CH2), 3.53 (s, 2 H, CH 2), 2.46 (s, 3 H, SCH 3), 1.42 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 141.5, 135.8, 129.4, 126.9, 125.1, 80.6, 53.3, 37.6, 27.9, 16.1.

MS (EI/CI): m/z (%) = 282 (10) [M + NH4 +], 265 (80) [M + H+], 226 (50) [C11H12O2S + NH4 +].

HRMS (EI/CI): m/z [M + H+] calcd for C15H20O2S: 265.1257; found: 265.1255

tert -Butyl 2-(4-Methylbenzyl)acrylate (4o)

Acrylate 4o was prepared by the general procedure described above, from Meldrum’s acid derivative 3o (0.50 g, 2.01 mmol) and 6 (1.08 g, 6.04 mmol).

Colourless oil; yield: 0.38 g (82%); R f = 0.65 (petrol-CH2Cl2, 2:1).

IR (neat): 2971, 2964 (C=CH2), 1704.1 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.15-7.06 (m, 4 H, Ar), 6.13 (dd, J = 1.5, 0.75 Hz, 1 H, C=CH2), 5.36 (dd, J = 3.0, 1.5 Hz, 1 H, C=CH2), 3.56 (s, 2 H, CH 2), 2.33 (s, 3 H, CH 3), 1.45 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 166.2, 141.9, 135.9, 135.5, 128.9, 128.8, 124.9, 80.5, 37.6, 27.9, 20.9.

MS (EI/CI): m/z (%) = 250 (32) [M + NH4 +], 233 (8) [M + H+], 194 (60) [C11H16O2 + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C15H24O2N: 250.1807; found: 250.1802.

tert -Butyl 2-(2,6-Dimethylbenzyl)acrylate (4p)

Acrylate 4p was prepared by the general procedure described above, from Meldrum’s acid derivative 3p (0.50 g, 1.91 mmol) and 6 (1.06 g, 5.72 mmol).

Colourless oil; yield: 0.40 g (85%); R f = 0.5 (petrol-CH2Cl2, 3:1).

IR (neat): 2978, 2964 (C=CH2), 1708 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ =7.12-7.00 (m, 3 H, Ar), 6.02 (dd, J = 3.4, 1.9 Hz, 1 H, C=CH2), 4.85 (dd, J = 3.8, 1.9 Hz, 1 H, C=CH2), 3.59 (s, 2 H, CH 2), 2.33 (s, 6 H, CH 3), 1.56 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 166.5, 139.3, 137.0, 135.4, 127.9, 126.3, 123.0, 80.7, 31.1, 28.0, 19.7.

MS (EI/CI): m/z (%) = 264 (25) [M + NH4 +], 247 (5) [M + H+], 208 (70) [C12H14O2 + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C16H26O2N: 264.1958; found: 264.1959.

tert -Butyl 2-(1-Naphthylmethyl)acrylate (4q)

Acrylate 4q was prepared by the general procedure described above, from Meldrum’s acid derivative 3q (0.50 g, 1.76 mmol) and 6 (0.875 g, 4.73 mmol).

Orange oil; yield: 0.43 g (92%); R f = 0.55 (petrol-CH2Cl2, 3:1).

IR (neat): 2978 (C=CH2), 1711 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.96-7.89 (m, 1 H, CH Ar), 7.89-7.83 (m, 1 H, CH Ar), 7.77 (d, J = 8.3 Hz, 1 H, CH Ar), 7.53-7.44 (m, 2 H, CH Ar), 7.42 (d, J = 8.3 Hz, 1 H, CH Ar), 7.34 (d, J = 7.2 Hz, 1 H, CH Ar), 6.14 (dd, J = 2.6, 1.5 Hz, 1 H, C=CH2), 5.10 (dd, J = 3.0, 1.5 Hz, 1 H, C=CH2), 4.06 (s, 2 H, CH 2), 1.51 [s, 9 H, C(CH 3)3].

¹³C NMR (75.5 MHz, CDCl3): δ = 166.4, 140.9, 135.0, 133.8, 131.9, 129.1, 128.6, 127.3, 127.2, 125.8, 125.5, 125.4, 125.2, 124.2, 124.2, 80.8, 34.7, 28.0.

MS (EI/CI): m/z (%) = 286 (12) [M + NH4 +], 269 (3) [M + H+], 230 (75) [C14H12O2 + NH4 +].

HRMS (CI): m/z calcd for C18H21O2 [M + H+]: 269.1536; found: 269.1538.

tert -Butyl 4-Methyl-2-methylenepentanoate (4r)

Acrylate 4r was prepared by the general procedure described above from Meldrum’s acid derivative 3r (0.50 g, 1.91 mmol) and 6 (1.06 g, 5.72 mmol).

Colourless oil; yield: 0.348 g (98%); R f = 0.55 (petrol-CH2Cl2, 4:1).

IR (neat): 2959 (C=CH2), 1710 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 6.05 (d, J = 1.9 Hz, 1 H, C=CH2), 5.39 (dd, J = 1.9, 1.1 Hz, 1 H, C=CH2), 2.13 (dd, J = 6.8, 1.1 Hz, 2 H, CH 2), 1.77 [tsept, J = 6.8, 3.4 Hz, 1 H, CH(CH3)2], 1.48 [s, 9 H, C(CH 3)3], 0.88 [d, J = 6.4 Hz, 6 H, CH(CH 3)2].

¹³C NMR (75.5 MHz, CDCl3): δ = 167.2, 141.8, 125.0, 80.7, 41.8, 28.5, 27.8, 22.7.

MS (EI/CI): m/z (%) = 202 (45) [M + NH4 +], 184 (5) [M + H+], 146 (50) [C7H12O2 + NH4 +].

HRMS (CI): m/z [M + NH4 +] calcd for C11H24O2N: 202.1802; found: 202.1803.

Acknowledgment

We are grateful to the EPSRC and GlaxoSmithKline Limited (CASE­ award to S.D.P.) for funding. Dr Anneke Lubben (Mass Spectrometry Service at the University of Bath) and the EPSRC Mass Spectrometry Service at the University of Wales Swansea are thanked for valuable assistance.

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