Carbenoids insertion

Interestingly, [Ee(F20-TPP)C(Ph)CO2Et] and [Fe(p2o-TPP)CPh2] can react with cyclohexene, THF, and cumene, leading to C-H insertion products (Table 3) [22]. The carbenoid insertion reactions were found to occur at allylic C-H bond of cyclohexene, benzylic C-H bond of cumene, and ot C-H bond of THF. This is the first example of isolated iron carbene complex to undergo intermolecular carbenoid insertion to saturated C-H bonds. 

Carbenoid N-H insertion of amines with diazoacetates provides a useful means for the synthesis of ot-amino esters. Fe(III) porphyrins [64] and Fe(III/IV) corroles [65] are efficient catalysts for N-H carbenoid insertion of various aromatic and aliphatic amines using EDA as a carbene source (Scheme 16). The insertion reactions occur at room temperature and can be completed in short reaction times and with high product yields. It is performed in a one-pot fashion without the need for slow... 

For 5-(2-diazo-l,3-dioxobutyl)-l-oxa-5-azaspiro[5,5]undecane (313), intramolecular carbenoid insertion into a (N)C—H bond represents quite an unusual way of constructing a P-laetam ring 285). 

Table 21. Rh2(OAc)4-catalyzed intramolecular carbenoid insertion into the N—H bond of JJ-lactams.

Concerning the mechanism of O/H insertion, direct carbenoid insertion, oxonium ylide and proton transfer processes have been discussed 7). A recent contribution to this issue is furnished by the Cu(acac)2- or Rh2(OAc)4-catalyzed reaction of benz-hydryl 6-diazopenicillanate 237) with various alcohols, from which 6a-alkoxypenicil-lanates 339 and tetrahydro-l,4-thiazepines 340 resulted324. Formation of 340 is rationalized best by assuming an oxonium ylide intermediate 338 which then rearranges as shown in the formula scheme. Such an assumption is justified by the observation of thiazepine derivatives in reactions which involved deprotonation at C-6 of 6p-aminopenicillanates 325,326). It is possible that the oxonium ylide is the common intermediate for both 339 and 340. 

The known examples of carbenoid insertion into an S—H bond have been supplemented by the Rh2(OAc)4-catalyzed synthesis of a-phenylthioketones from a-diazoketones and thiophenol 327). By this method, a number of primary and secondary acyclic a-diazoketones, ethyl diazoacetate and cyclic diazoketones such as 2-diazocyclopentanone, 2-diazo-6-methylcyclohexanone and 2-diazocyclohepta-none were converted at room temperature in good to high yield. 

The Cu(acac)2-promoted transformation 368 - 369 represents an intramolecular carbenoid insertion into the penicillin C5—S bond 347). The original report did not mention the low-yield formation of a second product to which the tricyclic structure 370 was assigned 348,349 >. In both 369 and 370, the original stereochemistry at C-5 of 368 has been inverted this is seen as a consequence of intramolecular nucleophilic a-face attack in a presumed azetidinium enolate intermediate. Attempts to realize a more flexible intermediate which then would have a chance to undergo p-face attack centered on the chain-extended diazoketone 371. Its catalytic decomposition led to the tricycle 372 exclusively, however, C7/N rather than C5/S insertion having taken place 349). 

Another remarkable property of iodorhodium(III) porphyrins is their ability to decompose excess diazo compound, thereby initiating carbene transfer reactions 398). This observation led to the use of iodorhodium(III) me.vo-tetraarylporphyrins as cyclopropanation catalysts with enhanced syn anti selectivity (see Sect. 2.2.3) s7, i°o) as wep as catalysts for carbenoid insertion into aliphatic C—H bonds, whereby an unusually high affinity for primary C—H bonds was achieved (see Sect. 6.1)287). These selectivities, unapproached by any other transition metal catalyst,... 

Recently, Yu and co-workers developed an operationally simple catalytic system based on [RuCl2(/>-cymene)]2 for stereoselective cyclization of a-diazoacetamides by intramolecular carbenoid C-H insertion.192 /3-Lactams were produced in excellent yields and >99% m-stereoselectivity (Equation (53)). The Ru-catalyzed reactions can be performed without the need for slow addition of diazo compounds and inert atmosphere. With a-diazoanilide as a substrate, the carbenoid insertion was directed selectively to an aromatic C-H bond leading to y-lactam formation (Equation (54)). 

Negishi first observed the insertion of the y-halolithium species 75 obtained by deprotonation of propargyl chloride into octylzirconocene chloride protonation of the product afforded the allene 79 (Scheme 3.20) [37]. The overall effect is insertion of an allenyl carbenoid. The a-halolithium equivalent 76 is conveniently generated by addition of two equivalents of base to 2-chloroallyl chloride [52] and affords the same products. The organome-tallic product 77 of allenyl carbenoid insertion is either in equilibrium with the propargyl... 

