Chiral camphor sultams

Aziridines of type A, with a chiral substituent located at the nitrogen atom have been applied successfully in asymmetric syntheses with a,p-unsaturated carboxylic acid derivatives derived from Oppolzer s chiral camphor sultam. " ... 

Camphor sultam derivatives have proved to be effective chiral auxiliaries in many different types of asymmetric reactions. As shown in Scheme 5-44, chiral camphor sulfam can be applied in the synthesis of (—)-pulo upone precursor 151 using an intramolecular Diels-Alder reaction. A Wittig reaction of 148 with 147 connects the chiral auxiliary to the substrate, and subsequent intramolecular Diels-Alder reaction via transition state 150 affords product 151. Compound 151 already has the stereochemistry of (—)-pulo upone 153.72... 

The formation of spirocyclopropanes from the reaction of diazodiphenylmethane and ( )-8-phenylmenthyl esters of acrylic acid and methyl fumarate occurred with a modest level of diastereofacial selectivity (136). In contrast, diastereoselectivities of 90 10 were achieved in the cycloadditions of diazo(trimethylsilyl)methane with acrylamides 65 derived from camphor sultam as the chiral auxiliary (137) (Scheme 8.16). Interestingly, the initial cycloadducts 66 afforded the nonconjugated A -pyrazolines 67 on protodesilylation the latter were converted into optically active azaproline derivatives 68. In a related manner, acrylamide 69 was converted into A -pyrazolines 70a,b (138). The major diastereoisomer 70a was used to synthesize indolizidine 71. The key step in this synthesis involves the hydrogenolytic cleavage of the pyrazoline ring. 

A chiral enolate derived from a bromoacetyl camphor sultam [(52) in turn prepared from Oppolzer s sultam63a b] undergoes an aza-Darzens reaction with modified amines to produce aziridme derivatives in high de.11 Cleavage yields aziridine carboxylates. 

A potential method for the preparation of novel amino acids via the highly selective addition of radicals to the glyoxylic oxime derivative of Oppolzer s camphor sultam (88) has been reported.181 Both Lewis acid and non-Lewis acid-mediated reaction conditions for the addition of alkyl radicals generated from alkyl iodides and Et3B/Bu3SnH were examined. A new chiral auxiliary based upon (R,R)-2,5-diphenylpyiTolidine has been used in the addition of phenylthiyl radicals to unsaturated methacrylamides. The selectivity was found to be better than that reported for the structurally related 2,5-dimethylpyrrolidine derivative.182... 

Utilization of a,(3-unsaturated amides derived from the chiral amine, namely, camphor sultam, has been made by several groups to test the feasibility of [l,3]dipolar cycloaddition reactions with these chiral systems. This methodology has been applied to the synthesis of (35,4/ )ethyl-l-azabicyclo[2.2.1]heptane-3-carboxylate (see above for non-specific syntheses).433... 

Oppolzer s camphor sultam, a well known chiral auxiliary, has been applied to the asymmetric synthesis of chial fluorine-containing amino acids <07OL2513>. Photoinduced addition of perfluoroalkyl iodides 189 to /V-acyloylcamphorsultam 188 in the presence of an aqueous solution of sodium sulfite provides alkyl iodides 190 with moderate to good stereoselectivities. Azide displacement with the major diastereomer of 190 proceeds with inversion of configuration. Subsequent removal of the sultam auxiliary and hydrogenation of the azide afford the chiral fluorine-containing amino acid 192. 

Stereoselective formation of carbocycles has been carried out through [RhCl(cod)]2 (cod = cyclooctadiene) catalyzed reaction of alkenylzirconocene chloride to co-carbonyl carboxymide <07TL6471>. When the camphor sultam auxiliary is incorporated into amide 206, the Rh(I)-catalyzed reaction of alkenylzirconocene chloride 207 forms the cyclization product 211 with high diastereoselectivity. The tt-facial differentiation of the double bond in 206 for the initial attack of vinyl group can be explained by taking into consideration either of the reactive conformers A or B. No matter which reactive conformer is involved, the attack of the vinyl group to the less crowded C p si-face would account for the observed chirality. 

In a series of papers24a c, Oppolzer et al. introduced another procedure for the enantioselec-tive amination of enolates based on the A-acyl camphor sultam 1 as a chiral template and 1-chloro-l-nitroso cyclohexane (2) as electrophile. 

