Synthesis of the A,B,C-Ring System of Hexacyclinic Acid

Stellfeld, Timo; Bhatt, Ulhas; Kalesse, Markus

doi:10.1021/ol048720o

Cited by 42 publications

(17 citation statements)

References 14 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, treatment of 3 a with 10 mol % of [AuClPPh 3 ]/AgSbF 6 6 in the presence of molecular sieves (4 Å) gave bicyclo[4.3.0]nonane derivative 4 a , a formal [4+2] cycloadduct, as a single stereoisomer in 92 % yield (Scheme ) 7. 8 Interestingly, the configuration of the product was different from that of the thermal Diels–Alder adduct 5 obtained stereoselectively by heating a solution of ( Z )‐ 3 a in toluene for 1.5 h 9. Thus, two diastereoisomers10 of the same bicyclo[4.3.0]nonane derivative were obtained selectively by choosing Au I ‐catalyzed or thermal conditions.…”

Section: Methodsmentioning

confidence: 99%

Gold‐Catalyzed Tandem Cyclization of Dienol Silyl Ethers for the Preparation of Bicyclo[4.3.0]nonane Derivatives

et al. 2010

View full text Add to dashboard Cite

We previously reported the geminal carbo-functionalization reaction of alkynes on treatment of 3-siloxy-1,3-dien-7-ynes 1 with [W(CO) 6 ] or [ReCl (CO) 5 ] under photoirradiation to give bicyclo[3.3.0]octane derivatives 2 in good yield (Scheme 1). [1] The reaction was thought to proceed through nucleophilic attack of the silyl enol ether moiety to the electrophilically activated alkyne followed by attack of the generated alkenyl metallic species A to the a,b-unsaturated silyloxonium moiety at the position b to the metal to give bicyclic carbene complex intermediate B, which gave the product through 1,2-hydrogen shift with regeneration of the catalyst. [2] We then thought of the possibility of carrying out a similar geminal carbofunctionalization reaction by employing one-carbon-atom elongated substrates (3-siloxy-1,3-dien-8-ynes 3) with the expectation that 5-exo attack of the silyl enol ether moiety followed by ring closure (geminal carbo-functionalization) would give bicyclo[3.3.0]octane derivative D having a carbene complex moiety as a substituent on the bridgehead carbon atom. As there is no a-hydrogen atom at the carbene complex moiety, 1,2-hydrogen shift is not possible and the behavior of this intermediate is intriguing (Scheme 1). We now report that 1,2-alkyl migration [3] occurred at the generated carbene moiety to give ring-expanded products by employing 3siloxy-1,3-dien-8-yne derivatives as substrates, to stereoselectively obtain synthetically useful bicyclo[4.3.0]nonane derivatives, whose configuration was different from that of the Diels-Alder adduct.We first examined the reaction of 3-siloxy-1,3-dien-8-yne 3 a with the geometry of the silyl enol ether moiety as (Z) [4] by using various electrophilic transition-metal catalysts. Although [W(CO) 5 (thf)] or [ReCl(CO) 5 ] gave the products in reasonable yield (45 % and 78 %, respectively), [5] the cationic gold catalyst gave the best result. Thus, treatment of 3 a with 10 mol % of [AuClPPh 3 ]/AgSbF 6 [6] in the presence of molecular sieves (4 ) gave bicyclo[4.3.0]nonane derivative 4 a, a formal [4+2] cycloadduct, as a single stereoisomer in 92 % yield (Scheme 2). [7,8] Interestingly, the configuration of the product was different from that of the thermal Diels-Alder adduct 5 obtained stereoselectively by heating a solution of (Z)-3 a in toluene for 1.5 h. [9] Thus, two diastereoisomers [10] of the same bicyclo[4.3.0]nonane derivative were obtained selectively by choosing Au I -catalyzed or thermal conditions. Next, we examined the reaction of 3-siloxy-1,3-dien-8-yne derivative 3 a with the geometry of the silyl enol ether moiety as (E) [4] under thermal and Au I -catalyzed conditions (Scheme 2). In this case, (E)-3 a did not undergo thermal Scheme 1. Tandem cyclization of dienol silyl ethers.Scheme 2. Au I -catalyzed and thermal cyclization of dienynes 3 a. E = CO 2 Me; TIPS = triisopropylsilyl; M.S. = molecular sieves; DCE = dichloroethane.

show abstract

Section: Methodsmentioning

confidence: 99%

Gold‐Catalyzed Tandem Cyclization of Dienol Silyl Ethers for the Preparation of Bicyclo[4.3.0]nonane Derivatives

et al. 2010

View full text Add to dashboard Cite

show abstract

“…45 Kalesse et al used the CM with methyl acrylate to install the conjugated ester functionality for an intramolecular Michael addition en route to the synthesis of the ABC-ring system (83) present in hexacyclinic acid and other bioactive compounds. 46 Several metathesis catalysts have been screened in this transformation, and the Hoveyda-Grubbs second-generation catalyst Hov-II and its activated analog Gre-II were proved to be the most potent, leading to the formation of 82 in 80% yield. CM of the same allylestrone 79 with the acrylamide derivative 84 was also evaluated for the synthesis of a 17b-hydroxysteroid dehydrogenase-type 1 inhibitor 86 (Scheme 21).…”

Section: Between Partners Of Type I and Type Iimentioning

confidence: 99%

5.26 Cross Metathesis

Żukowska

Grela

2014

Comprehensive Organic Synthesis II

View full text Add to dashboard Cite

“…A CM reaction catalyzed by 6 was used by Kalesse (Hannover, Germany) to install the conjugated ester functionality for a subsequent intramolecular Michael addition en route to antitumor hexacyclinic acid and (−)‐FR182877 20. Another impressive CM application of 6 was published by Koide et al (Pittsburgh) in the total synthesis of FR901464, an antitumor agent that regulates the transcription of oncogenes and tumor suppressor genes (Fig.…”

Section: Electron‐withdrawing Group (Ewg)‐substituted Hoveyda–grubbs mentioning

confidence: 99%