P-Heterocyclic Building Blocks:  Application to the Stereoselective Synthesis of P-Sugars

Abstract

A strategy relying on the utilization of stereoselective additions to allyldiphenylphosphonate esters and subsequent ring-closing metathesis (RCM) to access P-chiral P-heterocyclic building blocks for the synthesis of phosphono sugars is described. These building blocks possess several attractive components, including the following: (i) P(2) and C(6) stereogenic centers for directing stereoselective transformations; (ii) an activated C(3) methylene group that promotes base-mediated olefin transposition to generate vinyl phosphonates available for further stereoselective reactions; and (iii) a P(2)-stereogenic center containing an exchangeable phosphonate ester armed to attenuate the "stereochemical environment" at phosphorus. Taken collectively, these attributes contribute to a concise method for the stereoselective synthesis of an array of P-sugars.

Ene–Yne Metathesis of Allylphosphonates and Allylphosphates: Synthesis of Phosphorus-Containing 1,3-Dienes

“…Potassium isocyanoacetate was prepared and used as previously reported (0.20 equiv in methanol). 44 1 H, 13 C, and 31 P NMR spectra were recorded on either a 300 MHz, 400 or 500 MHz Varian spectrometer with the appropriate frequency reported. 1 H and 13 C NMR spectra obtained in CDCl 3 were internally standardized via the trace chloroform signals at 7.26 and 77.0 ppm, respectively.…”

“…44 1 H, 13 C, and 31 P NMR spectra were recorded on either a 300 MHz, 400 or 500 MHz Varian spectrometer with the appropriate frequency reported. 1 H and 13 C NMR spectra obtained in CDCl 3 were internally standardized via the trace chloroform signals at 7.26 and 77.0 ppm, respectively. 31 P NMR spectra obtained in CDCl 3 were standardized by use of triphenylphosphine in CDCl 3 as an external reference set to −6.0 ppm.…”

“…1 H NMR (300 MHz, CDCl 3 , ppm): δ 5.92−5.70 (m, 1H), 5.28−5.12 (m, 2H), 4.24−3.98 (m, 4H), 2.81 (dd, 2 J HP = 19.5 Hz, 3 J HH = 7.3 Hz, 2H), 1.30 (t, 3 J HH = 7.1 Hz, 6H). 13 C{ 1 H} NMR (75 MHz, CDCl 3 , ppm): δ 127.9 (d, 2 J CP = 10.4 Hz), 120.3 (d, 3 J CP = 15.3 Hz), 62.8 (d, 2 J CP = 7.0 Hz), 40.8 (d, 1 J CP = 109.8 Hz), 16.3 (d, 3 J CP = 6.9 Hz). 31 P{ 1 C. Optimization Procedure.…”

“…However, there are a limited number of examples of allylphosphonate reagents undergoing intermolecular (cross) alkene metathesis − and no examples of these reagents giving cross ene–yne metathesis. Early examples by Hanson and co-workers used unsaturated phosphonates and related compounds to construct P-heterocycles by ring-closing metathesis (RCM) − and later developed this procedure to synthesize alkenes in complex molecule synthesis. , Governeur, van Boom, and Schmidt also made P-heterocycles by RCM or ring-closing EYM, respectively. Some of the Grubbs catalysts used for alkene and ene–yne metathesis are shown in Scheme below.…”

Synthetic Approaches to Phosphasugars (2-oxo-1,2-oxaphosphacyclanes) Using the Anomeric Alkoxyl Radical β-Fragmentation Reaction as the Key Step

“…Nevertheless, asymmetric Abramov hydrophosphonylation enables optimization of the synthesis of phostones for the formation of the manno-isomers . The total synthesis of phostones using ring-closing metathesis has also been reported …”