Alkynyliodonium triflates

Feldman reported a route to dihydropyrroles, pyrroles, and indoles via the reaction of sulfonamide anions with alkynyliodonium triflates <96JOC5440>. Thus, upon nucleophilic addition of the anion of 91 to the p-carbon of the alkynyliodonium salt, the alkylidene carbene 92 is generated which can the undergo C-H insertion to the desired product 93. 

Likewise, the reaction of the lithium enolate of aminomalonate 126 with alkynyliodonium triflates 127 affords alkynylmalonates 128 in good yields (Scheme 52) [111]. The best yields in this reaction are observed when a freshly prepared solution of the lithium enolate in THF is added to a stirred cold solution of the iodonium salt. The use of potassium enolate instead of lithium, or addition of the reagents in a different order, results in lower yields of products 128. 

The bis(alkynyliodonium) triflate 152 reacts with the enolate anions of 15-diketones to afford the respective bis-insertion products 153 (Scheme 60) [122]. 

Recent examples of the rearrangement or alkynylation pathway include conversions of arylethynyl- and er -butylethynyl(phenyl)iodonium tosylates 24 and 25 to alkynylphosphonates, -selenides, and -tellurides with the appropriate anion salts in DMF (Scheme 50) [145-147], and a similar synthesis of push-pull selenides and tellurides from alkynyliodonium triflates containing electron-withdrawing groups in the alkynyl moiety [148]. 

General methods for the direct conversion of terminal alkynes (i.e. without silyl or stannyl activation) to alkynyliodonium triflates have not been described. The preparation of (tert-butylethynyl)phenyliodonium triflate from tert-butylacetylene with a 1 1 molar mixture of iodosylbenzene and triflic acid [PhlO-TfOH] has been reported78, but with other terminal alkynes, this procedure affords /l-(trifluoromethanesulfonyloxyvinyl)-iodonium triflates78. 

The contrasting behavior of alkynyliodonium tetrafluoroborates and alkynyliodonium triflates with triphenylphosphine (i.e. photochemical vs thermal activation) documented in the foregoing studies seems unlikely to be due to the different anions. Perhaps the thermal alkynylations are simply too slow to be observed at-78 °C in coordinating solvents such as THF, the conditions employed in the photochemical study. 

The presence of catalytic amounts of cuprous triflate or silver(I) sulfonates exerts a remarkable influence on the activation energy and regiochemistry of alkynyl(phenyl)-iodonium tosylate and mesylate decompositions5,6. Such reactions proceed in acetonitrile at room temperature and afford moderate yields of alkynyl tosylates and mesylates (equations 82 and 83)5,6. It is noteworthy, however, that the treatment of alkynyliodonium triflates (R = n-Bu, r-Bu) with cuprous triflate in acetonitrile does not afford alkynyl triflates6. Silver(I) catalysis has similarly been applied to the conversion of bis(alkynyliodo-nium) tosylates to bisalkynyl tosylates (equation 84)43. As might be expected, mono-tosylate esters are also produced in these reactions. 

The reactions of the lithium enolate of diethyl 2-[(diphenylmethylene)amino]malonate with several alkynyliodonium triflates are rare examples of enolate alkynylations with iodonium species other than the ethynyl(phenyl)- and (phenylethynyl)phenyliodonium ions (equation 125)16. Two experimental protocols were followed, i.e. addition of the enolates to the iodonium salts and vice versa, the former procedure giving higher yields of alkynylmalonates. As with other enolate alkynylations, these reactions are thought to involve alkylidenecarbene intermediates. It has been proposed, however, that the carbenes rearrange with migration of the diethyl 2-[(diphenyl) amino] malonate anion 16. 

Alkynyliodonium triflates exhibit two distinct modes of reactivity with bis(triph-enylphosphine)ethyleneplatinum(O)113. When (terf-butylethynyl)phenyliodonium triflate is mixed with the Pt(0) complex in degassed dichloromethane, ethylene insertion occurs, and a cationic 3-propargylplatinum(II) triflate is obtained (equation 147). Employment of l-propynyl(phenyl)iodonium triflate in degassed toluene, on the other hand, leads to a square planar cr-propynylplatinum(II) complex. 

