Insertion reactions intramolecular into

This photodriven benzannulation was used in the synthesis of indolocar-bazoles (Eq. 22) [96] and calphostins (Eq. 23) [97]. The thermal insertion of isonitriles into these same classes of carbenes provided a complementary approach to similar benzannulations [98-100]. Manganese alkoxycarbene complexes underwent both inter- [101] and intramolecular [102] photodriven benzannulation reactions with alkynes (Eqs. 24 and 25). 

Rhodium carboxylates have been found to be effective catalysts for intramolecular C—H insertion reactions of a-diazo ketones and esters.215 In flexible systems, five-membered rings are formed in preference to six-membered ones. Insertion into methine hydrogen is preferred to a methylene hydrogen. Intramolecular insertion can be competitive with intramolecular addition. Product ratios can to some extent be controlled by the specific rhodium catalyst that is used.216 In the example shown, insertion is the exclusive reaction with Rh2(02CC4F9)4, whereas only addition occurs with Rh2(caprolactamate)4, which indicates that the more electrophilic carbenoids favor insertion. 

The use of rhodium(II) acetate in carbenoid chemistry has also been extended to promoting intramolecular C/H insertion reactions of ketocarbenoids 277,280,280 ,). From the a-diazo-P-ketoester 305, highly functionalized cyclopentane 306 could thus be constructed in acceptable yields by regiospecific insertion into an unactivated... 

After elimination of ethoxytrimethylsilane, 7,7-dimethyl-1-norbomene (6) rearranges to 3,3-dimethyl-2-norbomylidene (7), which undergoes a 1,3-CH insertion reaction into the endo-6-H to give tricyclane 8. Nortricyclane formation has been shown to be the fastest intramolecular mode of stabilization of 2-norbomylidene.5,6... 

A very elegant expansion of the synthetic utility of this intramolecular amination was the insertion reactions into ethereal G-H bonds. Du Bois and co-workers have exploited this reactivity to prepare cyclic sulfamates that are then used as iminium ion equivalents. Upon treatment with a suitable Lewis acid, nucleophilic addition reactions... 

The intramolecular insertion reactions of nitrenoids into G-H bonds as described above provide an attractive alternative to conventional methods of amine formation. Both carbamate and sulfamate C-H insertions have been applied successfully to the total syntheses of natural products. - The first application of carbamate G-H insertion was reported by Trost in the total synthesis of methyl-L-callipeltose 118 (Equation (92)).230 Intermolecular G-H insertion of carbamate 117 using 10mol% Rh2(OAc)4, PhI(OAc)4, and DTBMP (2,6-di-/ / -butyl-4-methylpyridine) in dichloromethane (40 °C) furnished methyl-L-callipeltose 118 in 63% yield. In an another independent total synthesis of 118, Panek performed this step in refluxing benzene and improved the yield to 93%.231... 

Furans. Reaction of a,a-dimethoxy ketones with 1 affords a dihydrofuran (2) presumably via a carbene (a) that inserts intramolecularly into a C—H of an adjacent methoxy group. The reaction often results directly in a furan, since the elimination of methanol from 2 is facile. 

In recent years, several attempts have been made to prepare the first disilynes, compounds having Si-Si triple bonds,791 792 until Sekiguchi et al. in 2004 succeeded in the isolation and full characterization of the first member of this compound class.793 West et al. have studied the dehalogenation of 2,6-Mes2C6H3SiF3 761 with sodium, which has afforded the bis(silafluorene) derivative 762, whose formation may be rationalized in terms of two intramolecular insertion reactions of a bis(silylenoid) 763 into two C(.r/>z)-C(.r/>3) bonds (Scheme 99). 794... 

Carbenes and transition metal carbene complexes are among the few reagents available for the direct derivatization of simple, unactivated alkanes. Free carbenes, generated, e.g., by photolysis of diazoalkanes, are poorly selective in inter- or intramolecular C-H insertion reactions. Unlike free carbenes, acceptor-substituted carbene complexes often undergo highly regio- and stereoselective intramolecular C-H insertions into aliphatic and aromatic C-H bonds [995,1072-1074,1076,1085,1086],... 

