Stereoselective anti-SN2′-Substitutions of Secondary Alkylcopper-Zinc Reagents with Allylic Epoxides: Total Synthesis of (3S,6R,7S)-Zingiberenol

Abstract

Chiral secondary mixed alkylcopper-zinc reagents were prepared from the corresponding alkyl iodides and reacted with allylic epoxides via an anti-SN2′-substitution and retention of configuration of the chiral alkylorganometallic, leading to chiral allylic alcohols. This method was used in a total synthesis of the natural product (3S,6R,7S)-zingiberenol in 8 steps and 9.7% overall yield [dr (3S,6R) = 99:1; dr (6R,7S) = 81:19] starting from commercially available 3-methyl-2-cyclohexenone.

Recent advances in the synthesis of insect pheromones: an overview from 2013 to 2022

“…During this period, the synthesized isoprenoid pheromones were identified from Necrodes surinamensis (Col., Silphidae): 220 , Maconellicoccus hirsutus (Hem., Pseudococcidae): 221 , Anthonomus rubi (Col., Curculionidae) and Planococcus ficus (Hem., Pseudococcidae): 222 , 210,211 Thrips palmi (Thy., Thripidae): 223 , 212 Planococcus kraunhiae (Hem., Pseudococcidae): 224 , 213 Dysmicoccus neobrevipes (Hem., Pseudococcidae): 225 , 214 Leptinotarsa decemlineata (Col., Chrysomelidae): 226 , 215–220 Lasius meridionalis (Hym., Formicidae): 227 , 221,222 Ips confuses (Col., Curculionidae): 228 and 229 , 223 Urolepis rufipes (Hym., Pteromalidae): 230 , 224 Solenopsis invicta (Hym., Formicidae): 231 , 225 Solenopsis invicta (Hym., Formicidae): 231 and 232 ; 226 Astyleiopus variegatus (Col., Cerambycidae): 233 and 234 , 227 Amblypelta lutescens (Hem., Coreidae): 235 , 228 Monomorium pharaonis (Hym., Formicidae): 236 and 237 , 222 Aonidiella aurantia (Hem., Diaspididae): 238 229 Pseudococcus calceolariae (Hem., Pseudococcidae): 239 , 230 Anthonomus grandis (Col., Curculionidae): 240 , 231–233 Aspidiotus nerii (Hem., Diaspididae): 241 , 234 Pseudococcus longispinus (Hem., Pseudococcidae): 242 , 235–237 Dysmicoccus brevipes (Hem., Pseudococcidae): 243 , 238,239 Nipaecoccus viridis (Hem., Pseudococcidae): 244 , 240,241 Pseudococcus baliteus (Hem., Pseudococcidae): 245 , 242 Dolichovespula maculate (Hym., Vespidae): 246 , 243 Tibraca limbativentris (Hem., Pentatomidae): 247 , 244 Oebalus poecilus (Hem., Pentatomidae): 248 , 245 Murgantia histrionica and Halyomorpha halys (Hem., Pentatomidae): 249 , 245,246 Anoplophora malasiaca (Col., Cerambycidae): 250–252…”

Regio- and diastereoselective reactions of chiral secondary alkylcopper reagents with propargylic phosphates: preparation of chiral allenes

“…Recently, we reported a zinc-mediated anti-S N 2 0 -substitution reaction of alkylcopper reagents of type 1 with allylic substrates (2) leading to chiral alkenes of type 3 with excellent regioselectivity and high retention of conguration (see Scheme 1(b and c)). 6,7 These organocopper reagents were prepared from the corresponding alkyl iodide 4 via I/Li-exchange reaction leading to alkyllithium reagent 5. Subsequent transmetalation with CuBr$P(OEt) 3 afforded alkylcopper reagent 1.…”

“…6 Furthermore, we reported anti-S N 2 0 -substitutions of secondary alkylcopper-zinc reagents with allylic epoxides 2c leading to chiral allylic alcohols of type 3c (g : a > 95 : 5; (c)). 7 This method was used in the total synthesis of the natural product (3S,6R,7S)-zingiberenol. 7 Scheme 1 Stereoretentive preparation of chiral secondary alkylcopper reagents 1: (a-c): subsequent S N 2-and zinc-mediated anti-S N 2 0substitution reactions with allylic substrates.…”

“…7 This method was used in the total synthesis of the natural product (3S,6R,7S)-zingiberenol. 7 Scheme 1 Stereoretentive preparation of chiral secondary alkylcopper reagents 1: (a-c): subsequent S N 2-and zinc-mediated anti-S N 2 0substitution reactions with allylic substrates. (d): Anti-S N 2 0 -substitution with chiral propargylic phosphates leading to axially chiral allenes.…”