The influence of argon and ethylene bubbling on the product ratios is consistent with expected shifts of the dissociative equilibrium shown in equation 149113. Thus, the cr-alkynyl complexes are thought to arise via reactions of the alkynyliodonium triflates with the coordinatively unsaturated bis(triphenylphosphine)platinum(0) species 34113, a pathway that should be optimized as ethylene is removed (i.e. by argon). The -complexes, on the other hand, apparently originate from the undissociated platinum(0)-ethylene complex113, their yields being maximized as ethylene is introduced. 

In recent years, Feldman and co-workers have employed alkynyliodonium triflates for the synthesis of relatively complex heterocyclic structures. 

Conversion of the alkynyliodonium triflate 256 to the bicyclic dihydropyrrole 257 appears to be an example of alkylidenecarbene capture by a carbamate nitrogen atom (Scheme 72) (99H1283). Competitive insertion of the carbenic center into a CH-bond of the oxazolidine ring was not observed. 

Peter Stang and co-workers at the University of Utah have synthesized a family of alkynyliodonium triflate salts with the generic structure... 

Asymmetric syntheses of agelastatin A rapidly followed Weinreb s racemic synthesis, with Feldman and coworkers publishing the first stereospecific approach to the natural enantiomer [68,69]. This route employed a chiral alkynyliodonium triflate-alkylidenecarbene-cyclopentene transformation to form the key intermediate 69 from which (—)-6S could be efficiently assembled. Hale et al. initially reported a chiral formal synthesis of (—[-agelastatin A through the enantiospedfic preparation of an advanced intermediate from Weinreb s racemic route [70] and later described a total... 

Although a few plosions have been reported [43] with Phi—O —IPh2BF4 and also with perchlorates, we have not experienced any problems to date with any of the alkynyliodonium triflates or tosylates. Nevertheless, it is prudent to exercise due caution in the handling of all iodonium species. 

Equally characteristic and very useful are the NMR spectral data. The F spectrum has a sharp singlet at around —78 to —79 ppm for the ionic Cp3SOf for all alkynyliodonium triflates and at about —150 ppm for BF ". The aromatic region of the H NMR spectra for all alkynyl(phenyl)iodonium species is highly characteristic, with three distinct multiplets between 7.4 and 8.3 ppm in a 2 1 2 ratio. The ortho protons of the phenyl group resonate between 8.1 and 8.3 ppm, the para proton at about 7.7 ppm, and the meta protons around 7.5 ppm these may be compared with -7.6 ppm and —7.0 ppm for the ortho protons, and... 

Analogously, malonate 54 gave exclusively alkynylation products 55 in 33-95% yields with a variety of alkynyliodonium triflates [Eq. (21)] [20 a]. 

Reaction of P-functionalized alkynyliodonium triflates, 11, with LiNPh2 results in various push-pull ynamines, 67, in 43-66% isolated yields [56] [Eq. (27)]. Treatment of alkynyliodonium tetrafluoroborates with Me3SiN3 in wet CH2CI2 results in the stereoselective formation of (Zy-P-azidovinyl iodonium salts 68 [Eq. (28)] in 50-91 % isolated yields [57]. 

In contrast, alkynyl dialkyl phosphate esters, 78, are formed in good isolated yields by either the treatment of alkynyliodonium triflates with (R0)2P02Na or the reaction of terminal alkynes with [hydroxy(phosphoryloxy)iodo]benzene, 77 [Eq. (34)], or the sequential treatment of alkynylsilanes with PhIO Et20Bp3 followed by aqueous (R0)2P02Na [Eq. (35)) [61]. These new, alkynyliodonium-derived, acetylenic esters have potent biological activity [4] in particular, the alkynyl benzoates are protease inhibitors [62], whereas the alkynyl dialkylphos-phates, 78, are inhibitors of a bacterial phosphotriesterase [63]. 

The reaction of ArS(0)2SK [67] and (R 0)2PS2K [68] with alkynyliodonium salts results in alkynyl thiotosylates, 85, and alkynyl phosphorodithioates, 86, respectively [Eqs. (42), (43)] in good isolated yields. Interaction of thiocarboxylates, 87, with alkynyliodonium triflates gives the hitherto unknown alkynyl thiocarboxylates, 88 [Eq. (44)] [69]. 

All varieties of alkynyliodonium salts readily react with triphenylphosphine resulting in the corresponding alkynylphosphonium salts in excellent yields. For cample, reaction of alkynyliodonium triflates with PhjP in cold dichloromethane gives alkynylphosphonium salts, 95, in nearly quantitative yields [75] [Eq. (50)J. 