Intramolecular carbon-hydrogen insertion reactions have well known to be elTectively promoted by dirhodium(ll) catalysts [19-23]. Insertion into the y-position to form five-membered ring compounds is virtually exclusive, and in competitive experiments the expected reactivity for electrophilic carbene insertion (3°>2° 1°) is observed [49], as is heteroatom activation [50]. A recent theoretical treatment [51] confirmed the mechanistic proposal (Scheme 15.4) that C-C and C-H bond formation with the carbene carbon proceeds in a concerted fashion as the ligated metal dissociates [52]. Chemoselectivity is dependent on the catalyst ligands [53]. 

Carbenes and carbenoids can add to double bonds to form cyclopropanes or insert into C—H bonds. These reactions have very low activation energies when the intermediate is a free carbene. Intermolecular insertion reactions are inherently nonselective. The course of intramolecular reactions is frequently controlled by the proximity of the reacting groups.53... 

Alkylidenes (alkylidene carbenes) are valence isomers of alkynes. They have been prepared by alkyne pyrolysis, by homologation of ketones, and by generation of alkenyl anions bearing oc-leaving groups. Generated by any of these means, an alkylidene will insert intramolecularly into a remote C- H bond to form a new C—C bond and thus a cyclopentene. A concerted two-electron process, this reaction proceeds with retention of absolute configuration at the C - H site. 

Insertion reactions of silylene into a number of single bonds have been observed. The bonds include Si—O, Si N, Si H, Si halogen, strained C O, Si Si, O—H, N—H, and C—H (intramolecular only). Insertion into an X H bond can be initiated by the formation of silaylide (50) with the donation of a pair of electrons from a heteroatom X to form a bond to a divalent sihcon atom (Scheme 14.26). 

Phenyl azides (azidoarenes), introduced by Knowles and co-workers,[8 9] are the most abundantly used class of photophores. Examples include 4-azidophenylalanine (1) and 4-azido-3-nitrophenylalanine (4) (Scheme 1). Irradiation (<300 nm) of phenyl azide (13) generates nitrene 14, electrophilic in nature, which prefers insertion into O—H and N—H bonds over C—H bonds. Nitrenes are considerably less reactive and, therefore, more selective than carbenes. Nevertheless, due to their short life span (0.1-1 ms) they react indiscriminately with virtually any amino add residue in the target protein.1101 Intramolecular rearrangements do not compete effectively with intermolecular proton abstraction and insertion reactions (Scheme 4). 

Intramolecular insertion of alkenes into ir-allylpalladium complexes has been shown to proceed regio-selectively to yield five-membered rings.2621263 TTiis transformation is equivalent to a palladium ene reaction and is completed by a (3-hydride elimination. The C==C bond of ketenes is also capable of undergoing insertion into ir-allylpalladium intermediates.264 The final course of this reaction is dependent on the leaving group in the initial allyl-X precursor. For X = OAc, dienes are observed for X = Me0C02, a methoxycarbonyl adduct is obtained (equation 303).264... 

Asymmetric induction in intramolecular C-H insertion reactions was first reported by McKervey and co-workers [53], who used chiral Rh(II) prolinate 17a (Eq. 5.24). Although enantiocontrol was low, this report established the feasibility of the methodology and left open advances that were subsequently made by Ikegami and Hashimoto, who were able to convert a-diazo-p-ketoester 47 into cyclopentanone 48 with 18a (Eq. 5.25) with 32-76% ee, dependent on the substituent Z and the size of the ester alkyl group [54,116],... 

The preparation of azulene (Expt 6.16) provides an interesting series of rearrangements.9 The key step in the synthesis is the intramolecular insertion reaction, carried out under conditions of high dilution, of the ketocarbene (22) into the 1,2-position of the benzene ring. The unstable norcaradiene (23) which is formed then ring-opens to the bicyclic trienone (24), which isomerises to the more stable cross-conjugated trienone (25) during isolation. Dehydration of the trienone with a mixture of phosphorus pentoxide and methanesulphonic acid yields azulene. 

Activation by silicon of a P-C-H bond to an intramolecular carbene insertion reaction is exemplified by the silicon-directed Bamford-Stevens reaction.68 For example, thermal decomposition of P-trimethylsilyl /V-aziridinyl imines 72 in toluene (Scheme 8) [with or without Rh2(OAc)4 catalyst] results in the formation of allylic silanes 73 as major or exclusive products by the preferential insertion of the carbene intermediate into the C-H bond P to the silicon substituent. 

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