Valine-derived catalysts

Hashimoto has shown that the the valine-derived catalyst Rh2(S-BPTV)4 (5) is effective in intermolecular tandem cyclization/intermolecular cycloaddition resulting in the formation of 46 in 92% ee (Eq. (26) [10]. More recent studies have broadened the range of substrates that can be used in the reaction although the enantioselectivity is variable [38,39],... 

Sulfinamide 46, developed by the same group, represents the most recent addition to this family. Here, the original formyl group of the proline derived catalyst 16 was replaced by the t BuSO moiety, which resulted in high enantio selectivities (<97% ee at 0 °C with 10mol% catalyst loading Table 4.10) [Ilf]. The striking feature of this catalyst is its efficiency with imines derived from nonaro matic amines, namely, benzyl, allyl, propyl, isobutyl, and p methoxybenzyl amine (Table 4.10), which renders 46 superior to 43 and dwarfs other catalysts (e.g., 16,19, and 45). Needless to say, this new feature broadens the synthetic arsenal beyond the N aryl substrates and opens new synthetic avenues. In comparison, the valine derived catalyst 47 proved to be less efficient with imines derived from aromatic... 

From all the oxazaborolidine catalyst, the L-valine derived catalyst 115a gave the highest enantioselectivity and an excellent ratio endo/exo. Moreover oxazaborolidinone polymeric catalysts having oxyethylene crosslinkages (116) present better performance. 

A valine-derived oxazaborolidine derivative has been found to be subject to activation by Lewis acids, with SnCl4 being particularly effective.98 This catalyst combination also has reduced sensitivity to water and other Lewis bases. 

Helmchen and colleagues used equimolar amounts of L-valine derived oxazaboroli-dine 361a to catalyze the reaction of methacrolein with cyclopentadiene (equation 103). Cycloadduct 322 was obtained with 64% ee229. The enantioselectivity was increased to 86% ee by using 60 mol% of 361a and donor solvents like THF. The same catalyst afforded the endo cycloadduct of crotonaldehyde and cyclopentadiene with 76% ee. 

Yamamoto had earlier reported that Lewis acid activation of valine-derived oxazaborolidine 60 yielded a highly reactive and moisture-tolerant LLA catalyst 61 for the Diels-Alder reaction (Scheme 5.76) [145]. In later studies, activation of 60 with the super Bronsted acid, C,sF5CHTf2, was found to produce the even more reactive catalytic species BLA 62. During studies toward an enantioselective route to Platensimycin [146], BLA 62 was found to catalyze the Diels-Alder reaction between various monosubstituted dienes and ethyl acrylate to afford adducts... 

A vast array of chiral catalysts have been developed for the enantioselective reactions of diazo compounds but the majority has been applied to asymmetric cyclopropanations of alkyl diazoacetates [2]. Prominent catalysts for asymmetric intermolecular C-H insertions are the dirhodium tetraprolinate catalysts, Rh2(S-TBSP)4 (la) and Rh2(S-DOSP)4 (lb), and the bridged analogue Rh2(S-biDOSP)2 (2) [7] (Fig. 1). A related prolinate catalyst is the amide 3 [8]. Another catalyst that has been occasionally used in intermolecular C-H activations is Rh2(S-MEPY)4 (4) [9], The most notable catalysts that have been used in enantioselective ylide transformations are the valine derivative, Rh2(S-BPTV)4 (5) [10], and the binaphthylphosphate catalysts, Rh2(R-BNP)4 (6a) and Rh2(R-DDNP)4 (6b) [11]. All of the catalysts tend to be very active in the decomposition of diazo compounds and generally, carbenoid reactions are conducted with 1 mol % or less of catalyst loading [1-3]. 

Though either enantiomer of a yyn-aldol can be made by using the right auxiliary in an Evans aldol reaction the anti aldols cannot be made this way. The addition of a Lewis acid catalyst transforms the situation.13 Using the valine-derived chiral auxiliary 89, the same Z-boron enolate 111 is used but the aldehyde is added in the presence of a threefold excess of the Lewis acid Et2AlCl. The product is predominantly one enantiomer of an anh-aldol 112. 

