Carbonylation of Diazoalkanes

The replacement of the diazo group in diazoalkanes by carbon monoxide to afford the corresponding ketenes (Equation 8.1) might be a synthetically useful reaction since ketenes are versatile intermediates in organic synthesis [1-3]. 

According to theoretical calculations, there is a low-energy pathway for the direct interaction of diazomethane with carbon monoxide [4j. However, experimental results so far show only evidences for two-step pathways. These involve first the dediazotation of the diazoalkanes in thermal, photochemical, or transition metal mediated reactions [5] resulting in free carbenes (Equation 8.2) or transition metal coordinated carbenes (Equation 8.3), which under proper reaction conditions couple in the second step with carbon monoxide (Equation 8.4 or 8.5) to form ketene products. 

Modem Carbonylation Methods. Edited by Laszlo Kollar 

Copyright 2008 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim 

In the following discussion, we will review the known examples of the reactions depicted in Equations 8.2-8.5 with various X, Y, and ML groups, leading to direct or indirect experimental evidences of ketene formation. The scientific literature is covered till April 2007. 

---

The Wolff rearrangement is well known as a reaction of diazo ketones, i.e. of diazoalkanes with a carbonyl group in a-position. Reaction 34 demonstrates that diazotized aminonaphthols are mesomeric with naphthoquinone diazides (48b) and that they have therefore also the character of quinonoid diazo ketones (see also Section II.C of this chapter). Wolff rearrangements take place also thermally and catalyzed by silver ions. 

Transition metal complexes which react with diazoalkanes to yield carbene complexes can be catalysts for diazodecomposition (see Section 4.1). In addition to the requirements mentioned above (free coordination site, electrophi-licity), transition metal complexes can catalyze the decomposition of diazoalkanes if the corresponding carbene complexes are capable of transferring the carbene fragment to a substrate with simultaneous regeneration of the original complex. Metal carbonyls of chromium, iron, cobalt, nickel, molybdenum, and tungsten all catalyze the decomposition of diazomethane [493]. Other related catalysts are (CO)5W=C(OMe)Ph [509], [Cp(CO)2Fe(THF)][BF4] [510,511], and (CO)5Cr(COD) [52,512]. These compounds are sufficiently electrophilic to catalyze the decomposition of weakly nucleophilic, acceptor-substituted diazoalkanes. 

A practicable strategy to provide access to chiral pyrazolidine-3-carboxylic acid (16) makes use of asymmetric dipolar cycloaddition of diazoalkanes to u,p-unsaturated carboxylic acid derivatives. For this purpose a chiral auxiliary of the alkene component is used, e.g. Op-polzer s1166 1671 (lf )-2,10-camphorsultam.t164l As shown in Scheme 7, by reaction of (tri-methylsilyl)diazomethane (41) with /V-( aery I oy I )cam p h ors u 11 am (42), the AL(4,5-dihy-dropyrazoline-5-carbonyl)camphorsultam (43) is obtained. Reduction of 44 with sodium cyanoborohydride leads to A-(pyrazolidine-3-carbonyl)camphorsultam (45) as the 35-dia-stereoisomer (ee 9 1) in 65 to 80% yields.[164] The camphorsultam 45 is then converted into the methyl ester 46 by reaction with magnesium methylate without racemizationj1641... 

A technique that has proved to possess considerable usefulness in epoxide synthesis is addition of diazoalkanes. particularly of the parent eubatanoe djazomethane, to suitable carbonyl groups. 

The reactivity pattern of diazoalkanes in metal carbonyl chemistry is not only governed by the nature of the starting materials (8), but also depends... 

Reactions of the carbonyl group of inososes include the addition of diazoalkanes, dithioacetal formation, reduction, hydrogenolysis, and phenyl-hydrazone formation. The epoxide CXXX, which is formed from scyllo-inosose pentaacetate and diazomethane, is the starting material for a considerable series of seven-carbon derivatives.1 Some of the newer compounds of this group are discussed on pages 187 and 188. 

The problem of distinguishing between carbenoid and carbonium ion mechanisms of decomposition of diazoalkanes in protic media arises also in interpreting the base-induced decomposition of tosylhydrazones. In the original procedure for this widely-used reaction (W. R. Bamford and Stevens, 1952), the tosylhydrazone of a carbonyl compound is treated with the sodium salt of ethylene glycol in refluxing glycol. A mixture of olefins and alkoxyethanol is produced (equation 6). Many... 

