Reaction with Heterocumulene Derivatives

From the range of general methods available for the construction of the carbodiimide functionality, the intermolecular aza-Wittig-type reaction of phosphazenes and isocya- 

Five-membered heterocycles were obtained when ammonia or amine nucleophiles reacted with carbodiimides, generated in situ from phosphazenes by a cascade process 

The alkaloid (+)-cularine (72) was isolated by Manske in 1938 from plants belonging to the gemra Dicentra and Corydalis Recently, Rodrigues et al reported a diastereoselec- 

---

Cycloadditions The [2+2] cycloadducts derived from sulfurdiimides are seldom isolated but exchange reactions with heterocumulenes, proceeding via a [2+2] cycloaddition sequence, are often observed. In the reaction of diphenylketene with di-tosylsulfurdiimide at -15 °C the [2+2] cycloadduct 58 is formed, while at 70 °C the [3+2]... 

Many heteroatom nucleophiles can be added to heterocumulenes of the general structure Het1=C=Het2 to give carbonic acid derivatives of the type Het1—C—(=0)-Het2or3 (Section 7.1). Almost all of these carbonic acid derivatives can undergo SN reactions with heteroatom nucleophiles at the carboxyl carbon. In this way other carbonic acid derivatives are produced. A short survey of the... 

The palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a [42] and aziridine 20b [39] with the activated olefin 4a for the formation of five membered cyclic ether 21a and pyrrolidine derivative 21b has also been reported in our laboratories. The mechanistic issue is very much similar to that discussed in Scheme 9. Pd(0) catalyst added oxidatively to 20 to produce the 7r-allylpalladium complex 22. The Michael addition of a hetero nucleophile in 22 to the activated olefin 4a gives 23 which undergoes intramolecular nucleophilic attack on the inner 7r-allylic carbon atom to give the cy-clized products 21 and Pd(0) species is generated (Scheme 10). Similarly, the palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a with the N-losylimincs 24 is also known (Scheme 11) [43]. Intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes such as isocyanates, carbodiimides and isothiocyanates is also known [44,45]. Alper et al. reported the regio- and enatioselective formation of the thiaolidine, oxathiolane, and dithiolane derivatives by the palladium-catalyzed cyclization reaction of 2-vinylthiirane with heterocumulenes [46]. 

Dihydro- 1,3-oxazines (398) are cyclic intermediates in the synthesis of a-amino-y-oxo acid esters by reaction of acyliminoacetates with enamines derived from six-membered ketones240. Sulfur-containing heterocycloadducts 399 and 400 have been prepared by [4 + 2] cycloaddition of enamines to heterocumulenes like thioacyl isocyanates and acyl isothiocyanates241. 

The insertion reaction of heterocumulenes can be used to syuthesize carbodiimides having two different substituents. For example, the carbamate 157 derived from an isocyanate and bis(tributyltin)oxide can be reacted with an isothiocyanate to give a carbodiimide 158 with substituents derived from the isocyanate and the isothiocyanate. ... 

Larksarp et al. reported the regio- and enatio-selective formation of the thiaolidine, oxathiolane, and dithiolane derivatives (630) by the palladium-catalyzed cyclization reaction of 2-vinylthiirane 628 with heterocumulenes 629 (Scheme 193).271 The asymmetric reaction of 2-vinylthiirane 628 and car-bodiimide 629a was performed using (S)-tol-BINAP as a chiral phosphine ligand (Scheme 194). 

Reactions of [MCls-xMe,] (x = 1, 2 or 3) with heterocumulenes have led to insertions into the M—C bond. lV,lV -Dialkylacetamidinato derivatives were obtained (equation 33). N-Acetamides or N-thioacetamides were formed with isocyanates or isothiocyanates, respectively (equation 34). The rate of insertion varied in the order [MCl4Me] > [MCl3Me2] > [MCl2Me3], following the established order of acceptor properties of the methylmetal chlorides, the isocyanates being more reactive than the isothiocyanates. Hexa- or hepta-coordinated species were obtained. 

Methylene-l,3-different structures issued from reactions with olefins, isocyanides, heterocumulenes, and ketene derivatives is shown in Scheme 48. 

