Nitrous oxide as diazo transfer reagent

Nitrous oxide, commonly known as “laughing gas”, is formed as a by-product in several industrial processes. It is also readily available by thermal decomposition of ammonium nitrate. Traditionally, the chemical valorization of N2O is achieved via oxidation chemistry, where N2O acts as a selective oxygen atom transfer reagent. Recent results have shown that N2O can also function as an efficient diazo transfer reagent. Synthetically useful methods for synthesizing triazenes, N-heterocycles, and azo- or diazo compounds were developed. This review article summarizes significant advancements in this emerging field.


Introduction
Nitrous oxide was brought to the public's attention by Sir Humphry Davy, an inuential British chemist and inventor.In 1800, the 21-year-old Davy published a book entitled "Researches, Chemical and Philosophical; Chiey Concerning Nitrous Oxide, or Dephlogisticated Nitrous Air, and its Respiration". 1 This 580-page monograph is divided into two parts.The rst part provides a comprehensive review of the chemistry of nitrous oxide, summarizing the state of knowledge at the time.The second part explores the physiological effects of nitrous oxide with Davy giving detailed descriptions of the sensations caused by inhaling this gas.The book also summarizes the effects of nitrous oxide on various animals.Davy was fascinated by this gas, and his enthusiasm was contagious.As a result, nitrous oxide quickly became a popular recreational drug among the British upper class.
The use of nitrous oxide as a drug continues to make headlines today, 2 but other concerns have emerged.Nitrous oxide is a potent greenhouse gas (GWP = 300), contributing signicantly to global warming. 3Furthermore, it is an ozone-depleting substance. 4Various anthropogenic sources contribute to N 2 O emissions, many of which are linked to agriculture. 5However, mitigation strategies have primarily focused on industrial processes, where nitrous oxide is formed as a side product. 6The largest amount of industrial N 2 O is generated during the production of nitric acid (Scheme 1a). 7N 2 O is produced alongside the desired NO during the catalytic oxidation of ammonia, with the amount of N 2 O depending on the process

