1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

N-Phenyl-N-(trifluoromethylsulfonyl)propiolamides react with triphenylphosphane in the presence of various active methylene compounds CH2XY in a 1:1:1 molar ratio to furnish 1-phosphonium-5-oxabetaines, Ph3P+–C(R)=CH–C(O–)=CXY. These betaines are formed preferentially, but not exclusively, as E-diastereoisomers with respect to the vinylic double bond. In some cases, separation of the two diastereoisomers was achieved by fractionating crystallization. Structure determination by X-ray diffraction analysis revealed marked conformational differences around the CH–C(O–) single bond of E and Z-isomers and extended charge delocalization in the anionic part.


Introduction
Beside the well-known phosphonium ylides (Wittig ylides, methylenephosphoranes), various other types of zwitterions containing a tetravalent phosphonium moiety (phosphonium betaines) exist. They are often considered as reaction intermediates, but reports on their isolation and structural characterization are still less common. A very convenient access to such betaines is provided by the nucleophilic addition of tertiary phosphanes to electron-deficient alkenes, alkynes and allenes (phospha-Michael addition), which generates the betaines as reactive intermediates that can be transformed intra-or intermolecularly into a wide array of acyclic, carbocyclic and heterocyclic structures. In these processes, the tertiary phosphanes can act as nucleophilic organocatalysts (for reviews, see [1][2][3][4] or be incorporated in the (pre-)final products, typically as alkylidene phosphoranes which in turn may undergo Wittig olefination with elimination of Ph 3 P=O [1,5]. Recently, a study of the tributylphosphane-catalyzed reaction of ethyl 2-butynoate and ethanol by in-situ ESIMS and NMR techniques has been published [6], and mechanistic aspects of trialkylphosphane-catalyzed reactions of acetylenic ketones and esters with pinacolborane have been discussed [7,8].
In contrast to acetylenic esters and ketones, acetylenic carboxamides have rarely been exposed to nucleophilic phosphanes in organocatalytic or stoichiometric reactions. Recently, we have reported on the synthesis and reactivity of N-triflylpropiolamides 1 (Scheme 2). They turned out to be excellent substrates for transamidation reactions (reaction 1) [18], whereas tertiary phosphanes Ph 2 P-X (X = SiMe 3 , Cl) underwent Michael addition leading to silylphosphanylation (reaction 2) or hydrophosphorylation (reaction 3) of the C-C-triple bond, respectively [19]. We report now on three-component reactions of alkynes 1 with triphenylphosphane and active methylene com-pounds, leading to phosphonium betaines which are structurally different from those shown in Scheme 1.
Some betaines 3 were isolated solely as E-diastereoisomers, others as E/Z mixtures. In some cases, the two diastereoisomers were separated by fractionating crystallization from a mixedsolvent solution. In the case of 3a, a trace amount (≈2%) of the Z-isomer was detected in the reaction mixture by 1 H NMR (the chemical shift of the olefinic proton being characteristic), but got lost during work-up. An inspection of Figure 1 reveals no obvious reason for the obtained E/Z ratios. Beside characteristic spectroscopic data (vide infra), the diastereoisomeric betaines can also be distinguished by their colors: the isolated E-isomers are usually colorless, while the Z-isomers have a yellow shade. As an exception, E-3f was obtained as dark red needle-shaped crystals, in contrast to pale yellow blocks of Z-3f. All betaines could be stored unchanged at least for a year under a dry atmosphere. They appear to be somewhat hygroscopic, as the broad O-H absorption bands in their IR spectra (≈3400-3500 cm −1 ) and the presence of hydrogen-bonded water molecules in the crystal structure of E-3e (vide infra) indicate.
The formation of betaines 3 includes the elimination of the N-phenyltriflamide anion, which is known as an excellent leaving group in transamidation reactions with nucleophilic amines [18,22]. Therefore, it was interesting to know the performance of propiolic acid chlorides in the same betaine syntheses. We found that acid chlorides 4 indeed underwent the threecomponent reaction with N,N'-dimethylbarbituric acid and furnished betaines 3b, 3j and 3k, respectively, with about the same E/Z ratios as in Figure 1 (Scheme 5). However, the products were obtained in low yield, because unidentified side-reactions occurred and purification was cumbersome. Thus, propiolic acid chlorides are not well suited for these three-component reactions.
We propose two mechanistic pathways for the synthesis of betaines 3 from N-triflylpropiolamides 1 (Scheme 6). Both of them begin with the conjugate addition of PPh 3 at the C-Ctriple bond, leading to the vinyl anion intermediate 5. On pathway A, 5 is protonated by the active methylene compound to furnish the vinylphosphonium ion 6. These two steps have been proposed earlier for the formation of related betaines from acetylenic ketones and esters (see Introduction). A replacement of Scheme 6: Two mechanistic scenarios for the formation of betaines 3. the N-phenyltriflamide group by the conjugate base of the active methylene compound followed by deprotonation of the CHXY group converts 6 into the final betaine 3.
On an alternative reaction pathway (path B in Scheme 6), the initial vinyl anion 5 could be split into a 3-phosphonio-substituted propadienone 7 and the N-phenyltriflamide anion. The latter is able to deprotonate the active methylene compound, the anion of which finally would add to the propadienone. This pathway is notable insofar as propadienones (methylene ketenes) are short-lived compounds which have been generated by flash vapor pyrolysis at high temperatures and characterized spectroscopically or by follow-up products [23]. Under synthetically more convenient conditions, some propadienones have been generated at subambient temperature from 2-bromoacryloyl chlorides by 1,2-elimination induced by the [Mn(CO) 5 ] − anion [24]. For both strategies, the intermediate formation of the cumulene was confirmed in favorable cases by the isolation of [2 + 2] cyclodimerization products (e.g., 3,3-diphenylpropadienone → 2,4-diphenylmethylenecyclobutane-1,3-dione [24]).
As we have not obtained so far an experimental evidence for the intermediate formation of cumulenes 7, pathway B is currently speculative but may suggest a novel approach to propadienones.
The presentation of 1,5-zwitterions 3 with the negative charge residing on a carbon atom is more or less a formal one. The structural and spectroscopic data (vide infra) support the view that the mesomeric enolate structure 3' (see Scheme 3) significantly contributes to the bonding state and that an even wider delocalization of the negative charge, represented by formula 3", does occur. Therefore, these zwitterions are better described as 1-phosphonium-5-oxabetaines than -5-carbabetaines. Furthermore, they represent a novel type of phosphonium enolate betaines and may be considered as vinylogues of recently reported acylphosphonium zwitterions [25].

