Allene homologation

Indium-mediated allylation of trialkyl(difluoroacetyl)silane 70 in aqueous media gives homoallylic alcohol 71 exclusively (Scheme 60). Both water and THF are essential for the allylation reaction. It is worth noting that homoallylic alcohol 71 is formed exclusively under these reaction conditions. On the contrary, enol silyl ether 72 is a major product of the fluorinated acylsilanes reaction with other organometallic compounds than indium via a Brook rearrangement and defluorination. Indium-mediated allylsilylation of carbonyl compounds provides a facile route to 2-(hydroxyethyl)allylsilanes. The allene homologs are similarly prepared (Scheme 61).244,244a... 

Air-stable palladium(O) catalyst, [(Cy3P)2Pd(H)(H20)]BF4, catalyses carbonylation of propargylic alcohols to generate dienoic acids and esters (equation 167)286. Since propar-gyl alcohols are obtained from carbonyl compounds by acetyhde addition reactions, this sequence constitutes a three-carbon homologation. a-Allenic alcohols are converted to tt-vinylacrylic acids under similar conditions (equation 168)287. 

Here an alkynyl sulfoxide 55 is first carbocuprated with an organocopper reagent 56 to provide a vinylcopper intermediate 57, which is then zinc homologated with the primary zinc sp3-carbenoid 58 to yield the allylzinc intermediate 59. This, in a spontaneous syw-/)-climination, gives the corresponding allene 60. This protocol could also be adopted to the preparation of chiral allenes. 

Some synthetically important allenylmetallics, such as allenylzinc and allenylin-dium reagents, are prepared from allenylpalladium intermediates. These reactions are discussed in appropriate sections of this chapter. This section covers the reactions of allenylpalladium compounds without further transmetallation. Allenylpalladium complexes can be prepared from propargylic halides, acetates, carbonates, mesylates, alcohols and certain alkynes [83-87], The allenylpalladium compound prepared from 3-chloro-3-methyl-l-butyne has been isolated and characterized spectroscopically (Eq. 9.106) [83], It was found to couple with organozinc chlorides to produce homologated allenes quantitatively (Eq. 9.107). 

When propargylamine 183 was subjected to a homologative allenylation (Crabbe reaction) at 100 °C, the resulting allene underwent a spontaneous Diels-Alder reaction to give the adduct 184. This intramolecular cycloaddition-oxidation sequence provided a simple route to indole alkaloids such as hippadine and ds-trikentrin B [148]. 

In the synthesis of AG5473/5507 (324/325) by Guo et al., many attempts were made to homologate an aldehyde directly through an intermediate acyliminium ion, but without success [68], Finally, a less direct route involving the addition of pro-pargylsilane to 321 afforded the allene 322 with 10 1 diastereoselectivity (Scheme 19.59). Allene 322 was then ozonized to give aldehyde 323 in 90% yield. 

Allen MD, Buckle AM, Cordell SC, Lowe J, Bycroft M (2003) The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A. J Mol Biol 330 503-511... 

Rhodium catalysis has played a critical role in the development of this type of reaction. The rhodium-mediated [4 + 2] carbocyclization between dienes and unactivated olefins or alkynes is a notable early example of this concept [2]. Further investigations demonstrated the extension of this methodology to the reaction between a diene and an allene [3]. Expansion of the scope of this strategy, to both the intra- and intermolecular [5-1-2] homologs of the Diels-Alder reaction, was accomplished with a vinylcyclopropane and either an alkyne or an olefin to afford the carbocyclization adducts (Scheme 11.1) [4, 5]. 

It is noteworthy that the proximity of the copper sites in ceruloplasmin, and, indeed, the involvement of most of the correct ligand histidines, were predicted some time ago by Ryden (1982, 1984) strictly on the basis of sequence homologies to plastocyanin. A similar prediction was made for laccase based on sequence similarities around the cysteine regions (Briving et al, 1980). Proximity of the type II site to the type III site (e.g., a trinuclear site) was also predicted by Solomon and co-workers (Allen-dorf et al., 1985 Spira-Solomon et al, 1986) on the basis of spectroscopic analysis of azide binding to laccase. What could not have been foreseen... 

SCHEME 30. Allylic and allenic zinc reagents via methylene homologation... 

The first practical approach applying this strategy consisted of a carbocupration of an alkynyl sulfoxide 47 followed by methylene homologation of 48 with a zinc carbenoid and /3-elimination (equation 20)25. Yields of 1,1-disubstituted allenes 50 are good to high as outlined in Table 4. 

Brummond et al. published a study51 with substrates homologous to those from Brandsma et al.50 Indeed, using amino acid-derived allenes 21 (Scheme 5.11), under AgBF4 or AgN03 (20 mol%) catalysis, they obtained oxazines 22 accompanied by minor isomers 23. 

The haloboration-coupling sequence provided simple access to the stereochemically pure 3,3-disubstituted allylboron compounds 116 via one carbon homologation of the alkenylboron intermediates (Equation (20)).196 Bromoboration of allene afforded 117 which was converted into a tartrate for asymmetric allylboration (Equation (21)).197... 

ONE-STEP HOMOLOGATION OF ACETYLENES TO ALLENES PREPARATION OF 4-HYDR0XYN0NA-1,2-DIENE (1,2-Nonadien-4-ol)... 

A general procedure for the homologation of acetylenic compounds into allenes is described. The reaction conditions are mild and appear to be general, so that they can be applied to plain acetylenic substances as well as... 

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