Stereocontrolled Synthesis of (±)-Grandisol

Abstract

A synthetic approach to grandisol is described. The route to the cyclobutane core relies on an efficient intramolecular [2+2] cyclo­addition that establishes the required cis-ring fusion at the adjacent side chains of the cyclobutane ring. Using a new two-step lithium/halide homologation procedure, norgrandisol was efficiently converted into grandisol. This new approach enables the synthesis of grandisol in five steps from commercially available starting material in 22% overall yield.

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…”

“…The synthetic grandisol can be oxidized to the corresponding aldehyde (grandisal) and carboxylic acid (grandisoic acid), both previously described as pheromones of other insects. 233…”

“…The unnatural enantiomer was obtained in the same way starting from (−)-bornyl acetate. 237 One component of the sex pheromone of Anthonomus grandis, (+)-grandisol (240), was synthesized by Bartlett et al (2022) in six steps with an overall yield of 22%. 233 A photoinduced intramolecular [2 + 2] cycloaddition catalysed by copper(I) tri-ate was used as the key step to obtain the cis-congured cyclobutane scaffold (step c, Scheme 23).…”

“…237 One component of the sex pheromone of Anthonomus grandis, (+)-grandisol (240), was synthesized by Bartlett et al (2022) in six steps with an overall yield of 22%. 233 A photoinduced intramolecular [2 + 2] cycloaddition catalysed by copper(I) tri-ate was used as the key step to obtain the cis-congured cyclobutane scaffold (step c, Scheme 23). The synthetic grandisol can be oxidized to the corresponding aldehyde (grandisal) and carboxylic acid (grandisoic acid), both previously described as pheromones of other insects.…”

“…The synthetic grandisol can be oxidized to the corresponding aldehyde (grandisal) and carboxylic acid (grandisoic acid), both previously described as pheromones of other insects. 233 The sesquipiperitol (247) was identied as a minor component in the male-produced sex pheromone of Tibraca limbativentris, and stereoselective synthesis was reported by Lancaster 244,249 To determine the absolute conguration of the pheromone components, Khrimian et al (2020) started from a 4-substituted cyclohex-2-enone, and the key step was the rhodium-catalysed asymmetric 1,2addition of trimethylaluminum to the carbonyl group to furnish 1,10-bisaboladien-3-ol (zingiberenol) with dened congurations at C-6 and C-7 (step a, Scheme 24). Oxidative rearrangement of the tertiary allylic alcohol with pyridinium chlorochromate (PCC) (step b, Scheme 24) led to sesquipiperitone with the retention of the conguration at both stereogenic centers, which was further reduced with lithium aluminium hydride (LAH) to give the desired diastereomeric sesquipiperitols 247 (Scheme 24).…”