In situ elimination

Selenoxides are even more reactive than sulfoxides toward (3-elimination. In fact, many selenoxides react spontaneously when generated at room temperature. Synthetic procedures based on selenoxide eliminations usually involve synthesis of the corresponding selenide followed by oxidation and in situ elimination. We have already discussed examples of these procedures in Section 4.3.2, where the conversion of ketones and esters to their a, (3-unsaturated derivatives is considered. Selenides can... 

Figure 7. FTIR absorption spectra of precursor PBTB thin film (A) and during in-situ elimination (B and C) in bromine vapor at 23°C. Arrow indicates a superposed gas phase absorption band due to evolved HBr gas.

On the contrary, while working in the synthesis of the alkaloid ru-brolone, Bogerand Zhu (91TL7643) have found 0-alkyl a,/3-unsaturated oximes 98 to participate as effective 4ir components of an intramolecular Diels-Alder reaction with an electron-deficient dienophile. Thus, 98 was prepared from butane-1,4-diol and heated in triisopropylbenzene to furnish 2-pyrindine derivatives 99 by virtue of in situ elimination of alcohol (Scheme 25). 

Studying [3.3] sigmatropic rearrangements of difluoroallylic alcohols 4 (R = H, Et) under Daubcn-Dictsch conditions [reflux with ethyl vinyl ether in presence of mercury(II) acetate], has shown that in the case of R = Et, besides the rearrangement in situ, elimination of hydrogen fluoride occurs. It has been claimed that the dehydrofluorination is probably catalyzed by acetic acid which is formed in the course of the reaction.206... 

In the Horner-Emmons reaction (Scheme 3), the sulfonylphosphonate carbanion 5 is formed in the presence of NaH and then reacts with an aldehyde to produce the intermediate 6 that undergoes in situ elimination to yield the vinyl sulfones and phosphonate anion. The sulfonyl group can stabilize the anion in the sulfonylphosphonate 5. The vinyl sulfones that are produced by this method using aldehydes as starting materials are exclusively the E (trans) isomers. The E-isomers of the vinyl sulfones are shown in the NMR spectra based on the coupling constants of the vinylic protons. Although strongly basic conditions are used in the Horner-Emmons reaction and a-amino aldehydes are easily racemized, the amino acid vinyl sulfones prepared by this method still show substantial optical activity. However, the enantiomeric purity of these compounds has not been determined. 5 ... 

Selenides are oxidized to selenoxides that normally suffer an in situ elimination.111 Amines are destroyed,112 although its protection as amides or carbamates prevents the reaction with Collins reagent. Lactols are very quickly oxidized to lactones,113 unless a very great steric hindrance is present.114 Tertiary lactols suffer oxidation via its opened hydroxyketone form.115 The oxidation of tertiary lactols may be slow, so that an alcohol can be selectively oxidized. 

Sometimes, when a Swern oxidation produces a carbonyl compound possessing a good-leaving group at the 3-position, an in situ elimination occurs, resulting in the generation of a conjugated enone or enal. 

A number of a,/J-unsaUiraled acyl silanes have been prepared from silyl enol ethers of acyl silanes (Scheme 41)129. Addition of phenyl sulphenyl chloride to the silyl enol ether with subsequent elimination of chlorotrimethylsilane gives the a-(phenylthio)acyl silane. Oxidation to the sulphoxide followed by in situ elimination of benzenesulphenic... 

In the preparation of 2,6-dimethylhepta-1,5-diene, Expt 5.20, the final in situ elimination step is effected with thionyl chloride and is thought to proceed via a six-membered cyclic transition state.38... 

Horner-Wittig modification Alternatively, phosphine oxide reacts with aldehydes in the presence of a base (sodium amide, sodium hydride or potassium t-butoxide) to give an alkene. The phosphine oxide can be prepared by the thermal decomposition of alkyl-triphenylphosphonium hydroxide. Deprotonation of phosphine oxide with a base followed by addition to aldehyde yields salt of (3-hydroxy phosphineoxide, which undergoes further syn-elimination of the anion Ph2P02. The lithium salt of (3-hydroxy phosphineoxide can be isolated, but Na and K salt of (3-hydroxy phosphine oxide undergoes in situ elimination to give alkene (Scheme 4.26). 

