Akio Kamimura

Denitrohydrogenation of aliphatic nitro compounds and a new use of aliphatic nitro compounds as radical precursors

Abstract Aliphatic nitro groups are replaced by hydrogen on treatment with tributyltin hydride which proceeds via free radical chain processes. As the nitro group is selectively denitrated and other reducible groups are not affected with tributyltin hydride, this reaction can be used as a method for removing the nitro group from polyfunctional compounds. The radical intermediates generated via denitration can be also used for the carbon-carbon bond forming reactions.

β-Sulfonylnitroolefins as very reactive alkyne-equivalents in Diels-Alder reactions

Abstract Very reactive dienophiles, β-sulfonylnitroolefins, are prepared starting from β-nitro alcohols. The high activation due to the nitro and the sulfonyl groups promotes the Diels-Alder reaction to various dienes under mild conditions. Reductive elimination of the adduct with Bu 3 SnH gives cyclic 1,4-dienes.

Use of the Diels-Alder adduct of pyrrole in organic synthesis. Formal racemic synthesis of Tamiflu.

A new synthetic route to Tamiflu was developed via the Diels-Alder reaction of pyrrole and bromoacetylene.

Synthesis of Hydroximoyl Chlorides from Aldoximes and Benzyltrimethylammonium Tetrachloroiodate (BTMA ICl4)

Abstract Benzyltrimethylammonium tetrachloroiodate (BTMA ICl 4 ) acts as a convenient reagent to convert aldoximes to hydroximoyl chlorides by a simple procedure. When an aldoxime is treated with BTMA ICl 4 in dichloromethane, the suspension of BTMA ICl 4 shortly diasappears as the reaction proceeds. The resulting BTMA ICl 2 can be precipitated out by adding diethyl ether. Not only stable aromatic and heteroaromatic hydroximoyl chlorides can be isolated by this method but also rather unstable aliphatic hydroximoyl chlorides can be generated in situ. 1,3-Dipole trapping with a dipolarophile is performed in one flask and in some cases the chlorination is successfully performed in the presence of dipolarophile and triethylamine. Effect of MS 4A has been examined.

Oxidation of benzyl alcohols by semi-stoichiometric amounts of cobalt-doped birnessite-type layered MnO2 under oxygen atmosphere

Semi-stoichiometric oxidation of benzylic alcohols to benzaldehydes was readily achieved in heated toluene in the presence of cobalt-doped birnessite MnO2 under oxygen atmosphere. The oxidation took place selectively for benzylic alcohols, while allylic alcohols were oxidized slowly. No oxidation occurred for usual primary and secondary alcohols. Oxygen atmosphere was important to perform effective oxidation; i.e. the oxidation progressed much slower in nitrogen atmosphere. Cobalt-doped birnessite was the best catalyst for the oxidation, in which the amount of birnessite was reduced to 0.7 equivalent of alcohol, resulting in yields of aldehydes greater than 80%. The present method provides a useful green oxidation for benzylic alcohols.

Asymmetric synthesis of 2-alkyl-substituted 2,5-dihydropyrroles from optically active aza-Baylis-Hillman adducts. Formal synthesis of (-)-trachelanthamidine.

A series of optically active 2-alkyl-substituted 2,5-dihydropyrroles were prepared via the asymmetric aza-Baylis-Hillman equivalent reaction and subsequent ring-closure metathesis reaction. Optically active aza-Baylis-Hillman adducts underwent a smooth two-step conversion to N-allyl-beta-amino-alpha-methylene esters in high yield, which gave chiral 2,5-dihydropyrroles, potential precursors for the aza-heterocyclic synthesis, almost quantitatively through RCM reaction catalyzed by Grubbs catalyst. The conversion was carried out without loss of the optical purity of the starting material. Synthetic application of the method to (-)-trachelanthamidine was examined. Hydrogenation of 2,5-dihydropyrrole took place smoothly to give the corresponding 2,3-disubstituted pyrrolidine in good yield. The stereoselectivity of the hydrogenation was sensitive to the presence or absence of the protective group in the C2-side chain. The TBS-protected 2,5-dihydropyrrole gave a 1:1 mixture of the cis/trans isomers, while free alcohol afforded the trans-2,3-disubstituted pyrrolidine in a selectivity of 6:1. The formal synthesis of (-)-trachelanthamidine was achieved in 11 steps from a chiral sulfinimine. This methodology provided a convenient procedure for the preparation of C2-alkyl-substituted 2,5-dihydropyroles with retention of high optical purity.

Enantioselective preparation of 3,4,5-trisubstituted 4,5-dihydroisoxazoles and their stereoselective elaboration of 5-side chain

Abstract The magnesium ion-induced nitrile oxide cycloaddition to chiral α-silylallyl alcohols was examined. Treatment of chiral allyl alcohol with nitrile oxide in the presence of magnesium cation resulted in the smooth progress of the 1,3-dipolar cycloaddition to give optically active 4,5-dihydroisoxazoles in good yields. The present procedure serves as a good method for the preparation of multi-substituted 4,5-dihydroisoxazoles with high enantiomeric excess. When exposed to tetrabutylammonium fluoride (TBAF), the cycloadducts were converted into 4-substituted-5,6-dihydro-4H-[1,2]-oxazines in good yields without loss of optical purity. Acylsilanes, obtained by the oxidation of the cycloadduct, underwent stereoselective allylation reaction induced by Lewis acid to accomplish the elongation of C5-side chain in a stereoselective manner.

Catalytic asymmetric synthesis of α-methylene-β-hydroxy-ketones

Condensation of an α,β-unsaturated ketone, an aldehyde and trimethylsilyl phenyl sulfide or selenide, catalysed by a chiral (acyioxy)borane, and subsequent oxidative elimination gives the title adducts in high enantiomeric excess.

A new synthesis of allylic alcohols or their derivatives via reductive elimination from γ-phenylthio-β-nitroalcohols with tributyltinhydride

Abstract Allylic alcohols are readily prepared by the Bu 3 SnH-promoted elimination reaction from γ-phenylthio-β-nitroalcohls which are obtained by the joint reaction of nitroolefins, thiophenol, and aldehydes.

Conjugate addition of alkyl groups to α,β-unsaturated sulfoxides via Michael addition of nitroparaffins and subsequent denitration with tributyltin hydride

Abstract Michael addition of nitroparaffins to α,β-unsaturated sulfoxides is well effected in the presence of DBU. The nitro group in the adduct is replaced by hydrogen with Bu 3 SnH without influence to the sulfinyl function. The overall reations provide an efficient method for the conjugate addition of alkyl groups to α,β-unsaturated sulfoxides.