Ring‐Closing Strategy Utilizing Nitrile α‐Anions: Chiral Synthesis of (+)‐Norchrysanthemic Acid and Expeditious Asymmetric Total Synthesis of (+)‐Grandisol

Abstract

Chiral syntheses of two distinct small cycloalkanes, (1R,3R)‐(1Z)‐norchrysanthemic acid and (+)‐grandisol, were performed by characteristic ring‐closing methodologies using carbanions at the α‐position of nitriles (nitrile α‐anions). (i) (1R,3R)‐(1Z)‐Norchrysanthemic acid, a highly potent ingredient of synthetic pyrethroid containing a cyclopropane structure, was synthesized from readily available (S)‐epoxide derived from 3‐methyl‐but‐2‐en‐1‐ol in 7 steps in 23 % overall yield and with > 98 % ee. This sequence involves a trans‐selective cyclopropane formation using the nitrile α‐anion of (S)‐3‐mesyloxynitrile as the key step. The present chiral synthesis was performed with effective stereocontrol of both the chirality in the 1,3‐positions on the cyclopropane and the Z‐geometry of the propenyl group. (ii) (+)‐Grandisol, an insect sex pheromone possessing a characteristic cyclobutane structure, was synthesized from commercially available cyclopropyl methyl ketone (route A) or from commercially available 3‐cyanopropylzinc bromide and 1‐bromo‐1‐methylpropene (route B) in 10 or 8 steps in 6 % or 8 % overall yield and with 80 % ee. This sequence involves a Shi asymmetric epoxidation of a trisubstituted olefin and a straightforward Stork‐type asymmetric cyclobutane formation with clean SN2 stereoinversion using the nitrile α‐anion of the chiral epoxynitrile. The present expedient method is the second asymmetric total synthesis starting from achiral compounds.

Synthesis and Stereostructure-Activity Relationship of Novel Pyrethroids Possessing Two Asymmetric Centers on a Cyclopropane Ring

“…It is noteworthy that clean S N 2 reactions using tosylates (4 R )- 3 and (4 S )- 3 proceeded smoothly to produce four key cyclopropane carbonitrile nitrile precursors, (1 R ,2 S )- 4 , (1 S ,2 S )- 4 , (1 S ,2 R )- 4 , and (1 R ,2 R )- 4 , with excellent optical purities (all 98% ee, as determined by HPLC analysis). Related chirality-induced cyclopropane-forming reactions have been addressed in previous reports, namely a representative review [18], syntheses of liquid crystals [16], and syntheses of dihydroxy vitamin D 3 analogues [19], petrosterol [20], chiral cyclobutanes [21], bicifadin [22], norchrysanthemic acid [23], and grandisol [23].…”

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…”

Cyclopropanation of Propargyl Sulfonium Salts: Highly Diastereoselective Synthesis of Alkynylcyclopropanes

“…Alkyne-substituted cyclopropanes are prominent structural motifs in many natural products, biologically active molecules, and pharmaceuticals. − Meanwhile, the highly strained three-membered rings can also serve as versatile reactants in organic synthesis attributed to their high reactivity (Scheme c). − Over the past decades, several strategies for the preparation of alkynyl cyclopropane have been reported, such as the cyclopropanation of alkynyl carbenoids − or 1,3-enynes, − hydroalkynylation, − and some isolated examples. − However, there are few reports on the synthesis of alkynylcyclopropanes with three contiguous stereocenters. Thus, new synthetic approaches for the efficient construction of polysubstituted alkynylcyclopropanes from easily accessible materials in a highly diastereoselective manner would be instructive to make diverse molecules rapidly and easily.…”