1.2.3- Trisubstituted cyclopentenes

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 research groups of Mariano and West developed a photoinduced electrocydi-zation/nucleophilic addition sequence. Thus, irradiation of N-alkylpyridinium perchlorates as 5-19 in an aqueous solution led to the aziridine cations 5-20, which react in a nucleophilic addition with OH to give the isolable azabicyclo[3.1.0]hex-2-enols 5-21. These can be further transformed by a nucleophilic ring-opening of the aziridine moiety under acidic conditions to lead to useful unsymmetrically trans,trans-trisubstituted cyclopentenes 5-22 (Scheme 5.5) [10]. 

Upon fonnation of intermediate LI, conjugate addition to a chalcone and subsequent proton transfer is proposed to lead to enolate LIII (Scheme 37). An intramolecular aldol addition provides activated carboxylate LIV in which alkoxide acylation regenerates the catalyst and delivers p-lactone LVI which, upon decarboxylation, gives rise to a trisubstituted cyclopentene. 

Scheme 37 Proposed mechanism of trisubstituted cyclopentene formation...

Nair V, Vellalath S, Poonoth M, Suresh E (2006b) N-heterocyclic carbene-cata-lyzed reaction of chalcones and enals via homoenolate an efficient synthesis of 1,3,4-trisubstituted cyclopentenes. J Am Chem Soc 128 8736-8737... 

Movassaghi M, Schmidt MA (2005) N- Ielcrocyclic carbene-catalyzed amida-tion of unactivated esters with amino alcohols. Org Lett 7 2453-2456 Nair V, Vellalath S, Poonoth M, Mohan R, Suresh E (2006a) N- Ielcrocyclic carbene catalyzed reaction of enals and 1,2-dicarbonyl compounds stereoselective synthesis of spiro y-butyrolactones. Org Lett 8 507-509 Nair V, Vellalath S, Poonoth M, Suresh E (2006b) V-Heterocyclic carbene-catalyzed reaction of chalcones and enals via homoenolate an efficient synthesis of 1,3,4-trisubstituted cyclopentenes. J Am Chem Soc 128 8736-8737... 

Auxin-a and b share the same trisubstituted cyclopentene ring in their structures. The presence of that ring system was deduced by permanganate oxidation of auxin-a and b, which gave auxin-glutaric acid (D) as crystals. Starting from (.S )-3-methylpcntanoic acid, Kogl and Erxleben synthesized three possible stereoisomers of D, and proposed one of them to be identical with the acid derived from the natural products. 

Later, these authors reported the synthesis of chiral cis-l,3,4-trisubstituted cyclopentenes based on an enantioselective N-heterocyclic carbene-catalyzed domino annulation of a,p-unsaturated aldehydes and 4-oxoenoates [236]. The domino products were achieved in low to high yields (25-93%), in moderate to... 

In 2006, Nair disclosed the synthesis of ( )-tra s-l,3,4-trisubstituted cyclopentenes resulting from the addition of enals to chalcones catalysed by an achiral carbene." " Mechanistically, the addition of the generated homo-enol to enones to give adduct II, followed by intramolecular acylation to afford cyclopentane-fused p-lactone IV. The final cyclopentene 67 was formed by the in situ decarboxylation of the p-lactones (Scheme 20.32). The enantioselective variant of the process to access ds-cyclopentenes was reported by Bode et al. in 2007. ... 

A total synthesis of ( )-allosamizoline from a symmetrical trisubstituted cyclopentene has been reported, and a synthesis of allosamidin and its (1- 3) linked isomer includes a review of the preparation of the starting aminocyclitol and disaccharide moieties. The synthesis of allosamizoline and allosamidin and isomers is also mentioned in Chapters 3 and 18. 

Roberts RA, Schiill V, Paquette LA (1983) Electrophile-initiated Ring-opening Reactions of 2-Methylene-6,6-dimethylbicyclo [3.1.0] hexanes. New Methodology for the Synthesis of Highly Functionalized 1,2,3-Trisubstituted Cyclopentenes. J Org Chem 4 2076... 

