Diethyl 3-iodopropynylphosphonate: an alkylative .beta.-keto phosphonate equivalent

Abstract

CH2C12 (4 mL) was cooled to -78 °C, and DMSO (0.30 mL, 4.4 mmol) in CH2C12 (1 mL) was added slowly. The mixture was stirred at -78 °C for 2 min, and a solution of the alcohol (0.53 g, 1.8 mmol) in CH2C12 (5 mL) was added rapidly. The resulting mixture was stirred at -78 °C for 30 min, and triethylamine (1.4 mL, 1.0 g 10 mmol) was added. The mixture was stirred at -78 °C for 5 min and brought to 20 °C. Water (10 mL) was added, and the aqueous phase was extracted with CH2C12 (10 mL). The organic phases were dried (Na2S04) and concentrated to give 0.64 g of an oil, which was purified by flash chromatography23 (CH2C12, 10% EtOAc) to afford 0.47 g (89%) of 10: mp 102-103 °C; IR (CHC13 cast) 1775 cm"1;

Dialkyl 1-Alkynylphosphonates: a Range of Promising Reagents

“…The procedure for the hydration of 1-alkynylphosphonates 3 has remained unchanged since the first report in 1966 (Scheme 19). [32] Thus, treatment of diethyl 1-alkynylphosphonates 13 with aqueous H 2 SO 4 in MeOH in the presence of HgSO 4 gives, after reflux for 15 h [32] or at room temperature for 48 h, [60,91] a quantitative yield of pure diethyl 2-oxoalkylphosphonates 23. In all cases studied, the acetylenic phosphonates are transformed without formation of the isomeric ketophosphonates.…”

“…3-Hydroxypropynylphosphonate intermediates, readily obtained from the reaction of lithiated derivatives of protected propargyl alcohol with chlorophosphate (section B. 2), were converted into mesylates, and then either into iodides 57 by displacement with sodium iodide, [60] or bromides by use of Ph 3 P/ CBr 4 in CH 2 Cl 2 . [125] Subsequent treatment of the diethyl 3-iodopropynylphosphonate 57 with ketone enolates (formed using KHMDS/triethylborane in THF) gives the corresponding alkylation products 58, which were then hydrolyzed to the expected β-ketophosphonates 59 (Scheme 24).…”

Palladium(II)‐Catalyzed Hydration of Alkynylphosphonates to β‐Ketophosphonates

“…[14] However, the procedure for the hydration of alk-A C H T U N G T R E N N U N G ynylphosphonates has remained unchanged since the first report in 1966, [10,15] the potential of which in organic synthesis and/or in industrial processes has not been conveniently exploited. The reason for that is the catalysts known to date, HgSO 4 , [15,16] HgCl 2 , [17] and HgO·BF 3 [18] , are highly toxic mercury salts that, in addition, must be used in combination with either acids or bases in a longer reaction time. Obviously, these methodologies suffer from relatively strict reaction conditions, requiring highly toxic mercury reagents, poor substrate scope or unsatisfactory yield.…”

“…Although FeCl 3 was found to be very effective in the hydration of terminal alkynes to corresponding methyl ketones, [24] it was not active in the hydration of alkynylphosphonates and gave no product (entry 2). HAuCl 4 , NaAuCl 4 and PtCl 2 afforded the desired product in 10%, 1% and 53% yields, respectively (entries [9][10][11] [15][16][17]. The hydration proceeded slowly at room temperature (entry 17), however, the yield of product 2a increased greatly when the temperature was raised to 50 8C (entry 16) and the catalytic reaction could be achieved quickly within 2 h and afforded the corresponding product 2a in a quantitative yield when the temperature was raised to 80 8C.…”

“…It is noteworthy that when the highly functionalized alk-A C H T U N G T R E N N U N G ynylphosphonate 1o, a nucleotide analogue prepared from unique biologically activity ribonucleoside, [26] was used as the substrate (entry 15), a water molecule could easily be selectively added to the triple bond of 1o, clearly demonstrating the great potential of this new methodology to allow access to highly functionalized targets. Various phenyl alkynylphosphinates with isopropoxy (1p and 1q), ethoxy (1r) and n-butoxy groups (1s) were investigated; the respective products (2p-2s) were obtained in high yield (93-95%, entries [16][17][18][19]. Diphenyl phenylethynylphosphine oxide 1t could also be used as the substrate to give the desired product in 95% yield (entry 20).…”