Cyclopentenes, alkyl

A. l-(l-Cyclopenten-l-yl)piperidine (148) reaeted with N-methyl-3-bromopropylamine hydrobromide to yield 74% of a mixture of enamines (149) 112). The proposed mechanism involved an amine exchange to give the enamine 150 which underwent internal alkylation. 

Bifunctional molecules undergo intermolecular cyclizations with enamines through simple alkylations 112-114) and acylations 115). For example, the reaction between l-(N-pyrrolidino)cyclopentene and 1,4-diiodobutane produces, after hydrolysis, ketospirans 92 and 93 113). 

A low ion pair yield of products resulting from hydride transfer reactions is also noted when the additive molecules are unsaturated. Table I indicates, however, that hydride transfer reactions between alkyl ions and olefins do occur to some extent. The reduced yield can be accounted for by the occurrence of two additional reactions between alkyl ions and unsaturated hydrocarbon molecules—namely, proton transfer and condensation reactions, both of which will be discussed later. The total reaction rate of an ion with an olefin is much higher than reaction with a saturated molecule of comparable size. For example, the propyl ion reacts with cyclopentene and cyclohexene at rates which are, respectively, 3.05 and 3.07 times greater than the rate of hydride transfer with cyclobutane. This observation can probably be accounted for by a higher collision cross-section and /or a transmission coefficient for reaction which is close to unity. 

Dihydro-2iy-thiopyrans, derived from dimethylbuta-1,3-dienes, Na2S203-5H20 and various activated alkyl h des, ring contract on treatment with a strong base leading to vinyl cyclopropanes and cyclopentenes <96JOC4725>. 

NHC-promoted enolate formation from an enal, followed by a desymmetrising aldol event to generate P-lactones and loss of CO, has been exploited by Scheidt and co-workers to generate functionalised cyclopentenes 240 in high ee from enal substrates 238 (Scheme 12.52) [94]. Interestingly, the use of alkyl ketones in this reaction manifold allows the isolation of the p-lactone intermediates with acyclic diketones, P-lactones 239 are formed with the R group anti- to the tertiary alkox-ide, while with cyclic diketones the P-lactone products have the R group with a syn relationship to the alkoxide [95]. 

Palladium(II) complexes possessing bidentate ligands are known to efficiently catalyze the copolymerization of olefins with carbon monoxide to form polyketones.594-596 Sulfur dioxide is an attractive monomer for catalytic copolymerizations with olefins since S02, like CO, is known to undergo facile insertion reactions into a variety of transition metal-alkyl bonds. Indeed, Drent has patented alternating copolymerization of ethylene with S02 using various palladium(II) complexes.597 In 1998, Sen and coworkers also reported that [(dppp)PdMe(NCMe)]BF4 was an effective catalyst for the copolymerization of S02 with ethylene, propylene, and cyclopentene.598 There is a report of the insertion reactions of S02 into PdII-methyl bonds and the attempted spectroscopic detection of the copolymerization of ethylene and S02.599... 

Trost and co-workers have explored asymmetric transition metal-catalyzed allylic alkylations. Details on this subject have been well reviewed by Trost and others.90 With the use of asymmetric palladium-catalyzed desymmetrization of meso-2-ene-l,4-diols, cw-l,4-dibenzoy-loxy-2-cyclopentene can be converted to the enantiometrically pure cA-4-tert-butoxycar-bamoyl-l-methoxycarbonyl-2-cyclopentene.91 The product is a useful and general building block for synthesis of carbocyclic analogs of nucleosides as presented in Scheme 5.12. 

