Synthesis of Chiral β-Iodo- and Vinylorganophosphorus(V) Compounds by Fragmentation of Carbohydrate Anomeric Alkoxyl Radicals

Abstract

A new general methodology for the synthesis of chiral vinylphosphonate and vinylphosphine oxide carbohydrate derivatives has been developed using the anomeric alkoxyl radical fragmentation reaction as the key step. The synthetic sequence proceeded via β-iodophosphonate and β-iodophosphine oxide intermediates, which may be interesting synthons for the introduction of phosphorus into organic molecules. These vinylphosphonates could be easily transformed into 2-methylene-1-phosphapentofuranoses (3-methylene-1,2-oxaphospholanes) and β-aminophosphonates, isosteres of biologically active α-methylene-γ-lactones and β-amino acids, respectively.

Fifty Years of (Benz)oxaphospholene Chemistry

“…[143,144] Attempting to deprotect the p-methoxybenzyl (PMB) protectingg roup of aminoallenylphosphonates 206 using ceric ammonium nitrate (CAN), the group of Rabassod iscovered that arearrangement took place, yieldingspirodienone lactams Scheme47. [143,144] Attempting to deprotect the p-methoxybenzyl (PMB) protectingg roup of aminoallenylphosphonates 206 using ceric ammonium nitrate (CAN), the group of Rabassod iscovered that arearrangement took place, yieldingspirodienone lactams Scheme47.…”

“…During their work on phosphonylated carbohydrate derivatives, the group of Suarez reported an S N 2' substitution reaction on phospha-1-oxo-pentofuranoses 204 by glycine methyl ester producing oxaphospholene 205 (one diastereomer shown) (Scheme 51). [143,144] Attempting to deprotect the p-methoxybenzyl (PMB) protectingg roup of aminoallenylphosphonates 206 using ceric ammonium nitrate (CAN), the group of Rabassod iscovered that arearrangement took place, yieldingspirodienone lactams Scheme47. Synthesis of benzoxaphospholenes through treatment of salicaldehydes with trivalent phosphoruscompounds.…”

“…These well-documented strategies, for instance the electrophile-induced cyclization of allenylphosphonates, will continuet ob ean inspiration for syntheticc hemists in the preparation of novel compounds. [143,144] Moreover,t he chirality at the stereogenic phosphorus atomgenerally introduced at the moment one of the two alkoxide groups is replaced-is hard to influence. In certains ubstituted oxaphospholenes, the diastereoselectivity can be controlled to some extent and enantiopure oxaphospholenes have been isolated.…”

“…[110] Although control of stereogenic carbon centres can be accomplished by the use of chiral pool carbohydrates, this has been applied only once. [143,144] Moreover,t he chirality at the stereogenic phosphorus atomgenerally introduced at the moment one of the two alkoxide groups is replaced-is hard to influence. Syntheses employing chiral reagents that also allow control of the phosphorus stereogenic centre have not been reported so far.T hus, entries to optically active (benz)oxaphospholenes remains carcea nd the development of asymmetricm ethods would certainly represent av aluable addition to the field.…”

Fragmentation of Carbohydrate Anomeric Alkoxyl Radicals: Synthesis of Chiral Polyhydroxylated β‐Iodo‐ and Alkenylorganophosphorus(V) Compounds

“…In demonstration of such a utility, we set out to develop a new method for the synthesis of chiral vinylphosphine oxides and vinylphosphonates of generalized structure VII (Scheme ). We have described the preliminary results in a short communication and now report full details of this methodology and its extension to other saccharide models 14…”