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A diastereoselective (3 + 2) cycloaddition of N-sulfonyl ketimines with vinylethylene carbonates (VECs) in the presence of Pd2dba3·CHCl3 and PPh3 has been developed. The reaction of various substituted VECs and diverse cyclic N-sulfonyl ketimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to excellent yields with moderate to good diastereoselectivities. With the use of spiroketal-based diphosphine SKP as a chiral ligand, an asymmetric version of the current (3 + 2) cycloaddition was achieved, and chiral products were obtained in >99% ee in most cases.

Herein we describe the PhI(OAc)2-mediated 1,1- and 1,2-difunctionalization of alkenes with N-tosyl amino alcohols to form oxazolidine and morpholine derivatives. This transformation was realized under mild reaction conditions and allows application to various substrates furnishing the multi-substituted oxazolidines and morpholines with yields up to 98%. A deuterium-labeling experiment was carried out and the result indicated that a phenyl group migration occurred to generate oxazolidine products.

Three new main group ferrocenyldithiocarbamate complexes, viz., {Pb[(FcCH2)(CH2CH2OH)(NCS2)]2}·(FcCH2-3-oxazolidine-2-thione)·(H2O) (1), {Sb[(FcCH2)(CH2CH2OH)(NCS2)]3} (2) and {Bi[(FcCH2)(CH2CH2OH)(NCS2)]3} (3), (Fc = ferrocenyl) have been synthesized and characterized by elemental analyses and IR, 1H and 13C NMR spectroscopy as well as X-ray crystallography. The X-ray analysis of 1 indicates distorted trigonal bipyramidal geometry around Pb(II) and a cyclised product, 3-ferrocenylmethyl-oxazolidine-2-thione (4), co-crystallizes with 1. The geometry around Sb(III) in 2 is pseudo-octahedral, while 3 forms a dimer, displaying distorted square antiprism geometry around the Bi(III) center. Several attempts to synthesize the pure cyclised product 3-ferrocenylmethyl-oxazolidine-2-thione (4) using Pb(II) salts failed but 4 was fortuitously obtained in an attempt to synthesize the Cu(I) cluster by the comproportionation of {Cu[(FcCH2)(CH2CH2OH)(NCS2)]2} using copper powder. Interestingly, varying the reaction time yielded another completely desulfurized cyclised product 3-ferrocenylmethyl-oxazolidine-2-one (5). Both 4 and 5 have been characterized using spectroscopic techniques and X-ray crystallography, and the possible mechanism for the conversion of {Cu[(FcCH2)(CH2CH2OH)(NCS2)]2} to 3-ferrocenylmethyl-oxazolidine-2-thione (4) has been explained with the help of periodic UV-Vis and ESI-MS experiments. This investigation will pave a new pathway for the synthesis of similar cyclised products using similar safe and sustainable reaction conditions.

A palladium/copper-catalyzed oxy-carbonation of propargylic amides by halohydrocarbons and CO2 has been developed toward functionalized oxazolidine-2,4-diones. This multi-component reaction (MCR) was triggered by the oxidative addition of RX to Pd(0), followed by the sequential carboxylation of amide and trans-oxopalladation of an electron-deficient triple bond by RPdX species. Finally, the reductive elimination afforded products possessing tetra-substituted vinyl motifs and Pd(0). This protocol features simultaneous formation of three bonds, representing an efficient method for incorporation of CO2 into value-added heterocycles.

A Selectfluor™-catalyzed oxidative cyclization of ynamides affording oxazolidine-2,4-diones in yields from 69%–94% is described. The reaction is run under air and exhibits excellent chemo-selectivity and functional group compatibility. Preliminary mechanistic studies reveal that the solvent DMSO acts as an oxidant, and the redox reaction of Selectfluor™ with DMSO generates the real active catalyst HBF4in situ.

The metal-free carboxylative cyclization of propargylic amides with CO2 to oxazolidine-2,4-diones was achieved for the first time employing 1,5,7-triaza-bicyclo-[4.4.0]dec-5-ene (TBD) as an organocatalyst. This method allows for the efficient and selective synthesis of a variety of (Z) 5-alkylidene 1,3-oxazolidine-2,4-diones, and a variety of functional groups are well-tolerated under mild reaction conditions. Theoretical studies reveal that the bifunctional activity (base/H-bond donor) of TBD plays a key role in accelerating this reaction.