In order to establish the correct absolute stereochemistry in cyclopentanoid 123 (Scheme 10.11), a chirality transfer strategy was employed with aldehyde 117, obtained from (S)-(-)-limonene (Scheme 10.11). A modified procedure for the conversion of (S)-(-)-limonene to cyclopentene 117 (58 % from limonene) was used [58], and aldehyde 117 was reduced with diisobutylaluminium hydride (DIBAL) (quant.) and alkylated to provide tributylstannane ether 118. This compound underwent a Still-Wittig rearrangement upon treatment with n-butyl lithium (n-BuLi) to yield 119 (75 %, two steps) [59]. The extent to which the chirality transfer was successful was deemed quantitative on the basis of conversion of alcohol 119 to its (+)-(9-methyI mande I ic acid ester and subsequent analysis of optical purity. The ozonolysis (70 %) of 119, protection of the free alcohol as the silyl ether (85 %), and reduction of the ketone with DIBAL (quant.) gave alcohol 120. Elimination of the alcohol in 120 with phosphorus oxychloride-pyridine... 

The similar insertion of 93 into 1,2-diphenylcyclopropenone results in cy-clobutenones or o- and p-alkoxyphenols [49]. In the reaction of 93 with 1-alkynylcyclobutenols, 2-alkenyl-4-cyclopentene-l,3-diones are obtained via alkyl shift-ring expansion [50]. (Scheme 33)... 

The asymmetric allylic alkylation (AAA) reaction has been adapted for use with pyrrole nucleophiles <06JACS6054>. For example, treatment of pyrrole 55 and cyclopentene 56 with a palladium catalyst in the presence of a chiral additive gave pyrrole 57 in up to 92% ee. The latter was elaborated into piperazinone-pyrrole natural product, agelastatin A 94. 

Highly alkylated l-chloro-2-(trimethylsilyl)cyclopentenes 44, which are of interest as possible cyclopentyne precursors, were prepared by reacting 3-chloro-3-methyl-l-(trimethylsilyl)but-l-yne (45) with 1,1-dialkylated or 1,1,2-trialkylated ethylenes in the presence of titanium tetrachloride35. Because of the low S/v 1 reactivity of 45, the yields of the products were moderate. The stepwise [3 + 2]-cycloaddition mechanism discussed above was proven by the isolation of the intermediate acyclic adduct (in 74% yield) when 45 and isobutene were reacted in the presence of BCI3. Under these conditions, the intermediate 46 could be trapped by Cl since BCI4 is more nucleophilic than TiC.15 (equation 16). 

Castagnino, E., Corsano, S., and Strappavecchia, G.P., The preparation of a novel oxo-cyclopenten-2-phosphonate derivative, useful intermediate for 2-alkyl-substituted cyclopentenones synthesis, Tetrahedron Lett., 93, 1985. 

The 0/7/fo-alkylation of aromatic ketones with olefins can also be achieved by using the rhodium bis-olefin complex [C5Me5Rh(C2H3SiMe3)2] 2, as shown in Equation (9).7 This reaction is applied to a series of olefins (allyltrimethyl-silane, 1-pentene, norbornene, 2,2 -dimethyl-3-butene, cyclopentene, and vinyl ethyl ether) and aromatic ketones (benzophenone, 4,4 -dimethoxybenzophenone, 3,3 -bis(trifluoromethyl)benzophenone, dibenzosuberone, acetophenone, />-chloroacetophenone, and />-(trifluoromethyl)acetophenone). 

Sunlamp irradiation of butynyl iodide (6) in the presence of hexabutylditin generates an alkyl radical that reacts with an electron-deficient alkene (7) to form an (iodomethylene)cyclopentene (8) in moderate yield. This product can be reduced by Bu3SnH (AIBN) to the methylenecyclopentane (9).2... 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Complexes of nickel(II) or magnesium(II) with the chiral ligand DBFOX (Scheme 8) catalyze the DCR of nitrones with a-alkyl- and arylacroleins rendering preferentially the 5-carbaldehyde cycloadducts. However, the reactions with a-bromoacrolein catalyzed by the zinc(II) complex of the same ligand afford isoxazoline -carbaldehydes. The corresponding cobalt(II) complex is also active for the cycloaddition between cyclopenten-l-carbaldehyde and diphenylnitrone. 

