Asymmetric synthesis of α-substituted alkylphosphonates based on symmetrical dialkyl phosphites

Abstract

Chiral C2-symmetrical dialkyl phosphites and C3-symmetrical trialkyl phosphites, derived from (-)-borneol. (-)-menthol, and 1,2:5,6-di-O-isopropylidene-ct-n-glucofuranose, were studied as the starting reagents for the preparation of ctural organophosphorus compounds. The reactions of C2-symmetrical dialkyl phosphites and Cusymmetrical trialkyl phosphites with aldehydes and amines or aldehydes are accompanied by asymmetrical induction at the ~z-carbon atom to yield optically active c.~-aminoalkytphosphonates or ct-hydroxyalkylphosphonates, respectively. The stereoselectivity of the reaction depends on the structure of the starling compounds and the reaction conditions.

The difference in reactivity of (−)-mono and dimenthyl vs. diethyl alkylphosphonates in the α-lithiation reaction: Carbanionic synthesis of unknown (−)-dimenthyl 1-iodoalkylphosphonates and their first use in the radical iodine atom transfer addition (I-ATRA) and cyclisation (I-ATRC) reactions

“…Further application of (À)-dimenthyl phosphite was demonstrated in addition to aldehydes under conditions of the Pudovik and the Kabachnik-Fields reactions [9,10]. In particular, its condensation with trioxane (cyclic polymer of formaldehyde) followed by allylation of the resulted product, gave (À)-dimenthyl allyloxymethylphosphonate which underwent a sigmatropic [2,3] -Wittig rearrangement in 92% d.e [11].…”

Synthesis of optically active hydroxyphosphonates

“…Similarly, α-hydroxyphosphonates 2a-c were prepared by phospha-aldol addition of aromatic aldehydes to dimenthylphosphite as shown in Scheme 5 [9,13]. The reaction was performed at room temperature in the absence of solvent, with 1,8-diazabicyclo [5.4.0]undecene (DBU) as the catalyst, and according to a method described by us earlier [9] to give a mixture of (R)-and (S)-diastereomers of α-hydroxyphosphonates 2a-c, which were purified by crystallization from hexane to give (R)-diastereomers of 100% de purity.…”

“…The reaction was performed at room temperature in the absence of solvent, with 1,8-diazabicyclo [5.4.0]undecene (DBU) as the catalyst, and according to a method described by us earlier [9] to give a mixture of (R)-and (S)-diastereomers of α-hydroxyphosphonates 2a-c, which were purified by crystallization from hexane to give (R)-diastereomers of 100% de purity. Compounds 2a-c were identical to (R)-hydroxyphosphonates prepared by the reduction of ketophosphonates with sodium borohydride (Scheme 5).…”

“…While enantioselective syntheses of α-aminophosphonic acids have been studied extensively [4], the synthesis of enantiomerically pure α-hydroxyphosphonates has not yet developed sufficiently [5][6][7][8]. The previously employed methods provide access to many α-hydroxyphosphonates, but the use of chiral auxiliaries and/or catalysts is required to improve the stereoselectivity of these methods [9]. A possible method for the stereoselective introduction of the hydroxyl group is a stereoselective reduction of prochiral keto compounds.…”

Lipophilic aminophosphonates and their calix[4]arene derivatives: synthesis and membrane transport of biorelevant species

“…These are alkoxy groups at the phosphorus atom, the ␣-carbon atom, and the substituent at the nitrogen atom. ␣-Aminophosphonates with one, two, or three chiral fragments can be synthesized using commercial chiral reagents such as (R) and (S) ␣-methylbenzylamine, (1S)-endo-(‫-)מ‬borneol, (R)-(‫-)ם‬bornylamine, ‫-)ם(‬ and (‫-)מ‬menthol, and some others [30,31]. So, these compounds are good models for evaluation of transport enantioselectivitystructure relationships.…”