Alexandre Genoux
Alexandre Genoux received his MSc from Grenoble Alps University, including research at UC Santa Barbara with Prof. Liming Zhang and at the University of Cambridge with Prof. Robert Phipps.He earned his PhD from the University of Zurich in 2020 under the supervision of Prof. Cristina Nevado.From 2021 to 2023, he was a postdoctoral associate with Prof. Patrick L. Holland at Yale University, supported by the Center for Hybrid Approaches in Solar Energy to Liquid Fuels.Since 2024, he is a Marie Skłodowska-Curie Fellow with Prof. Kay Severin at the Ecole Polytechnique Fédérale de Lausanne (EPFL), exploring new synthetic avenues with nitrous oxide.conditions.Plants without abatement technologies are estimated to emit between 4 and 19 kg of N 2 O per ton of HNO 3 (100%).7b Another signicant source of nitrous oxide is the production of adipic acid. 8Adipic acid is obtained through the catalytic oxidation of a mixture of cyclohexanone and cyclohexanol with nitric acid, resulting in the formation of approximately 300 kg of N 2 O per ton of adipic acid (Scheme 1b).
While the formation of N 2 O during the production of nitric and adipic acid is a major concern, it also presents an opportunity.Some companies have developed processes that allow the isolation of N 2 O. 9 Nitrous oxide can then be sold, or used as a reagent in downstream applications. 10he targeted synthesis of nitrous oxide is achieved through the thermal decomposition of a concentrated ammonium nitrate solution (Scheme 2a). 11This process is performed on an industrial scale.However, it is not ideal because the production of NH 4 NO 3 involves a multi-step manufacturing route.An interesting alternative is the direct oxidation of ammonia with a catalytic system that provides high selectivity for N 2 O over NO and N 2 (Scheme 2b). 12Pilot tests 12 and advances in catalyst design 13 suggest that ammonia oxidation could become a feasible method for large-scale industrial N 2 O production.
The chemical valorization of nitrous oxide is traditionally achieved via oxidation reactions. 12,14-16N 2 O is a powerful oxidant from a thermodynamic standpoint, 14 and the byproduct, N 2 , is both easy to separate and harmless.Furthermore, N 2 O displays good solubility in organic solvents, enabling liquid-phase reactions in low-polarity media. 15A drawback of N 2 O as an oxidant is its kinetically inert nature.However, the high kinetic barrier can be overcome by using a catalyst and/or elevated temperatures and pressures.
An example of a catalytic process involving N 2 O is the hydroxylation of benzene (Scheme 3a).8b,12 This reaction is catalyzed by iron-containing zeolites.Nitrous oxide represents an interesting oxidant for this reaction because it provides phenol with high selectivity.Furthermore, one could couple the N 2 O-mediated phenol production with the N 2 O-liberating formation of adipic acid (phenol could be hydrogenated to give cyclohexanol, the precursor for adipic acid; see Scheme 1).The pilot-scale production of phenol using N 2 O as the oxidant has been realized by Solutia, together with the Boreskov Institute of Catalysis.8b, 12 The process has not yet been commercialized due to economic reasons, and because a circular phenol/adipic acid production would require additional N 2 O. 8b, 12 The non-catalyzed oxidation of olens using N 2 O at elevated temperatures and pressures gives ketones alongside N 2 . 15This type of reactivity forms the basis for the industrial production of cyclododecanone, as developed by BASF. 10 The process starts with the oxidation of 1,5,9-cyclododecatriene with N 2 O to give cyclododeca-4,8-dien-1-one as a mixture of isomers (Scheme 3b).Catalytic hydrogenation then provides the target cyclododecanone.It is worth noting that the N 2 O, which is used in this process, is obtained from the production of adipic acid. 10he reactions depicted in Scheme 3 demonstrate that nitrous oxide can be employed for the synthesis of bulk chemicals.][19][20][21][22] For the oxidation of highly reactive compounds, the inert nature of N 2 O can be advantageous, as it prevents potential overoxidation reactions.For example, N 2 O is frequently used for the oxidation of reactive main-group element compounds. 18hese reactions are typically performed in solution using atmospheric pressure of N 2 O.
The chemical activation of N 2 O under mild conditions can also be achieved with certain transition metal complexes. 19,20his capability has spurred efforts to develop reactions with N 2 O using homogeneous catalysts.Over the past few years, signicant progress has been made in this eld, with efficient catalysts being developed for a variety of oxidation reactions. 21,22ost of the reactions discussed thus far proceed via oxygen atom transfer and extrusion of dinitrogen.This review focuses on a different type of reactivity, namely the use of N 2 O as a diazo transfer reagent (Scheme 4).The formal by-product in these reactions is O 2− , which is released in the form of hydroxide, alkoxide, oxide salts (M I OH, M I OR, M II O), or water, depending on the substrate that was employed.
The use of N 2 O as a diazo transfer reagent was rst demonstrated by Wislicenus in 1892. 23By subjecting NaNH 2 to

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N 2 O at elevated temperatures, he was able to obtain NaN 3 .The 'Wislicenus reaction' is nowadays employed for the industrial production of NaN 3 . 24Despite this early success, N 2 O-based diazo transfer reactions have historically remained underdeveloped.However, signicant progress has been made in recent years, resulting in numerous synthetically useful processes.This review summarized signicant developments in this area.
Before discussing these advancements, we will describe the covalent capture of intact N 2 O by (semi-)metal complexes, frustrated Lewis pairs (FLPs), and organic nucleophiles.Only a few of these adducts were used in productive diazo transfer reactions, but they provide valuable insights into the underlying reactivity of N 2 O.

