Carbonylative cyclopentane

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

A general preparation of 2-acetonyl-2,4,6-triaryl-2//-thiopyrans 58 was discovered in the reaction of corresponding 2,4,6-triarylthiopyrylium perchlorates with ethanolic acetone catalyzed with various dialkylammonium salts (86GEP235455, 86JPR573). This preparative procedure was successfully extended to cyclohexane- and cyclopentane- 1,2-diones as the carbonyl components (89JPR853 90GEP280324). The action of bases on thiopyrylium salts may caused their dimerization to thiopyranyl derivatives under suitable conditions (89KGS479). 

The carbonyl n orbital is also assumed to be unsymmetrized arising from the out-of-phase interaction of the orbital attached to the more electron-donating aryl group (9 and 10). These unsymmetrizations of the carbonyl k orbital correspond well to syn addition (9) and anti addition (10), respectively. Thus, the electron-donation of the p-a orbitals controls the facial selectivities. The cyclopentane system was more sensitive to stereoelectronic effects, showing larger induced biases, than the adamantanone system [63]. 

Facial selectivities of spiro[cyclopentane-l,9 -fluorene]-2-ones 30a-30e were studied by Ohwada [96, 97]. The carbonyl tz orbital can interact with the aromatic % orbital of the fluorene in a similar manner to spiro conjugation [98-102]. The ketones 30 were reduced to alcohols by the action of sodium borohydride in methanol at -43 °C. The anti-alcohol, i.e., the syn addition product of the reducing reagent with respect to the substituent, is favored in all cases, irrespective of the substituent at C-2 or C-4 of the fluorene ring (2-nitro 30b syn anti = 68 32), 4-nitro... 

Epoxidation of substituted spiro[cyclopentane-l,9 -fluorene]-2-enes 68 with a peroxidic reagent was studied [98], The spiro olefins react with m-chloroperbenzoic acid (mCPBA) in chloroform at 3 °C to give a mixture of the epoxides. In all cases (2-nitro (68b), 4-nitro (68c), 2-fluoro (68d) and 2-methoxyl (68e) groups), the iyn-epoxides, i.e., the syn addition of the peroxidic reagent with respect to the substituent, is favored. For example, for 6 nsyn anti = 63 31 for 68c syn anti = 65 35. Thus, a similar bias is observed in both the reduction of the carbonyl derivatives of 30 and the epoxidation of the derivatives of 68. 

In chlorophyll iron as complex-forming metal is replaced by magnesium (Willstatter). The structure of chlorophyll differs from that of haemin as follows. In chlorophyll one propionic acid chain (a) in oxidised form has condensed with a methine carbon atom to form a cyclopentane ring which takes the position at (c) of the vinyl ethyl. Further the two carbonyl groups are esterified and one of the four pyrrole rings is partially hydrogenated... 

Interestingly, cyclopentane and cyclohexane derivatives, which contain one or two hydroxyl, carbonyl, or carboxyl groups, degrade more readily in the environment than do their parent compounds. In fact, microorganisms capable of degrading of cycloalkanols and cycloalkanones are ubiquitous in environmental samples. 

Simultaneously to the synthetic studies described above, our model studies had progressed. Although the synthetic challenge in this part of the project was marginal the structure elucidation of the final products was complicated [41]. Starting material for the syntheses was 1-acetyl-1-cyclopentene (58) which was converted into the frans-cyclopentane rac-59 by a Sakurai reaction and a carbonyl olefination (Scheme 16). The synthesis of czs-cyclo-... 

With the long chain a-diazo ketone. 6-diazo-7-tridecanone, 1,5-insertion could proceed with placement of the carbonyl outside the ring, or included in the ring. In fact, only the product 7, from the first of these two cyclization modes, is observed67. The alternative cyclopentane 9 is not formed. As with the a-diazo ester, the relative proportion of 1,2- and 1,5-products depends on the rhodium carboxylate employed. Throughout these studies, it has been observed that the olefin 8, obtained from 1,2-elimination, is cleanly Z-configured67 68. 

Shibata and co-workers have reported an effective protocol for the cyclization/hydrosilylation of functionalized eneallenes catalyzed by mononuclear rhodium carbonyl complexes.For example, reaction of tosylamide 13 (X = NTs, R = Me) with triethoxysilane catalyzed by Rh(acac)(GO)2 in toluene at 60 °G gave protected pyrrolidine 14 in 82% yield with >20 1 diastereoselectivity and with exclusive delivery of the silane to the G=G bond of the eneallene (Equation (10)). Whereas trimethoxysilane gave results comparable to those obtained with triethoxysilane, employment of dimethylphenylsilane or a trialkylsilane led to significantly diminished yields of 14. Although effective rhodium-catalyzed cyclization/hydrosilylation was restricted to eneallenes that possessed terminal disubstitution of the allene moiety, the protocol tolerated both alkyl and aryl substitution on the terminal alkyne carbon atom and was applicable to the synthesis of cyclopentanes, pyrrolidines, and tetrahydrofurans (Equation (10)). 

Rhodium-catalyzed cyclization/silylation/carbonylation of 1,6-diynes was proposed to occur via a-migratory insertion of CO into the Rh-C bond of dialkylidene cyclopentane intermediate Ik to form acylrhodium alkene intermediate Ilk (Scheme S-endo-[5-M gX2itory insertion of the silylated alkylidene moiety into the Rh-G bond of Ilk would form... 

The synthesis of this compound represents a notable departure from those discussed above. The presence of the carbonyl group at the 9 position of the cyclopentane ring, which classifies this compound as a PGE, removes one asymmetric center and thus somewhat reduces the stereochemical complexity of the synthesis. More importantly, this introduces the possibility of attaching the lower side chain by means of a 1,4-addition reaction the tram relationship of the two side chains should be favored by thermodynamic considerations. The very unusual functionality of the required Michael acceptor, that of a cyclopent-2-en-4-ol-l-one, leads to a rather lengthy albeit straightforward synthesis for the requisite intermediate. 

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