Asymmetric synthesis of trans-disubstituted cyclopropanes using phosphine oxides and phosphine boranes

Abstract

The stereocontrolled synthesis of trans-disubstituted cyclopropylketones has been achieved from beta-alkyl, gamma-benzoyl phosphine oxides via a three-step cascade reaction incorporating an acyl transfer, phosphinoyl transfer and cyclisation to form the cyclopropane. Using Evans' chiral oxazolidinone auxiliary and by masking the phosphine oxide moiety as a phosphine borane we have extended the method to the synthesis of enantiomerically-enriched trans-disubstituted cyclopropyl ketones.

Exploring the Reactivity of Donor-Stabilized Phosphenium Cations: Lewis Acid-Catalyzed Reduction of Chlorophosphanes by Silanes

“…NaBH 4 has been reported to reduce secondary chlorophosphanes to directly form the protected secondary phosphane–borane adduct, , which may then be deprotected if required, but does not reduce other PX bonds (X = OR, O) . Borane itself, BH 3 , does not reduce PCl bonds, instead forming chlorophosphane–borane adducts which may then be cleanly reduced to PH species with the protecting group intact; , a mixture of LiAlH 4 and NaBH 4 may also be used to form phosphane–borane adducts, generating the required BH 3 in situ …”

“…13 NaBH 4 has been reported to reduce secondary chlorophosphanes to directly form the protected secondary phosphane−borane adduct, 14,15 which may then be deprotected if required, but does not reduce other PX bonds (X = OR, O). 16 Borane itself, BH 3 , does not reduce PCl bonds, instead forming chlorophosphane−borane adducts which may then be cleanly reduced to PH species with the protecting group intact; 17,18 a mixture of LiAlH 4 and NaBH 4 may also be used to form phosphane− borane adducts, generating the required BH 3 in situ. 19 Silanes have been extensively used as mild reducing agents, with and without catalysts, 20−22 for the reduction of PO bonds to convert phosphane oxides to phosphanes, a reaction driven by the formation of strong SiO bonds.…”

The lithiation and acyl transfer reactions of phosphine oxides, sulfides and boranes in the synthesis of cyclopropanes

“…2) using an Evans oxazolidinone auxiliary to achieve asymmetric induction. 5 During the investigation of b-substituted cyclopropanation substrates we discovered that the diphenylphosphinoyl substituent was not compatible with the conditions used for the asymmetric alkylation (Step ii) resulting in loss of the auxiliary. 5 We successfully circumvented this problem by using diphenylphosphine borane 6 that could be converted to phosphine oxide 7 at a later stage (Step iv).…”

Toward a Synthesis of Fawcettimine-Type Lycopodium Alkaloids: Stereocontrolled Synthesis of a Functionalized Azaspirocycle Precursor

“…The second Mitsunobu reaction was then attempted to construct an azacyclononane framework. Interestingly, however, cyclopropyl ketone 16 was obtained in 84% yield insteadthe first example of the formation of a cyclopropyl ketone from a 3-hydroxypropyl ketone under conventional Mitsunobu conditions, to the best of our knowledge . Unfortunately, 16 could not be converted into an azacyclononane through intramolecular nucleophilic substitution of the nosyl amide in the presence of either KO t -Bu, TFA, or a Lewis acid such as ZrCl 4 , Sc­(OTf) 3 , AlCl 3 , or BF 3 ·OEt 2 .…”