Acrylates hexafluoroisopropyl

An important step in the development of asymmetric MBH reactions was the introduction of the quinidine-derived /Msocupreidine catalyst (/MCD) 44, by the Hatalceyama group [64, 65]. /MCD mediated the addition of acrylate 43 to a variety of aromatic and aliphatic aldehydes even at —55 °C in DMF, and afforded (R)-adducts in good yields (40-58%) and excellent enantioselectivity (ee up to 99%) (Table 5.3). The contribution of the 1,1,1,3,3,3-hexafluoroisopropyl acryl ester (HFIPA) to the reactivity of the system deserves comment. This ester displayed... 

A similar strategy was used in the synthesis of mycestericin E [68]. The configuration of the chiral allylic alcohol 53 was established via a /MCD-mediated MBH reaction between aldehyde 52 and the hexafluoroisopropyl acrylate 43 in a DMF/CH2C12 solvent mixture at low temperature (Scheme 5.11). 

The reactions of N arylidenediphenylphosphinamides with hexafluoroisopropyl acrylate (HFIPA) to give the corresponding aza MBH adducts in moderate to excellent yields with good enantiomeric excesses was also reported by Hatakeya ma [20] (Scheme 13.11). In contrast to the corresponding aldehydes, imines show the opposite enantioselectivity, and Hatakeyama and coworkers indicated that H bonding was responsible for the reversal in enantioselectivity. Michael addition... 

Hatakeyama and co-workers reported the highly enantioselective Baylis-Hillman reaction of 1,1,1,3,3,3-hexafluoroisopropyl acrylate with an aldehyde, which is catalyzed by the cinchona alkaloid catalyst 4 that was readily available from (+ )-quinidine (Equation 10.11) [25],... 

From a TiCVcatalyzed Baylis-Hillman reaction in the presence of 10-methylth-ioisoborneol, chiral adducts ensue. The acryloyl derivative 50 is a particularly interesting addend because either (/ )- or (5)-alcohols can be prepared by merely changing the solvent. Another variation employs hexafluoroisopropyl acrylate and ligand SI. ... 

The reaction of A -Fmoc-L-leudnal (139) with l,l,l>3,3>3-hexafluoroisopropyl acrylate (140) proceeded smoothly in the presence of a stoichiometric amount of cinchona alkaloid 141, even at very low temperature, to give a 6 1 mixture of j yw-ester 142 and dioxane derivative 143 (Scheme 1.62). However, the same reaction with N-Fmoc-o-leucinal (ent-139) turned out to be sluggish and only a mixture of dioxanones 143 was obtained in low yield. Thus, it can be concluded that the (/ )-selectivity of the chiral amine catalyst matches well with L-config-uration of the substrate, leading to high yn-selectivity. ... 

At almost the same time, Hatakeyama et al. investigated the (3-ICD catalyzed aza-MBH reaction of various aryl diphenylphosphinoyl imines 146 and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA), affording the (S)-product 147, in up to 97% yields with high ees, in DMF at low temperature (Scheme 2.70). Notably, the absolute stereochemistry of the aza-MBH adducts is opposite to that of adducts obtained from the analogous MBH reaction. With (3-ICD as catalyst, imines give rise to (5)-enriched adducts, in contrast to aldehydes, which afford (i )-products. A plausible mechanism was proposed. Moreover, the utility... 

Cinchona alkaloid derivatives can also serve as useful Lewis basic catalysts, as very well exemplified by their successful employment in the Morita-Baylis-Hillman (MBH) reaction and its aza variant (aza-MBH), which provide a convenient access to functionalised allylie aleohols and amines. As early as 1999 Hatakeyama and coworkers reported the use of p-isocupreidine (P-ICPD) as a catalyst for the reaction of aliphatic and aromatic aldehydes with 1,1,1,3,3,3-hexafluoroisopropyl acrylate, affording the desired adducts with very high enantioselectivities (Scheme 14.19). The concomitant formation of the dioxanone derivatives lowered the yield in the MBH adducts and caused difficulties in the experimental proeedure. Interestingly, the dioxanone derivatives had the opposite eonfiguration at the alcoholic stereocentre compared to the MBH produet, highlighting an intriguing mechanistic feature of this Lewis-base catalysed reaction. ... 

Scheme 14.19 MBH reactions of hexafluoroisopropyl acrylate catalysed by 5-ICPD.

Another class of reaction for which chiral tertiary amines are privileged catalysts is the Morita-Baylis-Hillman type (477, 478). One of the first applications of Cinchona alkaloids to mediate an asymmetric Morita-Baylis-Hillman reaction in a natural product synthesis was reported by Hatakeyama et al. in 2001 (479). Using a stoichiometric amount of (3-isocupreidine (568), a stereoselective addition of hexafluoroisopropyl acrylate (569) to aldehyde 570 could be carried out in good yield and with excellent selectivity (99% ee) (Scheme 119). The chiral p-hydroxy ester 571 was converted further into the epoxide 572, a known intermediate in the synthesis of epopromycin B (573). Epopromycin B (573) is a plant cell wall... 

Conditions for a highly enantioselective Baylis-Hillman reaction (142) + (143) (144) have been developed (Scheme 20). The new protocol relies on the use of 1,1,1,3,3,3-hexafluoroisopropyl acrylate (144) as an activated alkene and (3R,8R,9S)-10,ll-dihydro-3,9-epoxy-6 -hydroxycinchonane (145) as a chiral amine catalyst. The highest enantioselectivity (99% ee) was obtained for R = cyclohexyl. A mechanism has been proposed that highlights an important synergism of the tertiary nitrogen and the phenolic OH of the alkaloid (143) + (145) —> (146) + (147). 9 However, the reviewer feels that the proposed mechanism would be disfavoured by the entropy factor. 

Figure 6.7 Tentative and simplified intermediate structures formed in the reaction of imines, ArCH=NR, with hexafluoroisopropyl acrylate, R = Ar, Bz, Ms,...

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