A study on the synthesis of the novel cyclic α-aminophosphonates and 2-alkoxy-2- oxo-1, 4, 2-oxazaphosphinanes 4a–r has been carried out. The title compounds were obtained in good yields by one-pot procedure using o-aminophenol, alkyl dichlorophosphinite, and ketones or benzaldehyde. One of their geometric stereoisomers was isolated and characterized. Configurations of 4k and one isomer of 4r have been established by X-ray diffraction analysis. The synthetic methods provide an easy access to the organophosphorus heterocycles with the ring system mentioned above. The abnormal chemical shifts of alkyl-substitute protons in 1H NMR spectra were given reasonable explanation.

A study on the synthesis of the novel N-(cyclic phosphonate)-substituted phosphoramidothioates, i.e., O, O-diethyl N-[(trans-4-aryl-5, 5-dimethyl-2-oxido-2λ5-1, 3, 2-dioxaphosphorinan-2-yl) methyl] phosphoramidothioates 4a–1, from O, O-diethyl phosphoramidothioate (1), a benzaldehyde or ketone 2, and a 1, 3, 2-dioxaphosphorinane 2-oxide 3 was carried out (Scheme 1 and Table 1). Some of their stereoisomers were isolated, and their structure was established. The presence of acetyl chloride was essential for this reaction and accelerated the process of intramolecular dehydration of intermediate 5 forming the corresponding Schiff base 7 (Scheme 2).

Base-promoted (KOH or MeONa in MeOH, or NaH in THF) cycloisomerisation of partially benzylated, 1-substituted (R=Ph-C≡C, pyridin-2-yl, or Br) ald-1-ynitols leads to (Z)-configured five-, six-, and seven-membered exo-glycals. The reactivity of the ald-1-ynitols depends upon their configuration. The ald-1-ynitols were derived from 2,3,5-tri-O-benzyl-D-ribofuranose 1, and the corresponding, partially O-benzylated galactose, glucose, and mannose hemiacetals by ethynylation. The hex-1-ynitol 2 derived from 1 (61%) was transformed via the 1-phenylbutα-1,3-diyne 3 and the 1-(pyridin-2-yl)acetylene 5 into the five-membered exo-glycals 4 and 6 (in 66 and 72% yields, resp., from 2). The analoguous ethynylation of 2,3,4,6-tetra-O-benzyl-D-galactose 8 was accompanied by elimination of one benzyloxy (BnO) group to the hept-3-en-1-ynitol 9 (71%), which was trans- formed into the non-5-ene-1,3-diynitol 10 and further into the six-membered exo-glycal 11 (50% from 9). Addition of Me3SiC≡CH to the galactose 8 and to the gluco- and manno-analogues 16 and 24 gave epimeric mixtures of the silylated oct-1-ynitols (86% of 12L/12D 45 : 55, 94% of 17L/17D 7 :3, and 86% of 25L/25D 55 :45), which were separated by flash chromatography, and individually transformed into the corresponding 1-bromooct-1-ynitols. Upon treatment with NaH in THF, only the minor epimers 13L, 18D, and 26D cyclised readily to form the seven-membered hydroxy exo-glycals. They were acetylated to the more stable monoacetates 14L, 23D, and 28D (82–89% overall yield). Under the same conditions, the epimers 13D, 18L, and 26L decomposed within 12 h mostly to polar products. The difference of reactivity was rationalised by analysing the consequences of an intramolecular C(3)O-H···—OC(7) H-bond of the intermediate alkoxides on the orientation of —O-C(7) of 13L, 18D, and 26D and its proximity to the ethynyl group.

Functionalised bicyclic exo-glycals are readily obtained by base-catalysed (typically MeONa in MeOH) alkynol cycloisomerisation of ethynylated cyclic saccharides. Thus, base treatment of the phenylethynyl- and halogenoethynylated 1-O-acetyl-ribofuranoses 22 - 24 and the 4-ethynylated 1-thioglucopyranosides 30 - 33 gave - after deacetylation - selectively the (Z)-configured exocyclic enol ethers 26 - 28 (84 - 91%) and 34 - 37 (63-76%), respectively, resulting from a trans-5-exo-dig cyclisation. The ring closure to the trans-dioxahex-ahydroindans 34 - 37 is favoured by a concerted intramolecular protonation of the intermediate vinyl anion by the neighbouring HO-C(3). Cycloisomerisation of the 6-O-acetyl-4-(phenylethynyl)-1-thio-α-D-glucopyrano-side 39 occurred via the corresponding phenylethynylated allenes to provide the galacto-configured (Z)- and (E)-cis-dioxahexahydroindans 40 (30%) and 41 (51%). Surprisingly, the HO-C(4) unprotected α-D-galactopyranosyl-butα-1,3-diyne 15 and the β-D-glucopyranosyl-butα-1,3-diyne 51 (and its 2-bromoethynyl analogue) undergo a 6-exo-dig ring closure to the 2,5-dioxabicyclo[2.2.2] octanes 16 - 19 and 52/53, respectively, the ring closure requiring a boat conformation (B1,4 for 15, 1,4B for 51). Ring strain (anti-reflex effect) prevents an alkynol cycloisomerisation of 4-(phenylbuta-1,3-diynyl, bromoethynyl, or iodoethynyl) levoglucosan 56 - 59, and 56 reacted by elimination to the hex-1-ene-3,5-diyne 59 (82%), while isomerisation of 57 and 58 led to epimeric mixtures of the haloallenes 60 (82%) and 61 (68%).

An improved method for the synthesis of Diphenyl α-(diethoxythiophosphorylamino) methylphosphonates under mild conditions is described. It consists of the reaction of diethyl thiophosphoramidate (1) with triphenyl phosphite (3) and a substituted benzylaldehyde or ketone (2) by a one-pot procedure with the aid of acetyl chloride.