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DOI: 10.1055/s-0037-1611461
An Investigation of the Reactions between Azido Alcohols and Phosphoramidites
Our research work has been supported by NIH/NIGMS (1R01GM090270).Publication History
Received: 09 November 2018
Accepted after revision: 18 December 2018
Publication Date:
16 January 2019 (online)
Abstract
The reactions of several β-, γ-, and δ-azido alcohols with dibenzyl and dimethyl N,N-diisopropylphosphoramidites were examined. Detailed analysis of the intermediates and products formed from the reactions under different conditions provided useful information to gain insights into their mechanisms involving intramolecular Staudinger reaction, as well as the structure–reactivity relationships of both substrates. The reactions of γ- and δ-azido alcohols with dibenzyl N,N-diisopropylphosphoramidite could produce 6- and 7-membered cyclic phosphoramidates, thereby providing a new synthetic method for these biologically important molecules.
Key words
Staudinger reaction - azido alcohol - phosphoramidite - cyclic phosphoramidate - cyclizationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611461.
- Supporting Information
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References and Notes
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- 16 General Experimental Procedure for the Reactions Listed in Table 2 To the solution of an azido alcohol 5 or 7 (0.774 mmol in 8 mL of anhydrous toluene) were added 1.2 equiv of dibenzyl N,N-diisopropylphosphoramidite (4, 0.32 mL, 0.929 mmol) and then 1.2 equiv of tetrazole (1.98 mL 0.47 M solution in acetonitrile, 0.929 mmol). After the solution was heated at 80 °C with stirring for 2 h, it was diluted with dichloromethane, washed with 20 mL of 10% sodium bicarbonate solution and two 20 mL portions of brine water, dried with Na2SO4, and concentrated under vacuum. Silica gel column chromatography of the residue gave the desired product 13 or 14. 3-Benzyloxy-3-oxo-1,4,5-trihydrobenzo[7]-2,4,3-oxazaphosphepine (13) White solid, 60% yield. 1H NMR (300 MHz, CDCl3): δ = 7.48–7.12 (m, 9 H), 5.22–5.05 (m, 4 H), 4.27 (ddd, J = 17.2, 10.4, 8.0 Hz, 1 H), 3.92 (ddd, J = 28.3, 17.2, 5.6 Hz, 1 H), 3.48–3.36 (m, 1 H). FAB-HRMS: m/z calcd for C15H17NO3P [M + H]+: 290.0946; found: 290.0931. 2-Benzyloxy-2-oxo-5,5-dimethyl-1,3,2-oxazaphosphinane (14) White solid, 45% yield. 1H NMR (300 MHz, CDCl3): δ = 7.45–7.33 (m, 5 H), 5.04 (d, J = 10.0 Hz, 2 H), 3.98 (dd, J = 2.8, 14.0 Hz, 1 H), 3.84 (dd, J = 2.2, 11.2 Hz, 0.5 H), 3.73 (dd, J = 2.5, 11.4 Hz, 0.5 H), 3.26–3.10 (m, 1 H), 3.00 (dd, J = 4.6, 15.2 Hz, 1 H), 2.84 (ddd, J = 3.0, 7.0, 12.7 Hz, 0.5 H), 2.70 (ddd, J = 2.78, 7.5, 12.5 Hz, 0.5 H), 1.22 (s, 3 H), 0.79 (s, 3 H). FAB-HRMS: m/z calcd for C12H19NO3P [M + H+]: 256.1103; found 256.1105.
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