Addition to isonitriles

The addition of organomagnesium compounds to the carbonyl group of aldehydes and ketones has a long history, and remains one of the most important reactions for carbon-carbon bond formation. While the overall reaction is simple, it is susceptible to a number of side-reactions, and its 

It is noteworthy that the initial interaction is depicted as the formation of a carbonyl-organomagnesium complex, i.e. as electrophilic attack by magnesium at the carbonyl oxygen rather than (as described in elementary textbooks) nucleophilic attack by carbon at the carbonyl carbon. Such complex formation is usually fast, but in the presence of strongly coordinating ligands attached to magnesium it is retarded, with consequences for both the rate and the stereochemistry of the reaction. 

Besides the addition to the carbonyl group, three important side-reactions may occur reduction of the carbonyl compound to the corresponding alcohol, 

These side-reactions are rarely of preparative value, so the following discussion is centred on means of minimizing them. 

When the organomagnesium compound possesses tertiary (or several secondary) (3-hydrogen atoms, and the carbonyl compound is sterically hindered, reduction may be the predominant reaction. This mode of reduction may be suppressed to some extent in the presence of metal salts [A, 7], 

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As an extension of the known radical additions to isonitriles [87], aryl radical cyclizations to /V-acyl cyanamides provide new access to pyrrolo-quinazolines (Scheme 16) [88]. In a tandem process, the iminyl radical 41 resulting from the 5-exo cyclization onto the nitrile was used for a second cyclization step. In this way, the alkaloid luotonin A (42) was synthesized from cyanamide 43 in a single reaction. 

A number of reactions of organomagnesium compounds, giving rise to new organomagnesium compounds, are covered in other chapters. They include addition to carbon-carbon multiple bonds (see Chapter 4), addition to isonitriles (see Section 5.4), addition to carbon monoxide (see Section 6.5), thiophilic addition to carbon-sulfur double bonds (see Chapter 7) and addition to carbenes (see Section 9.1). 

Another very recent application of radical addition to isonitriles is the radical-mediated imidoylation of telluroglycosides 47 [25], These compounds were found to react with isonitriles under photothermal conditions to give 1-telluroimido-glycosides 48 through an atom transfer radical reaction (Scheme 20). Products 48 can be further transformed into imidic esters and 1-acyl glycosides, a class of derivatives that are part of important biologically active compounds. 

D. H. Shaw, H. O. Pritchard, Can. J. Chem. 1967, 45, 2749. A free-radical chain mechanism for the isonitrile-nitrile rearrangement in solution was definitely claimed by Riichardt in 1983 M. Meier, C. Riichardt, Tetrahedron Lett. 1983, 24, 4671. Radical addition to isonitriles had been previously claimed by Shono T. Shono, M. Kimura, Y. Ito, K. Nishida, R. Oda, Bull Chem. Soc. Jpn. 1964, 37, 635. 

Addition to Isonitriles. Silylstannanes undergo 1,1-addition to isonitriles giving synthetically useful silylstannyl imino-methanes (eq 11). These intermediates are readily converted into the corresponding iminomethyl-litium, -copper, or -cuprate reagents which undergo the expected 1,2- or 1,4-additions with appropriate electrophiles. ... 

Note that carbon monoxide inserts into the Zr-H bond of 1 (2 equiv.) to afford an T -formaldehydo-type complex [(Cp2ZrCl)]2(g-CH20) [200-202]. Iminoacyl zir-conocene complexes are formed after addition of 1 to isonitriles [203]. Carbon dioxide [183, 202] is reduced to formaldehyde with 1 (2 equiv.). C02-like molecules such as isocyanates RNCO [204], isothiocyanates RNCS [205], and carbodiimides RNCNR [204] are readily converted to the corresponding bidentate form-amido ligands. 

In addition to genetic factors evidenced by sponge systematics, environmental parameters, such as time and site of collection, appear to play a part in the isonitrile inventory of a given taxon. Examples from the genera Ciocalypta and Acanthella will be discussed in the following sections. 

Assuming that the metabolic pathways are similar in the biosynthesis of related isocyanoterpenes, these studies remain difficult, due in part to the competitive formation of other secondary metabolites. In addition to the common trio (-NC, NCS, -NHCHO) of the nitrogenous functions found attached to these skeletons, analogs such as -CN, -CNO, and -SCN foreshadow the complexity of identifying and selecting specific precursors to be targeted for incorporation into the family of marine isonitriles. 

The only examples dealing with [4 + 1] cycloadditions of alkylidenecyclo-propanes involve the additions of isonitriles to diacylmethylenecyclopropanes. 

The most important application of organolithium reagents is their nucleophilic addition to carbonyl compounds. One of the simplest cases would be the reaction with the molecule CO itself, whose products are stable at room temperature. Recently, it was shown that a variety of RLi species are able to react with CO or f-BuNC in a newly developed liquid xenon (LXe) cell . LXe was used as reaction medium because it suppresses electron-transfer reactions, which are known to complicate the reaction . In this way the carbonyllithium and acyllithium compounds, as well as the corresponding isolobal isonitrile products, could be characterised by IR spectroscopy for the first time. 

The trimeric compounds have been cleaved with a variety of neutral ligands [Eq. (41)] (154). With PPh3 the reaction proceeds smoothly, the rate and extent of reaction being dependent on the nature of R (the process occurs more readily when R is aromatic), but with isonitriles species of indeterminate constitution are obtained in addition to lAu C(OR )=NR (CNR")]. The cyclic complexes also underwent stepwise oxidative addition of bromine or iodine to yield (155) mixed gold(I)-gold(III) species, and finally the analogous gold(III) trimers. 

There are no routes yet to homoleptic metal isocyanide anions. If one considers the interesting products obtained from methyl iodide additions to molybdenum (43) and manganese (44) carbonyl isonitrile anions, negatively charged isocyanide complexes should have some interesting chemistry. Also, now that a simple route to [CpFe(CNR)2]2 complexes has been devised (45), the synthesis of the anion [CpFe(CNR)2] could provide a route to a range of products including heterometal-metal bonded systems. 

Radical chemistry has witnessed remarkable progress since the mid 1980s [1], In addition to common radical C2 synthons such as alkenes and alkynes [2], several radical Cl synthons are also available, including carbon monoxide, isonitriles, and sulfonyl oxime ethers [3, 4]. As featured in Scheme 6.1, a variety of combinations of radical Cl and C2 synthons are now possible, which makes radical methodologies more attractive and permits the design and implementation of a wide range of multicomponent processes. 

Examples of addition of perfluoroalkyl iodide to isonitriles have been reported [266,267]. 

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