DBU mediated 5-exo-dig cyclization of isothiocyanate and propargyl alcohol leading to valuable heterocyclic compounds has been accomplished. The different modes of nucleophilicity (either S-selective or N-selective) of isothiocyanates were found to depend on the substitution pattern of propargyl alcohol. The terminal propargyl alcohol and isothiocyanate underwent an N-nucleophilic attack to afford 3-substituted 4-methylene oxazolidine-2-thiones. In contrast, exclusive S-nucleophilic cyclization was observed with internal propargyl alcohol to produce (Z)-1,3-oxathiol-2-ylidenes and (Z)-N-(Z)-4-ethylidene-1,3-oxathiolan-2-ylidenes from secondary and primary propargyl alcohols, respectively. The formation of high Z-selectivity in the imine motif and alkene is the highlight of this new method as multiple selectivities over C[double bond, length as m-dash]N and C[double bond, length as m-dash]C in a single system are synthetically highly challenging. The Z-selectivity in imine and alkene may be attributed to electronic and steric factors respectively.

Proton gradient reactions are common, but those with inverse proton gradients are rare. Inspired by the phenomenon that stomach can release acid with microenvironment changes, an inverse proton gradient process along with a ring-closing of the precursors of oxazolidine molecular switches (i.e., ROF+X−s) was achieved within specific microenvironments both in solution and on solid substrate. Nucleophilicity and concentration of solution were found playing important roles in this process. Furthermore, benefits from this ring-closing process arose from inverse proton gradient, a potential application of ROF+X−s replacing their akalization products—ring-closed forms (RCFs) of oxazolidines in water-jet rewritable paper (WJRP) was developed. Influence of dissolving solvent and drying temperature on hydrochromic performances of ROF+X− based WJRP were inspected and compared to its corresponding RCF based WJRP. Results indicate that the former outperforms the latter in color depth, coloration speed and retention time. The water-jet prints on ROF+X− based WJRP exert excellent legibility, resolution, uniformity, and repeatability. This research achievement will not only promote the industrialization of oxazolidines derivatives based WJRP by greatly reducing production costs from a perspective of synthetic industrialization, but may also provide a reference for better understanding of similar microenvironment-induced phenomena of inverse proton gradient in complex biosystems.

Photooxidation of oxazoline (OXA) molecular switches through media-induced intramolecular ionization is reported. The formation of the photooxidation product occurs by attack of the flexible donor group (-CH2CH2OH) to the adjacent C[double bond, length as m-dash]C with 1O2 as the oxidant. The novel seven-membered ring sub-structure of the photooxidation product was inferred by HRMS, IR and 1H NMR spectroscopy. Additionally, acid released from solvent photolysis was found to affect the product formation and efficiency of the photooxidation.

One-pot reaction between 8-hydroxyquinoline-2-carboxaldehyde (HQC) and tris(hydroxymethyl)aminomethane (TRIS) followed by in situ cyclization yielded an oxazolidine based ligand which produced four mononuclear complexes of MnII(1), CoII(2), NiII(3), ZnII(4), a tetranuclear iron (FeIII4) complex (5) and a trinuclear cobalt (CoIICoIII2) complex (6). Magnetic studies show dominant antiferromagnetic interaction in tetranuclear iron (FeIII4) complex 5 and presence of the slow relaxation of magnetisation in 6. The compounds were also studied for their antibacterial properties. The oxazolidine ligand (H3L2) of this study showed good antimicrobial activity not only against Gram-positive bacteria but against Gram-negative bacteria too. The antimicrobial efficacy of the metal complexes (1-6) is also reported.

New recyclable chiral salen complexes Cr(III)1–7 were synthesized from various macrocyclic chiral ligands having multistereogenic chiral centers which work synergistically to give the best results in terms of the enantioselectivity and yield of the products. Among the synthesized complexes, the Cr(III)-4 salen complex efficiently catalyzed the ring opening reaction of various aromatic ester epoxides, trans-epoxides and meso-epoxides with anilines to furnish the corresponding β-amino-α-hydroxyl esters and β-amino alcohols with an excellent ee of up to 99% and a high yield of up to 95%. Furthermore, the chirally pure β-amino-α-hydroxyl esters were converted into pharmaceutically important oxazolidine ring systems. Moreover, the chromium catalyst was recycled up to 5 cycles with the retention of its activity.