The most extensively studied application of carbenoid insertion into organozirconocene species is the insertion of allyl carbenoids into zirconacycles and subsequent elaboration of the thus formed allylzirconocenes with electrophiles (Schemes 3.24—3.26) [48,53,55-60],... 

Many alkyl carbenoids insert into saturated and unsaturated zirconacycles to afford zirco-nacydohexanes and -hexenes 126, which give the expected products 127 upon hydrolysis (Scheme 3.30) [48,50,68], There should be comparable scope for further elaboration of the six-membered zirconacycles, as has already been established for the five-membered analogues. Yields are generally high, one exception being the insertion of lithiated chloroace-tonitrile into saturated zirconacycles, where double insertion predominates [50],... 

For application in organic synthesis, the regiochemistry of insertion of carbenoids into un-symmetrical zirconacydes needs to be predictable. In the case of insertion into mono- and bicydic zirconacydopentenes where there is an wide variety of metal carbenoids insert selectively into the zirconium—alkyl bond [48,59,86], For more complex systems, the regiocon-trol has only been studied for the insertion of lithium chloroallylides (as in Section 3.3.2) [60]. Representative examples of regiocontrol relating to the insertion of lithium chloroal-lylide are shown in Fig. 3.2. 

Scheme 3.38. Alternative mechanisms for carbenoid insertion into organozirconocenes.

Scheme 3.39. Alternative explanation for the regiochemistry of carbenoid insertion.

To complete this paragraph dealing with the synthesis of saturated oxazolo[3,4- ]pyridines and thiazolo[3,4- ] pyridines, it is worth mentioning that other routes relying on carbenoid insertion <2005TL143> or radical-induced cyclization <1996J(P1)793, 1998S665> have also been developed since CHEC-II(1996). 

Dirhodium(II) carboxylate catalysts have been used extensively for the catalysis of carbene insertions. In many cases, impressive selectivities have been achieved (19-21). In an effort to find selective catalysts for carbenoid insertions, Moody screened a series of dirhodium(II) carboxylate catalysts for their ability to catalyze carbenoid Si-H insertion (22). The authors surveyed the commercially available carboxylic acids, -10,000 of which are chiral. The members of this group that contained functionality that is incompatible to the reaction were culled out. The remaining chiral carboxylic acids (-2000 compounds) were then grouped into 80 different clusters. There is no discussion presented for the criteria used in the grouping of the acids. A representative acid from each cluster was then chosen for... 

Cyclic epoxides such as 124 can react in two ways with strong bases (a) via abstraction of a /3-proton to form allylic alcoholates 125 or (b) by deprotonation at the epoxide carbon atom forming the intermediate 126 and, after electrophilic substitution, the epoxides 128. If there is a suitable C—H bond in the vicinity of the C-Li moiety, intramolecular carbenoid insertion reactions to 127 may take place (equation 27) ° . ... 

Cyclooctadiene-l-epoxide (139) rearranges on treatment with s-BuLi/(—)-sparteine (11) at —90°C to form (l )-2,5-cyclooctadien-l-ol (140), but when boron trifluoride is added, a carbenoid insertion produces the bicyclo[5.1.0]octa-5-en-2-ol 141 with 11% ee (equation 30). Further examples are found elsewhere . 

Alkylation of P-lactams." Alkylation of the base- and acid-sensitive /5-lactam 1 can be effected efficiently hy carbenoid insertion into the N H bond using... 

Of the syntheses involving C-C bond formation, those in which the C(3)-C(4) bond is formed (55 — 56) are in general more important than those involving C(2)-C(3) bond formation (57 —> 56). However, carbenoid insertions of type (58) have been used to make (3-lactams (72JA1634). 

Peptide-Based Oxazoles by Rhodium-Mediated Carbenoid Insertion of Diazocarbonyl Compounds into an Amide N-H Bond Followed by... 

DMAD before carbenoid insertion leading to 6 took place. Thermolysis of 2-amino-l-azirines in the presence of acetylenic esters, for example heating 8 at 340° in vacuo, caused ring cleavage to the azadiene 9 which gave 10 with EP, and 13 with DMAD. A similar reaction between the spiroazirine 11 and EP gave 12.33... 

Compared with the single-bond construction approach of (3-lactam synthesis, the ketene-imine cycloaddition, which includes carbenoid insertion and the Staudinger reaction, have been widely used [56, 65]. Due to the ready availability of both imines and ketenes, the Staudinger reaction has provided a useful and economical approach for the synthesis of (3-lactams. In addition, the ketene-imine cycloaddition is efficient, which constructs the (3-lactam four-member ring in just one-step... 

Scheme 12.13. Synthesis of acetoxyodontoschismenol using a three-component zirconocene induced co-cyclization/carbenoid insertion/electrophilic trapping, by Whitby and co-workers [38].

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