Addition of Diazo Compounds

Addition of diazo compounds to metallic complexes allows the formation of metal carbenoid species which can react with unsaturated molecules to form C-C or C=C bonds. 

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The addition of diazo compounds generally leads to three membered tings, although in special cases, linear adducts with an intact diazo group [110] or l,3,4-oxadiazol-3-ines [111] can be isolated Most diazo compounds are unstable and yield oxirans and aziridines [112,113,114] Aziridines are obtained exclusively on reaction of certain polyfluorinated acyl imines with diazomethane [115]... 

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)). 

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

An important competing process with significant practical consequences is the catalytic dimerization of diazoacetate to form maleate and fumarate esters. Most catalysts suffer from this side reaction, leading to the use of the alkene as solvent in order to accelerate the productive pathway and the slow addition of diazo compound in order to minimize dimerization. Since this problem is generally shared across most catalyst architectures, it will be mentioned in discussions of individual asymmetric catalyst systems only in those instances where these precautions prove to be unnecessary. 

A -1,3,4-Thiadiazoline-1 -oxides (146) (Equation (18)) are formed by addition of diazo compounds (R2C=N2) to sulfines (R R C =S=0). The adducts from diazomethane and aryl substituted sulfines are unstable and give the thiadiazole (147) via a Pummerer-type aromatization <84CHEC-I(4)545>. The A -thiadiazoline-1,1-dioxide (149) has been produced by oxidation of the hydrazone (148) (Equation (19)) and treatment with sulfur dioxide <84CHEC-i(4)545>. 2-Alkylidenethiadiazolines can be obtained from the dipolar addition of diazo compounds to thioketenes <83CB66, 90TL3571, 92HCA1825>. 

Table 6. Cyclopentanones by Addition of Diazo Compounds to Substituted Cyclobutanones...

A reliable and versatile route to functionalized fullerenes has been found via the addition of diazo compounds [289], This route offers the possibility of obtaining... 

A major improvement addressing the issue of practicability and safety by avoidance of the direct use of (potentially) explosive diazo compounds was recently reported by Aggarwal and co-workers [82, 83], The direct addition of diazo compounds was replaced by use of suitable precursors which form the desired diazo compound in situ. The Aggarwal group developed this concept for the corresponding sulfur ylide type epoxidation (see Section 6.8) [82], and successfully extended it to aziridination [83]. Starting from the tosylhydrazone salt 66 the diazo compound is formed in situ under conditions (phase-transfer-catalysis at 40 °C) which were found to be compatible with the sulfur ylide type aziridination [82, 83], The concept of this improved method, for which sulfide 67 (Scheme 5.41) is the most efficient catalyst, is shown in Scheme 5.40. 

The ruthenium-catalyzed addition of diazo compounds to alkynes has led to the selective synthesis of functional 1,3-dienes by the combination of two molecules of diazoalkane and one of alkyne [106] (Eqs. 82,83). The stereoselective formation of these conjugated dienes results from the selective creation of two C=C double bonds rather than leading to the cyclopropene derivative. This is expected to be due to the possibility for the C5Me5RuCl moiety to accomodate two cis carbene ligands. 

The rhodium(II) acetate-catalyzed addition of diazo compounds 609 to isothiazolones 610 results in a ready conversion into 1,3-thiazinones 611... 

A solution of ethyl diazoacetate (10.41 g, 0.100 mol) in anhyd EtjO (30 mL) was slowly added with a syringe pump to a stirred solution of the catalyst (< 1.0 mmol) and the alkene (0.100 mol) in Et O (50 mL). Reactions were generally performed at 25 °C in air (reactions performed under did not noticeably result in improved yields). The needle of the addition syringe was placed just below the surface of the reaction solution, and Nj evolution commenced with each fractional addition of diazo compound. After addition of the first 15 mL of ethyl diazoacetate solution, the rate of addition was slowed to approximately one half of the initial rate. When addition was complete, the mixture was filtered through active, neutral alumina. The alumina was washed with EtjO (200 mL), and the EtjO in the combined filtrate was evaporated to a residual oil which was distilled under reduced pressure. The cyclopropanes so obtained contain < 3% of the formal carbene dimers, diethyl ( )- and (Z)-but-2-enedioate. Analytically pure samples were obtained by redistillation or by preparative GC. Cyclopropane isomers can be separated by GC on Car-bowax 20 M columns (Table 9). 

Although the addition of diazo compounds to cyclopropenes generally leads to diazabicyclo-[3.1.0]hexanes, in some cases these cannot be isolated and lead directly to diazoalkenes. A dihydropyridazine is also formed in some cases these are discussed later (Section 3.3.2.2.). Diazo compounds which are isolated directly from the addition to a cyclopropene are summarized opposite. 

The addition of diazo compounds to cyclopropenes often gives diazabicyclo[3.1. OJhexenes which rearrange under more vigorous conditions to pyridazines or dihydropyridazines these reactions are discussed elsewhere (see Sections 1.A.1.1.6.1.5.3.1. and 1.A.4.2.1.1.2.). In some cases, however, the bicyclic systems cannot be isolated and a pyridazine is produced directly from a cyclopropene examples of such reactions are the formation of 1/33.134 2135-138 3 io4... 

An important synthetic use of pyrazolines is in the formation of cyclopropanes. This particular ring system is often accessible by addition of diazo compounds to alkenes (subsection 6.1.2). Some examples of both thermal and photochemical processes of this sort are given in Scheme 6.12. 

Straightforward access to pyrazole carbene chromium complex LXI results from the 1,3-dipolar addition of diazo compounds to acetylenic chromium carbene LX the reagent thus obtained is a useful synthon for the preparation of novel heterocyclic systems such as pyrazole [1, 5-a]pyridine quinone LXIII derivatives [100] in low to moderate yield (10-51 o) according to the substituents (Figure 5). 

From Diazo-compounds. The addition of diazo-compounds to olefins provides a routine method for the synthesis of cyclopropane derivatives. The reaction can pro-... 

The addition of diazo compound to acetylenes gives pyrazole derivatives. 

Addition of diazo compounds to 1,3-enynes Gyclopropanes from ethyiene derivatives Pyrazoles from acetylene derivatives... 

Further appUcations of this catalyst class as Br0nsted acids were shown by Maruoka and coworkers in various enantioselective reactions, such as addition of aza-enamines and vinylogous aza-enamines to imines (178,179), addition of diazo compounds to in situ generated acyclic azomethine imines (Scheme 10.72) [180], and 1,3-dipolar cydoaddition reactions of cyclic azomethine imines with enol ethers and vinylogous aza-enamines (Scheme 10.73) (181). 

Scheme 10.72 Addition of diazo compounds to in situ generated acyclic azomethine imines.

Alkene Synthesis.—The alkene synthesis by two-fold extrusion processes (see Vol. 3, pp. 246, 693) is discussed in Chapter 2 of this Volume (p. 89). The addition of diazo-compounds to suitable thiones provides an alternative route to A -l,3,4-thiadiazolines, which give episulphides on pyrolysis and hence alkenes on further reaction with triphenylphosphine. The symmetrical 1,3,4-thia-diazoline represents the normal direction of cycloaddition, but the orientation of addition of diazomethane to adamantanethione is governed by the nature of the solvent, and the unsymmetrical adduct predominates in solvents of higher polarity. A -l,3,4-Thiadiazoline-2,5-dione (148) is generated by oxidation of... 

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