Covalent capture of nitrous oxide
The covalent trapping of N 2 O by (semi-)metal complexes leverages metal-ligand cooperation. 25-33A common theme in these reactions is the formation of a covalent bond at the terminal Natom of N 2 O along with a coordination bond to the other O/Natom (Scheme 5a-f).Nitrous oxide can also act as a simple ligand for metal complexes (without concomitant formation of a covalent bond to a main group element), but these cases will not be discussed further in this review. 34illhouse and coworkers have investigated reactions of the diphenylacetylene complexes Cp*M(PhC 2 Ph) (M = Ti, Zr) with N 2 O. 25 At low temperatures, azoxymetallacyclopentene complexes of type 1 were obtained (Scheme 5a).The zirconium complex was found to be thermally labile, undergoing extrusion of N 2 upon warming to room temperature.The titanium complex was more stable, allowing for a crystallographic characterization.More recently, it was found that the zirconium complex can be stabilized by N-alkylation with MeOTf. 26nsertion of N 2 O into a metal-carbon bond was also observed for samarium complexes.When a solution of (Cp*) 2 -SmBn(THF) in toluene was exposed to N 2 O, the dinuclear complex 2 was formed (Scheme 5b). 27Allyl complexes of the general formula (C 5 Me 5 R) 2 M(C 3 H 5 ) (R = H, Me; M = Sc, Y, Sm, La) were found to display a similar reactivity (Scheme 5c). 28ayton and coworkers reported that a "masked" terminal Ni(II) sulde complex is able to react with N 2 O to give the thiohyponitrite complex 4 (Scheme 5d). 29Liberation of N 2 was observed when a solution of complex 4 was heated in toluene at 45 °C for 6 days, resulting in the formation of a h 2 -SO complex as the main product. 30More recently, the Hayton group showed that a Zn(II) sulde analogous to complex 4 is also converted to a thiohyponitrite complex when exposed to N 2 O. 31 The cooperative metal-ligand activation of N 2 O is not restricted to transition metal complexes.Milstein and coworkers examined the reaction of N 2 O with dearomatized calcium pincer complexes supported by pyridine-based PNNtype ligands. 32A rapid transformation into dinuclear diazotate complexes ( 5) was observed at room temperature (Scheme 5e).
The reactions of low-valent silicon compounds with N 2 O typically proceed via O-atom transfer and liberation of dinitrogen. 18An exception to this reactivity pattern was reported by Inoue and coworkers.They showed that an oxatriazasilole, 6, is formed upon reaction of a silaimine with N 2 O (Scheme 5f). 33he reaction proceeds via a concerted 1,3-dipolar cycloaddition mechanism, rst proposed by Wiberg, 35 and later supported by computational studies. 36It is interesting to note that solutions of the cycloaddition product 6 are thermally very stable; no isomerization or decomposition was observed at temperatures up to 130 °C. 33he utilization of FLPs for the capture of N 2 O was rst investigated by Stephan and coworkers. 37,38When mixtures of the bulky phosphine PtBu 3 and the Lewis acids B(C 6 F 5 ) 2 R (R = C 6 F 5 or Ph) were exposed to an atmosphere of N 2 O, zwitterionic adducts of type 7 with P-N 2 O-B linkages were obtained (Scheme 6a).The thermal or photochemical activation of 7 resulted in the formation of (tBu 3 PO)B(C 6 F 5 ) 2 R along with the liberation of dinitrogen.
0][41] In contrast, phosphines with reduced steric hindrance or Lewis basicity do not form similar compounds.The borane can be exchanged for other Lewis acids.The adduct tBu 3 P(N 2 O)B(C 6 H 4 F) 3 is particularly well suited for exchange reactions because it contains the relatively weak Lewis acid B(C 6 H 4 F) 3 .For example, the dinuclear complex 8 was obtained when adding one equivalent of Zn(C 6 F 5 ) 2 , 39 whereas exchange with [Cp 2 ZrMe][MeB(C 6 F 5 ) 3 ] gave complex 9 (Scheme 6b). 40he capture of N 2 O can also be achieved by using an alane.The adduct tBu 3 P(N 2 O)Al(C 6 F 5 ) 3 (10) was obtained by slow addition of N 2 O to a cooled solution containing PtBu 3 (2 eq.) and Al(C 6 F 5 ) 3 (toluene) (Scheme 6c). 42The reaction with additional Al(C 6 F 5 ) 3 (toluene) resulted in N-O bond rupture, generating the highly reactive radical ion pair (tBu 3 Pc)[(C 6 F 5 ) 3 Al(Oc) Al(C 6 F 5 ) 3 ] that can activate C-H bonds.
The colorimetric detection of N 2 O was realized using a borane with a ferrocenyl (Fc) substituent as the Lewis acid in an FLP. 43Exposing a mixture of PtBu 3 and B(C 6 F 5 ) 2 Fc to N 2 O resulted in the formation of the adduct tBu 3 P(N 2 O)B(C 6 F 5 ) 2 Fc (11), accompanied by a color change from maroon to amber (Scheme 6d).A different UV-Vis-responsive FLP was created by using a phosphine containing a cycloheptatrienylcyclopentadienyl titanium sandwich complex as substituent. 44he use of a single-component FLP with a dimethylxanthene backbone allowed for the reversible binding of N 2 O. 45 Exposing a solution of this FLP in dichloromethane to one atmosphere of N 2 O resulted in the slow (t 1/2 ∼ 12 h) formation of the adduct 12 (Scheme 6e).Warming a solution of this adduct in dichloromethane to 50 °C for 2 h led to the quantitative removal of N 2 O.
In 2012, our group demonstrated that N-heterocyclic carbenes (NHCs) can effectively capture N 2 O. 46 When a solution of 1,3-dimesitylimidazol-2-ylidene (IMes) in THF was subjected to one atmosphere of N 2 O, the adduct IMes(N 2 O) was formed in high yield (90%).A similar compound was obtained using an imidazole-2-ylidene with Dipp wingtip groups (IPr).][49] The adducts can be described as zwitterionic imidazolium diazotates (13, I) or as nitrosoimines (13, II).Crystallographic analyses revealed a preference for a trans conguration for the N-N bond, even though exceptions have been reported. 48HC(N 2 O) adducts display good stability at room temperature.At elevated temperatures, the release of N 2 and formation of the corresponding ureas was observed.
The addition of Brønsted acids to IMes(N 2 O) resulted in the rupture of the N-N bond and the formation of N-heterocyclic iminium salts. 47This type of reactivity was used by Dielmann and coworkers for the synthesis of the dimer 15 (Scheme 7b). 50he latter was employed as a precursor for the synthesis of a chelate ligand.
N-N bond cleavage was also observed when IMes(N 2 O) was combined with nickel(0) 51 or cobalt(I) 52 complexes.A different type of reactivity was noted in reactions with vanadium(III) 53, 54 and uranium(III) 55

