Cyclopentanes disubstituted

Another photochemically induced domino process consisting of three steps was employed for the formation of 1,2-disubstituted cyclopentanes 5-39, as described by Tietze and coworkers. Irradiation of a mixture of 5-36, dimethyl malonate and catalytic amounts of the Lewis acid Me2AlCl in a Pyrex flask caused a Norish Type I cleavage of 5-36, followed by an intramolecular hydrogen shift to give the acyclic... 

C—H bond 174-280,28i por comparison, only trace amounts of cyclopentane resulted from the CuS04-catalyzed decomposition of 1 -diazo-2-octanone or l-diazo-4,4-dimethyl-2-pentanone 277). It is obvious that the use of Rh2(OAc)4 considerably extends the scope of transition-metal catalyzed intramolecular C/H insertion, as it allows for the first time, efficient cyelization of ketocarbenoids derived from freely rotating, acyclic diazoketones. This cyelization reaction can also be highly diastereo-selective, as the exclusive formation of a m is-2,3-disubstituted cyclopentane carboxylate from 307 shows281 a). The stereoselection has been rationalized by... 

Hydrosilylation of 1,6-dienes accompanied by cyclization giving a five-membered ring system is emerging as a potential route to the synthesis of functionalized carbocycles.81,81a,81b 82 As its asymmetric version, diallylmalonates 86 were treated with trialkylsilane in the presence of a cationic palladium catalyst 88, which is coordinated with a chiral pyridine-oxazoline ligand. As the cyclization-hydrosilylation products, //ww-disubstituted cyclopentanes 87 were obtained with high diastereoselectivity (>95%), whose enantioselectivity ranged between 87% and 90% (Scheme 25).83 83a... 

Molybdenum catalysts that contain enantiomerically pure diolates are prime targets for asymmetric RCM (ARCM). Enantiomerically pure molybdenum catalysts have been prepared that contain a tartrate-based diolate [86], a binaph-tholate [87], or a diolate derived from a traris-1,2-disubstituted cyclopentane [89, 90], as mentioned in an earlier section. A catalyst that contains the diolate derived from a traris-1,2-disubstituted cyclopentane has been employed in an attempt to form cyclic alkenes asymmetrically via kinetic resolution (inter alia) of substrates A and B (Eqs. 45,46) where OR is acetate or a siloxide [89,90]. Reactions taken to -50% consumption yielded unreacted substrate that had an ee between 20% and 40%. When A (OR=acetate) was taken to 90% conversion, the ee of residual A was 84%. The relatively low enantioselectivity might be ascribed to the slow interconversion of syn and anti rotamers of the intermediates or to the relatively floppy nature of the diolate that forms a pseudo nine-membered ring containing the metal. 

On the other hand, Beckwith rules [22] are useful guidelines for predicting the stereoselectivity in the cyclisation of substituted hexenyl radicals i) 1- or 3-substituted radicals give preferentially cij-disubstituted cyclopentane derivatives and ii) 2- or 4-substituted radicals give mainly rrans-disubstituted derivatives. These rules can be explained in terms of 1,3-diaxial interactions present in a chair-like transition state. Some examples which demonstrate such an effect are [19b] ... 

The inversion process accompanying Sn2 reactions may have particular significance in cyclic compounds. Thus, if we consider the disubstituted cyclopentane derivative shown undergoing an Sn2... 

Dauben s group utilized the same retrosynthetic disconnections, but chose to add more functionality to the cycloaddition precursor. From a simple frawi-disubstituted cyclopentane, Dauben used an aldol reaction of a cyclopropylvinyl aldehyde to prepare the cycloaddition precursor. The diazo-substituted (3-ketoester was completed using a Roskamp-Padwa coupling followed by diazo-transfer. Addition of rhodium acetate to the diazo substituted p-ketoester 179 led to an excellent 86% yield of the correct diastereomer (Scheme 4.42). 

The use of 13C-NMR spectroscopy in stereochemical assignment of disubstituted cyclopentanes has been investigated using dimethylcyclopentanes and mcthylcyclopentanols495. In 1,2-disubstituted derivatives the chemical shifts of the substituted and the methyl carbons are significantly smaller (2 to 5 ppm) in the cis than in the trans series. In 1,3-disubstituted cyclopentanes the sequence is the same, but the differences are often so small that a reliable assignment is possible only if both isomers are available. 

Thus, the hydroboration of 1-phenylcyclopentene with (—)-IpcBH, (99% produces, after crystallization, the chiral organoborane 126 with 94% ee. The reaction of 126 with Et2BH replaces the isopinocamphenyl group with an ethyl substituent (50 C, 16 h) and provides, after the addition of i-Pr2Zn (25 °C, 5 h), the mixed diorganozinc 127. Its stereoselective allylation leads to the fraw5-disubstituted cyclopentane 128 in 44% yield (94% ee trans cis = 98 2) see Scheme 43 ° . This sequence can be extended to open-chain alkenes and Z-styrene derivative 129 is converted to the anf/ -zinc reagent 130, which provides after allylation the alkene 131 in 40% yield and 74% ee (dr = 8 92). 