The reaction of heterocumulenes or alkynes with ortho-iodoanilines under a carbon monoxide atmosphere has been shown to give4(3ff)-quinazolinones or 2-quinolones, respectively. A related cyclocarbonylation reaction has been used to synthesize new cardanol and cardol derivatives in a regioselective manner. Versatile and efficient routes to various spirocyclic compounds, including [5,5]-, [5,6]- and [5,7]-spiroindolines, have been established by exploiting a sequence of palladium-catalyzed cyclization processes (eq 105). ... 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

The reaction of phosphine (produced in situ from magnesium phosphide and hydrogen chloride in dioxan solution) with 1,5-diketones gives106 the phosphorina-none derivatives (104). Carbonyl compounds and heterocumulenes (e.g. CO2, CS2) insert into the germanium-phosphorus bond of germaphospholans to form derivatives of the germaphosphepin system [e.g. (105)].106>107... 

On the basis of the above-mentioned calculations it seems that coordination chemistry is a viable alternative to stabilize this heterocumulene. However, the experimental access to metal complexes containing the tricarbon monoxide ligand remains a challenge. Thus, to date, the coordination chemistry of C3O is confined to [Cr(=C=C=C=0)(C0)s] (89), obtained by treatment of [n-Bu4N] [CrI(CO)5] with the silver acetylide derived of sodium propiolate in the presence of Ag" (Scheme 28) [105]. Reaction of the presumed Tt-alkyne intermediate complex 88 with thiophosgene generates the heterocumulene 89. Neither structural nor reactivity studies were undertaken with this complex. 

The palladium-phosphine-catalyzed cycloaddition reactions of vinyloxetanes 530 with aryl isocyanates or diaryl-carbodiimides led to 4-vinyl-l,3-oxazin-2-ones 531 or l,3-oxazin-2-imines 532, respectively (Scheme 101). In the absence of phosphine ligands (PPhs, bis(diphenylphosphino)ethane (DPPE), l,3-bis(diphenylphosphino)propane (dppp), no conversion of heterocumulenes was observed. Starting from fused-bicyclic vinyloxetanes, both types of cycloadditions proceeded in a highly stereoselective fashion, affording only the r-isomers of alicycle-condensed 1,3-oxazine derivatives <1999JOC4152>. 

Ketenes rarely produce [3+ 2]-cycloaddition products with diazo compounds. The reaction possibilities are complex, and nitrogen-free products are often obtained (5). Formation of a cyclopropanone represents one possibihty. Along these lines, the synthesis of (Z)-2,3-bis(trialkylsilyl)cyclopropanones and (Z)-2-trialkylsilyl-3-(triethylgermyl)cyclopropanones from diazo(trialkylsilyl)methanes and appropriate silyl- or germylketenes has been reported (256,257). It was found that subsequent reaction of the cyclopropanone with the diazoalkane was not a problem, in contrast to the reaction of diazomethane with the same ketenes. The high cycloaddition reactivity of diazomethylenephosphoranes also extends to heterocumulenes. The compound R2P(C1)=C=N2 (R = N(/-Pr)2) reacts with CS2, PhNCO and PhNCS to give the corresponding 1,2,3-triazole derivative (60). 

This approach to 1,2,4-dithiazolidine derivatives 124 was investigated in detail by L abbe and co-workers on the example of a reaction of 4-alkyl-5-arylimino-l,2,3,4-thiotriazolines 123 and related compounds with isothiocyanates and other heterocumulenes. In these reactions, in addition to compounds 124, l,2,4-thiadiazolidine-3-thiones 125 are formed (Equation 17) <1996CHEC-II(4)453>. 

The related 4-alky l-5-a Iky limino-1,2,3,4-th iatria/olcs 58 are much less stable than the corresponding aryl derivatives 52 and 55, and liberate nitrogen and sulfur to give the carbodiimides 59 in low yields (Equation 5). In many cases heterocumulenes 59 participate in consequent masked 1,3-dipolar reactions (see Section 6.09.6.2) with a second equivalent of compound 58 leading to complex reaction mixtures and explaining the low yields <1978J(P1)1440>. 

The 1,3-diazetidine derivatives are most commonly synthesized by the dimerization of heterocumulenes. At elevated temperature they undergo dissociation and are in equilibrium with their monomers. For example, 1,3-diazetidine 108, formed by the reaction of a-naphthyl isocyanate 106 with dicyclohexylcarbodiimide 107, upon thermal dissociation furnished products of its [2+2] cycloreversion reaction, that is, cyclohexyl isocyanate 110 and a-naphthylcyclohexylcarbodiimide 109 (Scheme 10) <1962AGE621>. 

---