Cyclopentene derivatives

Cyclopentene derivatives with carboxylic acid side-chains can be stereoselectively hydroxy-lated by the iodolactonization procedure (E.J. Corey, 1969, 1970). To the trisubstituted cyclopentene described on p. 210 a large iodine cation is added stereoselectively to the less hindered -side of the 9,10 double bond. Lactone formation occurs on the intermediate iod-onium ion specifically at C-9ot. Later the iodine is reductively removed with tri-n-butyltin hydride. The cyclopentane ring now bears all oxygen and carbon substituents in the right stereochemistry, and the carbon chains can be built starting from the C-8 and C-12 substit""" ... 

The carbonylation of dehydrolinalyl methyl carbonate (35) at room temperature affords the cyclopentene derivative 37 formed by the ene reaction of... 

The cyclohexadiene derivative 130 was obtained by the co-cyclization of DMAD with strained alkenes such as norbornene catalyzed by 75[63], However, the linear 2 1 adduct 131 of an alkene and DMAD was obtained selectively using bis(maleic anhydride)(norbornene)palladium (124)[64] as a cat-alyst[65], A similar reaction of allyl alcohol with DMAD is catalyzed by the catalyst 123 to give the linear adducts 132 and 133[66], Reaction of a vinyl ether with DMAD gives the cyclopentene derivatives 134 and 135 as 2 I adducts, and a cyclooctadiene derivative, although the selectivity is not high[67]. 

The cyclopentene derivatives 9 undergo both 1,5- and 1,7-dipolar electrocyclizations to yield mixtures of pyrazoles 10 and benzodiazepines 11. In addition, loss of nitrogen results in the carbenes 12, which cyclize to the tetrahydrocyclopent[fl]indenes 13.117... 

In the same way as arylcarbene complexes, alkenylcarbene complexes typically react with alkynes to provide [3C+2S+1C0] Dotz cycloadducts (see Chap. ccChromium-Templated Benzannulation Reactions , p. 123 in this book). However, some isolated examples involving the formation of five-membered rings through [3C+2S] cycloaddition processes have been reported [71]. In this context, de Meijere et al. found that /J-donor-substituted alkenylcarbene complexes react with alkynes to give cyclopentene derivatives [71a]. This topic is also discussed in detail in Chap.ccThe Multifaceted Chemistry of Variously Substituted a,/J-Unsaturated Fischer Metalcarbenes , p. 21 of this book. 

Sect. 2.1.1) and [3C+2S] cyclopentene derivatives. The product distribution can be controlled by choosing the appropriate reaction conditions [72]. Moreover, the cyclopentene derivatives are the exclusive products from the coupling of fi-pyrrolyl-substituted carbene complexes [72b,c] (Scheme 25). The crucial intermediate chromacyclobutane is formed in an initial step by a [2+2] cycloaddition. This chromacyclobutane rearranges to give the rf-complex when non-coordinating solvents are used. Finally, a reductive elimination leads to the formal [3C+2S] cyclopentene derivatives. 

Coupling of alkenylcarbene complexes and siloxy-substituted 1,3-dienes affords vinylcyclopentene derivatives through a formal [3C+2S] cycloaddition process. This unusual reaction is explained by an initial [4C+2S] cycloaddition of the electron-poor chromadiene system as the 471 component and the terminal double bond of the siloxydiene as the dienophile. The chromacyclohexene intermediate evolves by a reductive elimination of the metal fragment to generate the [3C+2S] cyclopentene derivatives [73] (Scheme 26). 

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... 

An interesting strategy for the diastereoselective synthesis of five-membered carbocycles was achieved by the reaction of alkenylcarbene complexes and lithium enolates derived from simple methyl ketones [79]. The use of more or less coordinating solvents (THF or Et20) or the presence of cosolvents such as PMDTA allows the selective synthesis of one or the other diastereoisomer of the final cyclopentene derivative (Scheme 32). 