Although the fate of the zinc ligands was not unambiguously ascertained, it appeared clearly that palladium to zinc transmetallation occurred prior to cyclization. Indeed, palla-dium-ene reactions are known but generally require higher temperatures and, when run in association with a subsequent Stille cross-coupling, trans- 1,2-disubstituted cyclopentanes were generated (equation 81)115,116. 

Some selected examples of such a pinacol rearrangement applied in the preparation of cy-clopentanones are shown in Table 2 further examples can be found in refs 35-39. A number of cyclopentenones, 2,2-disubstituted cyclopentane-1,3-diones and 2,2-disubstituted 3-methylenecyclopentanones were synthesized by this method. 

A modification of this method utilizes the direct conversion of l,2-bis(trimethyl-siloxy)cyclobutene in one step to 2,2-disubstituted cyclopentane-1,3-diones. For example, 2-ethyl-2-methylcyclopentane-l,3-dione (3) was obtained in 91% yield from 1.2-bis(trimethyl-siloxy)cyclobutene and butan-2-one 2,2-dimethylpropane-l,3-diyl acetal.41 Further examples... 

Table 3. 2,2-Disubstituted Cyclopentane-1,3-diones by the One-Step Conversion of 1,2-Bis-(trimethylsiloxy)cyclobutcnc with Acetals3...

Michael intramolecular alkylation. The reaction of f-butyl lithioacetate (1) with ethyl 6-iodo-2-hexenoate 2 in the presence of potassium t-butoxide in THF at - 78° results in a single trans-1,2-disubstituted cyclopentane (3). Reaction of 2 with f-butyl lithiopropionate (4) under the same conditions results mainly in syn-5, but when HMPT is also present anti-5 is mainly formed. Similar stereoselectivity is observed in reaction of 1 and 4 with ethyl 6-iodo-2-heptenoate in formation of... 

The ene reaction has proved to be particularly powerful in synthesis when carried out intramolecularly. The usual increase in rate for an intramolecular reaction allows relatively unreactive partners to combine. Thus the diene 6.13 gives largely (14 1) the cis disubstituted cyclopentane 6.15 by way of a transition structure 6.14. It is important to recognize that the selective formation of the ci j-disubstituted cyclopentane has nothing to do with the rules for pericyclic reactions. It is a consequence of the lower energy when the trimethylene chain spans the two double bonds in such a way as to leave the hydrogen atoms on the same side of the folded bicyclic structure. This... 

TMSOTf-mediated intramolecular cyclization of allylsilanes with alkylidene 1,3-dioxo moiety gives almost exclusively the fraws-l,2-disubstituted cyclopentanes 76 in high yield (equation 50). Other Lewis acids or fluoride ion can also promote similar reactions114. In the presence of the chiral auxiliary, such intramolecular cyclization gives the corresponding iraws-l,2-disubstituted cyclopentanes and cyclohexanes 77 (equation 51) in excellent enantioselectivity115. 

Disubstituted cyclopentane-1,3-diones and cyclohexane-1,3-diones were used as substrates. After formation of the aldol adducts subsequent intramolecular dehydration furnished products of types 94 and 96. The asymmetric intramolecular aldol reaction proceeds with a broad variety of natural amino acids as organocata-lysts. Among these L-proline was usually found to be the most versatile. For example, conversion of the 2,2-disubstituted cyclopentane-1,3-dione 93 in the presence of L-proline gave the desired product 94 in 86.6% yield and with enantioselectivity of 84% ee [97]. This example and a related reaction with a 2,2-disubstituted cyclohexane-1,3-dione 95 are shown in Scheme 6.42. Chiral induction depends... 

Cyclization of dienes.3 Cp2Zr also promotes cyclization of 1,6-dienes to trans-1,2-disubstituted cyclopentanes. Thus 1,6-heptadiene (1) on treatment with Cp2Zr followed by bromination affords the trans-dibromide 2. In contrast, use of a related reagent, Cp ZrCl (Cp = pentamethylcyclopentadienyl), effects cyclization to the isomeric ds-dibromide (equation I). Electrophiles other than bromine can... 

Cyclization of trienes.1 In combination with 2,2-bipyridyl (bpy), an iron(O) species prepared by reduction of iron(III) 2,4-pentanedionate with A1(C2H5)3 (3 equiv.) promotes cyclization of trienes (1) in which a 1,3-diene unit is tethered to an ally lie or homoallylic ether group. vic-Disubstituted cyclopentanes or cyclohexanes are formed, and the cisltrans disposition of the substituents is controlled by the geometry of the allylic double bond. Thus (Z,E-)1 is cyclized to trans-2, whereas (E,E)-1 is cyclized to cis-2. 

Turova-Polyak and co-workers have carried out extensive studies of naphthene isomerization with AICI3, particularly of the substituted cyclopentanes. The conversion of mono- and disubstituted cyclopentanes to cyclohexanes was reported as an analytical technique for the determination of cyclopentanes in mixture with paraffins (411). Ethyl-cyclopentane at room temperature gave an 18-20% yield of cyclohexane derivatives (412). At 140-145°, an 85% yield of 1,3,5-trimethyl-cyclohexane was obtained. This work was also extended to 1,1-dimethyl-cyclopentane (410), up to 95% of which was converted to methyl-cyclohexane at 115°. Similar conversions of alkylated cyclopentanes were also reported by Shulkin and Plate (375). These researches parallel similar work done in the United States. 

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