Oppolzer camphor sultam

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. 

Kim B. H., Curran D. P. Asymmetric Thermal Reactions With Oppolzer s Camphor Sultam Tetrahedron 1992 49 293-318... 

Oligomers Oppolzer s camphor sultam (see also camphor derivatives) Organometallics Organosilicon Organosulfur Organozirconocenes Orthoquinodimethanes Oxabutadienes Oxanorbornadiene(s) Oxazinolactams Oxazinones Oxazoles... 

Asymmetric cyclopropanol formation has been achieved with olefmic acylsulfonamides, which act like olefmic esters. Thus, their reaction with 1 provides a method for synthesizing cyclopropanols in an optically active form. As represented by Eq. 9.41, alkylation of Oppolzer s camphor sultam and reaction of the resulting unsaturated acylsulfonamides with 1 provides optically active bicyclic cyclopropanols having exclusively the structure shown in the equation [76],... 

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... 

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. 

CC>2Me preferably coordinates to the silver metal. Oppolzer s readily removable camphor sultam not only enforces absolute stereocontrol but also enables the underlying reaction cascade (presumably by lowering the pKa of the glycyl a-proton). Pyrrolidine 199 is converted to diol 200 by a 12-step reaction sequence. Since compound 200 corresponds to an advanced intermediate that has been converted to cyanocyline A <87JA1587>, attainment of 200 constitutes an efficient formal synthesis of this natural product. 

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... 

Camphor 93, a bridged monoterpene with one six- and two five-membered rings is available in both enantiomeric forms and was used by Woodward in the synthesis of vitamin B12. Sulfonation on camphor occurs on the bridgehead methyl group by a series of rearrangements described in the workbook. You will see in chapter 27 how Oppolzer s sultam 95 is used as a chiral auxiliary and in chapter 33 how oxaziridines such as 96 are used in asymmetric oxidation. Both are made from camphor-10-sulfonic acid 94. 

Optically pure sultams have been used by Oppolzer as chiral auxiliaries in various asymmetric transformations, including Diels-Alder reaction, aldoliza-tion, conjugate addition, his-hydroxylation, and catalytic hydrogenation [42,43]. In the literature, the most commonly used chiral sultam is derived from camphor (Oppolzer s sultam). The ready access to 80 and other chiral sultams from the Diels-Alder cycloadducts could further expand the scope of their use as chiral auxiliaries in asymmetric synthesis. 

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. 

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... 

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. " ... 

The asymmetric 3 + 2-cycloaddition of cyclic azomethine ylides with Oppolzer s acryloyl camphor sultam has been used for the construction of X-azabicyclo[7M.2.1] alkenes in optically pure form. The non-stereospeciflc 1,3-dipolar cycloaddition of electron-poor azomethine ylides and electron-rich enamines proceeds by a two-step mechanism via zwitterionic intermediates. The 1,3-dipolar cycloaddition of 4,6-diazaphenanthrene 6-phenacylide with a variety of dienophiles readily produces the fused heterocycles tetrahydrobenzo[/]pyrrolo[l,2-/z][l,7]naphthyridines. Sequential... 

Other uses of oxazinone enolates have been described by Williams, including the boron enolate 60, in the synthesis of diaminopimelic acid (62), the penultimate precursor of the essential amino acid i.-lysine (Scheme 10.8) [59], Acylated derivatives of Oppolzer s camphor sultam 63 can readily be alkylated in a highly diastereoselective fashion (Scheme 10.9) [60]. Thus, the imide derived from the condensation of 63 and 64 undergoes enolization and subsequent alkylation to furnish protected amino acid derivatives with high selectivity (cf 65, dr > 99 1) [61],... 

The use of amides and imides as chiral auxiliaries in [4 + 2]-cycloadditions has been the subject of numerous investigations. Oppolzer reported the use of camphorsultam 112 in asymmetric Diels-Alder reactions [26, 67. 68], The camphor sultam is readily available in both enantiomeric forms from cam-phorsulfonyl chloride. Acrylate 113 was found to react with cyclopentadiene in the presence of EtAlCl2 to give 115 with high selectivity (endo/exo = 99.5 0.5, dr = 97.5 2.5, Equation 10) [67]. Oppolzer also reported that triene 116 participated in an intramolecular Diels-Alder cycloaddition reaction to afford endo product 117 in 71 % yield and 96.5 3.5 dr (Scheme 17.19) [69]. This bicyclic product was subsequently converted into the pyridine alkaloid (-)-pulo upone (118). 

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