Maurice Santelli

trans-1,3-Divinylcyclopentanes bearing a ω-nitroalkyl chain (C₂ or C₃) in the 2-position were submitted to an intramolecular nitrile oxide cycloaddition process to give tricyclic isoxazoline precursors of 4-hydroxymethylbicyclo[3.3.0]octan-1-ol-3-ones or 5-hydroxymethyl-9-vinylbicyclo[4.3.0]nonan-1-ol-4-ones.

The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphenyl­phosphinomethyl)cyclopentane in combination with [Pd(C₃H₅)Cl]₂ affords a very efficient catalyst for the Heck reaction of protected alk-1-en-3-ols, -4-ols, -5-ols or -6-ols with aryl bromides. With 3-benzyloxyhex-1-ene or 4-benzyloxypent-1-ene, the (E)-1-aryl-3-benzyloxyhex-1-ene or (E)-1-aryl-4-benzyloxypent-1-ene derivatives were regio- and stereoselectively obtained. The protected ethylenic­ primary alcohols 4-benzyloxybut-1-ene, 4-tetrahydropyranyloxybut-1-ene, 5-tetrahydropyranyloxypent-1-ene and 6-tetrahydropyranyloxyhex-1-ene led in general to the (E)-1-aryl-4-benzyloxybut-1-ene or (E)-1-aryltetrahydropyranyloxyalk-1-enes as major isomers. However, with these substrates, the migration of the double bond was observed, and mixtures of isomers were obtained in most cases. The selectivities of the reactions depend both on electronic and steric factors. With electron-poor aryl bromides higher selectivities in favour of 1-arylalk-1-enol derivatives were generally obtained than with electron-rich aryl bromides. In the presence of sterically congested aryl bromides, larger amounts of products resulting from the migration of the double bond were observed. For example from 2,4,6-triisopropylbromobenzene and 6-tetrahydropyranyloxyhex-1-ene, 6-(2,4,6-triisopropylphenyl)hexanal was obtained as major product after deprotection. For most of these reactions, similar reactions-rates were observed with electron-poor and electron-rich aryl bromides. Several reactions can be performed with as little as 0.1% catalyst.

A range of aryl bromides undergo Heck reaction with ethylene glycol vinyl ether, in the presence of [PdCl(C₃H₅)]₂/cis,cis,cis‐1,2,3,4‐tetrakis[(diphenylphosphanyl)methyl]cyclopentane as catalyst, to give regioselectively protected arylacetaldehydes in good yields. The β‐arylation products were obtained in with 93–100 % selectivity with electron‐poor aryl bromides or heteroaryl bromides. Furthermore, this catalyst can be used at low loading, even for reactions with sterically hindered aryl bromides. The aryl vinyl ether intermediates undergo subsequent ketalisation to give the corresponding 2‐benzyl‐1,3‐dioxolane derivatives.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Desymmetrization of the anti-meso-acetylmethyldivinyl cyclopentane was realized through a three-step sequence involving reduction of the ketone moiety, bishomoallylic alcohol-directed epoxidation and Dess-Martin oxidation leading to the epoxy ketone as a single diastereoisomer. The epoxy ketone was efficiently converted to a trans-hydrindane unit, which constitutes an excellent precursor for the preparation of steroids and their seco-B analogues such as vitamin D₃ and its metabolites.

The acylation of an excess of racemic spirolactone 1 (6,9‐divinyl‐1‐oxaspiro[4.4]nonan‐2‐one) enolate by protected methyl (S)‐lactate or (–)‐bornyl carbonate occurs with a kinetic resolution. The resulting lactones were alkylated with 1‐iodobenzocyclobutenes to afford compounds that serve as precursors to nonracemic steroids such as 11α‐alkyloxycarbonyl‐11β,13β‐(γ‐carbolactone)‐17β‐vinylgonatri‐1,3,5(10)‐enes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane in combination with [Pd(η³-C₃H₅)Cl]₂ affords a very efficient catalyst for the Heck reaction of aryl bromides with pent-4-en-2-ol, 2-phenylpent-4-en-2-ol, or hept-6-en-3-ol. With pent-4-en-2-ol or hept-6-en-3-ol, the selectivity in favour of the formation of the 5-arylpentan-2-one or 7-arylheptan-3-one derivatives, respectively, depends on the substituents on the aryl bromide and on the base. Sterically congested and electron-rich aryl bromides gave selectively the linear ketones by migration of the double bond. With electron-poor aryl bromides, the formation of large amounts of (E)-1-arylalk-1-enol derivatives or side products was observed in some cases. Similar reactions rates were observed with electron-poor and electron-rich aryl bromides. Several reactions can be performed with as little as 0.01% catalyst. A wide variety of substituents, such as methoxy, dimethylamino, fluoro, trifluoromethyl, acetyl, benzoyl, formyl, carboxy, or cyano groups, on the aryl bromides are tolerated. The coupling of very sterically congested aryl bromides, such as 9-bromoanthracene or 2-bromo-1,3,5-triisopropylbenzene, also proceeds in good yields. Heck reaction with 2-phenylpent-4-en-2-ol gave the expected (E)-5-aryl-2-phenylpent-4-en-2-ol derivatives in high turnover numbers (TONs) and high selectivities in most cases. However, with some electron-poor aryl bromides the selective formation of 1-arylprop-1-ene derivatives resulting from a C-C bond cleavage was observed.