Shuji Kanemasa

Recent advances in synthetic applications of nitrile oxide cycloaddition (1981-1989)

The synthetic applications of nitrile oxide cycloadditions, developed in the 1980s, are briefly reviewed. Topics discussed in the present review are the modern developments on the generation methods of nitrile oxides, on the cycloadditions with multiple bonds other than carbon-carbon double and triple bonds, on reductive cleavage of the nitrogen-oxygen bonds of 2-isoxazolines, on the unmasking of functionalities, and on the asymmetric cycloadditions of nitrile oxides

Recent Advances in Azomethine Ylide Chemistry

Publisher Summary Azomethine ylides are planar molecules composed of one nitrogen and two terminal sp2 carbons. At most, four geometrical isomers are possible for these transient molecules. Their cycloadditions to olefin or acetylene dipolarophiles give rise to the formation of two sets of carbon-carbon bonds in a single step. Because of the structural complexity of azomethine ylide itself compared to other dipoles and the stereochemical selectivity in the cycloadditions, a number of stereoisomers are possible for the cycloadducts. These two points make azomethine ylides one of the most attractive 1,3-dipoles, both in the fields of ylide chemistry and synthetic organic chemistry. Azomethine ylides can be classified in groups according to their structure. This chapter concentrates on the most basic ylides, acyclic azomethine ylides, in order to catch the generalized concepts involved in the azomethine ylide chemistry. Accordingly, it also deals with the recent advances of the chemistry of acyclic azomethine ylides covering its preparation, cycloadditions, intramolecular cycloadditions, and synthetic applications.

Lewis acid-catalyzed nitrone cycloadditions to bidentate and tridentate α,β-unsaturated ketones. High rate acceleration, absolutely endo-selective and regioselective reactions

Abstract α,β-Unsaturated ketone dipolarophiles having bidentate or tridentate ligand structures, such as (E)-1-benzyloxy- and (E)-1-(2-phenylthioethoxy)-3-penten-2-one, are activated by a Lewis acid catalyst in 1,3-dipolar cycloadditions of nitrones. Dichlorodiisopropoxytitanium and chlorotriiso-propoxytitanium are especially effective. Lewis acid-mediated enhancement of stereo- and regioselectivity have been attained for the first time in intermolecular nitrone cycloadditions. Formation of dipolarophile/Lewis acid complexes is responsible for the remarkable Lewis acid catalysis.

Metallic Base-Induced and Lewis Acid-Catalyzed Nitrone Cycloadditions to Allyl Alcohol Dipolarophiles. Highly Effective Regio- and Stereocontrol.

Abstract Cycloaddition of N-(benzoylmethylene)aniline N-oxide as a reactive nitrone to allyl alcohol dipolarophiles are accelerated either 1) by pretreatment of the dipolarophiles with an organometallic compound such as ethylmagnesium bromide or diethylzinc, or 2) in the presence of a Lewis acid such as magnesium bromide or zinc bromide. These cycloadditions are highly regio- and stereoselective, both selectivities depending upon the kind of metals included in the organometallics or Lewis acid employed. These reactions offer the first example of regio- and stereocontrol of nitrone cycloadditions to nonactivated olefins.

CORNERSTONE WORKS FOR CATALYTIC 1,3-DIPOLAR CYCLOADDITION REACTIONS

This review covers the following subjects: (1) The chemistry of N-metalated azomethine ylide as a new 1,3-dipole containing a metal atom is studied. This 1,3-dipole, generated from (N-alkylideneamino)alkanoates upon treatment with a Lewis acid and amine base, undergoes rapid 1,3-dipolar cycloadditions toward electron-deficient alkenes. Especially, α,β-unsaturated carbonyl substrates show high rate acceleration to give pyrrolidine-2,4-dicarboxylates in a highly regio- and endo-selective manner. (2) This 1,3-dipolar cycloaddition reaction of (N-alkylideneamino)acetate can be switched into anti-selective Michael addition reaction by modification of substrate structures as well as reaction conditions. (3) Two types of heterocyclic chiral auxiliaries are demonstrated for the asymmetric 1,3-dipolar cycloadditions. One types are attached at the β-position of α,β-unsaturated esters. The resulting chiral α,β-unsaturated esters are successfully applied to the stereoselective asymmetric cycloadditions of N-metalated azomethine ylides. The other types include 4-benzyl-2,2,5,5-tetramethyloxazolidine-3-acrylamides which are based on the conformational control of the acrylamide reaction site and that of steric shielding of 4-benzyl amoiety. These are applied to the absolutely asymmetric nitrile oxide cycloadditions. (4) The nitrone cycloadditions to electron-deficient alkenes is attained in the presence of a Lewis acid catalyst. This provides the first catalytic stereo control of 1,3-dipolar cycloadditions. (5) The extremly effective rate enhancement of nitrile oxide 1,3-dipolar cycloadditions to the magnesium alkoxides of allylic alcohols. Maximum rate enhancement observed is 16,000 fold rate acceleration of the uncatalyzed reaction. This method offers the first successful rate acceleration in nitrile oxide 1,3-dipolar cycloadditions. (6) Use of magnesium alkoxide of allylic alcohols is also highly effectve in nitrone 1,3-dipolar cycloadditons, resulting in high stereo- and regioselectivities. (7) Catalytic enantioselective 1,3-dipolar cycloadditions are achieved by use of nitrones, nitronates, diazomethane, and nitrile oxides in the presence of tolerant chiral catalysts based on our R,R-DBFOX/Ph ligand.

