Asymmetric cycloaddition reactions

A stereoselective cycloaddition process which comprises

• combining a dienophile and a 1,3-diene in the presence of a non-racemic chiral catalyst to produce a stereoisomerically enriched product, wherein said dienophile is represented by formula 119, said 1,3-diene is represented by formula 118, and said chiral catalyst consists of a chiral tetradentate ligand having at least one schiff base nitrogen, a transition metal atom, wherein said transition metal atom is not titanium, which is not in its highest state of oxidation, and a counterion;
• ##STR54## in which each occurrence of Z independently represents C(R.sub.50), Si(R.sub.50), N, or P, wherein R.sub.50 represents a hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or --(CH.sub.2).sub.m --R.sub.7 ;
• Y represents O, S, or N(R.sub.50);
• and
• R.sub.1, R.sub.2, R.sub.3, and R.sub.4 represent independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or --(CH.sub.2).sub.m --R.sub.7 ;
• R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;
• and m is zero or an integer in the range of 1 to 8;
• and
• maintaining the combination under conditions whereby said chiral catalyst catalyzes a stereoselective cycloaddition reaction between said dienophile and said 1,3-diene.

A process of catalyzing a stereoselective cycloaddition reaction which comprises

• combining a dienophile, a 1,3-diene, and a non-racemic chiral catalyst, wherein said dienophile is represented by formula 119, said 1,3-diene is represented by formula 118, and said chiral catalyst consists of a chiral tetradentate ligand, a transition metal atom, wherein said transition metal atom is not titanium, which is not in its highest state of oxidation, and a counterion;
• ##STR56## in which each occurrence of Z independently represents C(R.sub.50), Si(R.sub.50), N, or P, wherein R.sub.50 represents a hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or --(CH.sub.2).sub.m --R.sub.7 ;
• Y represents O, S, or N(R.sub.50);
• and
• R.sub.1, R.sub.2, R.sub.3, and R.sub.4 represent independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or --(CH.sub.2).sub.m --R.sub.7 ;
• R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;
• and m is zero or an integer in the range of 1 to 8;
• and
• maintaining the combination under conditions whereby said chiral catalyst catalyzes a stereoselective cycloaddition reaction between said dienophile substrate and said 1,3-diene substrate.

A process for synthesis of stereoisomerically enriched chiral compounds, comprising reacting a dienophile substrate with a 1,3-diene substrate in the presence of a chiral non-racemic catalyst, wherein said chiral catalyst catalyzes stereoselective cycloaddition between said dienophile substrate and said 1,3-diene substrate to produce a product which is stereoisomerically enriched, wherein the 1,3-diene and dienophile substrates are represented by general formulas 118, and 119, respectively;

• ##STR63## in which each occurrence of Z independently represents C(R.sub.50), Si(R.sub.50), N, or P, wherein R.sub.50 represents a hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or --(CH.sub.2).sub.m --R.sub.7 ;
• Y represents O, S, or N(R.sub.50);
• and
• R.sub.1, R.sub.2, R.sub.3, and R.sub.4 represent independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or --(CH.sub.2).sub.m --R.sub.7 ;
• the chiral catalyst is represented by the general formula:
• ##STR64## the substituents R.sub.1, R.sub.2, Y.sub.1, Y.sub.2, X.sub.1, X.sub.2, X.sub.3 and X.sub.4 each, independently, represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or --(CH.sub.2).sub.m --R.sub.7 ;
• or any two or more of the substituents taken together form a carbocycle or heterocycle ring having from 4 to 8 atoms in the ring structure,
• with the proviso that at least one of R.sub.1, Y.sub.1, X.sub.1 and X.sub.2 is covalently bonded to at least one of R.sub.2, Y.sub.2, X.sub.3 and X.sub.4 to provide the .alpha.-iminocarbonyls to which they are attached as a tetradentate ligand, and at least one of Y.sub.1 and Y.sub.2 is a hydrogen;
• R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;
• m is zero or an integer in the range of 1 to 8;
• M represents a transition metal atom, wherein said transition metal atom is not titanium;
• and
• A represents a counterion or a nucleophile,
• wherein the catalyst is asymmetric.

