Staudinger reaction Subject

To demonstrate the feasibility of organic synthesis using this support, the authors immobilized a N-Boc protected glycin (22) on the support (Scheme 7.5). After deprotection imine formation readily occurs with an excess of benzaldehyde. The product was then subjected to a Staudinger reaction with phenoxyacetylchlor-ide to yield the polymer supported / -lactam (26) which could be released to give the yS-lactam (27) with TEA in methanol. 

Jarrahpour et al. [135] have described the synthesis of novel mono- and bis-spiro-[S-lactams 231 and 233, respectively, from benzylisatin 229 (Scheme 52). The starting substrate, benzylisatin 229 was prepared by reaction of isatin 228 with benzyl bromide and calcium chloride in DMF. The benzylisatin substituted imines 230 and di-imines 232 were further subjected to Staudinger reaction with ketenes derived from methoxy, phenoxy, and phthaloglycyl chlorides to afford novel mono- and bis-spiro-p-lactams 231 and 233, respectively. The configuration of benzylisatin 229 and monocyclic spiro-p-lactams 231 was established by X-ray crystallographic studies. These spiro-p-lactams will be studied as precursors of modified p-amino acids, (3-peptides and monobactam analogues. 

The research team of J. Tadanier prepared a series of C8-modified 3-deoxy-P-D-manno-2-octulosonic acid analogues as potential inhibitors of CMP-Kdo synthetase. One of the derivatives was prepared from a functionalized olefinic carbohydrate substrate by means of the Wohl-Ziegler bromination. The stereochemistry of the double bond was (Z), however, under the reaction conditions a cis-trans isomerization took place in addition to the bromination at the allylic position (no yield was reported for this step). It is worth noting that the authors did not use a radical initiator for this transformation, the reaction mixture was simply irradiated with a 150W flood lamp. Subsequently the allylic bromide was converted to an allylic azide, which was then subjected to the Staudinger reaction to obtain the corresponding allylic amine. 

In a similar manner, functionalized allyl amides were hydroformylated with a Rh-Alkanox 240 complex as exemplarily shown in Scheme 4.40 [83,84]. The aldehydes were subjected finally to the Staudinger reaction to produce P-lactams with potential anticancer activity. 

Historically, the first reactions involving thiocarbonyl ylides involve the preparation of thiiranes and 1,3-dithiolanes from diazomethane and thiocarbonyl compounds reported early in the last century by Staudinger and co-workers (12,13). Similar reactions have been smdied by Schonberg and co-workers (14—16) during the 1960s, but neither was the reaction mechanism understood nor have thiocarbonyl ylides been recognized as key intermediates. [For some remarks to this subject see (8) and (10) in (17).]... 

This is an excellent way of synthesizing the beta-lactam structure, and it has been the subject of several reviews (e.g.. Ref. 18). This is one of the reactions first reported by Staudinger, which is shown in Scheme 5.40. Many variants of this process have since been discovered. 

Treatment of enecarbamate 344 with sodium azide and ceric ammonium nitrate (CAN) in acetone furnished azidocarbazole 345. The low yield in this oxidative cychzation reaction is due to formation of the diastereomer consisting of stereochemical inversion at the azide-substituted carbon. At this point, azide reduction employing the Staudinger conditions of triphenyl-phosphine in a mixture of water and THF led to an amine, which was subjected to trichloroacetyl chloride in a solution of dichloromethane and triethylamine to yield amide 346 (Scheme 49). 

The mechanism of the Staudinger ketene imine cycloaddition reaction has been the subject of much debate and has recently been reviewed. The mechanism has been studied both computationally and experimentally. Experimental evidence gathered on solution phase reactions supports a two-step mechanism, in which addition of the imine nitrogen to the ketene carbonyl group occurs to generate an intermediate zwitterion. Subsequent cyclization of the zwitterion results in formation of the key C3-C4 a-bond. 

The antitumor antibiotic phloeodictine A1 (171) has been synthesized by Snider s group (Scheme 15.37). The unstable azide derived from 167 was subjected to a polymer supported tandem Staudinger-aza-Wittig followed by a retro Diels-Alder reaction to afford intermediate 170. Addition of 11-dodecenyl magnesium bromide followed by alkylation reaction and deprotection completes an efficient synthesis of phloeodictine A1 (171). 

Cycloaddition processes would appear to be attractive routes to ladder polymers since the growth reaction generally occurs by a concerted process which is not subject to the t3u anny of statistics. One of the earliest examples of this route was the attempt by Staudinger... 

The Staudinger concept of covalently bonded macromolecules introduced in 1922 and that pertaining to the random nature of all synthetic polymerization reactions— whether they proceed via chain or step growth— are the two cornerstones of polymer chemistry. Pol)mier chemists are thus used to dealing with averages to describe the samples they synthesize, because the samples are actually mixture of chains of different size. Similarly, the shape adopted by the macromolecule in solution is also subject to averages because the macromolecule continuously twists and turns around the chemical bonds of its backbone. One of the most popular areas of research since the early days of polymer chemistry was actually directed at minimizing the fluctuation of parameters such as the size and composition or shape of the macromolecules in order to prepare tailor-made pol)nners. 

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