Structural studies
The solid-state molecular structures of betaines E-3a, E-3b, E-3e and Z-3e were determined by single-crystal X-ray diffraction analysis and are shown in Figures 2-5. Some data charac-  terizing the bonding geometry of the P + -C1-C2-C3(-O)-C4 backbone are compiled in Table 1. For all molecules, the bond distances P-C1, C1-C2 and C2-C3 are in the typical ranges of the respective bond type and the values are more or less identical within the estimated standard deviations; exceptions can be seen, however, for E-3e vs Z-3e. On the other hand, the bond lengths C3-C4, C4-C5 and C3-O1 clearly indicate a partial double bond character, as can be expected when the negative charge is dispersed over the almost planar O-C3-C4-(X,Y) moiety (see formulae 3' and 3'' in Scheme 3). The NMR observation of magnetic non-equivalence of chemically equivalent atoms in the CXY fragment of some betaines (mainly those with X = Y = CN) also indicates that free rotation around the C3-C4 bond is slow on the NMR time scale around 295 K.
Notably, Z-3e does not undergo a 1,5-cyclization leading to a 5-methylene-2,2,2-triphenyl-2,5-dihydro-1,2λ 5 -oxaphosphole. Other studies have come to the conclusion, that the bonding situation in annelated oxaphospholes 8 (Scheme 7) is best described by the contribution of two canonical structures: an oxaphosphole 8A with a pentacovalent phosphorus atom and a P-O bond, and a betaine structure 8B with a phosphonium group and a P···O distance that varies with the electronic properties of the substituent R (Scheme 7) [26][27][28]. In Z-3e, the intramolecular P···O distance is 2.691 Å, significantly longer than in compounds 8 (2.00-2.36 Å), but still much shorter than the sum of the van der Waals radii (3.32 Å). A distance similar to that in Z-3e has been reported for a betaine III (Scheme 1) (PR 3 = PMe 2 Ph, R' = Ph, 2.597 and 2.620 Å in two symmetry-independent molecules [15]). Furthermore, the coordination around the phosphorus atom comes close to a trigonal-pyramidal geometry with the oxygen and the carbon atom C13 in apical positions: the angle O···P-C13 is 177.1° and the sum of bond angles involving atoms C1, C19 and C25 in the equatorial plane is 346.8 o (compared to 328.4° for an ideal tetrahedral coordina-  tion). All these data point to the description of Z-3e as a 1,5betaine with an attractive electrostatic interaction of phosphorus and oxygen. The 31 P NMR chemical shift (δ = 23.53 ppm) further confirms the presence of a tetracovalent phosphorus atom (see [28]).