A novel amphiphilic copolymer consisting of tetraphenylethylene-oxazolidine (TPE-OX) as a pH-sensitive chromophore and poly(ethylene glycol) methyl ether methacrylate (PEGMA) as a water-soluble chain has been well designed and synthesized. A self-assembled polymeric micelle based on the copolymer exhibited clear dual-emission switching between cyan and red with a decrease of pH value in Tris-HCl buffer solution due to the extended conjugation and emerging intramolecular charge transfer effect when opening the spiro-ring of OX moiety. Fluorescence imaging of HepG2 cells stained by the polymeric micelle shows switched luminescence from cyan to red with high selectivity and contrast, indicating that the polymeric micelle was an effective probe for intracellular pH detection. Additionally, the red emission of the polymeric micelle in lysosomes can reversibly switch back to the original cyan emission in response to the two lysosomal activity inhibitors chloroquine and bafilomycin, which demonstrates that the polymeric micelle has potential applications in detecting the activity of lysosomal and further autophagy in cancer cells.

The oxazolidine-2,4-dione motif is found frequently in biologically important compounds. A tandem phosphorus-mediated carboxylative condensation of primary amines and α-ketoesters/base-catalyzed cyclization reaction have been developed. These processes provide a novel and convenient access to various oxazolidine-2,4-diones in a one-pot fashion using atmospheric carbon dioxide and readily available substrates under very mild and transition-metal-free conditions.

We have previously reported on a study of the structure–activity relationship in a series of 2,3,4-substituted oxazolidines recently discovered by our group varying the substituent at the ring or stereochemistry of the oxazolidine ring. We discovered the cytotoxic and pro-apoptotic potential of compounds 1 and 2 with good selectivity against cancer cell lines. In the present study we describe the synthesis and cytotoxic evaluation against cancer cell lines (HL60, JURKAT, MDA-MB-231 and LNCaP) of a series of oxazolidines designed by isosteric replacement or rigidification of the oxymethylene spacer of compounds 1 and 2. Alkenes 3 and 4 retained the activity against MDA-MB-231 cells and they were more active on HL60, JURKAT and LNCaP cells. Considering LNCaP cells, E-isomer 4 was at least 7 times and about 3 times more potent than lead 1 and Z-isomer 3, respectively. Compound 4 exerted significant activity against LNCaP with IC50 in the low micromolar range (11 μM) without affecting VERO cells and PBMC proliferation (IC50 > 100 μM) indicating its low toxicity to normal cells.

A facile and catalytic asymmetric synthesis of the pentacyclic core of (-)-nakadomarin A, containing all the stereogenic centers of the natural product was achieved. The key intermediate involves the oxazolidine moiety as an iminium cation equivalent. An efficient method for the removal of the N-hydroxyethyl group is also described.

The 3-phenyl-2-(pyridin-2-yl)oxazolidine ligand (ppo) was synthesised and its coordination behaviour regarding Ni(II) and Pd(II) centres was studied. The reaction with K(2)PdCl(4) affords [Pd(N,N'-ppo)Cl(2)] (1), in which ppo binds to palladium via the pyridyl nitrogen and the oxazolyl nitrogen atoms. On the contrary, reaction with NiCl(2)·6H(2)O produces [Ni(N,O-ppo)(2)Cl(2)] (2), in which two ppo ligands are coordinated via the pyridyl nitrogen and the oxygen atom of the oxazolidine ring. The X-ray diffraction analysis of the complexes confirms a square planar geometry for Pd(II) in 1 and an octahedral configuration around Ni(II) in 2, which, to the best of our knowledge, represents the first reported example of a structurally characterised nickel-oxazolidine compound. In addition, both complexes prove to be active catalysts under mild conditions in the aza-Michael reaction of (E)-4-phenylbut-3-en-2-one (benzalacetone) with aliphatic amines.

A very mild protocol for fixation of carbon dioxide with 2-alkynamides in DMSO at 30 °C using a CO(2) balloon in the presence of K(2)CO(3) has been developed, which leads to an efficient assembly of oxazolidine-2,4-diones. It is observed that the regioselectivity was controlled by the aryl group.

