Stereospecific and highly stereoselective cyclopropanation reactions promoted by samarium.

Samarium metal and samarium diiodide have become important tools as selective cyclopropanating agents in organic synthesis due to their high chemo- and stereoselectivity. Therefore, Sm and SmI(2) are the ideal reagents to prepare cyclopropane derivatives. This tutorial review highlights C-C multiple bond cyclopropanation processes promoted by samarium or samarium diiodide.

Total regioselective transformation of aromatic aziridine 2-carboxamides into 2-aminoamides promoted by active manganese.

A novel, totally regioselective transformation of aromatic N-4-methoxyphenylaziridine 2-carboxamides into 2-aminoamides promoted by active manganese (Mn*) is reported. alpha-Amino ketones can be readily obtained by reaction of morpholine-derived 2-aminoamides with organolithium compounds.

Efficient and highly selective synthesis of enantiopure cis- or trans-3,4-disubstituted 1,2,3,4-tetrahydroisoquinolines.

An efficient synthesis of enantiopure 3,4-disubstituted 1,2,3,4-tetrahydroisoquinolines, by treatment of readily available (2R,1'S)- or (2S,1'S)-2-(1-aminoalkyl)epoxides with H(3)PO(4).BF(3) complex, under mild reaction conditions, is reported. Both enantiopure diastereoisomers (3S,4S)- and (3S,4R)-3-alkyl-4-hydroxymethyl-1,2,3,4-tetrahydroisoquinolines were available starting from the suitable syn- or anti-aminoepoxide, respectively.

General, stereoselective synthesis of (Z)-beta,gamma-unsaturated nitriles promoted by samarium diiodide.

A method to obtain (Z)-beta,gamma-unsaturated nitriles in high or good yields and with moderate or high stereoselectivity is described. The products were achieved through the photoinduced metalation of 3-acetoxy-4-chloronitriles with SmI2. The starting compounds were readily prepared, and a mechanism is proposed to explain this stereoselective beta-elimination reaction.

Addition reactions of iodomethyllithium to imines. A direct and efficient synthesis of aziridines and enantiopure amino aziridines.

An efficient and general synthesis of aziridines by the reaction of imines derived from p-toluenesulfonamides with in situ generated iodomethyllithium, with a simple and rapid experimental protocol, is reported for the first time. The reaction with the chiral aldimine derived from phenylalaninal allowed access to (2R,1'S)-2-(1'-aminoalkyl)aziridine with very high diastereoselectivity, in enantiopure form. A mechanism to explain this novel reaction is proposed.

Recent synthetic applications of manganese in organic synthesis.

While the organometallic compounds derived from many metals have found a broad application in organic synthesis, the use of organomanganese compounds has only recently been developed due to the passivity exhibited by commercial Mn in the direct metalation of organic compounds. In this Concept article, we highlight the potential of manganese and its organometallic compounds in organic synthesis by illustration of the studies previously reported by others and our laboratory in this field. Based on the transformations reported herein, organomanganese compounds could become important tools in the future of the organic synthesis, due to their high selectivity.

Stereoselective synthesis of (Z)-alpha-haloacrylic acid derivatives, and (Z)-haloallylic alcohols from aldehydes and trihaloesters or amides promoted by Rieke manganese.

A Mn*-promoted sequential process directed toward the synthesis of (Z)-alpha-halo-alpha,beta-unsaturated esters or amides is described. In both cases, the process takes place with complete Z-stereoselectivity. In addition, (Z)-alpha-chloro-alpha,beta-unsaturated ketones and carboxylic acids, and (Z)-haloallylic alcohols were readily prepared from (Z)-alpha-halo-alpha,beta-unsaturated amides derived from morpholine, or esters.

Totally selective synthesis of enantiopure (3S,5S)- and (3R,5R)-4-amino-3,5-dihydroxypiperidines from aminodiepoxides derived from serine.