NMR data of betaines 3
The 1 H, 13 C and 31 P data of the P-C3-C2-C1 chain in betaines 3 are listed in Table 2.
Based on the spectra of those betaines, for which the molecular geometry has been established by XRD analysis (vide supra), the stereochemistry at the P-substituted olefinic bond could be determined in all cases from characteristic chemical shifts of the olefinic proton and from 3 J(P,H) and 3 J(P,C) coupling constants. The olefinic proton signal of the E-isomers was found in the δ range 6.8-7.7 ppm, the signal of the Z-isomers at 7.9-8.4 ppm. In all cases where both diastereoisomers were available, the known relationship 3 J(P,H cis ) (in the E-isomer) < 3 J(P,H trans ) [29,30] -3l), the typical range being 23-27 ppm. As in other alkenes bearing a tetravalent phosphorus atom [29], the values of the E-isomers are always somewhat higher than those of the Z-isomers. Considering the question of an intramolecular P···O coordination in the Z-isomers (vide supra), the chemical shift values by themselves (compare: The signal of the P-C Ph (= C ipso ) nuclei can be distinguished reliably from the C-3 signal by the larger 1 J P,C coupling constant and its higher intensity. d Signal covered by other signals. e Not determined precisely, since one branch of the doublet signal is hidden. f An E:Z ratio between 54:46 and 60:40 was determined in different spectra of the E/Z mixture (CDCl 3 vs DMSO-d 6 , 1 H vs 31 P). Not all signals could be assigned reliably to one or the other isomer. The data presented here were assigned by analogy with the pure isomers of other E/Z pairs. g Z-3m was obtained only as the minor component in admixture with E-3m.

Conclusion
We have observed that the reaction of N-triflyl-N-phenylpropiolamides with triphenylphosphane results in undefined polymerization and formation of N-phenyltriflamide. In the presence of several active methylene compounds, however, a clean three-component reaction leads to a novel type of phosphonium betaines, which can formally be named 1,5-phosphoniumcarbabetaines, but because of the extended delocalization of the negative charge are better described as 1-phosphonium-5oxabetaines. The excellent leaving group character of the N-phenyltriflylamide anion ([N(Ph)SO 2 CF 3 ] − ) is a key factor in the reaction course, because analogous three-component reac-tions using propiolic acid esters as Michael acceptors are known to furnish another type of betaines in which the ester group (COOR) is retained. Questions on some mechanistic details, in particular at which stage of the reaction sequence the triflamide anion departs, remain to be answered.

Supporting Information
Supporting Information File 1 Experimental procedures, characterization data, NMR spectra ( 1 H, 13 C, 31 P, 19 F) and IR spectra for the synthesized compounds, and data for the X-ray crystal structure determinations.