π‐Excess σ²P=C–N–Heterocycles: Catalytic P‐Arylation and Alkylation of N‐Alkyl‐1,3‐benzazaphospholes and Isolation of P,N‐Disubstituted Dihydrobenzaza­phosphole P‐Oxides

Abstract

2-Unsubstituted N-alkyl-1,3-benzazaphospholes, diagonally P-C related to 2,3-unsubstituted indoles, were successfully arylated by aryl iodides and bromides or alkylated by neopentyl iodide by heating in DMF in the presence of a catalytic amount of PdCl 2 or H 2 PtCl 6 and a suitable base. In contrast to the known 2-arylations of indoles under these conditions, the reactions led to arylation in the 3-position and proceeded via highly moisture-sensitive intermediates to P-substituted 1,3-benzazaphosphole P-oxides. Thus, we present a novel route for the direct P-substitution of aromatic σ 2 P-heterocycles with electrophilic aryl/alkyl halides. Characteristic [a] 1 1 (0.99), PhI (1.1); CsOAc (1.97) PdCl 2 (0.5); 125; 18 3 (98) 2 1 (0.51), PhI (0.54);-PdCl 2 (0.5); 125; 18 1 (75); 3a (25) 3 1 (0.51), PhI (0.54);-PdCl 2 (0.5); 20; 18 1 (90); 3a (3) and imp. 4 1 (0.99), PhI (1.1); CsOAc (1.97) -; 20; 18 no conversion of 1 5 1 (0.99), PhI (1.1); CsOAc (1.97) -,125; 18 1 (90); 2a (1); 3a (9) 6 1 (0.99), PhI (1.1); CsOAc (1.97) -; 125; 48 1 (20); 2a (10); 3a (70) 7 1 (0.93), PhI (0.98); KOH (1.86) PdCl 2 (0.5); 125; 18 1 (7); 2a (27); 3a (66); [1 (5); 2a/2aЈ (32:13); 3a (50)] 8 1 (0.49), PhI (0.54); Cs 2 CO 3 (0.98) PdCl 2 (0.5); 125; 18 [1 (32); 2a/2aЈ (46:5); 3a (10); imp.] 9 1 (0.54), PhI (0.63); K 2 CO 3 (1.07) PdCl 2 (0.5); 125; 18 2a (60); 3a (15); imp.; [2a/2aЈ (65:12); 3a (16); imp.] 10 1 (0.49), PhI (0.54); Na 2 HPO 4 ·12 H 2 O (0.97) PdCl 2 (0.5); 125; 18 1 (15); 3a (85) 11 1 (1.10), PhI (1.61); CsOAc (2.20) H 2 PtCl 6 (1.0); 125; 18 2a (2); 3a (98) 12 1 (1.10), PhI (1.61); -H 2 PtCl 6 ·xH 2 O(1.0); 125; 18 1 (68); 3a (32) 13 1 (0.73), PhI (0.80); CsOAc (1.46) CuI (1.0); 125; 18 1 (48); 2a (9); 3a (43) 14 1 (0.73), PhI (1.07); CsOAc (1.46) Pt(PPh 3 ) 4 (1.0); 125; 18 3a (95) [b] 15 4 (2.08), PhI (2.15); CsOAc (2.08) Pd(PPh 3 ) 4 (1.0); 20; 18 no conversion of 4 16 4 (2.08), PhI (2.15); CsOAc (2.08) Pd(PPh 3 ) 4 (1.0); 60; 20 4 (19); 5/5Ј (10:9); 6 (62) 17 4 (2.08), PhI (2.15); CsOAc (2.08) Pd(PPh 3 ) 4 (1.0); 125; 18 4 (15); 5/5Ј (6:5); 6 (65); (5) [c] 18 1 (1.07), pyr-2-Br (1.13); CsOAc (2.14) PdCl 2 (0.5); 125; 18 2b (12:5); 3b (83) 19 1 (1.95), pyr-2-Br (2.06); [d] CsOAc (3.90) PdCl 2 (0.5); 125; 18 2b (15); 3b (85) [d] 20 1 (1.01), pyr-2-Br (1.13); CsOAc (2.02) CuI (2.0); 125; 18 1 (94); 3b (6) [a] Solvent DMF except for entry 19 (see footnote [d]); product ratios by 1 H integral ratios; values in brackets refer to 31 P integral ratios; differences may be caused by superimposed proton signals or insufficient relaxation of some P signals; imp.: impurities. [b] 31 P trace signal at δ = 47 ppm. [c] The small phosphorus resonance δ = 75.4 ppm (5 % int.) hints at minimal 2-phenylation (cf. ref. [12] ); unidentified trace signals at δ = 25.9 and 26.6 ppm. [d] This reaction was performed in DMA instead of DMF.

