Enhancement of stereoselectivities in asymmetric synthesis using fluorinated solvents, auxiliaries, and catalysts

Abstract

In this review, the drastic changes using fluorinated solvents, additives, auxiliaries, and catalysts in catalytic asymmetric transformations are presented.

HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes

“…This sharp contrast in the performance of both fluorinated alcohols in this transformation can be explained by their different properties. Thus, HFIP has higher acidity (p K a (TFE) = 12.37, p K a (HFIP) = 9.30); higher hydrogen bond ability (α TFE = 1.51, α HFIP = 1.96), which can facilitate the activation of epoxide ring; and much lower nucleophilicity ( N TFE = −2.78, N HFIP = −4.23) [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. This last parameter would explain the obtention of fluoroalkyl ether 5 as major product when TFE was essayed.…”

“…Other changes in reaction stoichiometry were also essayed but did not produce any amelioration. After the search for the best conditions, those described in entry 3, involving the use of HFIP at 45 • C, were selected as optimal, realizing that reaction was complete in less than 10 h. conversion of 3aa by using a series of HFIP/CH2Cl2 [16][17][18][19][20][21][22] mixtures were implemented (Table 1, entries 6-8), but turned out to be unsuccessful in all the cases. Lowering the reaction temperature to 25 °C also resulted in a drop in the conversion towards the desired product (Table 1, entry 9).…”

“…In the last years, our research group has become interested in the use of fluorinated alcohols as solvents and promoters of organic reactions [ 14 , 15 ]. The unique chemical and physical properties that fluoroalkyl alcohols have in comparison with their non-fluorinated analogues, such as their high hydrogen bond donor ability, high polarity and ionizing power, and low nucleophilicity values together with the slightly acidic character, make them perfect candidates as promoters of reactions involving ionic processes [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. On the other hand, fluorinated alcohols have already proven to be efficient promoters in the ring-opening reaction of epoxides with different nucleophiles [ 23 , 24 , 25 , 26 ].…”

1,1,1,3,3,3‐Hexafluoroisopropanol as a Remarkable Medium for Atroposelective Sulfoxide‐Directed Fujiwara–Moritani Reaction with Acrylates and Styrenes

“…Fluorinated alcohols have attractedi ncreasing attention from organic chemists as unusual media within which to perform varioust ransformations, including both transition-metal and organocatalyzedr eactions. [20] It has been observed that due to their unique properties, [20a] such as extreme polarity (1.068 E N T ), high acidity (pK a = 9.3), excellent hydrogen-bond-donor abilities (a = 1.96), and low nucleophilicity (N = À4.23), these solvents may exert an unexpected effect on an reactiono utcome, modifying not only the reactivity of ac atalytic system, but also its regio-a nd stereoselectivity.A ccordingly,c ommercially available HFIP has recently been employed in several CÀHa ctivation reactions and clearly outcompeted other organic solvents. [19] Intriguedb yt he unique features of HFIP,w ep erformed our previously developed sulfoxide-directed oxidative olefination in this polyfluorinated alcohol.…”

Hexafluoroisopropanol: the magical solvent for Pd-catalyzed C–H activation

“…Before its direct inuence in asymmetric C-H activation, the unprecedented impact of HFIP as a solvent in a Pd-catalyzed asymmetric hydrogenation reaction was realized by Uneyama's group long back. 77 Despite its uninterrupted application in other areas of homogeneous catalysis, 78 HFIP has just started its journey as a game changer in stereoselective C-H functionalization. 21a It is hypothesized that the weak coordination of uorinated alcohols stabilizes the active catalyst.…”