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ylidene are able to form adducts with N 2 O (Scheme 7c). 56nterestingly, it was possible to introduce a second N 2 O group by treating adduct 16 with rst potassium hexamethyldisilazide (KHMDS) and then N 2 O.
A direct double functionalization with two N 2 O groups was observed when a solution of lithiated IPr in THF was subjected to an atmosphere of N 2 O (Scheme 7d). 56 2 O capture can also be achieved by triazole-based carbenes: the triazolium diazotate 19 was isolated in 86% yield from a reaction of the corresponding carbene with N 2 O (Scheme 7e).57 Attempts to capture N 2 O with a mesoionic carbene featuring phenyl substituents at the 2-and the 4-position were unsuccessful.However, in the presence of B(C 6 F 5 ) 3 , the C-N 2 O-Bbridged adduct 20 was isolated (Scheme 8a).58 A similar situation was encountered with a carbene having tert-butyl wingtip groups and methyl substituents in 4/5-position: while direct N 2 O capture by the carbene could not be achieved, an adduct (21) was obtained in the presence of the Lewis acid B(C 6 F 5 ) 3 (Scheme 8b).49 In 1953, Meier reported that lithiated amines react with N 2 O. 59 In the case of Et 2 NLi, he was able to isolate tetraethyltetrazene, albeit in low yield.Meier proposed aminodiazotates as intermediates, but the isolation of these adducts was not attempted.Our group has re-investigated this type of reaction and found that aminodiazotates (22) are formed in good yields when solutions of lithium amides in THF are subjected to an atmosphere of N 2 O (Scheme 9).60 N 2 O adducts of type 22 can serve as precursors for the synthesis of triazenes, and more details about such transformations are given in Section 4.

Synthesis of azides
The standard procedure for the synthesis of NaN 3 involves the reaction between NaNH 2 and N 2 O (see Section 1). 23,24Meier showed that this chemistry can be extended to organic azides.He noted that a pale yellow oil, most likely phenyl azide, was formed in low yield when a solution of lithiated aniline in diethyl ether was exposed to N 2 O. 59 A more detailed investigation was conducted by Koga and Anselme in 1968. 61They showed that aryl azides (23) are formed by reactions of lithiated aromatic amines with N 2 O (Scheme 10).However, the yields of these diazo transfer reactions were poor (<35%).Signicantly higher yields were obtained when silylated aryl amides were used as starting materials in NMR-scale reactions. 62When the reactions were performed on a preparative scale, an increased amount of side products was observed.

