Synlett 2015; 26(03): 388-392
DOI: 10.1055/s-0034-1379601
letter
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Allyl Enol Carbonates for the Synthesis of Chiral Aldehydes Bearing All Carbon Quaternary Stereocenters via the Decarboxylative Asymmetric Allylic Alkylation (DAAA)

Eduardo Alberch
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N Cramer St, Milwaukee, WI 53211, USA   Fax: +1(920)2295530   Email: [email protected]
,
Colin Brook
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N Cramer St, Milwaukee, WI 53211, USA   Fax: +1(920)2295530   Email: [email protected]
,
Sharif A. Asad
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N Cramer St, Milwaukee, WI 53211, USA   Fax: +1(920)2295530   Email: [email protected]
,
Maria Shevyrev
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N Cramer St, Milwaukee, WI 53211, USA   Fax: +1(920)2295530   Email: [email protected]
,
Joseph S. Ulicki
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N Cramer St, Milwaukee, WI 53211, USA   Fax: +1(920)2295530   Email: [email protected]
,
M. Mahmun Hossain*
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N Cramer St, Milwaukee, WI 53211, USA   Fax: +1(920)2295530   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 08 August 2014

Accepted after revision: 23 October 2014

Publication Date:
07 January 2015 (online)


Abstract

A stereoselective synthesis of carbonates derived from 3-hydroxy-2-aryl acrylates was devised that can form the Z- or E-stereoisomer in very high Z/E ratios (50:1 and 1:99, respectively). The stereochemical outcome depends on the choice of base, addition of TMEDA and reaction temperature. The Z- and E-stereoisomers have different reactivities towards the DAAA reaction, with the E-stereoisomer displaying both greater reactivity and enantiodifferentiation with chiral ligands. The DAAA of E-stereoisomer analogues takes place in excellent yields ranging from 96–99% and enantioselectivities ranging from 42–78% ee.

