Intramolecular Pauson–Khand Reactions of Methylenecyclopropane and Bicyclopropylidene Derivatives as an Approach to Spiro(cyclopropanebicyclo[n.3.0]alkenones)

Abstract

The trimethylsilyl-protected enynes 9a-c and 14a,b with alkynyl substituents on the three-membered ring or on the double bond of a methylenecyclopropane or a bicyclopropylidene moiety were prepared in two steps from the alcohols 6a-c and 12a,b, respectively, by conversion to the iodides and their coupling with lithium (trimethylsilyl)acetylide (8) in 38-73% overall yields. The bicyclopropylidene derivative 9d was synthesized in 49% yield directly from bicyclopropylidene (3) by lithiation followed by coupling with (5-iodopent-1-ynyl)trimethylsilane (11). Enynes 9b-d were protiodesilylated by treatment with K2CO3 in methanol to give the corresponding unprotected enynes 10b-d in 53, 74 and 94% yield, respectively. Enynes 17a-c with a carbonyl group adjacent to the acetylenic moiety were synthesized from oxo derivatives 15a-c by Wittig olefination followed by coupling with 8 in 47, 18 and 12% overall yield, respectively. Pauson-Khand reactions of the methylenecyclopropane derivatives with a substituent on the ring (9a,b and 10a) as well as on the double bond (14a,b and their in situ prepared protiodesilylated analogues) proceeded smoothly by stirring of the corresponding enyne with [Co2(CO)8] in dichloromethane at ambient temperature followed by treatment of the formed complexes with trimethylamine N-oxide under an oxygen atmosphere at -78 degrees C to give tricyclic or spirocyclopropanated bicyclic enones 18a,b, 19a, 20a,b, 21a,b in good yields. Alkynylbicyclopropylidene derivatives 9c,d and 10c,d formed the corresponding cobalt complexes at -78 to -20 degrees C. Treatment of the latter with N-methylmorpholine N-oxide under an argon atmosphere at -20 degrees C gave the spirocyclopropanated tricyclic enones 18c, 19c and 18d in 31-45% yields. The structure of 19c was proved by X-ray crystal structure analysis. The cyclization of enynones 17a-c in MeCN at 80 degrees C gave the spirocyclopropanated bicyclic diketones 22a-c in 38-65% yields. Intramolecular PKRs of the enynes 25a,d with a chiral auxiliary adjacent to the triple bond gave the corresponding products 26a,d in 70 and 79% yield, respectively, as 5:1 and 8:1 mixtures of diastereomers, respectively. Addition of lithium dimethylcuprate or higher order cuprates to the double bond of the former furnished bridgehead-substituted bicyclo[3.3.0]octanones 27a-c in 57-86% yields. Protiodesilylation of 27a followed by acetal cleavage gave the enantiomerically pure spirocyclopropanated bicyclo[3.3.0]octanedione (1R,5R)- 29a with [alpha]D(20)=-148 (c=1.0 in CHCl3) in 55% overall yield.

Transition metals in organic synthesis: Highlights for the year 2005

“…Intramolecular Pauson-Khand reactions of alkynes tethered to methylencyclopropanes were described [1004]. A number of intramolecular Pauson-Khand reactions of 1,6-and 1,7-enynes [1005][1006][1007][1008][1009][1010] were reported.…”

Recent developments in the reactivity of methylene- and alkylidenecyclopropane derivatives

“…De Meijere et al have demonstrated that alkylidenecyclopropanes and even bicyclopropylidene moieties included in 1,6-and 1,7-enynes did favour the intramolecular PausoneKhand reactions in the presence of Co 2 (CO) 8 to furnish the corresponding spirocyclopropanated and/or cyclopropane-annelated bicyclo [3.3.0]octanones or bicyclo[4.3.0]nonanones in moderate-to-good yields (0e65%) after a subsequent treatment with N-methylmorpholine N-oxide (NMO). 123 Moreover, an asymmetric version of this methodology was developed by these authors by incorporating a chiral C 2 -symmetric acetal moiety adjacent to the triple bond in the starting material, which allowed the formation of the corresponding spirocyclopropanated cycloadduct with a diastereoselectivity of up to 78% de. In 2003, higher levels of diastereoselection of up to 100% de were achieved by Krafft …”

P111: Bilateral vital tubal ectopic pregnancy detected by color Doppler transvaginal ultrasonography

“…Moreover, a series of substituted bicyclopropylidenes 205a–i could be prepared by de Meijere et al. on the basis of the deprotonation of bicyclopropylidene 59 with n‐ BuLi and subsequent electrophilic substitution with a wide variety of electrophiles in good to high yields, as shown in Scheme 42a,44,110,111,112. Similar conditions were also applied to the formylation of the lithiated simple methylenecyclopropane with DMF, providing the corresponding aldehyde in 82% yield 113…”

“…In recent years, various functional group interconversions aside from the cyclopropane ring, such as esterifications,49b,c,57,97,122 halogenations,66 etherifications,123 phosphorylations,51,124,125 deacetylations,50b,56 deprotections of MOM derivatives,58 acid hydrolysis of phosphonate esters,66 nucleophilic substitutions of tosylates,121,126 or halogens42a,47,127,128 have been successfully developed. In addition, antiviral methylenecyclopropane phosphonates have been prepared by Zemlicka et al.…”