Isonitriles table

Table 1. Taxonomic classification of some marine sponges (I) and nudibranchs (II) containing isonitriles... 

Table 1 lists some taxa, sponges and mollusks from which isonitrile-related compounds were isolated. The partial list identifies selected sponges at the genus level with the geographical origin and compound type. 

The majority of marine isonitriles are sesquiterpenes with the molecular formula, C16H25N. Often cyclic, these are alkanes or alkenes possessing only a single isocyano-related functional group. In the mass spectrum, they exhibit a molecular ion at w/z 231, or an intense fragment ion at m/z 204, indicative of M+-HCN. Some are crystalline (see Table 2). With few exceptions most of the isothiocyano and formamido analogs are minor noncrystalline metabolites (see Table 3). 

Although the extraction of primary amines from a basic medium with chloroform is an inadvisable procedure, on account of the formation of trace amounts of the pungent isonitriles, the specific synthesis of isonitriles by the two-phase reaction of primary amines with chloroform is unreliable. However, the application of the phase-transfer technique [e.g. 1 -5] for the controlled release of dichlorocarbene facilitates the synthesis of isonitriles in relatively high yields (Table 7.12). 

Multicomponent condensations have also been described in these an isonitrile, a carbonyl compound and a suitable transition metal complex are combined in one step to afford heterocycloalkylidene complexes. Examples of the use of isolated or intermediate isonitrile complexes for the preparation of aminocarbene complexes are given in Table 2.4. 

Table 2.4. Heteroatom-substituted carbene complexes prepared from isonitrile complexes.

Besides the addition of non-carbon nucleophiles to carbonyl and isonitrile complexes (Tables 2.2, 2.4), heteroatom-disubstituted carbene complexes can be prepared by direct addition of stable or latent carbenes to suitable complexes. The synthetic routes sketched in Figure 2.12 are those commonly used for preparing imidazoline-2-ylidene or imidazolidine-2-ylidene complexes. 

Cyclopeptide alkaloids 91-96 were synthesized in analogy to 90 (Table 1). Isonitrile derivatives of 85 could be used in the same way. 

Here we are concerned mainly with alkylamines. Detailed SCF charge analyses [43] indicate that any gain in total charge translates into a downfield shift, which is the trend exhibited by alkylamines, but also by nitroalkanes and isonitriles. Examples are offered in Table 6.5 (see also Fig. 6.6), along with pertinent ionization potentials, indicated in kcal/mol ... 

Carbene complexes undergo benzannulation under photochemical conditions with carbon monoxide to give the indolocarbazoles via a ketene intermediate, or aminobenzannulation with /t-butyl isonitrile under thermal conditions via a ketenimine (Equation (77) Table 3) <1997TL6787, 2001T5199>. 

Isonitriles 6, formed by dehydration of 6-(formylamino)penicillanates, can be alkylated by stabilized nucleophiles such as (bromomethyl)benzene and methyl 2-bromoacetate (see Table 2)8-9. In this case alkylation also takes place preferentially from the least hindered a-side of the enolate8,9. The corresponding cephalosporin isonitriles decompose on attempted alkylation8. 

The carbonyl groups in nickel carbonyl may be replaced by isonitriles as well as by phosphines etc. 162) in general all the carbonyl groups are replaced in the direct reaction, but a compound (MeNC)3Ni(CO) has been obtained. Cotton and Zingales have measured the infrared spectra of a few of these compounds in the triple-bond region (46), and some interesting facts emerge. The frequencies are shown in Table III and it is clear that... 

The product of Equation 41 is generally of the form RNC—AgX. A recent review of isonitrile complexes (53) reveals that all the entries in Table I form such species, and that all those not circled may be prepared by direct alkylation... 

Table I. Elements Forming Isonitrile Complexes by Direct Alkylation (53)...

Table II. Relative Reactivities of Isonitrile Complexes as Determined by...

A similar anchimeric rate-accelerating effect was observed for I and III (Table II). The infrared spectrum of I indicates that the isonitrile band is shifted by 34 cm.-1 to higher frequencies and that of III by 77 cm.-1. Hence in both complexes the isonitrile group is more ionic than in benzyl isonitrile and the same arguments should apply as to complex II. 

Table III. Electrical Conductivities of Iron Isonitrile Complexes...

Figure 3. Linear relationship of AE vs. log o-o for iron isonitrile complexes (I) ( O referring to line I are listed in Table III) and of AE vs. log a0for polyacenes...

Various approaches have been used to prepare pyrroles on insoluble supports (Figure 15.1). These include the condensation of a-halo ketones or nitroalkenes with enamines (Hantzsch pyrrole synthesis) and the decarboxylative condensation of N-acyl a-amino acids with alkynes (Table 15.3). The enamines required for the Hanztsch pyrrole synthesis are obtained by treating support-bound acetoacetamides with primary aliphatic amines. Unfortunately, 3-keto amides other than acetoacetamides are not readily accessible this imposes some limitations on the range of substituents that may be incorporated into the products. Pyrroles have also been prepared by the treatment of polystyrene-bound vinylsulfones with isonitriles such as Tosmic [28] and by the reaction of resin-bound sulfonic esters of a-hydroxy ketones with enamines [29]. 

Pyrrolidines and pyrrolidinones can be synthesized on insoluble supports by intramolecular carbometallation of alkenes (Entry 1, Table 15.4) and by Ugi reaction of support-bound isonitriles with amines and 4-oxo acids (Entry 4, Table 15.4). In Entry 5 in Table 15.4, the pyrrolidinone ring is formed by intramolecular Diels-Alder reaction of a furan with a fumaric acid derivative. 2-Pyrrolidinones have also been prepared by treatment of resin-bound O-mesitylenesulfonyl cyclobutanone oximes with... 