One-pot Prato reactions of C60 with amino acids and aldehydes afford five new fullerene derivatives, including two unexpected thiazolidine and oxazolidine fulleropyrrolidines. In particular, L-cysteine (1), paraformaldehyde and C60 in refluxing toluene solution affords an unexpected new thiazolidine-fulleropyrrolidine derivative 3 (instead of 2) via 1,3-dipolar cycloaddition, whose structure was characterized in detail. A possible reaction mechanism for the formation of 3 is proposed. These suggest that the active hydrogen of S–H in 1 is essential for the formation of the thiazolidine ring in 3. To confirm further this conclusion, reactions of C60 with different amino acids (5, 7) and aldehydes (3-(methylthio)proplonaldehyde (9) and 2-thiophenaldehyde (11)) were also studied, resulting in the synthesis of other three new thio-derivatives of C60 (6, 10, 12) as well as an oxazolidine fulleropyrrolidine (8).

threo-N-Alkoxycarbonylamino epoxides 5a–d, containing the oxazolidine moiety, were converted into trans-4,5-disubstituted-2-oxazolidin-2-ones 2 with total regio- and stereoselection by means of nucleophilic intramolecular attack of the carbamate moiety to the protonated oxirane ring. Theoretical calculations confirmed both the regioselection and the preference of the cyclocarbamation reaction vs. the intermolecular attack by the solvent, arising from different behaviour in comparison with the analogous iodonium ions.

In the reactions of bis(α-amino acidato)copper(II) with formaldehyde and benzamide, competing processes occur and the preferred pathway depends on the nature and number of the α-carbon substituents of the chelated amino acid, and the pH of the reaction medium. Aldol-type condensation yields complexes with oxazolidine ring(s) while Mannich aminomethylation results in the formation of complexes with N-methylbenzamido pendant arm(s). The crystal structure determination of bis(3-methylbenzamido-5-methyloxazolidine-4-carboxylato)copper(II) dihydrate establishes its formation from a combination of both processes, in which aldol condensation occurs first. The chemistry of these reactions is rationalized with a proposed reaction scheme. The synthesized compounds are characterized by infrared spectroscopy and microanalysis.

The asymmetric synthesis of the enantiomeric pair of (+)- and (–)-dihydropinidines has been accomplished. Our strategy was based on the enantioselective construction of both enantiomers of the natural products by using a single chiral source, (R)-phenylglycinol. Both routes were carried out by similar processes, except for either the presence of an imine or 1,3-oxazolidine intermediate. Excellent diastereoselectivity was observed in the reaction of chiral imines and 1,3-oxazolidines with organometallic reagents, to give the chiral amines in high chemical yields. The absolute configuration of both amines was determined by converting each of them into dihydropinidine. The asymmetric synthesis of the (+)- and (–)-dihydropinidine piperidine alkaloids was realized in four steps each and in 46 and 59% overall yield, respectively, from 6 and 11.

Formaldehyde-derived oxazolidine derivatives 4–7 of the β-adrenoreceptor antagonists metoprolol 1, atenolol 2 and timolol 3 have been synthesised. Conformational analysis of 1–3 and the oxazolidine derivatives 4–7 has been performed using 1H NMR spectroscopy and computational methods. The 1H NMR studies show that for the aryloxypropanolamine β-adrenoreceptor antagonists there is a predominance of the conformer in which the amine group is approximately antiperiplanar or trans to the aryloxymethylene group. Both 1H NMR data and theoretical studies indicate that the oxazolidine derivatives 4–7 and the aryloxypropanolamine β-adrenoreceptor antagonists 1–3 adopt similar conformations around the β-amino alcohol moiety. Thus, oxazolidine ring formation does not dramatically alter the preferred conformation adopted by the β-amino alcohol moiety of 1–3. Oxazolidine derivatives of aryloxypropanolamine β-adrenoreceptor antagonists may therefore be appropriate as prodrugs, or semi-rigid analogues, when greater lipophilicity is required for drug delivery.

