76739-64-5

Upstream product

• 127-09-3 sodium acetate 
• 82343-68-8 (butene-3-yl)-1 oxo-2 cyclopentanecarboxylate de methyle 
• 77346-96-4 3,3,6-Trimethyl-2,3-dihydro-4H-3a,6a-propano-pentalen-1-one 
• 77346-98-6 C₁₅H₂₂O 
• 77346-99-7 (1S,3aS,6aR)-1,9,9-Trimethyl-7-methylene-dihydro-3a,6a-propano-pentalen-2-one 
• 82054-18-0 3,3-Dimethyl-3a-(4-trimethylsilanyl-but-3-ynyl)-hexahydro-pentalen-1-one 
• 849180-11-6 2-(1-but-3-enyl-2-methylene-cyclopentyl)-pent-4-yn-2-ol 
• 83043-52-1 (3aS,4S,6aR)-1,1,3,4-Tetramethyl-1H,4H-3a,6a-propano-pentalene 

Relevant academic research and scientific papers

A Total Synthesis of (+/-)-Modhephene

A new approach to the propellane system via a key photochemical oxa-di-?-methane rearrangement has culminated in a synthesis of the sesquiterpene hydrocarbon (+/-)-modhephene (1).

A facile tandem radical cyclization route to propellanes and its application to a total synthesis of modhephene

A facile and versatile tandem radical cyclization route to propellanes from dieneyne compounds was developed and was applied to the total synthesis of modhephene.

APPLICATION OF THE α-ALKYNONE CYCLIZATION : SYNTHESIS OF rac-MODHEPHENE

Using the thermal α-alkynone cyclization 89 as the key step, modhephene 1, a sesquiterpene with a -propellane skeleton was synthesized.

Total Synthesis of Modhephene

A new approach to the natural propellane modhephene is described.Critical to the success of this synthesis was a dianion-mediated cyclopentannulation procedure, a heteroatom-assisted stereoselective hydrogenation, a regioselective lactonization, and a dimethylation of a carbonyl.

Synthesis of the naturally occurring [3.3.3]propellane (±)-modhephene featuring a photocycloaddition-reductive fragmentation diquinane construction

Modhephene has been synthesized in 11 steps and 21% overall yield from cyclopentadiene, by a stereoselective route that features a photocycloaddition-fragmentation sequence for the construction of the diquinane core.

Application of the α-Alynone Cyclization: Synthesis of rac-Modhephene

rac-Modephene 1, the first sesquiterpene with a propellane C-skeleton and its epimer rac-epi-modhephene 27, were synthesized starting from bicyclooct-1(5)-en-2-one (2).The key step of the construction of the -propellane system is an application of the α-alkynone cyclization, namely 3 ->4 and 11 ->14.The preferred formation of the propellanes 4 and 14 in this step shows that the insertion of the postulated alkylidene carbene intermediate into tertiary C,H-bonds outweighs the one into the secondary ring-C,H bonds leading to 12/13 and 15/16, respectively.The two starting materials for the α-alkynone cyclization, 3 and 11, were prepared from 2 by the reaction shown in the Scheme 3.The further elaboration and separation of the cyclization product 4 and 14 to rac-modhephene 1 and its epimer 27 are outlined in the Scheme 5.

HIGHLY STEREOCONTROLLED SYNTHESIS OF PROPELLANE SESQUITERPENES. (+/-)-MODHEPHENE AND (+/-)-EPIMODEPHENE

Stereospecific total synthesis of (+/-)-modhephene (2) and (+/-)-epimodhephene are reported.Conjugate addition of 1-trimethylsilyl-1-butyn-4-yl cuprate (BF3-etherate catalysis) to bicyclic ketone 6, fluoride ion-promoted deblocking of the terminal acetylene, and ene reaction, gave tricyclic enone 11.Sequential Wittig methylenation, regiocontrolled epoxidation, and Lewis acid catalyzed isomerization afforded ketone 14 whose double bond relocation and Wolff-Kishner reduction led exclusively to 2.In a still shorter route to 3,3-butelyl cuprate addition to 6 was utilized to gain access to 7.Thermolysis of this intermediate, methylenation, and double bond isomerization were found to deliver pure 3 successfully.

Carbocationic rearrangements of silphinane derivatives

Solvolysis of silphin-α and -1β-yl mesylates (18α-OMs and 18β-OMs) gave rise to mixtures of silphinene (4), bridgehead alcohol 22-OH (or its acetate), and α-terrecyclene (5) accompanied by trace amounts of isocomene (1) and modhephene (2). The 103 higher solvolysis rate determined for 18α- OMs over its epimer signifies a concerted rearrangement to a more stable tertiary bridgehead carbocation (36) which undergoes a second rearrangement and elimination to α-terrecyclene (5) (see Scheme 5 in the paper). Isocomene and modhephene presumably arise from a minor competing pathway resulting from 7→1 hydride shift to the silphin-7-yl ion (38 ≡ 11) which partitions between methyl and cyclopentane ring rearrangements. Acetolysis of secosilphinyl nosylate 21 (X = ONs) is accompanied by π participation leading directly to 38 and from there to a 2:1 mixture (6%) of isocomene and modhephene. TiCl4-mediated heterolysis of silphin-1α-yl trifluoroacetate (18α-O2-CCF3) initiates a complex rearrangement pathway to 3-chloro- 1,4,4,11-tetramethyltricyclo[5.3.1.033,8]-undecane (24). α-Terrecyclene (5) was converted to various oxygenated terrecyclane derivatives by dihydroxylation, hydroboration, and epoxidation (see Scheme 3 in the paper) and to its exocyclic isomer β-terrecyclene (34, see Scheme 4 in the paper). The observed rearrangements of the silphinyl mesylates (see Scheme 5 in the paper) afford chemical precedent for a biogenetic pathway that links terrecyclanes (e.g. quadrone), isocomene, and modhephene to the silphinane family of cyclopentanoid sesquiterpenes formally derivable from caryophyllene (see Scheme 1 in the paper).

Synthesis of tricyclopentanoid sesquiterpenes via rearrangement routes: (±)-modhephene, (±)-epimodhephene and (±)-isocomene

Based on model studies with dispiroundecane 10, dispiroundecane 1 has been synthesized and rearranged to (±)-modhephene 6 and (±)-isocomene 7. The epimeric dispiroundecane 9 yields (±)-epimodhephene 12. A total of thirteen rearrangement products (6, 7, 12, 37, 38, 39, 42, 44, 55, 57, 64, 67) have been isolated from 1 and/or 9, including six unnatural triquinanes. Two of these (55, 57) are formed by unusual 1,3- and 1,4-shifts, respectively. A mechanistic rationale on the basis of force field calculations is given.

α-Carbonyl Radicals for Total Synthesis of Natural Products

Intramolecular cyclization of α-carbonyl radicals to the trimethylsilylacetylenic side chain gives bicyclic vinylsilane ketones and enones.Application of the cyclization to total synthesis of (+/-)-modhephene is described.