Synthesis of N,P‐Disecondary o‐Arylphosphanylanilines via o‐R1NHC6H4P(R)O2Et Precursors and Preliminary Study of Cyclocondensations with (EtO)3CH/NH4PF6

“…The three P‐C q doublets of the intermediate 5b appear significantly upfield from those of 6b· x HPF 6 , as is typical for phosphonium compounds compared to related phosphine oxides (cf. Table S1), and confirm the 3‐ethoxy‐1,3‐benzazaphospholinium structure of 5b , suggested by the aforementioned similarity of the phosphorus resonance δ = 73.4 to the chemical shift values of R 3 P + OR species , , . The N‐ethylation to the syn ‐ and anti ‐stereoisomers of 7c was concluded from the downfield shifted N + Me, N + CH 2 and N + CH 2 P proton and 13 C resonances, typical for quaternary alkylammonium salts, and the upfield CH 3 (Et) 13 C signals at δ = 9–9.5 (cf.…”

“…The different 2 J PH coupling constants of the PCH a H b proton signals of the latter reflect the cis ‐ (larger) and trans ‐orientation towards the O‐atom of the P=O group . The 13 C and 31 P data of 6a , b· x HPF 6 are similar to those of neutral P‐oxo‐1,3‐benzazaphospholines 6a , b (Δ δ ≤ 2) and 6 Bn , Ph . The three P‐C q doublets of the intermediate 5b appear significantly upfield from those of 6b· x HPF 6 , as is typical for phosphonium compounds compared to related phosphine oxides (cf.…”

“…In addition, a substantial amount of (EtO) 3 PO and various minor or trace products were detected. 5b exhibits a downfield 31 P resonance at δ = 73, lying close to that of the zwitterionic P ‐F 3 B – O‐substituted P ‐ethyl‐benzazaphospholium compound ( δ = 71.5), formed from moisture and II (R = Et, R 1 = CH 2 CMe 3 ), close to the 86 ppm signal observed in the reaction of 2a , and between the P resonances of Ph 3 POEt + BF 4 – ( δ = 62) and n Bu 3 POEt + BF 4 – ( δ = 98), a range that is often observed for C 3 PX + species (X = OR etc.) .…”

“…The origin of TEP was not studied in detail, but formation by H + ‐catalyzed reaction of PF 6 – with EtOH is probable since solutions of 5b / 6b· x HPF 6 in MeOH display in the ESI‐HRMS spectra peaks for [(MeO) 3 PO + H/Na + ] beside the somewhat stronger peaks for [(EtO) 3 PO + H/Na + ]. This reaction, together with PF 6 ‐salt formation of side products, caused a decreasing content x of HPF 6 in 6a , b· x HPF 6 during workup and furnished in late fractions of column chromatographic separations small amounts of HPF 6 ‐free 6a and 6b , already obtained by us using catalytic P‐alkylation or arylation of 1 H ‐1,3‐benzazaphospholes …”

“…N , N′ ‐Disubstituted benzimidazolium salts I are well known compounds and highly useful precursors for benzanellated N‐heterocyclic carbenes (bNHC) and transition metal complexes or catalysts with bNHC ligands , . The homologous 1,3‐benzazaphospholium salts II (R = Et, R 1 = Me, neopentyl), however, have scarcely been investigated, and benzodiphospholium salts are known only as semi‐ylide salts III (R = Me, Ph, X = Br, PF 6 ) with pentavalent phosphorus (Scheme ). Both II and III react readily with water to form phosphine oxides IV (R 2 = H) [3] and ring‐opened products, respectively, with cleavage at the ylidic PCP bridge.…”