Synthesis of triazenes
Aromatic triazenes of the general formula (aryl)N 3 R 2 have been investigated extensively in the context of synthetic organic chemistry. 63An important feature of aryl triazenes is the possibility to replace the N 3 R 2 group under acidic conditions by a broad range of other functionalities.The substitution reactions proceed via diazonium compounds, and aryl triazenes are oen referred to as "masked diazonium salts". 64ryl triazenes of type (aryl)N 3 R 2 are typically prepared by coupling of aryldiazonium salts with secondary amines. 63In 2015, our group reported an alternative synthetic procedure involving nitrous oxide. 60Solutions of lithium amides in THF were allowed to react with N 2 O, resulting in the formation of aminodiazotates (22).The latter were not isolated, 65 but combined directly with aryl Grignard reagents to give aryl triazenes of type 24 (Scheme 11).
A key advantage of the N 2 O-based methodology for synthesizing triazenes is that it can be extended to alkynyl (25) and alkenyl triazenes (26).These compounds are difficult to access by alternative procedures. 66,67Alkyl triazenes can also be prepared by this method, as illustrated by the synthesis of 1isobutyl-3,3-diisopropyltriazene (27).However, the yield of 27 was low (12%).
Alkynyl triazenes are attractive starting materials for application in organic synthesis (Scheme 12). 66From a practical standpoint, it is worth noting that alkynyl triazenes are not particularly sensitive to air or moisture.Furthermore, they can be puried by chromatography, and they exhibit good thermal stability.
The synthesis of alkynyl triazenes by coupling of lithium amides rst with nitrous oxide and then with an alkynyl Grignard reagent restricts the functional groups that can be employed.To overcome this limitation, we have developed a synthetic route for a terminal alkynyl triazene, 35 (Scheme 13). 84Subsequent functionalization of 35 allowed to prepare alkynyl triazenes with a range of functional groups including esters, alcohols, cyanides, phosphonates, and amides.

Synthesis of N-heterocycles
The reactions of alkenes and alkynes with N 2 O generally proceed via O-atom transfer and liberation of dinitrogen. 15An interesting exception to this type of reactivity was reported by Banert and Plea. 85When cyclooctyne or cycloocten-5-yne were treated with nitrous oxide (∼50 bar) in the presence of nucleophiles (amines or alcohols), the formation of pyrazoles of type 37 was observed (Scheme 14).The reactions were proposed to proceed via heterocycles of type 38.In the case of cyclooctyne, the intermediate could be isolated if the reaction was performed without nucleophiles.
Cui and coworkers have shown that nitrous oxide can be used for the synthesis of benzotriazines. 86Aromatic amides or Azobenzene can be obtained by reaction of phenylcalcium iodide and N 2 O (see Section 6).A related diazo transfer reaction was observed when a dimeric biphenylcalcium complex was mixed with N 2 O. 87 Benzo[c]cinnoline (41) was obtained in 55% yield (Scheme 16).
Triazolopyridines are valuable starting materials for heterocycle synthesis. 88Our group has shown that triazolopyridines can be prepared using nitrous oxide. 89,90A range of lithiated 2benzylpyridines could be converted into triazolopyridines of type 42 upon reaction with N 2 O (Scheme 17a).
The diazo transfer reaction can be combined with a C-C bond-forming reaction.Heterocycles of type 43 were obtained by coupling of organolithium reagents with 2-vinylpyridines, followed by N 2 O-induced triazole formation (Scheme 17b).The carboxylic acid 44, on the other hand, was prepared in 89% yield by deprotonation of methyl 2-(pyridin-2-yl)acetate, followed by reaction with N 2 O and hydrolysis (Scheme 17c).

