Oppolzer sultam aldol reaction

Scheme 3.69 Stereocontrol of Oppolzer sultam aldol reaction by choice of counter ion.

Oppolzer et al. used (2M)-bornanc-10, 2-sultam as an effective chiral auxiliary to achieve a highly enantioselective syn-aldol reaction17 (Scheme 2.1p). Treatment of A-propionylsultam (46) with dibutylboron triflate and Hunig s base at -5°C in CH2CI2 followed by addition of aldehydes at -78° C provided, after a simple crystallization, the pure vyn-aldols 47a. It is noteworthy that no anti-aldol product was observed in the aldol reactions with any of the aldehydes. From the1 nuclear magnetic resonance (NMR) study, it was confirmed that the boron... 

Dianion aldol condensation reactions with Evans oxazolidinones or Oppolzer sultams as chiral auxiliaries have been demonstrated to be a useful method to generate the core skeleton of furofurans with diastereoselectivities of 5 1-20 1. Stereoselective total syntheses of the furofuran lignans (-l-)-eudesmin, (+)-yangambin, (—)-eudesmin, and (-)-yangambin according to this procedure have been reported (Equation 102) <2006TL6433>. 

Tandem radical addition-aldol-type reaction of a,/3-unsaturated oxime ethers bearing an Oppolzer sultam auxiliary leads to stereoselective incorporation of alkyl groups in the 5- and 3-positions in tetrahydrofurans (Scheme 77) <2005AGE6190>. The observed /ra r,/ra r-stereoselectivity was explained by invoking a cyclic six-membered ring transition state. 

The first enantioselective total synthesis of (-)-denticulatin A was accomplished by W. Oppolzer. The key step in their approach was based on enantiotopic group differentiation in a meso dialdehyde by an aldol reaction. In the aldol reaction they utilized a bornanesultam chiral auxiliary. The enolization of A/-propionylbornane-10,2-sultam provided the (Z)-borylenolate derivative, which underwent an aldol reaction with the meso dialdehyde to afford the product with high yield and enantiopurity. In the final stages of the synthesis they utilized a second, double-dlastereoditferentiating aldol reaction. Aldol reaction of the (Z)-titanium enolate gave the anf/-Felkin syn product. The stereochemical outcome of the reaction was determined by the a-chiral center in the aldehyde component. 

The use of these auxiliaries in anti aldol reactions has been described, though not by generation of the anticipated ( )-enolate. Instead, the typical (Z)-enolate is formed, and then precomplexation of a Lewis acid with the reacting aldehyde diverts the reaction away from a cyclic transition state [23]. The contrasting stereochemical trends of the catalyzed and non-catalyzed reactions are evident in an early approach to muamvatin (Scheme 9-13) [24]. Alternatively, Oppolzer has reported the Lewis acid catalyzed anti aldol reaction of a silyl enol ether derived from sultam 38 [25]. In general, however, this methodology has seen limited use in the synthesis of complex natural products. 

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]. 

Oppolzer and coworkers [147, 454] have developed a class of reagents based on the enantiomeric bomane-2,10-sultam skeleton 1.133. These chiral auxiliaries are easily prepared from the enantiomeric 10-camphosulfonic adds [455]. Saturated or a,P-unsaturated TV-acylsultams 1.134, occasionally prepared from Af-silyl precursors [396], have been used very frequently. Asymmetric alkylations, animations and aldol reactions of enolates or enoxysilane derivatives of 1.134 (R = R CH2) [147, 404, 407, 456-460] are highly selective. The a,(3-unsaturated TV-acylsultams 1.134 (R = R R"C=CH) suffer highly stereoselective organocuprate 1,4-additions [147, 173], cyclopropanations [461], [4+2] and [3+2] cydoadditions [73,276,454,462], OSO4 promoted dihydroxylations [454,463] and radical addi-... 

Oppolzeds sultams 1.133 are also efficient auxiliaries in asymmetric aldol reactions [209,404,407,457,1271], Boron, titanium or Sn (IV) enolates of W-pro-pionoylsultams lead stereoselectively to either enantiomeric syn aldol at -78°C. These products are easily purified by fractional crystallization (Figure 6.83). After treatment with Li0H/H202 and CH2N2, syw-P-hydroxyesters are obtained with an excellent enantiomeric excess. The drawback of this method is the need to use an excess of aldehyde to obtain good chemical yields. As in the case of oxazolidi-... 

An interesting asymmetric aldol reaction utilizing enantiomerically homogeneous bomane sultam derived boron enolates has recently been reported by Oppolzer et al. The reaction of aldehydes with boron enolates (57), generated from acyl sultams (58) under standard enolization conditions (Pr 2NEt/Bu2BOTf/0 C), provides syn aldol products (59) with extremely high ratios of (59) to (60) as shown in Scheme 29. Results from the aldol reactions with representative aldehydes are summarized in... 

De Brabander et al. have reported a very rapid enantioselective synthesis of the Prelog-Djerassi lactonic acid through an asymmetric aldol reaction [88] (Scheme 44). The Oppolzer sultam-derived A-propionyl derivative 215 was used to desymmetrize meso-dialdehyde 216, and the diastereoselectivity was found to be 80 %. Oxidation of the resulting lactol 217 to lactone 218 was followed by oxidative removal of the chiral auxiliary. The unwanted diastereoisomer resulting from the aldol reaction was removed chromatographically after the oxidation step. 

The Oppolzer group has developed aldol reactions with amide enolates 140. The selectivities observed by this approach are good, and the four possible diastereomers 141-144 can be obtained by the appropriate selection of conditions (Scheme 10.30). Very often V-acylbornane-10,2-sultams 141-142 are solid materials that can be purified by simple crystallization. This approach is still used up to date. ... 

Typically, in these aldol additions sy -aldol adducts are formed, in which the chiral auxiliary induces the absolute configuration. The sultam methodology by Oppolzer is particularly useful as both enantiomeric aldols may be generated from the same auxiliary, by adjusting the reaction conditions (Scheme 3.69). Thus, in route A the enolborinate is generated and adduct 353 is formed [113]. If, however, in route B the lithium or the stannyl enolates are used the predominant aldol adduct is 355. The overaD selectivity of route B is lower than the one of route A. In addition to the formation of the syn-adducts 353 and 355, the two anti-diastereomers 354 and 356 are observed in small quantities for the lithium enolate whereas 354 is suppressed by using a tin enolate. 

Oppolzer s sultams also provided a solution to the problem of the asymmetric acetate aldol addition based upon a Mukaiyama reaction of sUyl ketene N,0-acetal 276, derived from N-acetylsultam 92 (R = H). In the titanium tetrachloride-mediated reaction with various aldehydes, the diastereoselectivity is not particularly high - as typical for aldol additions of a-unsubstituted enolates. 

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