Cyclopentenols synthesis

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

Crimmins reported the synthesis of enantiomerically pure cyclopentenol derivative 8 from diene 6 using ring-closing olefin metathesis followed by treatment with UBH4 [Eq. (6.7)] ... 

As an application of this procedure, Snapper succeeded in the formal total synthesis of (+)-astericanolide. Treatment of iron complex 62, which is prepared from cyclopentenol derivative 60 and iron complex 61, with MeaNO gives fused cyclobutene derivative 63. ROM of cyclobutene of 63 using Ig under ethylene gas smoothly proceeds to produce an eight-membered ring of 64 via Cope rearrangement. The resulting product 64 is converted into Wender s intermediate for the synthesis of (+)-astericanolide ... 

Similar treatment of carbonate roc-20 with Pd(0)/L (2 mol%), BPA (3 mol%), and water in CH2CI2 afforded indenol 21 in 88% yield with 97% ee (Scheme 2.1.4.26) [37]. Indenol 21 and cyclopentenol 9d are useful building blocks for the synthesis of an HlV-protease inhibitor and a chiral catalyst for asymmetric Diels-Alder reactions, respectively [38]. 

Other approaches to the stereoselective total synthesis of nonaromatic steroids include the carbocationic, biomimetic cyclizntion reactions. Generally, these cyclizations begin with the synthesis of an appropriately functionalized cyclopentenol. Acid-catalyzed cyclization forms the B-C-D rings of the steroid nucleus with the natural relative stereochemistry in a single step. 

Because it is often possible to control the stereochemical orientation of substituents on a cyclic array, Baeyer-Villiger cleavages of substituted cyclic ketones have been used extensively in the stereocon-trolled syntheses of substituted carbon chains. An asymmetric synthesis of L-daunosamine intermediate (30) from a noncarbohydrate precursor employed the cyclopentenol (28), prepared in optically pure form (95% ee) from 2-methylcyclopentadiene using asymmetric hydroboration (Scheme 8). Stereoselective epoxidation, conversion to Ae ketone and regioselective Baeyer-Villiger oxidation afforded lactone (29). 

The osmylation of l-[Af-methylphenylsulfoximinomethyl]-l-hydroxy-2-cyclopentenols and -2-cyclohexenols, obtained in turn from the corresponding 2-cycloalkenones by the addition of lithiated, V,.S -dimethyl-5-phenylsulfoximine, occurs from the same side as the sulfoximino functionality with complete Ik topicity. Subsequent thermal elimination of the sulfoximine group allows the synthesis of optically pure 2,3-dihydroxycycloalkanones. This method can, therefore, be regarded as proceeding via an auxiliary-controlled osmylation92-93. 

Table 3 Synthesis of Fused Carbocycles, j5,y-Unsaturated Ketones and 3-Cyclopentenols from Diene-Magnesium Reagents...

In the laboratory of G.A. Molander, a general route for the synthesis of eunicellin diterpenes was developed and was applied for the asymmetric total synthesis of deacetoxyalcyonin acetate. One of the key steps was an inramolecular NHK coupling reaction between an enol triflate and an aldehyde. The cyclopentenol product was formed in high yield as a 2 1 mixture of diastereomers. The undesired diastereomer could be transformed to the desired one using a Mitsunobu reaction. 

Hydroxy-2-cyclopentenones. The reagent reacts with ketone enolates to form functionalized cyclopentenol derivatives which on exposure to TBAF leads to 4-hydroxy-2-cyclopentenones. A successfiil application of the method to the synthesis of the... 

Further studies on the development of synthetic routes to pseudoguaianolides have resulted in the stereospecific synthesis of ( )-ambrosin (593)/ ( )-damsin (592)/ ( )-helenalin (595)/ ° and the seco-pseudoguaianolide psilos-tachyin C (594) cf. Schemes 61 and 62). An elegant feature of these synthetic routes is the use of a common cyclopentenol intermediate (591) (R = H or CH2Ph) derived from norbornadiene (588) (Scheme 60) cf. Vol. 6, p. 90). 

After development of the procedure for synthesis and cyclization of the 3-methyl-2-cyclopentenol in a model series, the aldehyde 95 was converted to the required cyclopentenol, 118 (Scheme 17). 

Trimethylsilylhomopropargylmagnesium chloride was used as a masked 2-butanone synthon, on reaction with 95. Hydration with concomitant desilylation, followed by oxidation of the resultant hydroxy ketone and base cyclization yielded the cyclopentenol (118) after reduction. Despite success on the model system, cyclization of the cyclopentenol (118) proceeded only in low yield, to give the olefins 119 and 120. Oxidative ring enlargement " of the major isomer 119 formed the target enone 121, completing the alternate formal total synthesis of alnusenone. Both 119 and 120 provided 122 on demethoxylation. 

At the inception of the above-described synthetic scheme for the synthesis of alnusenone, two possible cyclic allylic alcohols were considered for initiation of the cyclization step. As well as the cyclopentenol 118, the 4-methyl-2-cy-... 

Pd(0)-catalyzed allylation of purine derivatives with cyclopentenol esters and other alicydic allylic esters is a key step in the preparation of natural and unnatural carbanucleosides with antiviral activity. Carbanucleosides cannot be hydrolyzed as conventional nucleosides are since the anomeric carbon atom is absent therefore, their activity and stability render carbanucleosides valuable compounds. Although much work has been performed with aUylic acetates, a few examples of the application of allylic carbonates in carbanucleoside synthesis have been reported and their number will increase in the future. Two earlier examples by Trost and co-workers are in Scheme 30, including the numbering system of the purine skeleton. Other examples refer to more couplings of purines with flve-membered or with six-membered... 

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