The mechanism for the addition of diazoalkanes to a C=—O double bond is generally written along lines similar to those discussed so far (Scheme 1 X" = N2+). The initial adduct is also the progenitor of the various rearrangement pathways. However, the subject of mechanism is by no means settled, with 1,3-dipolar cycloadditions and carbonyl ylide formation" considered to be prominent alternatives. In general, successful epoxidation of carbonyl compounds improves with increasing electron-poor character of the C—O bond. When the diazoalkane is electron poor, yields of epoxide diminish. 

Condensation with carbonyl compounds. Formation of epoxides from aldehydes by reaction with sulfonium ylides is subject to asymmetric induction. The latter species have been generated from 91, 92, and 93, and also those derived from monoterpenes, e.g., 94 " and 95.- Of course the ylides can be obtained in situ by deprotonation of sulfonium salts or copper-catalyzed decomposition of diazoalkanes (with the carbenoids trapped by the sulfides). 

A simple and versatile method for the synthesis of aziridinium salts involves the reaction of a diazoalkane with an iminium salt (82TL285, B-83MI 102-01). The aziridinium salt thus formed was oxidized to an aminoaldehyde by DMSO (Scheme 39). A key step in the preparation of the oxindole alkaloid gelsemine (104) involves the carbonylation of the unsaturated aziridinium ion (103) with disodiumtetracarbonyl picrate-dioxane complex under a CO atmosphere followed by base-promoted epimerization and deprotonation (Scheme 40) <92JOC1035>. 

Reaction with diazoalkanes. Catalytic amounts of nickel carbonyl decompose diazoalkanes to products evidently formed from an intermediate carbene. Use of a large excess of reagent in the presence of ethanol leads to formation of carboxylic acid esters in yields of 20-25%. 

The preparation of diazirines 147, the cyclic isomers of diazoalkanes, almost always proceeds by synthesis of diaziridines from carbonyl compounds followed by dehydrogenation [Eq. (2)]. 

Examples of substrates [23] with heteroatom double bonds (C = X) are presented in the rosette of Scheme 5. Here we feature the efficient denitrogenation of diazoalkanes, diazoquinones, the hydrazone of benzil, and benzophenone oxime into the respective carbonyl products [23]. On the other hand, the bis-oxime afforded furoxane, while the phosphorane led to methyl maleate on elimination of triphenylphosphine oxide [23], Thiones are oxidized to the corresponding S-oxides and the iodonium ylide yields the labile w c-trione [23],... 

The twofold extrusion of nitrogen and sulfur and selenium and sulfur from 1-thia- and l-selena-3,4-diazolines(77), readily available from the reaction of diazoalkanes with thio- and selenaketones, respectively, as well as from the reductive coupling of carbonyl compounds such as 78, is the preferred method for preparation of olefins of type I and II (98,99). Examples of the extrusion method, developed by Barton (100), and the McMurry reaction (101) are given in Scheme 1. 

FIGURE 10.7 Computed transition state structure in carbonylation of bound diazoalkane at the BP86 level of theory. Reproduced with permission from reference 88. Copyright 2007, American Chemical Society. 

Table 2-1 shows ten types of synthetic process. Methods 1 and 2 are based on aliphatic amines, 3-5 on derivatives of carbonyl compounds, 6 on hydrocarbons with a relatively acidic CH proton, and 7-9 are reactions of diazoalkanes obtained by one of the types 1-6. Reaction 10 involves a diazo ketone, which can be obtained by reaction 9, the first step of the Arndt-Eistert synthesis. 

Structurally interesting derivatives of diazoalkanes are those substituted at C(l) by a carbonyl group, in particular the a-diazo ketones. Wolff (1900, 1902, 1912 Wolff and Hall, 1903) who synthesized them first, assumed originally a structure of a 1,2,3-oxadiazole (5.11) for a-diazo ketones (5.10). 

There are three leading reviews on metal carbenoid transformation, written by Doyle (1986), by Brookhart and Studabaker (1987), and by Maas (1987). They include aspects of synthesis and of mechanism. The more recent reviews in Trost and Fleming s Comprehensive Organic Synthesis were written by Helquist (1991, use of diazoalkanes) and by Davies (1991, diazo carbonyl compounds). The review of Ye and McKervey (1994) on a-diazocarbonyl compounds also contains examples of metal carbenoid transformations. The book of Hegedus (1994) contains representative syntheses of complex organic molecules obtained by transition metal-catalyzed reactions of diazo compounds. 

Pyrazolines formed by cycloaddition of diazoalkanes to unsaturated carbonyl compounds have been studied vigorously for their conversion into 1,2-diazepinones <83TL5469, 9iJHC369>,... 

---