A further method for preparing hydantoins is the N-alkylation of other hydantoins with reactive alkyl halides in the presence of strong bases [154]. Hydantoinimines have been synthesized from polystyrene-bound isonitriles by an Ugi-type multicomponent condensation (Entry 15, Table 15.13). 

Imidazo[l,2-fl]pyridines are formed upon treatment of isonitriles with aldehydes and 2-aminopyridines (Entry 14, Table 15.14). 2-Aminoazines other than 2-aminopyr-idine can also be used in this multicomponent reaction, yielding the corresponding fused imidazoles [179-183]. 

The multicomponent Ugi-type condensation of aldehydes, secondary amines, azide, and polystyrene-bound isonitriles has been reported to yield tetrazoles in acceptable yields (Entry 9, Table 15.20). Tetrazoles have also been prepared from... 

One approach to tetrahydropyridinones is the Lewis acid mediated hetero-Diels-Alder reaction of electron-rich dienes with polystyrene-bound imines (Entries 3 and 4, Table 15.23). The Ugi reaction of 5-oxo carboxylic acids and primary amines with support-bound isonitriles has been used to prepare piperidinones on insoluble supports (Entry 5, Table 15.23). Entry 6 in Table 15.23 is an example of the preparation of a 4-piperidinone by amine-induced 3-elimination of a resin-bound sulfinate followed by Michael addition of the amine to the newly generated divinyl ketone. The intramolecular Pauson-Khand reaction of propargyl(3-butenyl)amines, which yields cyclopenta[c]pyridin-6-ones, is depicted in Table 12.4. 

Table 4.46. 13C Chemical Shifts of Representative Nitriles [77 a, 353] and Isonitriles [353, 354] ((5C in ppm). Where Available, One-Bond 13C- 14N Couplings (in Hz) are given in Parentheses.

The substitution chemistry of the Ru(II) and Os(II) porphyrins is synopti-cally presented in Scheme 1 and Table 4. The lability of the trans-U in MCO(P)L may be used to prepare a large variety of complexes MCO(P) L with other ligands L where the donor atom may be any oxygen-, nitrogen-, or sulfur donor (reaction path a of Scheme 1 and Table 4), cyanide (paths a, b) or carbon monoxide (c) [190]. Coordinated cyanide in [OsCO(OEP)CN]- can be transformed into isonitrile with methyifluorosulfonate [191]. 

Other examples, such as the conversion of (R)-(+)-H2NCH(CH3)(C6H5) into the corresponding isonitrile (R)-(+)-CNCH(CH3)(C8H5) and its organometallic derivatives (68-70) have been discussed in a review (51) and are included in Table I (Section XVII). 

Adducts ofB(C6F5)3 that have been studied in detail either in solution or the solid state are collected in Table I along with selected solution NMR spectroscopic data and metrical parameters. In particular, both the nB NMR chemical shift35 and the separation between the resonances for the meta and para fluorine atoms in the 19F NMR spectrum109 are quite sensitive to the environment about the boron center and the strength of the LB-B(C6F5)3 interaction. Indeed, as shown in Fig. 1, a rough empirical correlation between these two NMR parameters is observed. Anomalies arise for two classes of LB more linear bases like nitriles or isonitriles that do not pyramidalize the boron center as severely and the RM1 adducts (M = Al, Ga). 

R CN (Table 2) [86]. The molecular structure of the 2,2-dimethylpropanonitrile derivative contains unsymmetrically bridging alkylidene amide ligands. Reaction of the yttrium and erbium hydride species with isonitrile results in the formation of a formidoyl moiety (Table 2) [87], Surprisingly the Ln-N interaction is in the range of the nitrile product A similar molecular structure was found in the oximato complex [Cp2Gd(/i-t/2-ONCMe2)]2 (Gd-Nav 2.42(1) A) [88]. 

Whereas amino groups are used most frequently as intramolecular Lewis bases (Tables 5-7), stable unsupported intermolecular complexes are typically accomplished by carbene-type donors, such as carbenes, isonitriles and ylides (Table 8). To my knowledge, no unsupported intermolecular adduct of ethers, amines or phosphanes have been structurally characterized so far (except for the more ionic cyclopentadienyl derivatives62). 

Apart from the unique adduct 5150, in which two plumbylene moieties are bridged by a MgBr2(thf)4 molecule viaBr —> Pb interactions [Pb—Br 296.4(2) pm], and few cyclopen-tadienyl derivatives where chelating amines interact with the two-valent tetrel atom62, unsupported adducts of Lewis bases with tetrylenes have been restricted to carbene-type bases so far. However, only donor carbenes, such as Arduengo carbenes, isonitriles or ylids, form simple adducts with dative C —> E interactions (Table 8). Carbenes or analogous species which also exhibit a substantial acceptor ability form multiple bonds instead (see Section III). 

Linderman and his group applied so-called convertible isonitriles [47] for this type of glycosylamine-based Ugi reaction. The Osilylprotected isonitrile 32 was reacted with tri-O-pivaloylarabinosyl imines or tetra-O-pivaloylgalactosyl imines (Scheme 22). The diastereoselectivity ranked in the same range as that given in Table 4.3. 

Table 4.5 Ugi and Passerini reactions with glycosyl isonitriles...

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