In the middle of the 198O s some silyl enolates derived from homochiral esters were reported to enable highly enantioselective synthesis of aldols [106]. Later, Oppolzer et al. disclosed the utility of camphor sultam as a chiral auxiliary for asymmetric aldol reactions [107]. Braun et al. have recently achieved high levels of asymmetric induction in the aldol reaction of ketones with homochiral silyl enolate 43 (Scheme 10.38) [108]. 

The sulfur ylides 254 used in the stereoselective [2,3]-sigmatropic rearrangement are generated by copper(I)-catalyzed Doyle-Kirmse reaction of aryl sulfides 253 and diazo compounds bearing Oppolzer s camphor sultam auxiliary 252 in the presence of chiral diamine ligand S, S)-259 <05JA15016>. These intermediate ylides undergo spontaneous... 

Radicals bearing a chiral amide group, derived from Oppolzcr s camphor sultam, are intermediates in radical reactions with allylstannanes . The allylations yield the two isomeric products with high selectivities. 

Chiral auxiliaries are capable of controlling the absolute steric course of radical reactions. 8-Phenylmenthyl ester or an amide derived from Oppolzer s camphor sultam can be utilized for enantioselective ring closure to cyclopentane, the chiral auxiliary directing the addition to the alkene. The reductive radical cyclization of 8-phenylmenthyl 2-phenylthio-6-heplenoale at 80 °C gives four isomeric cyclopentane derivatives in an overall yield of 90 % 3. The reaction proceeds with modest cis irons ratio, but a considerably higher RiS selectivity of 80 20. 

For ease of comparison, the chirality sense of the camphor sultam is inverted from that reported in the literature [184] so that the favored approach at C2 is toward the Si face for all three examples. 

Oppolzer and his coworkers have made extensive use of the sultam group as a chiral auxiliary246,276-280. Thus they were able to achieve efficient Diels-Alder addition of less reactive dienophiles by introducing 2.10-camphor sultam 130 (the enantiomeric... 

Recently, Curran and coworkers had demonstrated that chiral radicals derived from camphor sultam give high levels of asymmetric addition in cyclization reactions with... 

Highly selective Diels-Alder reactions with other chiral auxiliaries attached to the dienophile have been documented. For example, chiral 2-oxazolidinones or the camphor sultam auxiliaries have proven particularly useful. Such cycloaddition reactions, catalysed by an alkylaluminium chloride, occur with a variety of dienes to give adducts in high yield and with very high diastereoselectivity. In many cases these adducts can be obtained diastereomerically pure by crystallization. The reactions are thought to occur by way of complexed ion pairs (e.g. 129), in which the substituent on the auxiliary shields one face of the dienophile from attack by the diene. For example, 2-methylbutadiene (isoprene) gave the adduct 127, which was converted into (i )-(+)-a-terpineol 128 (3.92). ... 

Chelation is also thought to play an important part in directing the facial selectivity of cycloadditions with the camphor sultam auxiliary. A variety of dienes can be used and adducts are obtained with very high diastereomeiic excesses. Both inter-and intramolecular cycloaddition reactions are amenable to the use of a chiral auxiliary. An intramolecular example is illustrated in Scheme 3.93, in which the diene and dienophile are tethered and in which cycloaddition leads to predominantly one of the two diastereomeric trans-fusQd bicyclic (endo) products. The dienophile is thought to adopt the s-cis conformation, with the aluminium atom complexed to the carbonyl and one of the two sulfone oxygen atoms. 

Many of the chiral auxiliaries described earlier serve excellently in asymmetric Diels-Alder reactions. The Evans oxazolidinones (116)t l and the Oppolzer camphor sultams (117)t l are exceptionally good in this regard and, as shown, actually give opposite products. 

Two other alkylations were based on readily-available chiral auxiharies. PhUippe Karoyan of the Universite Pierre et Marie Curie observed Tetrahedron Lett. 2008, 49, 4704) that the acylated Oppolzer camphor sultam 20 condensed with the Mannich reagent 21 to give 22 as a single diastereomer. Andrew G. Myers of Harvard University developed the pseudoephedrine chiral auxiliary of 23 to direct the construction of ternary alkylated centers. He has now established J. Am. Chem. Soc. 2008,130, 13231) that further alkylation gave 24, having a quaternary alkylated center, in high diastereomeric excess. 

Leahy and co-workers recently reported that camphor sultam is an excellent chiral auxiliary to achieve almost quantitative enantioselectivity in the reaction of aliphatic aldehydes (Scheme 17) (28). However, aromatic aldehydes fail to undergo reaction under their conditions. 

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