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Approaches to the synthesis of d,1-alnusenone via non-enzymic, biogenetic-like polyolefin cyclizations


Trust, Ronald Irving (1974) Approaches to the synthesis of d,1-alnusenone via non-enzymic, biogenetic-like polyolefin cyclizations. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/BD4H-E898.


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Several 4-methyl-4-polyalkenyl-2-cyclohexenols were synthesized in the hope that their acid-promoted cyclizations would yield polycyclic compounds in which the first two ring junctures formed would have a cis,anti,trans backbone, a procedure which is well precedented in the literature. Compounds of this stereochemistry bear a structural relationship to the pentacyclic triterpenes alnusenone and friedelin, thus offering a possible route to these and other triterpenoid compounds. Consequently, the model compounds 58 and 82 were synthesized. Their cyclizations in formic acid yielded complex mixtures of products with varying degrees of cyclization. Using stannic chloride as cation initiator in dichloromethane, these two alcohols cyclized to afford good yields of tricyclic products with high degrees of stereoselectivity. The structure of the tricyclic olefin 68, formed in 32% yield from alcohol 58, is believed to be that shown based on fact that the first three centers formed must be in a cis,anti relationship in order for cyclization to occur, and that the fourth center is trans to the third by previous analogies and by spectral data. Absolute confirmation of the structure is pending the results of an x-ray analysis. The structures of the olefins 109 and 110, formed in 62% yield from the alcohol 82, were confirmed by alternate synthesis of their hydrogenation product. Based on the results of these model studies, alcohol 51 was synthesized, and its cyclization was studied in hopes of obtaining the pentacyclic olefin 50. A compound with spectroscopic data consistant with the structure of 50 was isolated on brief treatment with stannic chloride in dichioromethane. Unfortunately, the yield was only 12%. In order to establish the structure of the pentacyclic olefin as 50, a sequence of reactions was devised to transform the olefin into the pentacyclic ether D-6. The required two carbon atoms were introduced via an eight-step sequence, affording the pentacyclic aldehyde 191 in 6.5% yield from olefin 50. Attempts to deoxygenate the carbonyl oxygen were unsuccessful. The structure of the olefin is believed to be 50 on the basis of its nmr spectrum, which shows an angular methyl group at 1.05 ppm, assigned to the methyl at C6-b, since it would lie in plane of the C-11,12 double bond. The other stereochemically possible product is the trans,anti,cis,anti,cis olefin 204. In addition to being an unlikely product on mechanistic grounds, the structure of this olefin would place the C-6b[...] out of the plane of the double bond, thereby placing its chemical shift at higher field.

The yield and selectivity in the cyclization reaction appears to decrease as the number of alkyl substituents on the internal double bonds is increased. This is explained on the basis of the stronger interactions that would develop in the transition states in the substituted cases, as opposed to those with a lesser degree of olefin substitution.

In a related study the cyclopentenol 194 was cyclized with stannic chloride to afford a 37% yield of the pentacyclic olefin 195 which was successfully transformed into a known compound, the enone D-4. Like the ether D-6, D-4 was used previously as an intermediate in the first total synthesis of alnusenone (Ireland and Welch, 1970). Successful transformation of olefin 195 into enone D-4 served to confirm the structure of and also constituted another formal total synthesis of alnusenone.

Item Type:Thesis (Dissertation (Ph.D.))
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Ireland, Robert E. (advisor)
  • Bergman, Robert G. (advisor)
Thesis Committee:
  • Unknown, Unknown
Defense Date:8 August 1973
Record Number:CaltechETD:etd-01292007-151243
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:402
Deposited By: Imported from ETD-db
Deposited On:29 Jan 2007
Last Modified:21 Dec 2019 01:27

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