Substituted cyclopentene

Scheme 5 details the synthesis of / -cormorsterone (14) from 17. Oxidative scission of both carbon-carbon double bonds in 17 with ozone, followed by two straightforward operations, furnishes intermediate 38. The stability of the oxime in these systems is noteworthy, and is attributed to its hindered nature. At this juncture, it is instructive to note that substituted cyclopentene rings, like the... 

This type of reaction however works only for methylmetallic reagents. A general synthesis of this type of substituted cyclopentenes has been developed employing /T-dimethylamino and P -trimethylammonio-o ,/i-unsaturated sulfones 21. 

Fischer alkenylcarbene complexes undergo cyclopentannulation to alkenyl AT,AT-dimethylhydrazones (1-amino-1-azadienes) to furnish [3C+2S] substituted cyclopentenes in a regio- and diastereoselective way along with minor amounts of [4S+1C] pyrrole derivatives. Enantiopure carbene complexes derived from (-)-8-(2-naphthyl)menthol afford mixtures of trans,trans-cycloipentenes and ds,ds-cyclopentenes with excellent face selectivity [75]. The mechanism proposed for the formation of these cyclopentene derivatives is outlined in Scheme 28. The process is initiated by nucleophilic 1,2-attack of the carbon... 

Scheme 1 RCM-based formation of a densely substituted cyclopentene in the first total synthesis of madindoline A (7) and ewf-madindoline B (8) [21]...

Jahn combined the formation of the enolate 2-713 resulting from an intermolecu-lar Michael addition of 2-711 and 2-712 with a radical reaction (Scheme 2.157) [363]. The enolate 2-713 did not undergo any further transformations due to the lack of appropriate functionalities. However, after formation of a radical using a mixture of ferrocenium hexafluorophosphate (2-714) and TEMPO, a new reaction channel was opened which afforded the highly substituted cyclopentene 2-715a diastereoselec-tively. 

The molybdenum initiators also allow for functionalization of the polymer end groups. The use of appropriately substituted alkylidene ligands553,554 and functionalized termination agents555 have both been described. A more convenient approach using chain transfer agents has also been developed, initially with substituted cyclopentenes,509 and then with 1,3-dienes and styrenes.556... 

There is, no doubt, a decrease in the homoaromatic stabilization when conjugation is interrupted in two (bishomoaromatic) or more places (Paquette et al., 1977a Paquette, 1978). In spite of this, several bishomoaromatic cations have been well characterized. The simplest bishomoaromatic the 4-cyclopentyl cation [29] is, as yet, unknown (see Olah et al., 1972, and references cited therein). The cation [29] was not detected by NMR studies, nor was it invoked as an intermediate in the solvolysis of appropriately substituted cyclopentenes. 

The predominance of steric over electronic factors has been also used to explain the product distribution obtained by addition of I2 in pyridine which takes place exclusively at the least substituted cyclopentene double bond of 79. Under similar conditions the reaction of the unsubstituted diene 78 occurs by direct addition at the cyclohexene double bond98. 

It will be noted that the isomerization to cyclopentene proceeds with a considerably lower energy of activation than the other cyclopropane isomerizations so far discussed. As a result these reactions have been investigated kinetically at temperatures about 100° lower than those not having a vinyl substituent. A number of substituted vinylcyclopropanes have been studied and the Arrhenius parameters for their isomerizations to substituted cyclopentenes determined. The results are shown in Table 4. From the results in Table 4 it can be seen that the isomerizations... 

However, the strain of the oxirane is not the only determining factor in the aip competition, as illustrated by c -substituted cyclopentene oxides of type 22 which are known to give /3-deprotonation with lithium amides in nonpolar solvents (Scheme 8) . 

The first study was performed by Milne and Murphy, who found that the rearrangement of substituted cyclopentene oxide 69 into 70 by a stoichiometric amount of the dilithiated homochiral base 71 derived from norephedrine occurred in excellent yield and good ee... 

Ruthenium catalysts, coordinated with an N-heterocyclic carbene allowed for the ROMP of low-strain cyclopentene and substituted cyclopentenes (10,23). Suitable ruthenium and osmium carbene compounds may be synthesized using diazo compounds, by neutral electron donor ligand exchange, by cross metathesis, using acetylene, cumulated olefins, and in an one-pot method using diazo compounds and neutral electron donors (24). The route via diazo compounds is shown in Figure 1.7. 