Synthesis of azo compounds
In 1953, Beringer, Farr and Sands published a study describing reactions of organolithium reagents with N 2 O. 91 For phenyllithium, they observed a mixture of products, including biphenyl, triphenylhydrazine, phenol, and a small amount (7%) of azobenzene 45 (Scheme 18a).Similar products were found by Meier when using PhNa instead of PhLi.Meier also showed that PhCaI can be converted into azobenzene. 92In this context, it is worth noting that aryl Grignard reagents are largely inert towards N 2 O. 92,93 In 1995, the reaction between PhCaI and N 2 O was reinvestigated by Hays and Hanusa. 94By optimizing the procedure, they were able to obtain azobenzene with a yield of up to 61% (Scheme 18a).However, they noted difficulties in obtaining reproducible results.
Azo-bridged ferrocene (46) was obtained in 25% yield by reaction of lithiated ferrocene with N 2 O (Scheme 18b). 95A related reaction was used to synthesize azo-bridged ferrocene oligomers. 96-Heterocyclic carbenes are able to form stable covalent adducts with N 2 O (see Section 2 and Scheme 7).In the presence of AlCl 3 , adducts of type 13 can be coupled to arenes (Scheme 19a).97 The resulting azo compounds are of interest as dyes.They are produced industrially via different routes, and they have found diverse applications.98 The N 2 O-based methodology has a good scope with regard to the arene coupling partner, and NHC(N 2 O) adducts with alkyl or aryl wingtip groups can be employed in these reactions.
Azoimidazolium dyes with N-aryl substituents were found to display interesting chemistry.Upon reduction, stable aminyl radicals were formed. 99Moreover, they can be used as precursors for mesoionic carbene ligands. 100he AlCl 3 -mediated coupling chemistry can be extended to N 2 O adducts of mesoionic carbenes. 101Azoimidazolium salts of type 48 were formed by coupling of arenes with 16 (Scheme N-Heterocyclic olens (NHOs) display a highly polarized exocyclic C]C double bond, making them strong bases and nucleophiles. 102In 2019, our group reported that NHOs with Dipp, mesityl or xylyl wingtip groups are able to activate N 2 O. 103 When a solution of the respective NHO in acetonitrile was subjected to an atmosphere of N 2 O, azo-bridged dimers of type 50 were obtained (Scheme 20).The yields were not high (∼50%), but the products were easily isolated because they crystallized from solution.Reactions between NHOs and N 2 O can also give diazoolens, and more details about these transformations are given in the next section.
The dimers 50 were found to be very strong electron donors, with rst oxidation potentials between −1.32 and −1.38 V (vs.Fc/Fc + ).Upon reduction, stable radical cations or dicationic imidazolium salts were obtained. 103

Synthesis of diazo compounds
The reaction of N 2 O with methyllithium was rst investigated by Müller and coworkers. 104They found that diazomethane (51)  was formed aer basic workup (Scheme 21a).A yield of 70% was obtained under optimized conditions. 105he formation of diazomethane was also evidenced in reactions of the ylide Ph 3 P]CH 2 with N 2 O (Scheme 21b). 106owever, the yield of CH 2 N 2 in this transformation was low (20-25%).
During their investigations about reactions of cyclic alkynes with N 2 O, Banert and Plea were able to isolate the diazo compound 52 in 95% yield (Scheme 21c). 85Upon warming to room temperature, loss of dinitrogen was observed, resulting in a mixture of compounds.
Erker and coworkers have investigated the reactivity of a carbene-stabilized boraalkene. 107The reaction with N 2 O gave a mixture of the diazo compound 53 and the oxaborirane 54 (Scheme 22).The authors propose that the compounds are derived from the same intermediate, a (2 + 3) cycloaddition product of the starting material and N 2 O.
Diazoolens of the general formula R 1 R 2 C]CN 2 (R 1/2 = alkyl, aryl, or H) are highly reactive compounds, which rapidly lose N 2 . 108In 2021, the Hansmann group reported that N 2 O could be used for the synthesis of a room-temperature-stable diazoolen (diazoalkene). 109The reaction of a mesoionic NHO 110 with N 2 O gave diazoolen 55 along with amide 56 (Scheme 23a).The diazoolen could be isolated in 41% yield.A crystallographic analysis of 55 revealed a bent heterocumulene group.The unusual stability of 55 was attributed to both resonance stabilization and polarization of the C-CN 2 bond.108a, 109 'Normal' N-heterocyclic olens can also react with N 2 O to give diazoolens of type 57 (Scheme 23b).First examples were published by our group in 2021, 111 and a new member of this compound class with R 1 = R 2 = Me was recently disclosed by Bismuto and coworkers. 112he use of triazole-based NHOs allowed access to diazo-olens of type 58 (Scheme 23d). 113It is worth noting that both 57 and 58 can also be prepared by using the more conventional diazo transfer reagent p-tosyl azide instead of N 2 O. 114 While nitrous oxide is more atom-economical, the use of p-TsN 3 avoids the formation of the potentially problematic side product water.
N-Heterocyclic diazoolens display intriguing chemistry, as evidenced by recent studies (Scheme 24).8][119] The N 2 group of N-heterocyclic diazoolens can be exchanged for isocyanides or for CO to give novel heterocumulenes. 110,113,120ycloaddition reactions with dipolarophiles give pyrazole derivatives, 111,121 and methanol was found to promote the dimerization of N-heterocyclic diazoolens. 122he conversion of NHOs to diazoolens requires the presence of a terminal CH 2 group.Gellrich and coworkers reported that a gem-dimethylated NHO was still able to activate N 2 O. 123 They observed cleavage of the exocyclic double bond to give the urea 59 along with azine 60 (Scheme 25).The latter was formed by denitrogenative coupling of 2-diazopropane.
Recently, the Hansmann group reported the synthesis of the diazophosphorus ylide 61. 124The diazo compound was obtained by combining carbodiphosphoranes Ph 3 P]C]PR 3 (R = Ph or nBu) with nitrous oxide (Scheme 26).The ylide serves as a selective transfer reagent for the fragments Ph 3 PC and CN 2 .Furthermore, carbon-atom transfer was observed in reactions of 61 with aldehydes and ketones.