Enantioselective Michael addition reactions of malononitrile catalyzed by chiral Lewis acid and achiral amine catalysts

Abstract Reactions of malononitrile with 3-(2-alkenoyl)-2-oxazolidinones or 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles can be doubly activated by the use of catalytic amounts (10 mol% each) of both ( R , R )-DBFOX/Ph·Ni(ClO 4 ) 2 ·3H 2 O and amines, to give the Michael adducts in high chemical yields with satisfactory enantioselectivities.

Regiocontrol of nitrile oxide cycloadditions to allyl alcohols. Synthesis of 4-substituted and 4,4-disubstituted 5-hydroxymethyl-2-isoxazolines

Abstract The first regiocontrol of nitrile oxide cycloadditions is described. Reaction of benzonitrile oxide with (E)-2-butenol is highly accelerated by the presence of a magnesium alkoxide, and this reaction proceeds in an exclusively regioselective manner to produce 5-hydroxymethyl-4-methyl-3-phenyl-2-isoxazoline as the sole cycloadduct. Synthetic applications to other substituted allyl alcohols are discussed.

Metal ion-mediated diastereoface-selective nitrone cycloadditions. Reaction mechanism for the reversal of regloselectivity observed in the magnesium and zinc ion-mediated nitrone cycloadditions of allylic alcohols

Magnesium and zinc ion-mediated cycloaddition reactions of a carbonyl-conjugated nitrone, (Z)-N-(benzoylmethylene)aniline N-oxide to the allylic alcohols bearing a chirality at α-position give isoxazolidine-5-alcohol and isoxazolidine-4-alcohol derivatives, respectively, both in highly lk-1,2-inductive manners. α,α-Disubstitution of allylic alcohol dipolarophiles virtually inhibits the zinc ion-catalyzed reaction paths, and use of a coordinating solvent in the magnesium ion-catalyzed reactions leads to the reversal of regioselectivity. Reaction mechanism for the metal ion-catalyzed competitive cycloadditions is proposed.

Generation of nitrile oxides through O-metalation of hydroximoyl chlorides. Chelation-controlled syn-selective cycloaddition of nitrile oxides to α-substituted allyl alcohols

Abstract New generation of nitrile oxides by treatment of hydroximoyl chlorides with organometallics is reported. Their cycloadditions to the allyl alcohols bearing a chiral center at the 1-position proceed in a syn-selective manner, providing the first example of stereocontrol of 1,3-dipolar cycloaddition by the aid of metal chelation.

Exclusively endo-selective lewis acid-vatalyzed hetero diels-alder reactions of (E)-1-phenylsuifonyl-3-alken-2-ones with vinyl ethers

Abstract ( E )-1-Phenylsulfonyl-3-alken-2-ones as new hetero 1,3-dienes undergo smooth hereto Diels-Alder reactions with vinyl ethers in the presence of a catalytic amount of Lewis acid such as ZnI 2 , Eu(fod) 3 , and TiCl 2 ( i -PrO) 2 . The reactions are absolutely endo -selective producing 2,4- cis -3,4-dihydro-2 H - pyrans in excellent yields, the configuration at 3-position depending upon the stereochemistry of the starting vinyl ethers. Reductive ring opening reactions of the 3,4-dihydro-2 H -pyran cycloadducts with Et 3 SiH/TiCl 4 lead to 6-alkoxy-l-phenylsulfonyl-2-hexanones, and the sulfonyl-stabilized carbanions derived from the 3,4-dthydro-2 H -pyran cycloadducts are alkylated followed by reductive desulfonylation to give 2,4,6-trisubstituted 3,4-dihydro-2 H -pyran derivatives.