Alkylidenes nucleophilic attack

Allenes react with isocyanates to give the a-alkylidene-/Mactams. The highly reactive chlorosulfonyl isocyanate (CSI) is often used. Initial nucleophilic attack of the central allenic carbon atom to the central isocyano carbon atom produces an allylic cation intermediate, which cyclizes to the /i-lactam. 

Porphyrin rings are formed in nature by a process that is remarkably similar to that shown above. Though the sequence contains some rather unusual features, the coupling process also involves nucleophilic attack on to an alkylidene pyrrolium cation. This may be generated from the precursor porphobilinogen by elimination of ammonia. 

CHMe2). The steric hindrance for nucleophilic attack on position 1, in addition to approximately equal charge densities in positions 1 and 3, facilitates attack by the hydroxide ion to position 3 in 108, with simultaneous elimination of a CN anion (a kind of tele-substitution (78JHC731). Then, a thermally allowed 1,5-hydrogen transfer in 122 leads to stable l-alkylidene-3-hydroxy-isochromanes 123 (88T6217). 

The reaction of iV-(2,4-dinitrophenyl)amino acids with base in aqueous dioxane has been shown to give benzimidazole iV-oxides (7). The rate-determining step is likely to be formation of an iV-alkylidene-2-nitrosoaniline intermediate (6), which is followed by rapid cyclization and decarboxylation.19 The loss of carbon dioxide from perbenzoate anions has been investigated by mass spectrometry and electronic structure calculations. The results, including isotopic labelling experiments, support a mechanism involving initial intramolecular nucleophilic attack at either the ortho- or ipso-ring positions. They also indicate that epoxides may be intermediates en route to the phenoxide products.20 There has also been a theoretical study of the formation of trichlorinated dibenzo-/ -dioxins by reaction of 2,4,5-trichlorophenolate ions with 2,4-dichlorophenol.21... 

For the corresponding cyclization of acetylenic amides 418, Nagasaka etal.347,347a used a mixture of silver(i) triflate and lithium hexamethyldisilazide as the precatalyst. The process is probably initiated by the coordination of AgN(SiMe3)2 (generated in situ from AgOTf and LHMDS) to the triple bond, followed by nucleophilic attack of the lithium amide at the activated alkyne which affords (ZVy-alkylidene-y-butyrolactams 419 in high yields (Scheme 122). 

Nucleophilic attacks either at C or at N can give alkylidene complexes, for example,... 

Acylate anions can be made by nucleophilic attacks of lithium alkyls on metal carbonyls, for example, W(CO)6 + LiR - Li[(C0)5WC(0)R]. They are precursors of alkylidenes which will be discussed shortly. 

Lu and Xie have reported a three-component coupling for the synthesis of Q -alkylidene-y-lactams 69 (Scheme 22) [62]. Treatment of AT-(2,4-dienyl)alkynamide 66 with an aryl iodide 67 affords a a-vinylpalladium intermediate 70 through regioselective insertion of the active ArPdX species into the triple bond. Subsequent intramolecular carbopalladation of the diene affords 7r-allylpalladium complex 71, which undergoes nucleophilic attack by amines 68 at the less hindered terminus to afford the product 69. 

Ring closure of Af-(]-cyanoalkyl)alkylidene Af-oxides (these compounds are nitrones, cf. Section 4.2) is induced by nucleophilic attack by the thiophenate ion (Scheme 2.1.10). The reactions are accelerated by the addition of small amounts of piperidine, but inhibited by temperatures above the melting points of the nitrones. In these reactions, 4-phenylthioimidazoles (23) are formed usually in 80-90% yields. Deficiencies in the general process include the problems of first making the nitrones, and the fact that other thiolate nucleophiles (methyl, ethyl, benzyl) are much less successful, giving only low yields of 4-alkyIthioimidazoles [63]. 

The difference is interestingly exemplified in the differing modes of reaction of hydrazoic acid with some alkylidene (and arylidene) oxazolone derivativesThe alkylidene compound 174 behaves as an a, -unsaturated carbonyl compound with the hydrazoic acid adding to the exocyclic double bond. A subsequent ring opening with further addition leads to the formation of the diazide 175 (equation 75). In contrast the exocyclic double bond of the arylidene compound 176 is unreactive, and nucleophilic attack occurs at the... 

Nucleophilic attack on the 2-chlorine of 126 by triethyl phosphite accounts for the formation of the phosphonates 127, which are useful in the synthesis of 2-alkylidene derivatives analogous to 123 via the Wadsworth-Emmons reaction.139... 

The Larock method for annulation between vicinal iodo-arylamines and 1,2-dienes in the preparation of indoles can be adapted for preparation of azaindoles using corresponding azine substrates. Thus, substituted-3//-pyrrolo[2,3-fc]pyridin-3-ones can be prepared from 2-amino-3-iodopyridine derivatives by a palladium carboannulation process with al-lenic compounds (Scheme 104). The bicychc products, the methylene derivatives 308, and the alkylidenes 309 can be oxidatively cleaved with ketone formation. The reaction may proceed by formation of a pyridinylpaUadium complex followed by the rr-allyl complexa-tion of aUenic derivatives 310. Since the polar substituents on terminal carbons of the 7r-allyl system influence the regiochemistry of the reactions, nucleophilic attack of the nitrogen atom on the most electron-deficient carbon atom of the rr-allyl system affords either of the... 

P,P-Disubstituted alkylidene derivatives of oxindole, azlactone, and y-butyrolactone are used as precursors of vinylogous enolates, which are highly stabilized owing to the heteroaromatic nature of the enolate components. Although these a,p-unsaturated carbonyl systems can act as electrophilic Michael acceptors, the presence of two p-substituents seems to suppress nucleophilic attack on the P-carbon. 

In Fischer-type alkylidene complexes, the carbene carbon atom very readily undergoes nucleophilic attack. Unlike the acyl complexes such as Mn(COMe)(CO)5, in pen-tacarbonylcarbene complexes nucleophilic attack occurs at the carbene carbon atom and not at carbonyl ligands. This fact cannot be explained on the basis of positive... 

B.i.b. Alkynes Containing Proximate 1,3-Dicarbonyl Groups. 2-Propargyl-1,3-dicarbonyl compounds react with alkenyl triflates or alkenyl/aryl/heteroaryl halides to give 2,3,5-trisubstituted-furans (Scheme 4). The process probably proceeds through an oxypalladation step that involves a nucleophilic attack of a stabilized enolate across the activated carbon-carbon triple bond, reductive elimination of a palladium(0) species from the resultant oxypalladation adduct, and isomerization of the initially formed alkylidene derivative. 

After nucleophilic attack on the central allenyl carbon, the resulting n-allyl intermediate is trapped by an intramolecular nucleophilic reaction, giving the initial 3-alkylidene-2,3-dihydrofuran product, and regenerating the palla-dium(O) catalyst. A mildly acidic work-up allows aromatisation, giving the final product. 

In 1964, Fischer prepared and characterized unambiguously the first metal carbene complex 3 obtained by nucleophilic attack of phenyl lithium at tungsten hexacarbonyl followed by 0-alkylation. This was followed by Schrock s synthesis of a high oxidation state metal alkylidene complex 4 obtained by a-hydrogen abstraction from tris(neopentyl) tantalumfv) dichloride (Scheme 1.1)/ ... 

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