Dichlorocarbene synthesis

If water is not rigorously excluded from sodium trichloroacetate dichlorocarbene synthesis, what side reaction occurs ... 

Isonitnle synthesis from pnmary amines and dichlorocarbene or dibromocarbene... 

Contents Introduction and Principles. - The Reaction of Dichlorocarbene With Olefins. - Reactions of Dichlorocarbene With Non-Olefinic Substrates. -Dibromocarbene and Other Carbenes. - Synthesis of Ethers. - Synthesis of Esters. - Reactions of Cyanide Ion. - Reactions of Superoxide Ions. - Reactions of Other Nucleophiles. - Alkylation Reactions. - Oxidation Reactions. - Reduction Techniques. - Preparation and Reactions of Sulfur Containing Substrates. -Ylids. - Altered Reactivity. - Addendum Recent Developments in Phase Transfer Catalysis. 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

The addition of dichlorocarbene, generated from chloroform, to alkenes gives dichlorocyclopropanes. The procedures based on lithiated halogen compounds have been less generally used in synthesis. Section D of Scheme 10.9 gives a few examples of addition reactions of carbenes generated by a-elimination. 

The concept of five-membered ring heterocyclic synthesis by transformation of the initial adduct of the ADC compound and substrate is not limited to cyclization of substitution products. l,3,4-Oxadiazol-2-ones (30, Scheme 3) result from heating the initial DEAZD-dichlorocarbene adduct.72 Treatment of the Diels Alder adducts 96 with zinc in acetic acid gives pyrroles in good yield (Eq. 17).151 The reaction has been extended to the synthesis of dipyrroles from the appropriate Diels-Alder adduct (96, R = pyrrol-2-yl). 

The rational synthesis of 11 started from 4,5-benzocycloheptenone ethylene ketal 16 which was reduced to the dihydrocompound 17 with lithium in liquid ammonia. Cyclopropanation of the latter with dichlorocarbene then gave the adduct 18, the ketal oxygens of 7 7 presumably coordinating with the carbene and directing it... 

Tochtermann reported the addition of dichlorocarbene to the racemic glycal 52, whose cyclopropyl-allyl rearrangement leads to the 2//-pyran. The synthesis of the optically pure (+)-(2S,3R,7S) and (-)-(2f ,3S,7f )-glycal precursors has also been achieved. As pointed out, optically pure glycals are versatile precursors for carbohydrate synthesis <00EJO1741>. 

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). 

Studies by the submitters have indicated that the procedure reported here is the preferred method for the preparation of bicyclo[3.2.1]octan-3-one. It employs readily available, inexpensive reagents, and the overall yield is good. In addition, the method can be used for the synthesis of the difficultly accessible next higher homologues of bicyclo[2.2.2]oct-2-ene as well as for derivatives of norbornene. Bicyclo[3.2.2]nonan-3-one and l-methylbicyclo[3.2.1]octan-3-one have been prepared by a similar route6 in 60% and 47% yields, respectively (based on adduct). However, the preferred procedure for the formation of the dichlorocarbene adduct of bicyclo[2.2.2]oct-2-ene is that of Seyferth using phenyltrichloromethylmercury. Even in this case the overall yield is moderate (37%). 

Some of the ring expansion reactions discussed in Section 2.03.3.3.1 can be extended to five-membered heterocycles containing two or more heteroatoms. Reaction of imidazoles and pyrazoles with dichlorocarbene, for example, gives chloropyrimidines together with small amounts of chloro-pyrazines or -pyridazines, and oxidative ring expansion of 1-aminopyrazole with nickel peroxide gives 1,2,3-triazine (this, in fact, constitutes the only known synthesis of the unsubstituted triazine). There are, however, a number of interesting and useful transformations which are unique to five-membered polyheteroatom systems. 

Dehydrochlorination of pentachlorocyclopropane, formed from trichloroethylene and sodium trichloroacetate as a source of dichlorocarbene, yields tetrachloro-cyclopropene [150], a particularly versatile reagent for various applications. It is a reasonably reactive dienophile [151], a reagent applicable to heterocyclic synthesis [152], and an electrophile for aromatic substitutions [153] and additions to alkenes [154] in the presence of Lewis acids. 

However, the fact that dichlorocarbene reacts with methyl bicyclo[l. 1.0]butane-l-carboxylate (4) to generate exclusively pentadienes 5 and 6 in a total yield of 41 % renders this type of reaction impracticable for the synthesis of bicyclo[l.l.l]pentanes.3 Numerous examples have indeed shown that the reaction between bicyclo[1.1.0]butanes and carbenes are synthetically practical routes for pentadiene preparation4 9 and interesting evidence has been obtained to indicate that a concerted mechanism occurs.10-11... 

Hi) By formation of seven- from six-membered rings The expansion of a di- or a tetra-hydropyran ring fused to a three-membered ring has been used as a synthetic approach to oxepins. Thus the synthesis of oxepin (193) was attempted by thermal dehydrochlorination of a tetrahydropyran (equation 57) obtained from a dichlorocarbene addition reaction (65CI(L)184). Unfortunately the equilibrium appeared to favor the keto tautomer to the apparent exclusion of the enolic oxepin form (193). 

Dihalocyclopropanes are generally prepared by the addition of dihalocarbenes to alkenic substrates. As indicated in the introduction, the first synthesis of a dihalocyclopropane was accomplished by Doering and Hoffmann by the addition of dichlorocarbene, generated from chloroform and potassium r-butoxide (Bu OK), to cyclohexene giving dichloronorcarane (1), as shown in equation (l).s... 

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