Esters as chiral auxiliaries

Waldmann H., Braun M. Amino Acid Esters As Chiral Auxiliaries in Asymmetric Cycloadditions Gazz. Chim. Ital. 1991 121 277-284... 

Dipolar cycloaddition reactions are of main interest in nitrile oxide chemistry. Recently, reviews and chapters in monographs appeared, which are devoted to individual aspects of these reactions. First of all, problems of asymmetric reactions of nitrile oxides (130, 131), including particular aspects, such as asymmetric metal-catalyzed 1,3-dipolar cycloaddition reactions (132, 133), development of new asymmetric reactions utilizing tartaric acid esters as chiral auxiliaries (134), and stereoselective intramolecular 1,3-dipolar cycloadditions (135) should be mentioned. Other problems considered are polymer-supported 1,3-dipolar cycloaddition reactions, important, in particular, for combinatorial chemistry... 

Use of tartrate esters as chiral auxiliaries in the asymmetric reactions of allenyl boronic acid also have been reported Ikeda, N. Aral, I. Yamamoto, H. J. Am. Chem. Soc. 1986,108, 483 Haruta, R. Ishiguro, M. Ikeda, N. Yamamoto, H. Ibid. 1982,104, 7667. 

H. Waldmann and M. Braun, Amino acid esters as chiral auxiliaries in asymmetric cycloaddi-tions, Gazz. Chim. Ital. 121 111 (1991). 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

Asymmetric cycloaddition reactions with amino acid esters as chiral auxiliaries 91G227. 

An alternative strategy for achieving asymmetric control may be by covalent attachment of a chiral auxiliary to the carbenoid. This strategy has so far met with rather limited success in cyclopropanation reactions (see eq. (3) for a similar palladium-catalyzed reaction). However, the use of a-hydroxy esters as chiral auxiliaries with stabilized rhodium(II) vinylcarbenoids allowed entry into both series of enantiomeric vinylcyclopropanes with predictable stereochemistry. Optical yields are fair to excellent [14] and the outcome of the reaction was rationalized on the basis of interactions between the carbonyl oxygen of the chiral auxiliary and the carbenoid carbon. The strategy led to an efficient synthesis of optically active hydroxy vitamin D3 ring A [28]. 

New asymmetric reactions utilizing tartaric acid esters as chiral auxiliaries (formation of N- and A,0-heteroeyeles by nucleophilic addition of iminoderivatives or 1,3-dipolar cycloaddition of nitrile oxides and nitrones) 03SL1075. 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries . This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycies (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5)-N-[p-(tert-butyl)phenylsulfonyl]prolinate [Rlni — TBSP)4] 539 as a chiral catalyst (equation 212)- . ... 

Two year later, Pinel group used (S) proline and (S) pyroglutamic esters as chiral auxiliaries for the diastereoselective hydrogenation of 2 methylnicotinic acid with up to 35% de [50]. They tried to improve diastereoselectivity of these reactions, but no better result was obtained (Scheme 10.37). 

Asymmetric induction occurs when (S)-l-phenylethylamine hydrochloride is used as the ammonium salt [57], which prompted Waldmann to investigate amino acid methyl esters as chiral auxiliaries the reaction of (S)-isoleucine methyl ester with cyclopentadiene in the presence of 35% aqueous formaldehyde solu-tion/tetrahydrofuran (9 1) afforded the best stereoisomeric ratio (93 7) [62],... 

A similar scenario as for the dihydroxylation has recently been opened for the diamination Muniz et al. reported experimental studies on the asymmetric dia-mination of olefins with osmium(VIII) imido complexes using (-)-8-phenyl-menthyl esters as chiral auxiliaries [114-116]. The reaction of (Nt-BuljOsO with enantiopure acrylates and methacrylates yielded only two out of four possible stereoisomers, whose absolute configurations are inconsistent with a concerted [3-1-2] mechanism of olefin face differentiation. The authors considered a stepwise mechanism via an osma-2-azetidine intermediate as reasonable pathway (Fig. 16). 

Impressively short is a total synthesis by Ian Paterson [281], who uses a lactate ester as chiral auxiliary. This is subsequently converted into a ketone via a Grignard reaction with its Weinreb amide. The boron-mediated aldol reaction, after an oxidative work-up, gives the aldol with a diastereoselectivity of >98 %. Since also the reaction with propionaldehyde shows the same diastereoselectiv-... 

Transition metal-catalysed methods for carbenoid insertion into C-H bonds remain well documented. The asymmetric intramolecular Cu(II)-catalysed C-H insertion reactions of (i) a-diazo-/ -keto esters and phosphonates and (ii) a-diazo sulfones have been described. One can note that the optimal reaction conditions have been found to be quite similar regardless of the nature of the carbenoid precursor the best conditions featured CUCI2 as Cu(II)-source, bis(oxazoline) (68) as chiral ligand and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate (i.e., NaBARF) as additive. Under the so-optimized reaction conditions, each of these carbenoid sources have been eonverted into five-membered cyclopentanone-based derivatives (69), whereas a-sulfonyl diazo esters (70) have led to six-membered cyclic compounds (71), thus featuring a distinct but well-known selectivity. In a related work, the asymmetric C-H insertion cyclization of (70) to (71) has also been achieved under Rh(II)-catalysis, using a combination of Rh2(5-pttl)4 (72) as chiral catalyst and menthyl ester as chiral auxiliary. As already mentioned in the previous section, allene-containing substrates (49) have been shown to undergo an intramolecular C-H insertion process under Rh(II)-catalysis. ... 

Waldmann has looked at the possibility of using proline esters as chiral auxiliaries for aqueous Diels-Alder reactions (Table 1.7) [53] ... 

Waldmann, H. (1990) Proline benzyl ester as chiral auxiliary in Barbier-type reactions in aqueous solutions, Synlett, 627-8. 

Alder reactions on sugar acrylate esters as chiral auxiliaries... 

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