Diastereoselective addition of Di‐(trimethylsilyl)phosphite to chiral N‐(R)‐α‐methylbenzyl and N‐(1‐methoxycarbonyl‐iso‐pentyl) Schiff bases of various aldehydes

Abstract

The addition of bis-(trimethylsilyl)phosphite to chiral imines of several aldehydes was diastereoselective. The separation of predominant diastereoisomers of a majority of formed aminophosphonic acids has been observed. Moreover, the ferrocene-derived acid 5d occurred in diastereoselectivity up to 100%. C

Addition of dimethyl phosphite to imines bearing the L‐methionine moiety and its surprisingly poor chiral assistance

“…Studying a case of phosphite addition to leucine analogues, diastereoselectivity was much higher, from de = 14% for the thienyl derivative until de = 100% for the ferrocene one 7. Certainly, the tendency remained the same; we noticed that in both cases, the highest stereoselectivity occurred for ferrocene derivatives (vide supra), less selectivity occurred for 2‐furyl ones ( de = 67% for the leucine analogue 7 vs. de = 20% for the methionine one), and dramatically less for 2‐thienyl derivatives (vide supra). Higher diastereoselectivity of ferrocene derivatives has been discussed in light of the Houk model 15, which provided the explanation suggesting that “diastereoselection is reinforced due to the stabilizing interaction between the phosphorus atom orbital and the ferrocenyl substituent” [7, p. 328].…”

“…Imines 2a–d 8–11 have been prepared using a previously published method 7 by simple mixing of an aldehyde 1a–d with methionine methyl ester hydrochloride in dichloromethane in the presence of triethylamine. They were isolated and used for further conversions without previous purification (Scheme ).…”

“…Moreover, valine is largely used as a chiral auxiliary in the Schoellkopf reagent, the precursor for amino acid synthesis 14. Studying a case of phosphite addition to leucine analogues, diastereoselectivity was much higher, from de = 14% for the thienyl derivative until de = 100% for the ferrocene one 7. Certainly, the tendency remained the same; we noticed that in both cases, the highest stereoselectivity occurred for ferrocene derivatives (vide supra), less selectivity occurred for 2‐furyl ones ( de = 67% for the leucine analogue 7 vs. de = 20% for the methionine one), and dramatically less for 2‐thienyl derivatives (vide supra).…”

“…We have reported the formation of N ‐(1‐meth‐ oxycarbonyl‐3‐methylbutyl)‐ aminomethylphospho‐ nic acids, i.e., aminophosphonic systems derived from l ‐leucine, where the diastereoselectivity varied from de = 14% up to de = 100% 7. Moreover, we observed the self‐separation of predominant diastereoisomers of studied leucine‐derived aminophosphonic acids.…”

Bromotrimethylsilane (TMSBr)

“…This method is based on obtaining silylated esters of phosphonic acid in the reaction of TMSBr and then converting it into the acid. In this case (17), the formation of only one diastereomer was observed. Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.…”