The reaction of JV,iV-dimethylhydrazones (1-amino-1-azadienes) and alkenylcarbene complexes mainly produces [3C+2S] cyclopentene derivatives (see Sect. 2.6.4.5). However, a minor product in this reaction is a pyrrole derivative which can be considered as derived from a [4S+1C] cycloaddition process [75]. In this case, the reaction is initiated by the nucleophilic 1,2-addition of the nitrogen lone pair to the metal-carbon double bond followed by cyclisation and... 

S+1C] Cycloadducts have also been obtained in the reaction of alkenylcarbene complexes with electronically neutral 1,3-dienes by appropriate choice of the reaction conditions (see for comparison Sect. 2.6.4.4). Thus, performing the reaction in THF at 120 °C in a sealed flask the formal [4S+1C] cyclopentene derivative is generated in moderate yield [74a, 85] (Scheme 39). The key step... 

At this point the catalytic process developed by Dotz et al. using diazoalkanes and electron-rich dienes in the presence of catalytic amounts of pentacar-bonyl(r]2-ds-cyclooctene)chromium should be mentioned. This reaction leads to cyclopentene derivatives in a process which can be considered as a formal [4S+1C] cycloaddition reaction. A Fischer-type non-heteroatom-stabilised chromium carbene complex has been observed as an intermediate in this reaction [23a]. 

Small amounts of cyclopentene derivatives are detected in cyclopropanation reactions of electron-deficient dienes, but they may result from thermal rearrangement of the corresponding vinyl cyclopropanes and not from a direct [4+1] cycloaddition... 

An excellent example of a RCM/ROM domino process is shown in the total synthesis of the piperidine alkaloid (-)-halosaline (6/3-19) by Blechert and coworkers (Scheme 6/3.3) [231]. The key step is the reaction of the enantiopure cyclopentene derivative 6/3-17 to give 6/3-18 with 5 mol% of the catalyst 6/3-13. Further transformations of 6/3-18 led to the natural product 6/3-19. 

The thermal reaction of dipropynylsilanes with AII3B also involves 1,1- and 1,2-allylboration of the triple bond (or vice versa) (Scheme 50). l-Sila-3-bora-2-ethylidene-4-cyclopentene derivatives 119 are formed quantitatively at room temperature. They undergo an intramolecular 1,2-allylboration on heating for 3h to give the corresponding bicyclic compounds 120 quantitatively <2002JOM(649)232>. 

The carbene obtained by heating compound 68 with DMAD at first gave a cyclopropene derivative, which underwent further transformations (z/rro-substitution and cyclization) to afford tricyclic product 69 in 40% yield <1999TL1483>. The thermolysis carried out in the presence of ArCH=C(CN)2 and DMAD used in excess led to the formation of highly functionalized cyclopentene derivatives 70 <2003TL5029, 2005TL201>. 

With a similar sequence it has been established that the assumed structural formula for genipic acid is not the correct one 475), as the cyclopentene derivative in (4.64) does not behave like the natural product itself. 

RCM, followed by dihydroxylation of the double bond, is one of the most used methods for the synthesis of these compounds. For two syntheses of (—)-swainsonine 230, the five-membered ring is formed by RCM, followed by cis-dihydroxylation. Blechert et al. <2002JOC4325> prepared the precursor 2,5-dihydropyrroline 234 by domino ring-opening/ring-closing metathesis of an amino cyclopentene derivative 233 (Scheme 49). 

A regioselective [3 + 2]-cycloaddition approach to substituted 5-membered carbo-cycles was made available by the use of allenylsilanes [188]. The reaction involves regioselective attack of an unsaturated ketone by (trimethylsilyl)allene at the 3-position. The resulting vinyl cation undergoes a 1,2-silyl migration. The isomeric vinyl cation is intercepted intramolecularly by the titanium enolate to produce a highly substituted (trimethylsilyl)cyclopentene derivative. 