The conjugate addition of the phenyldimethylsilyl-cuprate reagent to cinnamate and crotonate esters and amides 1 of various known chiral auxiliaries, a–e, is diastereoselective. The sense of the diastereoselectivity of silyl-cuprate addition to the esters 1b–d, 8 and 9 is different from established precedent based on carbon-cuprates, but is normal for silyl-cuprate addition to the amide 1a, the imides 1e and 21, and the oxazolidine 6. The chiral auxiliary e gives the best results of those tested, and the silicon-containing group can be removed from the chiral auxiliary using alkoxide ion in aprotic media, making available β-silyl esters 27–29 of high enantiomeric excess, with recovery of the chiral auxiliary 30.

A series of bis(oxazolidine)pyridine ligands (the PyBodines) were newly designed and synthesized for the development of a highly efficient, tailor-made catalyst for the [3+2] cycloaddition of azomethine imines with propiolates. The PyBodine(l-Ala)-Cu(OAc)2 catalyst was selected on the basis of solid-phase catalysis/CD-HTS and exhibited high efficiency, producing the (R)-adducts with excellent enantioselectivity.

A concise synthesis of the marine alkaloids ()-lepadins A-C from a phenylglycinol-derived tricyclic lactam is reported. Key steps from the stereochemical standpoint involve stereoselective cyclocondensation, double bond hydrogenation, oxazolidine opening, hydroboration- oxidation, and Horner-Wadsworth-Emmons reactions.

The readily available and inexpensive new chiral oxazolidine in combination with Ti(O(i)Pr)(4) was found to catalyze the reaction of an alkynylzinc reagent with various types of aldehydes to generate chiral propargylic alcohols with high enantioselectivities (up to 95%) and excellent yields (up to 98%).

In part because of their straightforward and modular syntheses from readily available enantiopure starting materials, and their capacity to bind a wide variety of transition metals, chiral, chelating nitrogen-donor ligands have played a prominent role in asymmetric catalysis. A large number of highly enantioselective transformations rely upon these ligands whose reported classes are built around amine, imine, pyrrole, pyrrolidine, oxazoline and oxazolidine donor groups, among others. In this Perspective, we examine a selection of transformative developments in asymmetric catalysis by metal complexes of bi- and polydentate members of this ligand family. We describe approaches to ligand design and synthesis, structure and bonding in coordination complexes, and limitations and future challenges.

The condensation of a 2- substituted- 2- aminoethanol with methyl 2 - formylbiphenyl- 2- carboxylate produces only two of the four possible axially chiral 6,7- dihydrodibenz[ c, e] oxazolo[ 3,2- a] azepin-( 4bH)- ones ( fused oxazolidine lactams), with kinetically controlled diastereoisomer ratios of up to 96 : 4. Within each lactam product the central chirality of the oxazolidine- fused benzylic position C( 4b) is relayed to the biaryl axis with unit efficiency, the mis- matching of these stereogenic elements being prohibited due to strain, as predicted by molecular mechanics calculations. Diastereoisomeric lactam pairs can be equilibrated by heating with acid, and under these thermodynamic conditions reversed diastereoisomer ratios of up to 26 : 74 are observed. Edwards, David J. House, David Sheldrake, Helen M. Stone, Susan J. Wallace, Timothy W. 42 ROYAL SOC CHEMISTRY CAMBRIDGE 197MN

The BF3·Et2O promoted coupling of tetra-O-benzyl-α-D-galactopyranosyl trichloroacetimidate with a silyl enol ether carrying an oxazolidine ring leads to the α-C-glycosylmethyl ketone (32%, 95% ds) that is converted into the title α-C-glycosyl amino acid by carbonyl oxygen removal (Barton–McCombie) and oxidative cleavage (Jones) of the heterocyclic ring, and into the β-isomer by anomerization and the same two-step sequence.

Iodolactonisation of heptadienoic acid derivatives 2 and 3 having oxazolidin-2-ones or a sultam as chiral auxiliary gave the chiral iodolactones 4 and 5 in moderate to excellent enantiselectivity.

Oxazolidine vinyl oxirane 1, a novel and highly versatile building block for the preparation of enantiopure D-(+)-erythro-sphingosine and analogues, has been prepared by chloroallylboration of the Garner aldehyde with absolute stereocontrol and in good yield.

The indolizidine alkaloid, (+)-monomorine I 1, has been prepared in an asymmetric synthesis employing the highly diastereoselective reaction of a 1,3-oxazolidine with a Grignard reagent.