Acetylacetone has also been the subject of several studies when used as 1,3-dicarbonyl compound suitable to engage in a Michael reaction with nitroalkenes under H-bonding catalysis. In this context, Takemoto s catalyst 68a and valine-derived thiourea 74 have been tested in the reaction with acetylacetone with nitrostyrene furnishing good results, although no extensive study was carried out in order to evaluate the substrate scope with regard to the substitution at the nitroalkene. On the other hand, several functionalized thioureas have been expressly surveyed in this reaction, providing a detailed study... 

In the same year, through the development of a new electron-deficient, valine-derived triazolium catalyst precursor. Gravel and co-workers realized a highly enantioselective intermolecular cross-benzoin reaction of aldehydes with a-keto esters. Excellent enantioselectivity was observed between aliphatic aldehydes (1.5 equiv.) and various aryl ct-keto esters (up to 98% yield, 94% ee) (Scheme 7.8). 

In 2005, we developed a new type of LLA catalyst system with a valine-derived oxazaborolidine and tin(IV) chloride for enantioselective Diels-Alder reaction (Fig. 5) [43]. Remarkably, SnCU can be used in excessive catalyst loading without compromising enantioselectivity, which means that the achiral Lewis acid mediated racemic pathway should be significantly slower than the LLA catalyzed enantioselective pathway. When excessive SnCU were used, it can neutralize incidental Lewis base impurities (e.g., moisture introduced during reaction set-up). In fact, the reaction can even proceed smoothly when various Lewis bases, such as water and amines, were added in, making this reaction system highly robust. The robustness of this catalyst system has set an example and high bar for future development of acid catalysis. 

During our synthetic study on a Robinson annulation approach toward platensi-mycin, we used a carbon based Brpnsted acid to activate the valine derived oxazaborolidine catalyst to prepare a key chiral building block [46]. This new... 

Later, the same group succeeded in achieving a cascade Michael/nitro-Mannich/ acetalization reaction by the combination of covalent enamine catalysis and noncovalent bifunctional base/Br0nsted acid catalysis [32]. The fuUy substituted piperidines with diverse substitution patterns were prepared efficiently starting from simple aliphatic aldehydes, Ts-protected imines, and trani -P-nitro alkenes (Scheme 9.36). This finding effectively incorporated prolinol silyl ether-catalyzed Michael addition of aldehyde 65 to nitroalkene 75 and valine-derived bifunctional thiourea-mediated nitro-Mannich reaction of y-nitro aldehyde 106 to imine 105 in the cascade process, providing a complementary contribution to the well-known single catalyst-promoted triple cascade reactions and two catalyst-promoted reaction cascades. 

In 1999, Hashimoto and coworkers demonstrated the first successM examples of the intermolecular cycloadditions of carbonyl ylides derived from a-diazo ketones with dimethyl acetylenedicarboxylate (DMDA) using fV-benzene-fitsed phthaloyl-(5)-valine-derived Rh catalyst, Rh2(5-BTPV)4 with high enantioselectivity (up to 92% ee) (Scheme 7.21) [57]. 

In the same year, KoCovsky et al. published their very powerful activator Sigamide A 4. Instead of proline, they used A-methyl valine derived Lewis bases as activators. After intensive catalyst screening, it mrned out that the N-methylation is as crucial as converting the valine carboxyl terminus into a bulky, aromatic secondary amide. The 3,5-di-tcrt-butylphenyl moiety showed excellent results in terms of yield (95%) and selectivity (94% ee). A wide... 

An oxazaborolidinone derived from valine is also an effective catalyst. In one case, the two enantiomeric catalysts were completely enantioselective for the newly formed... 

The stereoselective allylation of carbon-nitrogen multiple bonds have also been studied. The addition of allylzinc bromide to aromatic imines derived from (. S j-valine esters was affected by reversibility, which caused the lowering of the diastereoisomeric ratio with increasing reaction time. The retroallylation reaction could be avoided by performing the reaction in the presence of trace amounts of water or by using CeC - 7H2O as the catalyst with a decreased reaction rate.71... 

Chiral oxazaborolidines. Enantioselective reduction of ketones with a reagent prepared from BH, and the chiral vic-amino alcohol 1 (12,31) is now known to involve an oxazaborolidine. Thus BH3 and (S)-l, derived from valine, react rapidly in THF to form 2, m.p. 105-110°, which can serve as an efficient catalyst... 

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