A conceptually surprising and new route to prostaglandins was found and evaluated by C.R. Johnson in 1988. It involves the simple idea to add alkenylcopper reagents stereo-selectively to a protected chiral 4,5-dihydroxy-2-cyclopenten-l-one and to complete the synthesis of the trisubstituted cyclopentanone by stereoselective allylation of the resulting enolate. 

Borane may react sequentially with 3 mol of alkene to form mono-, di-, and trialk-ylboranes. Both the alkene structure and reaction conditions affect product distribution. Trialkylboranes are usually formed from terminal olefins [Eq. (6.57)] and unhindered disubstituted alkenes such as cyclopentene irrespective of the reactant ratio.340 The reaction cannot be stopped at the mono- or dialkylborane stage. In contrast, hindered disubstituted olefins (e.g., cyclohexene) and trisubstituted alkenes are converted mainly to dialkylboranes [Eq. (6.58)]. Careful control of... 

Asymmetric hydroboration.1 Hydroboration of 1-phenyl-1-cyclopentene with IpcBH2 (100% ee) results in a dialkylborane (1) containing the traws-2-phenylcyclopentyl group of 100% ee. However, hydroboration of prochiral trisubstituted alkenes usually results in alkylisopinocampheylboranes of 50-85% ee. Most of these products are solids, and selective crystallization (usually from ether) can give the optically pure dialkyboranes. In some cases resolution can be achieved by allowing the impure borane to age for several... 

The relative stabilities of olefinic bonds at various positions in the steroid nucleus have a direct bearing on reactions of several kinds, including elimination reactions Chapter 3), enolisation of ketones (Chapter 4) and the equilibration of olefinic structures (Chapter 5). Infrared absorption spectra in the region 1600-1700 cm""i, which for cyclohexene (1650 cm" ) and cyclopentene (1613 cm " ) reflect the greater strain (5-6 kcal/mole) present in cyclopentene [43], have been employed [44,45] to obtain some indication of the relative stabilities of cis-disubstituted and trisubstituted double bonds. The data are summarised in Table 2. 

The addition of cyclopropenone 1,3-propanediyl ketal to electron deficient olefins produces cyclopentanone ketals 4,4,5-trisubstituted 3,3-[l,3-propanediylbis(oxy)]cyclopentenes 1 in 42-86 % yield with high regioselectivitv. Presumably diradicals or zwitterions are not involved as reactive intermediates, and the reaction starts with nucleophilic attack of the strained cyclopropene olefin onto the electron-deficient olefin2. 

In 2009, Tanaka and co-workers achieved Rh-catalyzed highly enantioselective intermolecular hydroacylation reactions of aliphatic aldehydes 48 with 1,1-substituted acrylamides 49 by using a cationic Rh/QuinoxP complex as the catalyst (Scheme 8.24a). Unfortunately, the reaction of simple benzaldehyde with acrylamide 49a was sluggish and the enantioselectivity was moderate, but utilizing (i ,R)-Me-DuPhos as the ligand could improve both yield and enantioselectivity (Scheme 8.24b). When cyclopentene-substituted amide 49b was subjected to the standard reaction conditions, a thermodynamically stable hydroacylation product 50b was generated with excellent diastereoselectivity (>99 1 dr) and enantioselectivity (97% ee), although dramatically reduced reactivity was observed (5% yield) (Scheme 8.24c). This report represents the first example of an asymmetric hydroacylation reaction of a trisubstituted alkene. 

The allylic methyl group in 76 successful directs the bulky cobalt-alkyne complex to the opposite face of the cyclopentene with 8 1 diastereoselectivity. It is notable that, even in the absence of additives, this intramolecular PKR with a trisubstituted alkene provides useful yields of product. 

The trisubstituted titanacycles 8 and 10, derived from the reaction of 1 with two equivalents of cyclopentene and with one equivalent of endo-dicyclopentadiene respectively, can react with AlMea and give the corresponding methyl-bridged complexes. The yield can not be quantitative as the reaction temperature... 

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