The great majority of o-acetylide transition metal complexes are prepared by interaction of a metal halide with acetylide, RC C", or the formal oxidative addition of terminal alkynes or alkynyl stannanes to the metal center. As amply demonstrated in the previous section, alkynyliodonium salts may serve as electrophilic acetylene equivalents. In other words, transition metal complexes may act as nucleophiles in reactions with alkynyliodonium species. Indeed, the reaction [81] of the square planar Vaska s complex, 106, and its Rh analog, 107, with a variety of alkynyliodonium triflates in toluene results in 89-96% isolated yield of the hexa-coordinate o-acetylide complexes, 108 and 109 [Eq. (58)]. Reaction is essentially instantaneous and occurs with retention of stereochemistry around the metal center. 

Interaction of alkynyliodonium triflates with bis(triphenylphosphine)ethylene Pt(0) complex, 115, may lead to either the o-alkynylplatinum(II) complex, 116, or the novel q -pro-pargyl/allenyl Pt complex, 117 (Scheme 3-8), depending both upon the group R and the exact... 

Scheme 3-8 Reaction of alkynyliodonium triflates with a Pt(0) complex.

Several iodonium- and bis(iodonium) norbomadienes and other polycyclic adducts have been synthesized by [2-1-4] cycloaddition reactions of alkynyliodonium triflates with cyclic 1,3-dienes [458,460-464]. In particular, the bis-iodonium acetylene 331 undergoes Diels-Alder reactions with cyclopentadiene 329, furan... 

Alkynyl(phenyl)iodonium salts have found synthetic application for the preparation of various substituted alkynes by the reaction with appropriate nucleophiles, such as enolate anions [980,981], selenide and telluride anions [982-984], dialkylphosphonate anions [985], benzotriazolate anion [986], imidazolate anion [987], N-functionalized amide anions [988-990] and transition metal complexes [991-993]. Scheme 3.291 shows several representative reactions the preparation of Ai-alkynyl carbamates 733 by alkynylation of carbamates 732 using alkynyliodonium triflates 731 [989], synthesis of ynamides 735 by the alkyny-lation/desilylation of tosylanilides 734 using trimethylsilylethynyl(phenyl)iodonium triflate [990] and the preparation of Ir(III) a-acetylide complex 737 by the alkynylation of Vaska s complex 736 [991]. 

The intramolecular variant of the alkylidene carbene cyclization is achieved by treating functionalized alkynyliodonium salts with a suitable nucleophile. These cyclizations are exemplified by the following works the preparation of various functionalized 2,5-dihydrofurans by treatment of 3-alkoxy-l-alkynyl-(phenyl)iodonium triflates with sodium benzenesulfinate [1002], employment of the alkylidene carbene cyclization in the total syntheses of natural products agelastatin A and agelastatin B [1003] and preparation of the tricyclic core of ( )-halichlorine through the use of an alkynyliodonium salt/alkylidenecarbene/1,5 C—H insertion sequence [1004]. In particular, Wardrop and Fritz have employed the sodium benzenesulfinate-induced cyclization of alkynyliodonium triflate 751 for the preparation of dihydrofuran 752 (Scheme 3.295), which is a key intermediate product in the total synthesis of ( )-magnofargesin [1002]. 

The synthesis of ynamines was investigated later. The first example was reported by Stang and co-workers in 1994, but this transformation was limited to the synthesis of push-pull ynamines (Scheme 6, A) [56]. An important breakthrough was reported by Feldman and co-workers [57] and Witulski and co-workers [58], who demonstrated that alkynyliodonium triflates could be used for the synthesis of... 

The alkynylation of phosphorus nucleophiles has been less investigated (Scheme 7). Ochiai and co-workers first demonstrated in 1987 that the alkynylation of triphenyl-phosphine was possible with alkynyliodonium tetrafluoroborate salts under light irradiation (Scheme 7, A) [69]. The reaction most probably involves radical intermediates. In 1992, Stang and Critell showed that light irradiation was not needed if alkynyliodonium triflates were used [70]. Later, this methodology could be extended to other triaryl- or alkyl phosphines [71, 72]. In 1990, Koser and Lodaya also reported the synthesis of alkynylphosphonates by the Arbusov reaction of alkynyliodonium tosylates with trialkyl phosphites (Scheme 7, B) [73]. Alternatively, the same compotmds can be obtained by the reaction of alkynyliodonium tosylates with sodium phosphonate salts [74]. 

---