A process of realizing a stereoselective cycloaddition between a dienophile substrate and a 1,3-diene wherein the 1,3-diene and dienophile substrates are represented by general formulas 118 and 119, respectively:

• ##STR66## in which each occurrence of Z independently represents C(R.sub.50), Si(R.sub.50), N, or P, wherein R.sub.50 represents a hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or --(CH.sub.2).sub.m --R.sub.7 ;
• Y represents O, S, or N(R.sub.50);
• and
• R.sub.1, R.sub.2, R.sub.3, and R.sub.4 represent independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or --(CH.sub.2).sub.m --R.sub.7 ;
• R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;
• and m is zero or an integer in the range of 1 to 8;
• which method comprises reacting said dienophile with said 1,3-diene in the presence of at least a catalytic amount of a chiral metallosalenate catalyst, wherein said chiral metallosalenate catalyst does not comprise titanium.

A process of resolving enantiomers from a racemic mixture of a chiral dienophile, or a racemic mixture of a chiral 1,3-diene having general formulas 118 and 119, respectively:

• ##STR68## in which each occurrence of Z independently represents C(R.sub.50), Si(R.sub.50), N, or P, wherein R.sub.50 represents a hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or --(CH.sub.2).sub.m --R.sub.7 ;
• Y represents O, S, or N(R.sub.50);
• and
• R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;
• and m is zero or an integer in the range of 1 to 8;
• and
• R.sub.1, R.sub.2, R.sub.3, and R.sub.4 represent independently for each occurrence hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or --(CH.sub.2).sub.m --R.sub.7 ;
• the method comprising contacting said racemic mixture of the dienophile or 1,3-diene with an achiral 1,3-diene or dienophile, respectively, able to react with the racemic substrate in the presence of a chiral catalyst having the formula:
• ##STR69## in which Z.sub.1, Z.sub.2, Z.sub.3 and Z.sub.4 each represent a Lewis base;
• the C.sub.1 moiety, taken with Z.sub.1, Z.sub.3 and M, and the C.sub.2 moiety, taken with Z.sub.2, Z.sub.4 and M, each, independently, form a heterocycle;
• R.sub.1, R.sub.2, R'.sub.1 and R'.sub.2 each, independently, are absent or represent a covalent substitution with an organic or inorganic substituent permitted by valence requirements of the electron donor atom to which it is attached;
• R.sub.40 and R.sub.41 each independently are absent or represent one or more covalent substitutions of C.sub.1 and C.sub.2 with an organic or inorganic substituent permitted by valence requirements of the ring atom to which it is attached,
• or any two or more of the R.sub.1, R.sub.2, R'.sub.1, R'.sub.2, R.sub.40 and R.sub.41 taken together form a bridging substituent,
• with the proviso that C.sub.1 is substituted at at least one site by R.sub.1, R'.sub.1 or R.sub.41, and C.sub.2 is substituted at at least one site by R.sub.2, R'.sub.2 or R.sub.40, and
• at least one of R.sub.1, R'.sub.1 and R.sub.41 is taken together with at least one of R.sub.2, R'.sub.2 and R.sub.40 to form a bridging substituent so as to provide Z.sub.1, Z.sub.2, Z.sub.3 and Z.sub.4 as a tetradentate;
• M represents a transition metal, wherein said transition metal is not titanium;
• and
• A represents a counterion or a nucleophile,
• wherein each R.sub.1, R.sub.2, R'.sub.1, R'.sub.2, R.sub.40 and R.sub.41 are selected to provide at least one stereogenic center in said tetradentate ligand,
• under conditions wherein one enantiomer of the racemic dienophile or 1,3-diene reacts selectively in a cycloaddition with the achiral 1,3-diene or dienophile, respectively, leaving the other enantiomer of the racemic substrate substantially unchanged.