Synthesis diazo compound catalysis

The synthesis of thiepins 14 was unsuccessful in the case of R1 = i-Pr,79 but if the substituents in the ortho positions to sulfur arc /erf-butyl, then thiepin 14 (R1 = t-Bu R2 = Me) can be isolated in 99% yield.80 Rearrangement of diazo compound 13 (R1 = t-Bu R2 = H), which does not contain the methyl group in position 4, catalyzed by dimeric ( y3-allyl)chloropalladium gives, however, the corresponding e.w-methylene compound. The thiepin 14 (R1 = t-Bu, R2 = H) can be obtained in low yield (13 %) by treatment of the diazo compound with anhydrous hydrogen chloride in diethyl ether at — 20 C.13 In contrast, the ethyl thiepin-3,5-or -4,5-dicarboxylates can be prepared by the palladium catalysis method in satisfying yields.81... 

The metal-catalyzed decomposition of diazo compounds has broad applications in organic synthesis [1-8]. Transient metal carbenoids provide important reactive intermediates that are capable of a wide variety of useful transformations, in which the catalyst dramatically influences the product distribution [5]. Indeed, the whole field of diazo compound decomposition was revolutionized in the early 1970s with the discovery that dirhodium tetracarboxylates 1 are effective catalysts for this process [9]. Many of the reactions that were previously low-yielding using conventional copper catalysts were found to proceed with unparalleled efficiency using this particular rhodium catalysis. The field has progressed extensively and there are some excellent reviews describing the breadth of this chemistry [5, 7, 10-17]. 

There are several possibilities for asymmetric synthesis in catalysed cyclopropanation and very substantial progress has already been made especially with catalyst development. The option of covalently attaching chiral auxiliaries to diazo compounds or to substrates, e.g. alkenes for cyclopropanation, has been discussed above in the subsection on diastere-oselectivity. The fact that many of the processes require metal catalysis makes the alternative option of using chiral catalysts particularly attractive and potentially more rewarding for commercial exploitation. The double option of combining the use of a chiral catalyst with a diazo compound carrying a chiral auxiliary is also available. For convenience, the double option is also included in this subsection. 

For comprehensive reviews that provide numerous examples of cyclopropanation based on Rh- and Cu-carbene catalysis, see M. P. Doyle, M. A. McKervey, and T. Ye, Modem Catalytic Methods for Organic Synthesis with Diazo Compounds, Wiley New York, 1998 M. P. Doyle and D. C. Forbes, Chem. Rev., 1998, 98, 911 and M. P. Doyle, J. Org. Chem., 2006, 71, 9254. 

Some insight into the nature of these catalyzed cyclizations is provided by the synthesis of benzobicyclo[3.1.0]hexene 17. Intramolecular cycloaddition under base catalysis (from the tosylhydrazone 14) or by heating compound 18 gave the [3.3.0] bicyclic product 16 but, in the boron trifluoride catalyzed reaction, the [3.2.1] bicyclic product 13 was formed. In the base-catalyzed reaction the intermediate 4,5-dihydro-3//-pyrazole 16 suffered tautomerization (to give 19). The diazo compound 13 cannot tautomerize, and gave a quantitative yield of benzobicyclohexene 17 when heated. These boron trifluoride catalyzed addition reactions do not involve the free diazo compound and in this particular case the cyclic A -tosyl intermediate 12 could be isolated from the reaction mixture. ... 

Miscellaneous Reactions. In addition to the key reactions above, DDQ has been used for the oxidative removal of chromium, iron, and manganese from their complexes with arenes and for the oxidative formation of imidazoles and thiadia-zoles from acyclic precursors. Catal)ftic amounts of DDQ also offer a mild method for the oxidative regeneration of carbonyl compounds from acetals, which contrasts with their formation from diazo compounds on treatment with DDQ and methanol in nonpolar solvents. DDQ also provides effective catalysis for the tetrahydropyranylation of alcohols. Furthermore, the oxidation of chiral esters or amides of arylacetic acid by DDQ in acetic acid provides a mild procedure for the synthesis of chiral a-acetoxy derivatives, although the diastereoselectivity achieved so far is only 65-67%. ... 

Cooperative catalysis in multi-component reactions highly enantioselective synthesis of y-hydroxyketones with a quaternary carbon stereocenter, (b) X. Han, M. Gan, H. Qin, J. Ji, X. Zhang, L. Jiang, W. Hu, Synlett 2011, 1717-1722. Trapping of oxonium ylides with Michael acceptors highly diastereoselective three-component reactions of diazo compounds with alcohols and ben-zylidene Meldrum s acids/4-oxo-enoates. 

Doyle et al. (34) were the first group to generate isomiinchnones from diazo imides using Rh(II) catalysis. For example, isomiinchnone 60 was produced from diazo imide 59, but attempts to trap this species with ethyl acrylate were unsuccessful. The only material identified was the isomiinchnone hydrolysis product. This use of Rh(II) to generate a rhodium-carbenoid species from an a-diazo carbonyl compound is reminiscent of the first successful synthesis of... 

The diazo reactions in this chapter are characterized by processes run either in the gas phase, in relatively inert matrices, or in — typically, but not exclusively — aprotic and comparatively apolar solvents, either thermally or photolytically or with transition metal catalysis of various types. The metastable intermediates are carbenes (RR C ), i. e., neutral, apparently divalent, carbon compounds, or their transition metal complexes (coined carbenoids, see later in this section). It is interesting to recall that the synthesis of a compound that we now call a carbene, namely methylene (H2C ), was already attempted in the early 19th century, i.e., before the tetravalency of carbon was established. Dumas (1835) and Regnault (1839) thought then that it should be possible to obtain a compound consisting of one carbon and two hydrogen atoms by dehydration of methanol (a compound of which only the atomic ratio 1C 4H lO was then known). ... 

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