Several examples of ring-closing metathesis indicate the highly selective nature of this reaction.161,162,224-226 The application of various Mo and Ru carbene catalysts allow formation of five-, six-, and seven-membered mono- and bicyclic rings. Formation of substituted cyclopentenes, for example, was shown... 

The complex 8W (R = Me) can also be used in a stoichiometric metathesis sequence to effect the ring closure of unsaturated ketones so as to form 1-substituted cyclopentenes, cyclohexenes and cycloheptenes in good yield, e.g. equation 24. The C=C bond reacts first to give [W]=CH(CH2)3C0(CH2)0(CH2)3Ph, which then undergoes an internal carbonyl-olefination reaction13. 

Cyclopentene annelation. The known rearrangement of vinyl cyclopropanes to cyclopentenes (cf. 7, 190 9, 83, 265) can be used to obtain silyl-substituted cyclopentenes. The precursors, (l-trimethylsilylcyclopropyl)ethylenes (2), are usually prepared by addition of 1 to an aldehyde or a ketone followed by cyclopropanation (C2HjZnI, CH2I2) of the adduct. The products are then dehydrated by TsOH to 2 (equation I).1... 

These silyl-substituted vinyl cyclopropanes are stable to acid but rearrange thermally to silyl-substituted cyclopentenes in which the double bond occupies the more substituted position.2 Example ... 

Most reactions of this category involve the base-induced generation of alkylidene-carbenes (R2C = C ) which undergo an intramolecular 1,5-carbon-hydrogen insertion providing a useful route for the construction of substituted cyclopentenes a competing intramolecular pathway is rearrangement to alkynes. 

This formation of (i-lactones is strongly related to a serendipitous finding made by Nair et al. (Nair et al. 2006b Chiang et al. 2007 Phillips et al. 2007). Interestingly, they found that the IMes-catalyzed coupling of a,P-unsaturated aldehydes with a,P-unsaturated ketones led to the stereoselective formation of Pms-substituted cyclopentenes... 

Furan was demonstrated to function as a 1,3-propene dipole when it was dihapto-coordinated to a rhenium 7t-base, which enhanced the nucleophilicity of the uncoordinated C-3-position. As represented in Scheme 30, the 2,5-dimethylfuran complex 50 (Tp = hydridotris(pyrazolyl)borate Melm = 1-methylimidazole) reacted with Michael acceptors to form substituted cyclopentenes <2003JA14980, 20050M2903>. 

In 1995, Mioskowski and co-workers reported a new carbenoid 1,2-alkyl rearrangement of a-hydroxy-substituted cyclopentene and cyclohexene oxides treatment of such systems with 3 equiv of an organolithium resulted in the formation of two products, as exemplified by the synthesis of dihydrojasmone and its regioisomer 99 (Scheme 44) <1995JA12700>. 

In 1996, Mioskowski and co-workers expanded on this second observation to advance the classical reductive alkylation chemistry of epoxides first reported by Crandall and Lin in 1967 (Scheme 47, Equation 6) <1967JA4526, 1967JA4527, 19830R345>. Mioskowski and co-workers proposed a similar pathway for the formation of cyclopentenol 102 from methoxy-substituted cyclopentene oxide 101 lithiation, carbenoid formation, insertion into the excess organolithium, followed, in this case, by LiOMe elimination (rather than Li20) (Scheme 47, Equation 7) <1996CC549>. 

Treatment of the semicarbazone (55) under Wolff-Kishner conditions (KOH, NaOMe, KOBu, no solvent) has been utilized to synthesize the substituted cyclopentenes cis- and trans-(,S6 equation 17). In DE<3 at 225 C, the normal Wolff-Kishner product was obtained. ... 

The reaction of allenylsilanes with electron deficient ir-systems constitutes a powerful and general method for the tegio- and stereo-selective preparation of substituted cyclopentenes. As first reported, (trimethylsilyl)allenes function as three-carbon nucleophiles in TiCU-promoted (trimethylsilyl)cyclopen-tene annelations (Scheme 31). The annelation process involves the polarization of an a,p-unsaturated carbonyl compound by TUTU to generate an alkoxyallylic cation. Regiospecific electnqrhilic substitution of this cation at C-3 of the allenylsilane produces a silicon-stablizied vinyl cation. A 1,2-shift of the tri-... 

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