A route to 2-phenyl-4,5-dihydrooxazole-4-carbonitrile N-oxide 7 has been developed starting from (S)-serine methyl ester and involving dehydration of the 4-nitromethyl derivative 13 using m-tolylene diisocyanate and triethylamine. Cycloaddition of the nitrile oxide to styrene afforded a 55:45 mixture of diastereoisomeric dihydroisoxazoles 21 and 22; furazan N-oxides 19 and 20 were also formed in a competing dimerisation. The analogous (R)-oxazolidine-4-carbonitrile oxide 8, also prepared from (S)-serine methyl ester, reacted similarly with styrene, oct-1-ene and diethyl fumarate to afford ca. 1:1 mixtures of adducts. The structures of the dihydrooxazole–dihydroisoxazole adduct 21 and furazan N-oxide 20 were determined by X-ray crystallography.

A short, efficient approach to the p-methoxybenzylidene-protected paclitaxel (Taxol) side chain through benzaldehyde benzoylimine-chiral enolate condensation, followed by DDQ-mediated oxazolidine formation and hydrolysis is described; the C-7-triethylsilyl derivative of baccatin III undergoes esterification with this side chain in the presence of DCC and DMAP to provide after acid hydrolysis paclitaxel in excellent overall yield.

Under kinetic control, the stereochemical course of the condensation between (–)-ephedrine and p-cyano-or p-nitro-benzaldehyde is solvent dependent; no noticeable stereoselectivity was observed in chloroform whereas diastereo-differentiation occurred in methanol.

The molecular structures and absolute configurations of cyanocycline A (I) and related compounds have been determined by single crystal X-ray diffraction methods using diffractometer-measured data. Compound (I) contains the molecular structure of naphthyridinomycin with a hydroxy-group replacing a cyano-group. When the pH at which crystallization is carried out is changed, the oxazolidine ring of (I) changed reversibly from the closed to the open form in the bis(hydrogen halide) salts. Two nitrogen atoms are quaternized in the bis(hydrogen halide) salts: one forms an ion-pair with a halide anion and the other has a short intramolecular contact with the oxygen of atom the hydroxymethyl group. The remaining halide anion in these salts forms a bifurcated intermolecular hydrogen bond with two hydroxy groups.

Ornithine is a direct biosynthetic precursor to naphthyridinomycin, and the oxazolidine nitrogen is derived intact from serine.

The anodic oxidation of enediamines leads to an unexpected cyclisation involving solvent moisture to give an indolo-oxazolidine in a good yield.

A useful diastereoselective synthesis of aldols using chiral 3-acyl-1,3-oxazlidine-2-thiones, (1), (4), (7), and (9), is reported and its application to the synthesis of a chiral azetidinone (11) is described.

New chiral five-membered heterocycles, (4S)-(4) and (4R)-4-ethyl-1,3-oxazolidine-2-thione (5), (4S)-4-isopropyl-1,3-oxazolidine-2-thione (6), and (4R,5S)-4-methyl-5-phenyl-1,3-oxazolidine-2-thione [(4R,5S)-MPOT](7) have been developed. Among these heterocycles, (4R,5S)-MPOT (7) proved to be an excellent chiral reagent for analytical and efficient separation of racemic products from transformations of chiral carboxylic acids and amino acids.

A synthesis of (R)- or (S)-2-alkyl-1,2,3,6-tetrahydropyridines (1), starting from (R)- or(S)-phenylglycinol and Zincke's salt (2), and proceeding via the new oxazolidine derivative (5) as a key intermediate, is described.

The Knorr reaction when conducted in an aprotic polar solvent provides a new route to oxazolidine-2-thiones.

The reaction of 2,6-diacetylpyridine with 1,3-diamino-2-hydroxypropane in methanol in the presence of lead(II) cations leads to the isolation of lead(II) complexes of an oxazolidine-containing Schiff base macrocycle formed by ring-contraction; the ligand is hexadentate and the lead is N-bonded to one thiocyanate to form a monocationic complex.

Growth of cultures of Streptomyces clavuligerus(ATCC 27064) in an 18O2-containing atmosphere resulted in efficient and equal incorporations of molecular oxygen into the oxazolidine ring and the allylic hydroxy group of clavulanic acid.

