The Versatility of α-Chloropropargyl Phenyl Sulfide Affords High Stereo- and Regioselectivities in Indium-Promoted Coupling Reactions under Mild Conditions

Abstract

Coupling reactions between alpha-chloropropargyl phenyl sulfide (11) and a series of aldehydes under aqueous conditions are reported. Not only is good stereoselectivity observed between syn and anti isomeric products, but excellent regioselectivity is also witnessed. In reactions using indium metal as a promoter, the propargyl functionality (12) is retained, unlike the use of more traditional metals that result in formation of products containing a mixture of both propargyl (12) and allene (13) moieties. The reaction is postulated to proceed via either a chelated or nonchelated route, controlled by the presence or absence of indium (III) chloride, and may be used to create synthetically useful building blocks. The formation of epoxyalkyne (14) molecules, which are found in many natural products and have wide use as synthetic templates, is presented as one example.

The Barbier–Grignard-type arylation of aldehydes using unactivated aryl iodides in water

“…The experimental procedures may be simplified since isolation of organic products and recycling of water-soluble catalysts and other reagents can be made by simple phase separation. However, while the allylation [26][27][28] , propargylation [29][30][31] , benzylation 32 , alkynylation 33 and alkylation 34 of carbonyl compounds, along with the aldol-type reaction 35 , have been successful with various metals in water, a direct Barbier-Grignard-type carbonyl arylation with unactivated aryl halide in water has yet to be developed. This is largely due to the fact that a highly active metal is required to break a non-activated C(sp 2 )-halogen bond (as well as to react with the carbonyl once the organometallic intermediate is formed).…”

Product Class 6: Oxonium Salts

“…[117] The selenonium ion is also used as a selanylating reagent [118] and the known selenopyranium ion condenses with carbonyls. [119] Scheme 9 Preparation of an Epoxide [102] 65−75% 2-Hydroxy 5-Oxo Esters 14; General Procedure: [117] To a stirred mixture of the selenide 13 (0.2 mmol) and CH 2 Cl 2 (5 mL) at rt was added Me 3 OBF 4 (0.4 mmol) under N 2 . After 2 h, the CH 2 Cl 2 was removed under reduced pressure.…”

“…[100,101] For example, epoxides 12 may be obtained by treatment of sulfides 11 with an oxonium salt (Scheme 9). [102][103][104] Aryl sulfides have also been used in palladium cross-coupling reactions. [105] Vinyl sulfides have been used as masked carbonyl compounds.…”

“…[105] Vinyl sulfides have been used as masked carbonyl compounds. [106] 2-Ethynyl-3-phenyloxirane (12, R 1 = Ph); Typical Procedure: [102] To a stirred mixture of the hydroxy sulfide 11 (100 mg, 0.394 mmol) in CH 2 Cl 2 (8 mL) was added Me 3 OBF 4 (66 mg, 0.435 mmol). The mixture was kept at rt for 8 h, before a soln of 7% aq NaOH (5 mL) was added, and the resulting mixture was stirred for 20 min.…”

Synthesis of Organochalcogen Compounds using Non-Conventional Reaction Media

“…Mitzel and co‐workers described the indium‐promoted coupling reaction between ( R )‐chloropropargyl phenyl sulfide 146 and a series of aldehydes 24 using water as the solvent. Good regioselectivity and excellent syn / anti stereoselectivity were observed in the obtained β ‐hydroxy sulfides 147 .…”