Metal catalyst-free substitution of allylic and propargylic phosphates with diarylmethyl anions

Abstract

Substitution of secondary allylic phosphates with the anions derived from Ar2CH2 with BuLi or LDA proceeded regioselectively and stereoselectively without a metal catalyst, affording inversion products in good yield. Similarly, propargylic phosphates gave propargylic products selectively.

SN2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

“…( S , E )‐5‐[( tert ‐Butyldimethylsilyl)oxy]pent‐3‐en‐2‐yl diethyl phosphate (17a): According to the general procedure for the phosphorylation of an alcohol, a mixture of alcohol 21a (97.9% ee , 291 mg, 1.34 mmol), diethyl chlorophosphate (0.290 mL, 2.02 mmol), and N ‐methylimidazole (0.190 mL, 2.41 mmol) in CH 2 Cl 2 (7 mL) was stirred at rt for 5 h to give phosphate 17a (413 mg, 87% yield): liquid; R f 0.41 (hexane/EtOAc, 1:1); [ α ] D 23 = –11 ( c = 1.04, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ = 0.06 (s, 6 H), 0.90 (s, 9 H), 1.31 (dt, J = 1.0, 6.4 Hz, 3 H), 1.32 (dt, J = 1.0, 6.4 Hz, 3 H), 1.41 (d, J = 6.4 Hz, 3 H), 4.03–4.14 (m, 4 H), 4.17 (d, J = 4.0 Hz, 2 H), 4.95 (ddq, J = 6.6, 6.0, 6.4 Hz, 1 H), 5.73 (ddt, J = 15.4, 6.0, 1.4 Hz, 1 H), 5.82 (dt, J = 15.4, 4.0 Hz, 1 H); 13 C NMR (100 MHz, CDCl 3 ) δ –5.3, 16.1 (d, J = 7 Hz), 18.4, 22.2 (d, J = 5 Hz), 25.9, 62.7, 63.5 (m), 75.2 (m), 129.5 (d, J = 5 Hz), 131.5. The 1 H and 13 C NMR spectra were identical with those reported …”

“…According to the general procedure for the phosphorylation of an alcohol, a mixture of the above alcohol (130 mg, 0.532 mmol), diethyl chlorophosphate (0.115 mL, 0.798 mmol), and N ‐methylimidazole (0.076 mL, 0.96 mmol) in CH 2 Cl 2 (5 mL) was stirred at rt for 3 h to produce 17c (140 mg, 69% yield): 96.5% ee by HPLC (Chiralpak IC, hexane/ i PrOH = 95:5, 1.0 mL/min, t R /min = 8.30 ( R ‐isomer, minor), 8.91 ( S ‐isomer, major): liquid; R f 0.26 (hexane/EtOAc, 4:1); [ α ] D 24 = –2 ( c = 1.37, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ = 0.06 (s, 6 H), 0.90 (s, 9 H), 0.91 (d, J = 6.8 Hz, 3 H), 0.93 (d, J = 6.8 Hz, 3 H), 1.29 (dt, J = 1.0, 7.2 Hz, 3 H), 1.32 (dt, J = 1.0, 7.2 Hz, 3 H), 1.92 (d of sept., J = 6.0, 6.8 Hz, 1 H), 4.00–4.15 (m, 4 H), 4.18 (dd, J = 4.2, 1.8 Hz, 2 H), 4.57 (dt, J = 6.0, 7.6 Hz, 1 H), 5.73 (ddt, J = 15.4, 7.6, 1.8 Hz, 1 H), 5.83 (dt, J = 15.4, 4.2 Hz, 1 H); 13 C NMR (100 MHz, CDCl 3 ) δ –5.3, 16.10 (d, J = 7 Hz), 16.14 (d, J = 7 Hz), 17.6, 18.0, 18.3, 25.9, 33.3 (d, J = 7 Hz), 62.7, 63.4 (d, J = 5 Hz), 84.0 (d, J = 6 Hz), 126.1 (d, J = 3 Hz), 133.8. The 1 H and 13 C NMR spectra were identical with those reported …”

“…The absolute configuration of 15a was confirmed by the consistency of the retention time of 16a (Scheme ) on the chiral HPLC column with that derived from enantioenriched alcohol 20 via 17a and 18a of the known stereochemistry (Scheme and Scheme ). The inversion of the configuration of diphenyl phosphate 14a by Ph 2 CHLi was thus established.…”

“…The regioselectivity of the allylic substitution was substituent‐dependent for the sterically more biased allylic phosphates 17b , c than the reported phosphate 17a (Scheme , footnote [a]). Consequently, the substitution reaction of alkyl phosphates 14a – c (Scheme ) was a better choice for the synthesis of sec ‐alkyl substituted diphenylmethane derivatives, as the substitution is independent of the regiochemistry.…”

Benzylic Methylene Functionalizations of Diarylmethanes

“…Direct functionalization of benzylic CÀ H bond of diaryl/ heteroarylmethane could be broadly achieved via three approaches viz., 1) deprotonation of diaryl/heteroaylmethane utilizing strong bases to produce a carbanion followed by a subsequent nucleophilic substitution or addition reaction [5] 2) transition-metal-catalyzed deprotonative cross-coupling processes (DCCP); [6] and 3) direct oxidative coupling reactions or radical pathway resulting in the formation of benzylic radical [7] (Scheme 1).…”