Ir-catalyzed alkylation with a nitro compound was applied in a synthesis of flS,2R)-tra s-2-phenylcyclopentanamine, a compound with antidepressant activity (Scheme 9.41) [45]. The reaction of cinnamyl methyl carbonate with 4-nitro-l-butene gave the substitution product with 93% ee in 82% yield. A Grubbs I catalyst sufficed for the subsequent RCM. Further epimerization with NEts yielded a trans-cyclopentene in 83% yield via the two steps, while additional reduction steps proceeded in 90% yield. 

The reaction of 1,3-disubstituted bicyclo[2.1.0]pentanes with tris(4-bromophenyl)ammoniumyl hexachloroantimonate (the latter in catalytic amounts) leads to the corresponding cyclopentene after 1,2-hydrogen or 1,2-alkyl migration in the intermediary 1,3-cation-radicals (Adam and Sahin 1994 Scheme 7.47). 

Cycloalkenes such as cyclohexene, 1-methylcyclohexene, cyclopentene, and nor-bornene are hydrosilylated with triethylsilane in the presence of aluminum chloride catalyst in methylene chloride at 0 °C or below to afford the corresponding hydrosilylated (triethylsilyl)cycloalkanes in 65-82% yields [Eq. (23)]. The reaction of 1-methylcyclohexene with triethylsilane at —20 °C occurs regio- and stereoselectively to give c/i-l-triethylsilyl-2-methylcyclohexane via a tra x-hydrosilylation pathway. Cycloalkenes having an alkyl group at the double-bonded carbon are more reactive than non-substituted compounds in Lewis acid-catalyzed hydrosilylations. ... 

In 2007, Scheldt and co-workers reported the intramolecular desynunetrization of 1,3-diketones utilizing triazolinm pre-catalyst 249 (Scheme 39) [129], Generation of a homoenolate is followed by P-protonation and aldol reaction. In accordance with the proposed mechanism by Nair (Scheme 37), acylation occurs followed by loss of carbon dioxide. Cyclopentenes are formed in enantioselectivities up to 94% ee. The scope of this reaction is limited to aryl substitution of the diketone and alkyl substitution of R. 

Ito, M. Matsuumi, M. Murugesh, M. G. Kobayashi, Y. Scope and Eimitation of Organocuprates, and Copper or Nickel Catalyst-Modified Grignard Reagents for Installation of an Alkyl Group onto cis-4-Cyclopentene-l,3-diol Monoacetate. J. Org. Chem. 2001, 66, 5881-5889. 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

Azadienes of this sort were studied simultaneously by Mariano et al., who reacted mixtures of (1 ,3 ) and (1E, 3Z)-l-phenyl-2-aza-l,3-pentadiene 275 with several electron-rich alkenes, e.g., enamines and enol ethers (85JOC5678) (Scheme 61). They found the (l ,3 )-stereoisomer to be reactive in this process affording stereoselectively endo 276 or exo 277 piperidine cycloadducts in 5-39% yield, after reductive work-up with sodium borohydride. The stereochemistry of the resulting adducts is in agreement with an endo transition state in the case of dienophiles lacking a cis alkyl substituent at the /8-carbon (n-butyl vinyl ether, benzyl vinyl ether, and 1-morpholino cyclopentene), whereas an exo transition state was involved when dihydropyrane or c/s-propenyl benzyl ether were used. Finally, the authors reported that cyclohexene and dimethyl acetylenedi-carboxylate failed to react with these unactivated 2-azadienes. 

Sn2 ring opening by attack of a nucleophile on an ethenyl substituent (e.g. Scheme 60) has assumed importance in natural products synthesis (80JCS(P1)2084, cf. 81JA5969). The cyclopentene oxide (63) is a versatile synthon for alkylated, functionalized cyclopentanes (Scheme 61) (81JA2112). 

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