Abstract The coupling of 2-azabicyclo[2.2.1]hept-5-en-3-one and trimethylsily-lacetylene or phei rlacetylene under Domino Heck conditions gives compounds 2a-c and 4a-c in moderate yields and cyclopentene derivatives, 3a-c in low yields. The procedure can be of use for the synthesis of alkynyl bicyclic lactams. 

Cyclopentene derivatives (3a-c) were also characterized by FUR and various NMR techniques. N-H, C = O and C = C peaks were identified in expected fields (Table 37.2). 

Enantioselective cyclic ether is synthesized by molybdenum-catalyzed olefin metathesis. Cyclopentene derivative 85a is reacted with 5 mol% of chiral molybdenum catalyst 76 to give pyran derivative 86a in high yield and high ee... 

Unlike the well-known chemistry of the vinylcyclopropane-cyclopentene rearrangement, there is no general method for the rearrangement of alkynyl-cyclopropane to cyclopentene derivatives. One specific example is the pyrolysis of l-ethynyl-2-methylcyclopropane to methylenecyclopentene and other compounds [5]. At 530°C, l-ethynyl-2-methylcyclopropane (1) undergoes a [1,5]-hydrogen shift to give hexa-l,2,5-triene (2), which further isomerizes to methy-lenecyclopentenes 3 and 4 in 38 and 29% yield, respectively (Scheme 1). 

It is obvious from these trials that it is rather difficult to realize smooth transformation of alkynylcyclopropanes to cyclopentene derivatives. This difficulty presumably arises from the longer distance between the alkyne terminus and the cyclopropane ring compared with that between the latter and an alkene ter-... 

The McMurry reaction (the reductive dimerization of carbonyl compounds giving olefins after treatment with the low-valent titanium reagents TiCla/Mg and TiCla/Zn in THF at 40°C) (CR891513) is a key step in the synthesis of photochromic cyclopentene derivatives. Later, it has been shown that TiCU, which is easier to handle than TiCls, can be used. The cyclization products are formed in 50-60% yields (98S1092,03EJO155). The advantages of this method are that the reactions can be scaled and inexpensive starting materials can be used. 

Murakami et al. reported a ring-closing metathesis reaction of allenynes using Schrock s molybdenum alkylidene complex [37]. Treatment of allenynes ISl with a catalytic amount of the complex 15 2 in toluene at rt gave cyclopentene derivatives 1 S3 in good yield. Two possible reaction mechanisms were proposed, one through a vinylidene complex 154 and the other through a carbene complex, but based on several mechanistic studies, they favored the vinylidene complex pathway, which is shown here (Scheme 5.42). 

Saa and coworkers reported a remarkable cycloisomerization of alkynal to cycloalk-ene derivatives with loss of a CO molecule [30] some examples are shown in Table 6.3. Heating 5-alkynal 94a in AcOH (90 °C, 24h) with [Ru(Cp)(CH3CN)3]PF6 (5 mol%) afforded the cyclopentene derivative 9Sa in 90% yield. Ketone 94e afforded the cyclopentene 9Se in moderate yield, whereas the ester 94f gave the noncyclized product 96 with loss of one carbon unit (Table 6.3) (Scheme 6.32). 

Thujene, 179, is reported to give rise to about 807, of (— )-trans-4-hydroxy-/3-thujene 180) and 20% of ( — )-c -sabinol, 181.20i Provided that no free-radical reaction in addition to a type II photooxygenation reaction takes place and that one is allowed to apply the experience obtained with cydohexene derivatives to cyclopentene derivatives, the... 

Irradiation of 2,5,5-trimethyl-2-prop-l-ynylcyclopentanone in pentane (0.1 M) for 72 hours gave, with 70% total conversion, the cyclobutane 3 as the major product (38%) together with various open-chain products and cyclopentene derivatives.150... 

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