Triethylsiloxymethyl‐N,N‐dimethylamine, Et₃SiOCH₂NMe₂: A Dimethylaminomethylation (Mannich) Reagent for O–H, S–H, P–H and Aromatic C–H Systems

Abstract

Triethylsiloxymethylamine, Et3SiOCH2NMe2, readily synthesized in high yield by the hydrosilylation reaction between Et3SiH and DMF, is an excellent (N,N‐dimethylamino)methyl transfer agent to a representative range of aliphatic alcohols, thiols, and Ph2PH (E–H) materials. The reactions are almost instantaneous at room temperature in inert solvents and require no activating agents to produce E–CH2NMe2 products in high yields and illustrate the title compound as an excellent addition to the family of organic reagents. For aromatic alcohols, electrophilic substitution of the aromatic ring occurs in high yield. Crystal structures of new materials such as the cholestero–CH2NMe2 derivative, 2–4‐[bis(N,N‐dimethylamino)methyl]‐1‐naphthol, and the phosphine oxide derived from Ph2PCH2NMe2 are reported.

Aminomethylation of Aminoferrocene, [(η5-C5H5)Fe(η5-C5H4NH2)], and (Anilino)chromiumtricarbonyl, [(η6-C6H5NH2)Cr(CO)3], by O-Triethylsilyl-hemiaminal, (Et3SiOCH2NMe2): The Role of Disparate Organometallic Electronic Effects in Modifying Product Outcomes

“…The isolated O -silylhemiaminals, for example, Et 3 SiOCH 2 NMe 2 ( 1 ), have synthetic applications for aminomethyl transfer to a range of elements when reacted with protic species (E–H). Thus, facile aminomethylation of alcohols, thiols, phosphines, and amines can be achieved in high yields under mild, catalyst-free reaction conditions, as illustrated in eq . ,, Dixon and co-workers used the cyanation of in situ-generated O -silylhemiaminals to synthesize α-amino nitriles in excellent yields …”

Aminomethyl Transfer (Mannich) Reactions Between an O‐Triethylsilylated Hemiaminal and Anilines, RnC6H5−nNH2 Leading to New Diamines, Triamines, Imines, or 1,3,5‐Triazines Dependent upon Substituent R

“…We recently reported that Et 3 SiOCH 2 NMe 2 (1)i sahighly efficient Mannich reagent, with the ability to transform ar ange of RE-H species, E = O, S, N, P, to the corresponding dimethylamino derivatives, RE-CH 2 NMe 2 ,u nder mild conditionsa nd generally without the need for either ac atalyst or an activating coreagent. [1,2] In each case, Et 3 SiOH is formed whichi se asily removed under vacuum. In the case of the reaction of 1 with aniline the final product obtainedw as hexahydro-1,3,5-triphenyl-1,3,5-triazine,( PhNCH 2 ) 3 .H owever,u sing NMR spectroscopy we were able to observe the transience of the previously unreported triamine, (Me 2 NCH 2 ) 2 NPh and to trap and characterize its Mo(CO) 4 derivative.…”

“…We now report the use of this chemistry for reactions with substituted anilines,w ith R n C 6 H 5Àn NH 2 ,R = H, 4-CN, 4-NO 2 ,4 -Me, 4-Ph, 4-MeO,4 -Me 2 N; R 2 C 6 H 3 NH 2 ,R 2 = 3,5-(CH 3 ) 2 ,3 ,5-(CF 3 ) 2 ; R 3 C 6 H 2 NH 2 ,R 3 = 3,5-Me 2 -4-Br; and a" super-bulky" aniline Ar*NH 2 [Ar* = 2,6-bis(diphenylmethyl)-4-tert-butylphenyl]. [3] This group of amines range from significantly electron-rich to electron-poor materials, coupled with as pecific sterically demandingm aterial.…”

“…We recently reported that Et 3 SiOCH 2 NMe 2 ( 1 ) is a highly efficient Mannich reagent, with the ability to transform a range of RE‐H species, E=O, S, N, P, to the corresponding dimethylamino derivatives, RE‐CH 2 NMe 2 , under mild conditions and generally without the need for either a catalyst or an activating co‐reagent . In each case, Et 3 SiOH is formed which is easily removed under vacuum.…”