Silver salts and DBU cooperatively catalyzed domino reaction of propargylic alcohols with trifluoromethyl ketones: direct method to trifluoromethyl‐substituted 5‐alkylidene‐1,3‐dioxolane derivatives

Abstract

A general and efficient synthesis of trifluoromethyl-substituted 5-alkylidene-1,3-dioxolanes using AgNO 3 and DBU cooperatively catalyzed domino reaction of propargylic alcohols and trifluoromethyl ketones is described. The reaction tolerates a broad range of functional groups, and the desired products are obtained in good to excellent yields (62-99%) with acceptable diastereoselectivities. a Reaction conditions: 1 (0.3 mmol), 2 (0.36 mmol), AgNO 3 (10 mol%), DBU (10 mol%), toluene (1.0 ml), r.t., 24 h. b Isolated yield. c Determined using 19 F NMR.

Reactivity of 2-Nitropyrrole Systems: Development of Improved Synthetic Approaches to Nitropyrrole Natural Products

“…Alternatively, treatment of propargylic alcohol 19 with trifluoroacetophenone in the presence of silver nitrate and DBU successfully afforded ketal 41 as a mixture of two diastereomers (d.r. 1:1) in 85% yield . However, the subsequent hydrolysis of ketal 41 turned out to be challenging; even strong acid such as aqueous HCl (1M) in THF was not able to hydrolyze the ketal at room temperature, and use of elevated temperatures only led to decomposition.…”

“…7,13 As expected based on our cross-coupling study, Sonogashira coupling of 4-iodo-2-nitropyrrole 33b and terminal alkyne 18 13 successfully afforded propargylic alcohol 19 in 90% yield (Scheme 7). As the regioselective hydration of internal propargylic alcohols has been reported to be a challenging task, 14 three strategies were devised for parallel investigation to effect the desired conversion of 19 into 39: (1) introduction of a neighboring acetate group (e.g., 40) to assist regioselective hydration, 15 (2) ketone assisted indirect hydration via a ketal intermediate (e.g., 41), 16 and (3) CO 2 -promoted direct or indirect hydration via a cyclic carbonate intermediate (e.g., 42). 17 Accordingly, alcohol 19 was initially converted into the corresponding acetate 40 in 75% yield, with expectation that the neighboring acetate group would assist the desired regioselective alkyne hydration (Scheme 7).…”

“…1:1) in 85% yield. 16 However, the subsequent hydrolysis of ketal 41 turned out to be challenging; even strong acid such as aqueous HCl (1M) in THF was not able to hydrolyze the ketal at room temperature, and use of elevated temperatures only led to decomposition.…”

Highly Diastereoselective Synthesis of Syn‐1,3‐Dihydroxyketone Motifs from Propargylic Alcohols via Spiroepoxide Intermediates

“…Ar ecent report from Li and Zhao demonstrated the possibility of propargylic alcohol cyclisation with concomitant incorporation of as uitably reactive aryl trifluoromethyl ketone (Scheme 2C). [9] In seeking to apply this latter approach to dihydroxyketone synthesis,w ec onsidered that aketone candidate would ideally be 1) symmetrical, to avoid introducing an additional chiral centre,2 )compatible with epoxidation, and 3) economical and readily available.O ur studies commenced with ketones K1-5,u sing 4a as am odel substrate (Table 1). K1, K2,a nd K3 proved unsuitable;b oth K1 and K2 gave no conversion (Entries 1, 2), while K3 afforded the undesired trichloroacetate derivative (Entry 3).…”

Highly Diastereoselective Synthesis of Syn‐1,3‐Dihydroxyketone Motifs from Propargylic Alcohols via Spiroepoxide Intermediates

“…[9] In seeking to apply this latter approach to dihydroxyketone synthesis,w ec onsidered that aketone candidate would ideally be 1) symmetrical, to avoid introducing an additional chiral centre,2 )compatible with epoxidation, and 3) economical and readily available.O ur studies commenced with ketones K1-5,u sing 4a as am odel substrate (Table 1). [9] In seeking to apply this latter approach to dihydroxyketone synthesis,w ec onsidered that aketone candidate would ideally be 1) symmetrical, to avoid introducing an additional chiral centre,2 )compatible with epoxidation, and 3) economical and readily available.O ur studies commenced with ketones K1-5,u sing 4a as am odel substrate (Table 1).…”