Preparation of TADDOL Derivatives for New Applications

Abstract

Substitution of one or both TADDOL OH groups by other functional groups X, Y is key to new applications of this cheap chiral auxiliary. The Appel reaction and treatment with SOCl2 provide the mono- and dichlorides, respectively. The chlorides are, in turn, replaced by various nucleophiles, and further modifications give a large variety of derivatives, including mono- and ditritylated dioxolanes. The new compoundsavailable in either enantiomeric formare ready to be used in enantioselective synthesis and as dopants in liquid crystals.

Preparation of TADOOH, a Hydroperoxide from TADDOL, and Use in Highly Enantioface- and Enantiomer-Differentiating Oxidations

“…Both the formation of the tetrahedral intermediate and the rearrangement are catalyzed by acid and by base, and either step may be ratedetermining. Without detailed kinetic measurements, as in the present case, a mechanistic discussion is bound to be rather speculative 19 ). For the reactions of the cyclobutanones with TADOOH 3, we make the following assumptions: i) the Criegee adducts are formed rapidly (cyclobutanones are highly reactive carbonyl compounds 13 ) 20 ); ii) only the exo-adducts (cf.…”

“…Substitution reactions with replacement of TADDOL OH groups are facile and surprisingly clean, considering the fact that they must occur by the S n 1 mechanism, and that the intermediate cation(s) could undergo various reactions, besides being trapped by a nucleophile 6 ). Thus, both OH groups of TADDOL 1 are replaced by Cl with SOCl 2 in 82% yield [18], while the Appel reaction stops cleanly at the stage of the monochloride 2, which is isolated in 72% yield [19]. The subsequent replacement of Cl by OOH (2 3 3 in Scheme 1) has been achieved in various ways 7 ).…”

TADDOLs, Their Derivatives, and TADDOL Analogues: Versatile Chiral Auxiliaries

“…Analogous reactions occur also with the TADDOL that is unsubstituted in the 2-position of the dioxolane ring, as well as with the 2-methoxyphenyl isomers. Bottom: Phosphanes and phosphides cause reduction and/or elimination of chlorides and bromides derived from TADDOL; starting from the chloroamine, the monoamine forms in a yield of approximately 50 %, [72] the bis(diphenylmethylene)dioxanone in about 15 %, the tetraphenylbutadiene in up to 80 %, and the corresponding epoxide in about 85 % yield. [89] Cl/P substitution is successful with TADDOL derivatives only by way of the Michaelis ± Arbuzov reaction.…”

“…a1) The diazide [75] (CSD Refcode: NIBZIH), the dichloride 6 [75] (NICBUW), and the chloroamine [76] all have one heteroatom above the dioxolane ring whereas the second one extends forward. a2) In the structure of the fluoroalcohol [72] (HOLYAI), both heteroatoms extend to the rear. b1) The hexaphenyl derivative 1 g without inclusion [67] (anomalous, VUSLEA) and b2) with inclusion [68] (normal, POPJOT).…”

Synthesis and application of azolium ionic liquid tagged TADDOL catalysts

“…2 In principle, ionic liquid tags could be tethered either to the aryl groups of the carbinol substructures or to the substituents in position 2 of the dioxolane ring. 25 We chose the latter possibility for its straightforwardness. In order to have much structural flexibility we established the TADDOL moiety at an early stage and various IL-tags were linked at a later stage by means of a propargyl group enabling Cu-catalyzed Meldal-Sharpless click reaction.…”