Phosphorane activated

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

The best results were achieved by employing N-(3-dimethylaminopropyl)-N -ethylcar-bodiimide hydrochloride (EDC) as coupling agent. After Fmoc deprotection with piperidine in N,N-dimethylformamide, additional diversity could be introduced by acylation of the liberated amine position. Finally, the acyl cyano phosphoranes could be efficiently cleaved by ozonolysis at -78 °C or by utilizing freshly distilled 3,3-dimethyloxirane at room temperature [65]. The released compounds constituted highly activated electrophiles, which could be further converted in situ with appropriate nucleophiles. 

Details have appeared39 of the addition of PH-tetraoxyspirophosphoranes to aldehydes and activated ketones. These phosphoranes also add to activated acetylenes,40 e.g. diethyl acetylenedicarboxylate with (50) gives a mixture of cis- and trans-(51). Further addition of (50) to (51) at higher temperatures gives the bisphos-phorane (52). Metallation of the spirophosphorane (53) followed by reaction with... 

The most common method for the generation of the metal alkylidene species seems to be a-elimination from an intermediate dialkyl-metal species. This procedure gives the most active catalysts. Above we mentioned the addition of other carbene precursors, which leads to active catalysts. Other methods to generate the metal alkylidene species involve alkylidene transfer from phosphoranes [16] or ring-opening of cyclopropenes [17], In Chapter 16.4 we will describe a few compounds that are active by themselves as metathesis catalysts. 

The synthesis of an optically active chiral phosphorane in which the optical activity is solely connected with the P atom implies, for instance, the preparation of a trigonal bipyramid or a tetragonal pyramid with five different achiral ligands which would, at least theoretically, entail the possible formation in the first case of ten or in the second case of fifteen diastereoisomers requiring separation, a formidable task even in the absence of stereomutation. The problem has nevertheless been solved using three different approaches exploiting the particular properties of spirophosphoranes, as hereafter detailed. 

Even if some of the optically active spirophosphoranes mentioned above can exist as single species in the solid state, all of them are more or less rapidly transformed, when dissolved, into binary mixtures of diastereoisomers114-129 such as 12 and T3. However, a third type of synthesis yielded pure, optically active phosphoranes not subject to change when dissolved129. This was obtained by the stereospecific synthesis of the oxazaphos-pholidine 53130 (Scheme 5) derived from the —(1R, 2S)enantiomer of ephedrine by means... 

The scheme followed more recently by Moriarty et al139 again involved a racemic phosphine (64, in Scheme 7), used to synthesize a racemic phosphorane 65, but the optically active ligand was introduced only at that point, to replace NMe2. As before, two diastereoisomers, 66a and b, were obtained, as proved by the two series of signals in the 31P, lH and 13C NMR spectra, and of the S and J values which were determined for the... 

Alkynes react with alkyl and aryl azides to give 1,2,3-triazoles (389 — 390). Suitable phosphoranes behave similarly thus (391) with cyanazide N3CN provides the 1,2,3-triazole-1-carbonitrile (392). Alkenes which are activated by electron-withdrawing groups, or are strained, give 1,2,3-triazolines (393) with azides. 

On the other hand, optically active 43 and 44 were synthesized as follows.401 Treatment of 2,3,4-tri-0-benzyl-l,5-di-0-tosyl-D-arabinitol (277) with three equimolar proportions of methylenetriphenylphos-phorane gave the cyclic phosphorane (278), which was stereoselectively converted into the cyanohydrin (279) by way of the corresponding C-methylene and inosose derivatives. Compound 279 was converted into 43 and 44 by way of the corresponding carboxylic acid (280), and unsaturated nitrile (281), respectively. Compound 39 was derived from the inosose (282), obtained from quebrachitol, through a 21-step conversion.402 Introduction of a hydroxymethyl group into 282 was accom-... 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

An aliphatic alcohol is oxidized with active M11O2, producing an aldehyde that reacts in situ with a stabilized phosphorane. The overall yield of the desired unsaturated ester is 80%. Curiously, the oxidation of the alcohol with M11O2 under the same reaction conditions and in the absence of phosphorane delivers only a 12% of the corresponding aldehyde. 

Wittig reactions of cyclohexanone derivatives in their inclusion compounds with the chiral host 5 gave optically active reaction products. For example, when a mixture of finely powdered 1 1 inclusion compound of 5b with 4-methyl-(15a) or 4-ethylcyclo-hexanone (15b) and phosphorane (16) was kept at 70 °C, the Wittig reaction in the solid state was completed within 4 h. To the reaction mixture was added diethyl ether-petroleum ether (1 1), and then the precipitated triphenylphos-phine oxide was removed by filtration. The crude product left after evaporation of solvent from the filtrate was distilled in vacuo to give (-)-4-methyl- (17a) of 42% ee (73 % yield) or (-)-4-ethyl-l-(carboethoxymethylene)cyclohexane (17b) of 45 % ee (57 % yield), respectively [9], Similar reaction of the 1 1 inclusion compound of 5c and c /. v - 3,5 - dime th y I c y c I o h e x a n o n e (18) with 16 gave 19 of 57 % ee in 58 % yield [9],... 

Equimolar quantities of benzhydrol and the phosphorane (3a) were also reacted in dimethyl sulphoxide solution. Apart from bis(benzhydryl) ether (18%) and catechol monobenzhydryl ether (39%), a small amount of benzophenone (17%) was obtained. It was shown that, in the absence of phosphorane, benzhydrol is not oxidised to benzophenone by dimethyl sulphoxide. Reaction similar to that outlined in Scheme 1 is a likely possibility. Again, the alcohol is activated by reaction with the phosphorane toward nucleophilic attack, in this case by dimethyl sulphoxide. Significantly, oxidation of alcohols by dimethyl sulphoxide is usually carried out using the Pfitzner-Moffatt reagent (dicyclohexyl carbodiimide and anhydrous phosphoric acid in dimethyl sulphoxide) (13) whereas the reaction using the phosphorane (3a) is carried out under neutral conditions. Unfortunately, however, attempts to improve the yield of benzophenone have hitherto failed. 

Activated Phosphoranes for the Cyclodehydration and Chlorination of Simple Diols... 

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