Camphor sultam

The Gabriel-Cromwell aziridine synthesis involves nucleophilic addition of a formal nitrene equivalent to a 2-haloacrylate or similar reagent [29]. Thus, there is an initial Michael addition, followed by protonation and 3-exo-tet ring-closure. Asymmetric variants of the reaction have been reported. N-(2-Bromo)acryloyl camphor-sultam, for example, reacts with a range of amines to give N-substituted (azir-idinyl)acylsultams (Scheme 4.23) [30]. 

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... 

The camphor sultam derivative 21A was used in a synthesis of epothilone. The stereoselectivity of the aldol addition was examined with several different aldehydes. Discuss the factors that lead to the variable stereoselectivity in the three cases shown. 

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... 

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],... 

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... 

The 3 + 2-cycloaddition of commercially available Me3SiCHN2 with camphor sultam-derived dipolarophiles produces 3-trimethylsilyl-substitutcd-A1 -pyrazolincs which on acid treatment convert into optically active A2-pyrazolines.60 The nucleophilic addition of ethyl diazoacetate with /V-cthoxycarbonyl-/V-(2,2,2-trichlorocthylidcne)a-mine produces a new diazo intermediate (35), which by 1,3-dipolar cycloaddition followed by a sigmatropic rearrangement of the cycloadduct (36) furnishes a substituted pyrazole (37) (Scheme 13).61. 

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... 

The hemiacetals of (+)- and (-)-A -glyoxyloylborane-10,2-sultam 23a and 23b and their imines 23c and 23d reacted with allyl iodide in the presence of indium in DMF at 0 °C to give the corresponding a-hydroxy and a-amino camphor sultam derivatives 24a and 24b and 24c and 24d with high diastereoselectivites (86-90% de). Cleavage of the auxiliary then furnished a-hydroxy and ot-amino acids <02JCS(P1)1314>. 

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. 

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. 

Also for stereoselective radical reactions such as radical additions or radical cyclizations, the camphor sultam 2 is suitable as an auxiliary (Scheme 7). The acyl radical which was gener-... 

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. 

Scheme 101 Double asymmetric induction with the camphor sultam auxiliary...

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