The structure of the copper(II) complex C12H24O8N2Cu formed during the synthesis of the DL-threonine is that of an oxazolidine, a fact which enables a reaction mechanism to be established for this synthesis of threonine.

Methyl (6S)-7-hydroxy-5,5,9,9-tetramethyl-8-oxa-4-thia-1 -azabicyclo[4.3.0]non-2-ene-3-carboxylate (2) is converted into methyl 5,5,9-trimethyl-4-thia-1 -azabicyclo[4.3.0]nona-2,6,8-triene-3-carboxylate (14) by lithium aluminium hydride–aluminium chloride in ether. The rearrangement is also induced by aluminium chloride in ether, toluene-p-sulphonyl chloride in pyridine. and methanesulphonyl chloride–triethylamine in dichloromethane.Methanolic hydrogen chloride rapidly converts the lactol (2) into a mixture of acetals; the minor acetal is then isomerised under the reaction conditions to the thermodynamically preferred major acetal, which is considered to be the (7S)-isomer (12). Deuterium-incorporation studies suggest that the iminium ion (15) is involved in the transformation of derivative (2) into the acetal (12).The lactol (2) affords the methylthio-derivative (6) with acidified methanethiol and the phenylthio-derivative (7) with acidified benzenethiol. Treatment of the former material with sodium periodate yields the sulphoxide (8), which is further oxidised to the disulphoxide (9). Raney nickel converts the sulphoxide (8) mainly into the oxazolidine (17), although complex reactions ensue when the thioacetals (6) and (7) and the disulphoxide (9) are treated with this reagent.

U.v. irradiation of perfluoro-N-fluoromorpholine in the presence of perfluorocyclobutene yields perfluorobicyclobutyl, perfluoro-NN′-bimorpholyl, and perfluoro-(N-cyclobutylmorpholine). Pyrolysis of the last product gives perfluoro-(N-vinylmorpholine), photochemical bromination of which provides perfiuoro-[N-(1,2-dibromoethyl)-morpholine], a compound also formed, together with N-(2-bromo-1,2,2-trifluoroethyl)octafluoromorpholine, when the vinyl derivative is subjected to photochemical hydrobromination. U.v. irradiation in silica–Pyrex apparatus of perfluoro-N-fluoromorpholine, either alone or in the presence of oxygen, yields, inter alia, the N–O–N compound perfluoro-[N-(morpholino-oxy)morpholine]. Pyrolysis of this product gives perfluoromorpholin-N-oxyl, perfiuoro-NN′-bimorpholyl, perfiuoro-(6-morpholino-oxy-2-aza-5-oxahex-1-ene), perfiuoro-(6-morpholino-oxy-2-aza-5-oxahex-2-ene), perfluoro-5,6-dihydro-2H-1,4-oxazine, perfluoro-N-fluoromorpholine, and, if the decomposition is carried out at low pressure, a compound believed to be perfluoro-[N-(morpholino-oxymethyl)oxazolidine]. Perfluoro-(4-morpholino-oxy-3-oxabutyric) acid and its amide can be obtained via hydrolysis of the azahexenes. Perfluoromorpholin-N-oxyl reacts with nitric oxide, tetrafluoroethylene, and perfluorobut-2-yne to give perfluoromorpholyl nitrite, perfiuoro-[1,2-bis(morpholino-oxy)ethane], and perfiuoro-[N-(morpholino-oxy)morpholine] and perfluorobiacetyl, respectively. Flow pyrolysis of perfluoro-N-fluoromorpholine in platinum yields carbonyl fluoride, carbon tetrafluoride, hexafluoroethane, perfluoro-2-azapropene, perfluoro-2-azabut-2-ene. perfluoro-(N-methyloxazolidine), perfluoro-5,6-dihydro-2H-1,4-oxazine, and, possibly, N-fluorodifluoromethyleneamine, but apparently not perfluoro-4-oxa-2-azahex-2-ene, as proposed previously; this can be rationalised by a breakdown mechanism that is consistent with the formation of the azahexenes when perfiuoro-[N-(morpholino-oxy)-morpholine] is pyrolysed and with the production of 6-chloro-octafluoro-5-oxa-2-azahex-2-ene when perfluoromorpholine is heated with chlorine in the presence of potassium fluoride.E.s.r. data for perfluoromorpholin-N-oxyl are presented.