Heptafluoro-2-butene, which is readily available in a laboratory synthesis from hexa-chlorobutadiene, may be used as a synthon for perfluoro-2-butyne in cycloaddition reactions where in situ elimination occurs [322] (Figure 7.92). 

OrBenzeneselenenylation. The introduction of a conjugated double bond to a carbonyl compound can take advantage of the facile selenenylation by the Se-substituted morpholine at room temperature. Subsequent oxidation and in situ elimination completes the process which is readily adaptable to a-ketoesters. 

Aiylsulfinimines 8.8 are oxidized by oxaziridine 2.83 with an excellent selectivity [510] (Figure 8.5). The products of these oxidations are precursors of chiral amines and P-aminoesters ( 6.1.4 and 6.8.3). The asymmetric oxidations of aryl-selenides 8.9 with 2.83 (X = Cl) in CCI4 are also highly selective, but the rapid racemization of the selenoxides in the presence of moisture makes it difficult to isolate optically pure products [749, 1515], Uemura and coworkers [1516] have circumvented this problem by performing in situ elimination of selenic acid from the chiral selenoxide. They obtained chiral cyclohexylidene methylketones through this oxidation/elimination strategy. 

Alkyl phenyl sulfoxides. The methoxysulfonium salts obtained from reaction of the sulfenate ester with alkyl halides decompose in situ (elimination of MeX in analogy to the Arbusov reaction), leading to the sulfoxides. 

When llLi which contained LiBr was used in the synthesis of llTiCpCL, MeBr elimination readily occurred in situ, leading directly to IZaTiCpCl (63% yield). ° The closely related species 12aTi3aCl ° (62% yield) and 12aTilCl ° as well as the dipropyl analogue 12bTiCpCl (45% yield) were obtained similarly. The in situ elimination can even occur twice as is evidenced by the preparation of the spiro titanocene derivative (12a)2Ti from TiCL and llLi/ LiBr (30% yield). °... 

Fragmentation of an adduct with release of a nitrile, CO2 or N2 are most common and the latter provide an irreversible method for the formation of a new diene or aromatic compound. Cycloaddition of a pyran-2-one or a 1,2-diazine (pyridazine) with an alkyne gives an intermediate bridged compoimd that loses CO2 or N2 to generate a benzene derivative (see Scheme 3.46). Many other aromatic and heteroaromatic compounds can be prepared likewise. For example, a synthesis of lavendamycin made use of the inverse electron demand Diels-Alder reaction between the 1,2,4-triazine 116 and the enamine 117, followed by in situ elimination of pyrrolidine and retro Diels-Alder reaction, releasing N2 and the substituted pyridine 118 (3.88). 2... 

Acetic anhydride I pyridine Preferential dehydration of alcohols by in-situ-elimination via acetates... 

Selenoxides are even more reactive than amine oxides toward p elimination. In fact, many selenoxides react spontaneously when generated at room temperature. Synthetic procedures based on selenoxide eliminations usually involve synthesis of the corresponding selenide followed by oxidation and in situ elimination. We have already discussed examples of these procedures in Section 4.7, where the conversion of ketones and esters to their a,j5-unsaturated derivatives was considered. Selenides can also be prepared by electrophilic addition of selenenyl halides and related compounds to alkenes (see Section 4.5). Selenide anions are powerfiil nucleophiles that can displace halides or tosylates and open epoxides. Selenide substituents stabilize an adjacent carbanion so that a-selenenyl carbanions can be prepared. One versatile procedure involves conversion of a ketone to a bis-selenoketal which can then be cleaved by w-butyllithium. " The carbanions in turn add to ketones to give jS-hydroxyselenides. Elimination gives an allylic alcohol. 

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