The transformation of enantiopure (2R,4R)- and (2S,4S)-N,N-dibenzyl-1,2:4,5-diepoxypentan-3-amine, 1 and 2, into the corresponding enantiopure (3S,5S)- and (3R,5R)-3,5-dihydroxy-3-aminopiperidines, 3 and 4 respectively, is described. The opening of the two epoxide rings with a range of amines takes place with total regioselectivity and high yields, in the presence of LiClO4. A mechanism to explain this transformation is proposed.

CrCl2-promoted stereospecific and stereoselective alkyl- and silylcyclopropanation of alpha,beta-unsaturated amides.

An efficient chromium-promoted alkyl- or silylcyclopropanation of alpha,beta-unsaturated amides is described. These reactions can be carried out on (E)- or (Z)-alpha,beta-enamides in which the C-C double bond is di-, or trisubstituted. This process takes place with total stereospecificity and the new stereogenic center is generated with high or total stereoselectivity.

Stereoselective synthesis of (Z)-alpha-halo-alpha,beta-unsaturated esters, and amides from aldehydes and trihaloesters or amides promoted by manganese.

Preliminary results of a Mn-promoted sequential process directed toward the stereoselective synthesis of different (Z)-alpha-halo-alpha,beta-unsaturated compounds are described.

Stereospecific and stereoselective alkyl and silylcyclopropanation of alpha,beta-unsaturated amides.

A novel chromium-promoted alkyl- and silyl cyclopropanation of (E)- or (Z)-alpha,beta-unsaturated amides in which the C-C double bond is di-, or trisubstituted is described. This process takes place with total stereospecificity, and the new stereogenic center is generated with high or total stereoselectivity. A mechanism is proposed to explain the cyclopropanation reaction.

Sequential reactions promoted by manganese: completely stereoselective synthesis of (E)-alpha,beta-unsaturated amides, ketones, aldehydes, and carboxylic acids.

A complete E-selective synthesis of alpha,beta-unsaturated amides through a sequential reaction of a range of dichloroamides with a variety of aldehydes promoted by Rieke manganese (Mn*) is reported. A mechanism based on a sequential aldol-type reaction and a completely stereoselective beta-elimination is proposed to explain these results. The unsaturated amides obtained are readily and efficiently transformed into alpha,beta-unsaturated ketones, aldehydes, or carboxylic acids without loss of the diastereoisomeric purity of the C-C double bond.

Totally selective reaction of CO2 with enantiopure amino epoxides under mild reaction conditions. synthesis and synthetic applications of enantiopure (4R,1'S)- or (4S,1'S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes.

The reaction of chiral (2R,1'S)- or (2S,1'S)-2-(1-aminoalkyl)epoxides 1 or 2 with CO2, generated from acidic treatment of an aqueous solution of NaHCO3 at room temperature, efficiently afforded enantiopure cyclic carbonates 3 or 4, respectively, with total selectivity. Compounds 3 and 4 were readily transformed into the corresponding diols 7 and 8 by reaction with LiAlH4 or by basic hydrolysis. When compounds 3 or 4 were allowed to react with methyllithium at -78 degrees C, O1-acetylalkane-1,2-diols 9 and 10 were obtained with total or high selectivity.

Stereospecific cyclopropanation of highly substituted C-C double bonds promoted by CrCl2. Stereoselective synthesis of cyclopropanecarboxamides and cyclopropyl ketones.

We describe herein a CrCl(2)-promoted cyclopropanation of alpha,beta-unsaturated amides. This reaction can be carried out on (E)- or (Z)-alpha,beta-enamides in which the C-C double bond is di-, tri-, or tetrasubstituted. In all cases the process is completely stereospecific and only a single diastereoisomer is obtained.

The first cyclopropanation reaction of unmasked alpha,beta-unsaturated carboxylic acids: direct and complete stereospecific synthesis of cyclopropanecarboxylic acids promoted by Sm/CHI3.

A samarium-promoted cyclopropanation of unmasked alpha,beta-unsaturated acids is described. This reaction can be carried out on (E)- or (Z)-alpha,beta-unsaturated carboxylic acids. In all cases the process is completely stereospecific and stereoselective.