Conclusions
In synthetic chemistry, nitrous oxide is well known for its ability to act as an oxygen-atom transfer reagent.The present review highlights a distinct reactivity of N 2 O: diazo transfer.Although the application of N 2 O for diazo transfer dates back to the 19th century, it is only in recent years that these reactions have received increased interest.
High-yielding diazo transfer reactions with N 2 O were realized with a range of compounds including lithium amides, metalated arenes and alkanes, N-heterocyclic carbenes, Nheterocyclic olens, and carbodiphosphoranes.The reactions with these nucleophiles are likely initiated by an attack at the terminal nitrogen atom of N 2 O.In the case of carbenes and amides, the corresponding diazoates could be isolated and characterized.For other nucleophiles, spontaneous N-O bond rupture gave directly nitrogen-containing products.
Several of the compounds described in this review can be prepared by using alternative synthetic procedures.In this case, the advantages and disadvantages of the N 2 O-based methodology must be balanced considering specic constraints (yields, costs, time, availability of N 2 O, etc.).For some compounds, nitrous oxide remains the sole viable option for synthesis to date.Alkynyl triazenes, for example, can thus far only be accessed with N 2 O.These activated alkynes are very attractive starting materials for synthetic organic chemistry. 66verall, we hope to have shown with this review that nitrous oxide is more than a simple O-atom donor.Efficient diazo transfer was observed in reactions with a range of carbon-and nitrogen-based nucleophiles.We are condent that there is signicant room for further developments.Nitrous oxide has the potential to become a routinely used reagent in synthetic organic and inorganic chemistry.

Scheme 1
Scheme 1 Nitrous oxide is formed as a side product during the industrial production of nitric acid (a) and adipic acid(b).

Scheme 3
Scheme 3The use of nitrous oxide as an O-atom donor: synthesis of phenol by catalytic oxidation of benzene (a), and synthesis of cyclododecanone by non-catalytic oxidation of 1,5,9-cyclododecatriene, followed by hydrogenation(b).
Scheme 6 Covalent capture of nitrous oxide by frustrated Lewis pairs (FLPs).

Scheme 8
Scheme 8 Covalent capture of N 2 O by mixtures of N-heterocyclic carbenes and B(C 6 F 5 ) 3 .

Scheme 12
Scheme 12 Alkynyl triazenes as versatile starting materials in synthetic organic chemistry.

Scheme 21
Scheme 21 Synthesis of diazomethane (a and b) and addition of N 2 O to a cyclic alkyne (c).