Supporting Information

 
  • References and Notes


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  • 11 Procedure for the Synthesis of Allyl Enol Carbonate (E)-1: In a typical procedure, to a flask were added anhyd THF (7 mL) via syringe, followed by NaHMDS (1 M solution in THF; 1.73 mL, 1.73 mmol, 1 equiv) and TMEDA (0.26 mL, 1.73 mmol), both reagents being added at r.t. After the mixture was stirred for 5 min, 3-hydroxy-2-phenylacrylate (400 mg, 2.08 mmol) was dissolved in anhyd THF (2 mL) in a separate flask and was then transferred to the reaction flask containing the NaHMDS/ TMEDA mixture via syringe at r.t. The flask was rinsed with additional THF (1 mL) to aid in the quantitative transfer of the phenyl acrylate (total volume of THF in reaction flask 10 mL). The mixture was allowed to stir at r.t. for 20 min, at which point allylchloroformate (0.184 mL, 1.73 mmol) was added dropwise via syringe at r.t. The resulting solution was then allowed to stir at r.t. for 45 min. The reaction was monitored by taking a small aliquot (0.1 mL) via syringe from the reaction flask, passing it through a small silica plug (pasteur pipette was used for this purpose), concentrating the solvent under vacuum and taking a 1H NMR measurement. After this time, the reaction mixture was passed through a silica plug (4 cm diameter medium-porosity fritted funnel, 2 cm of silica). The silica plug was rinsed through with additional solvent (25 mL) to ensure quantitative elution of product. The solvent was then concentrated under reduced pressure at r.t. (carbonate may decarboxylate at higher temperatures) yielding carbonate (E)-1 as a yellow oil, the product being pure enough for synthetic purposes. 1H NMR (300 MHz, CDCl3): δ = 8.36 (s, 1 H), 7.40 (s, 5 H), 5.94 (ddt, J = 17.0, 10.1, 6.0 Hz, 1 H), 5.39 (dd, J = 17.3, 1.4 Hz, 1 H), 5.32 (d, J = 12.0 Hz, 1 H), 4.72 (dt, J = 6.1, 1.2 Hz, 2 H), 4.30 (q, J = 7.1 Hz, 2 H), 1.34 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 166.5, 151.9, 145.97, 131.3, 130.6, 130.1, 128.1, 128.1, 120.4, 118.8, 69.9, 61.3, 14.4. HRMS: m/z calcd for C15H16O5: 276.0998; [M + H]+ found: 277.1062.Procedure for the Synthesis of Allyl Enol Carbonate (Z)-1: To a dry flask was added anhyd THF (3 mL), via syringe and the flask was cooled to 0 °C. Next LiHMDS (1 M solution in toluene; 937 μL, 0.937 mmol) was added via syringe, followed by TMEDA (140 μL, 0.937 mmol). The reaction mixture was stirred for 5 min, after which 3-hydroxy-2-phenylacrylate (180 mg, 0.937 mmol) dissolved in THF (0.9 mL) was added dropwise via syringe to the reaction mixture at 0 °C. The resulting solution was stirred for 30 min, at which point allylchloroformate (100 μL, 0.937 mmol) was added dropwise via syringe. The resulting solution was allowed to stir for 1 h. After this time, the mixture was poured into a silica plug (4 cm diameter medium-porosity fritted funnel, 2 cm of silica). The silica plug was rinsed through with additional solvent (25 mL) to ensure quantitative elution of product. The solvent was then concentrated under reduced pressure at r.t. (carbonate may decarboxylate at higher temperatures) yielding carbonate (Z)-1 as a yellow oil, the product being pure enough for synthetic purposes. 1H NMR (300 MHz, CDCl3): δ = 7.52 (s, 1 H), 7.35 (s, 5 H), 5.90–6.03 (m, 1 H), 5.42 (dd, J = 17.3, 1.6 Hz, 1 H), 5.33 (dd, J = 10.5, 1.1 Hz, 1 H), 4.74 (dd, J = 5.9, 1.5 Hz, 2 H), 4.33 (q, J = 7.1 Hz, 2 H), 1.33 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 165.4, 152.0, 140.1, 133.2, 130.8, 128.6, 128.6, 128.2, 127.8, 120.4, 119.83, 69.6, 61.26, 14.2.
  • 12 General Procedure for the DAAA Reaction of Allyl Enol Carbonates: To a dry flask was added Pd2(dba)3·CHCl3 (4.7 mg, 0.0045 mmol) followed by (R,R)-ANDEN-phenyl Trost ligand (8.8 mg, 0.0108 mmol). To the flask was added a mixture of anhyd and degassed hexane–toluene (6 mL, 2:1) at r.t. and the mixture was allowed to stir for 30 min. After several minutes of stirring, the mixture turned into a bright yellow color (occasionally a slight pink hue was observable) with a small amount of beige precipitate. The resulting mixture was cooled to –20 °C and was transferred via cannula to a separate flask containing (E)-2-(ethoxycarbonyl)-2-phenylvinyl allyl carbonate (50.0 mg, 0.18 mmol) dissolved in hexane–toluene (1 mL, 2:1) which was already cooled to –20 °C. The reaction mixture was allowed to stir at this temperature for 24 h, after which time the mixture was observed a cloudy yellow/green solution. The completion of reaction was monitored by TLC. After the reaction was complete, the solution was passed through a silica plug (1 cm fritted funnel, 2 cm silica, medium porosity filter) which was washed through with CH2Cl2 (25 mL). The solvent was concentrated under vacuum to yield ethyl 2-formyl-2-phenylpent-4-enoate as a yellow oil. 1H NMR (300 MHz, CDCl3): δ = 9.95 (s, 1 H), 7.23–7.44 (m, 5 H), 5.76 (m, 1 H), 5.13 (d, J = 18 Hz, 1 H), 5.07 (d, J = 9.9 Hz, 1 H), 4.28 (q, J = 7.1 Hz, 2 H), 3.14 (dd, J = 6.3, 13.8 Hz, 1 H), 2.88 (dd, J = 8.1, 13.8 Hz, 1 H), 1.25 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 196.3, 170.6, 135.0, 132.6, 129.0, 128.5, 127.8, 119.1, 65.6, 61.6, 37.5, 14.0. HRMS: m/z [M + H] calcd for C14H16O3: 233.1177; found: 233.1000.
  • 13 McDougal NT, Virgil SC, Stoltz BM. Synlett 2010; 1712