General and Highly α-Regioselective Zinc-Mediated Prenylation of Aldehydes and Ketones

Abstract

A simple, efficient, and general α-prenylation approach for the synthesis of a variety of α-prenylated alcohols has been successfully developed. A wide range of α-prenylated alcohol derivatives could be obtained in good yields by highly α-regioselective zinc-mediated prenylation of various aldehydes and ketones with prenyl bromide at 120 °C in HMPA. By simply altering the reaciton solvent and temperature, the method allows the achievement of a highly notable opposite regiocontrol, providing the expected regiochemical product. The method provides a convenient route for the direct α-prenylation of carbonyl compounds in a highly α-regioselective manner using a cheap and convenient mediator. Two possible pathways are proposed to account for the formation of these synthetically difficult-to-obtain molecules.

Synthesis, Absolute Configurations, and Biological Activities of Floral Scent Compounds from Night-Blooming Araceae

“…Eventually, satisfactory yields of alcohol 18 were obtained by the addition of prenylzinc bromide to aldehyde 16 . This method, used for the synthesis of rosiridol by Hong et al and then further developed by Zhao et al, , involves the primary formation of the γ-addition product 17 followed by an in situ rearrangement to the thermodynamically more stable α-isomer induced by heating in polar-aprotic solvents such as HMPA or DMPU. From alcohol 18 , the racemic target compound rac - 6 was uneventfully obtained by acetylation with acetic anhydride.…”

“…NaCl and dried over MgSO 4 . The solvent was removed under reduced pressure, and the crude product was purified by column chromatography on silica (pentane/diethyl ether 10:1) to yield cyclopentanone 12 as a yellowish oil (14.5 (22), 319 (12), 253 (55), 251 (30), 163 (100), 157 (28), 155 (17), 145 (16), 135 (32), 121 (26), 119 (37), 96 (50), 91 (36), 79 (29), 77 (36), 69 (22), 67 (13), 55 (18), 41 (28); IR (ATR, neat): ν∼ [cm −1 ] = 3060 (w), 2962 (m), 2870 (w), 1736 (s), 1576 (m), 1470 (m), 1439 (m), 1266 (w), 1149 (m), 1066 (m), 1021 (m), 910 (m), 805 (m), 733 (s), 687 (s).…”

Protecting‐Group‐Free Synthesis of 3‐Amino‐3‐α‐prenyl‐oxindoles through the Direct Prenylation of Isatin‐Derived Imines

“…The representative results are summarized in Table . Taking in account that in previous works the use of polar aprotic solvents such as hexamethylphosphoramide (HMPA) or 1,3‐dimethyl‐2‐imidazolidinone (DMI) has proven to be crucial to conduct α‐regioselective prenylation,[12a], [12b] the reaction was performed with prenylzinc at 120 °C for 12 h in DMI initially. As expected, α‐product 2a was formed as a major product in 64 % yield (entry 1).…”

“…Following our interest in the regioselective prenylation and its application and the synthesis of oxindole derivatives, herein we report a facile and general zinc‐mediated method for the α‐prenylation of isatin‐derived imines in a sealed tube to afford 3‐amino‐3‐prenyl‐2‐oxindoles in good to excellent yields. This protocol uses cheap and safe zinc as the mediator and readily available prenyl bromide as the prenyl source; it features high regioselectivity, efficiency, and high yield.…”

Synthesis and antibacterial activity of a series novel 5,7-diisoprenyloxyflavone derivatives

“…Apigenin (5,7,4´-trihydroxyflavonoid; Figure 1), a bioflavonoid widely found in citrus fruits, has been found to exert a variety of pharmacological effects, Page 2 / 10 including antibacterial, anticancer, and antiproliferative effects (Banerjee et al, 2015;Liu et al, 2013;Eumkeb, Chukrathok, 2013;Choi et al, 2010;Turktekin et al, 2011;Ruivo et al, 2015). The prenyl moiety is widely found in many drugs and natural products (Zhao et al, 2011;Winans et al, 1999). Prenylation has been reported to produce flavonoids with enhanced antibacterial, antioxidant, anti-inflammatory, larvicidal, cytotoxicity, and estrogenic activities (Rao et al, 2009;Vogel et al, 2008;Vogel et al, 2010).…”