The first sequential reaction promoted by manganese: complete stereoselective synthesis of (E)-alpha,beta-unsaturated esters from 2,2-dichloroesters and aldehydes.

Alpha,beta-unsaturated esters were obtained with complete control of stereoselectivity utilizing a sequential reaction of dichloroesters with a variety of aldehydes, promoted by active manganese. This methodology is generally applicable, and the C-C double bond can be di- or trisubstituted. A mechanism based on a successive aldol-type reaction/beta-elimination is proposed to explain these results.

Efficient addition reaction of bromonitromethane to aldehydes catalyzed by NaI: a new route to 1-bromo-1-nitroalkan-2-ols under very mild conditions.

[Structure: see text] A catalytic NaI-mediated novel synthesis of 1-bromo-1-nitroalkan-2-ols was carried out by reaction of bromonitromethane with a variety of aldehydes, under very mild conditions. When the reaction was performed with chiral N,N-dibenzyl alaninal, the corresponding enantiopure (1S,2S,3S)-3-dibenzylamino-1-bromo-1-nitrobutan-2-ol was obtained with good stereoselectivity. The structure of this enantiopure bromohydrin was established by X-ray analysis.

Efficient nitro-aldol reaction using SmI2: a new route to nitro alcohols under very mild conditions.

A novel method to obtain racemic 1-nitroalkan-2-ols by reaction of bromonitromethane with a variety of aldehydes and promoted by SmI2 is reported. On the basis of these results, the chiral version has also been performed with chiral N,N-dibenzyl amino aldehydes, affording the corresponding enantiopure 3-amino-1-nitroalkan-2-ols with good stereoselectivity.

Synthesis of enantiopure (alphaS,betaS)- or (alphaR,betaS)-beta-amino alcohols by complete regioselective opening of aminoepoxides by organolithium reagents LiAlH4 or LiAlD4.

The reaction of chiral (2R,1'S)- or (2S,1'S)-2-(1-aminoalkyl)epoxides, 1 or 2 with a variety of organolithium compounds to obtain the corresponding (alphaS,betaS)- or (alphaR,betaS)- beta-amino alcohols in enantiopure form is reported. In both cases, the opening of the oxirane ring at C-3 proceeded with total regioselectivity. Moreover, the ring opening of aminoepoxides 1 or 2 by hydride (utilizing LiAlH4) to obtain the corresponding (2S,3S)- or (2R,3S)-3-aminoalkan-2-ols is also described.

Aldol-type reactions of unmasked iodoacetic acid with carbonyl compounds promoted by samarium diiodide: efficient synthesis of carboxylic 3-hydroxyacids and their derivatives.

An easy, direct, general, and efficient samarium diiodide-mediated preparation of 3-hydroxyacids 1 in high yield by reaction of different aldehydes or ketones with commercially available iodoacetic acid is described. The application of different esterification procedures to the crude 3-hydroxyacids so obtained afforded the corresponding 3-hydroxyesters. Also, the cyclization of crude 3-hydroxycarboxylic acids allowed the preparation of beta-lactones.

Direct reaction of dibromoacetic acid with aldehydes promoted by samarium diiodide: an easy, efficient, and rapid synthesis of (E)-alpha,beta-unsaturated carboxylic acids with total stereoselectivity.

A promoted SmI2 direct reaction of dibromoacetic acid with different aldehydes, followed by an elimination reaction also promoted by samarium diiodide, affords (E)-alpha,beta-unsaturated carboxylic acids 2 with total stereoselectivity. A mechanism to explain this transformation is proposed.

Synthesis of enantiopure allylamines by reductive alkylation of amino epoxides with organolithium reagents.

[reaction: see text] Transformation of enantiopure (2R,1'S)-2-(1-aminoalkyl)epoxides 1 into the corresponding allylamines 2 is described. The opening of the epoxide ring with different organolithium compounds takes place with total selectivity and in high yields.