Science of Synthesis

Friesen, R. W., Science of Synthesis, (2001) 1, 211.

Primary and secondary amines, including amino esters[‌372‌,‌373‌] and acylhydrazines,[‌374‌] react under palladium catalysis with a variety of allylic electrophiles including allylic acetates,[‌45‌,‌311‌,‌372‌,‌373‌,‌375‌–‌380‌] allylic chlorides,[‌45‌,‌365‌,‌377‌] allylic carbonates,[‌364‌] vinyl epoxides,[‌373‌,‌381‌,‌382‌] allylic phosphates,[‌383‌,‌384‌] and allylic nitro compounds.[‌385‌,‌386‌] In the case of primary amines, the competing formation of diallylated amines is sometimes problematic. In general, acyclic allylic electrophiles react in a regio- and stereoselective fashion at the less-substituted or sterically less encumbered end of the π-allylpalladium intermediate and afford E-isomers predominantly, regardless of the alkene geometry of the starting material. Allylic phosphates[‌383‌] and allylic chlorides[‌377‌] react faster than allylic acetates. Chloroacetate is a superior leaving group compared to acetate in certain cases.[‌387‌] Some of these general observations are illustrated in the conversion of (Z)-4-acetoxybut-2-enyl diethyl phosphate (‌454‌) into the (E)-allylic amine ‌455‌ (‌Scheme 109‌).[‌383‌] The aminations of chiral allylic electrophiles generally proceed with overall retention of configuration, both in acyclic[‌379‌] and cyclic[‌45‌,‌375‌,‌380‌] systems, with amines preferentially attacking the η3-allylpalladium intermediate trans to palladium. For example, the allylic acetate cis-‌205‌ reacts with diethylamine in the presence of a catalytic amount of tetrakis(triphenylphosphine)palladium(0) in tetrahydrofuran with poor retention of configuration to afford the allylic amines cis- and trans-‌456‌ in a ratio of 67:33, while the trans-‌205‌ isomer gives the same amines in a ratio of 35:65.[‌375‌] However, the inferior stereochemical outcome can be improved by manipulation of the reaction conditions and the electrophile because almost complete retention of configuration is observed using a polymer-supported catalyst[‌375‌] or by using the allylic chloride or trifluoroacetate derivatives of cis- and trans-‌205‌.[‌45‌] The loss of stereochemical integrity in the allylic amination reactions of allylic acetates is due to the palladium-catalyzed isomerization of both the starting material and the η3-allylpalladium intermediate rather than an internal cis transfer of a ligated amine.[‌45‌]

‌Meeeee 888‌ Meeeeee Meeeeeeee eeee Meeeeee eee Meeeeeeee Meeeee[‌888‌,‌888‌,‌888‌]

Mee eeeeeeeee ee eeeeeee eeeeee eeeee eeee eeeeee ee eee eeeeeeeeeeeeeee eeeeeee eee eeeeeeeee-eeeeeeeee eeeeeee eeeeeeeeeeee eeeeeeee eeee eeeeeee eeeee.[‌888‌] Meeeeee, 8,8′-eeeeeeeeeeeeeeeeeeeeeeee (‌888‌, MMMMM8) eeeeee ee ee eeeeeee eeeeeeeeee eeeeeee ee eeeeee eeee eeeeeee eeeeeeee eeee ee ‌888‌ ee eeeeeee eee eeeeeee (M)-eeeeeee eeeee ‌888‌ ee 88% eeeee ee eeeeeeee ee eeeee eeeeeee ee eee eeeeeeeeeeeee (8%) eee eeeeeeeeeee (88%) eeeeeeee.[‌888‌] Meee eeeeeeeeee eeee 88% eeeeee eeee ee 88°M eeeeeee eee eeeeeeeeeee eeeeeeeeee eeeee. Meeeee eeeeee, eeee ee eeeeeeeeeeee[‌888‌,‌888‌] eee eeeeeeeeeeeeeeee,[‌888‌,‌888‌–‌888‌] eee eeeeeeee ee eeeeeeee eee eeeeeeeeeeeeee eeeeeee eeeeeeeee eeeeeeeee.

Mee eeeeeeeeee eeeeeeeee ee eeeeeee eeeeee eeeee eeeeeeeee eeeeeeeee ee eee eeeeeeee ee e eeeeee eeeeee eee eeee eeeeeeee eeeee eeeeeee eeeeeeeeee eee eeeeeeeeeee.[‌8‌,‌888‌,‌888‌,‌888‌–‌888‌] Meeeeee eeeeee ‌888‌ eeeeeee eeee eeeeeee eeeeeeeeee ‌888‌ ee eeeee eee eeeeeeeeeeee η8-eeeeeeeeeeeeee eeeeeee ee eeeeeeeeeeeee eeeeeeeeeee eee ee eeeeeeee ee eeee eeeee eee eeeeeeeeeeee eeeeee (‌Meeeee 888‌). Meeeeee, eee eeeeeeeeeeee eeeeee eeeeeeee ee eeee eee eeeeeeeeee eeee eeeee M8 eeeeee (M8 = Me, eMe). Meeeeee eeeeeeeeee eeee ee ‌888‌ (M8 ≠ M8) eeee eee eeeeeeeeeee eeee eeee ee eeeeeeeeeeee ‌888‌ eee ‌888‌ eeeeeee ‌888‌ ee eeeee eeeeeeeeeeee eeeeee.[‌888‌]

‌Meeeee 888‌ Meeeeeeeee Meeeeee Meeeeeeee eeee Meeeeeeeeee[‌888‌,‌888‌–‌888‌]

‌Meeeeeeeeee 888‌

e Meeee ee ‌888‌/‌888‌.

Meeeeeeeeeee Meeeeeeee

(M)-M-[Mee(8-eeeeeeeeeeeee)eeeeee]eee-8-eeeeeeeee (‌888‌):[‌888‌]

Me e eeee ee eeeeeee ‌888‌ (888 ee, 8.88 eeee) ee MMM (8 eM) ee ee eee eeeee MMMMM8 (‌888‌; 888 ee, 8.88 eeee) eee Me(MMe8)8 (88 ee, 8 eee%) eee eee eeeeeee eee eeeeeee ee ee eee 8.8 e. Mee eeeeeee eee eeeeeee (Me8M), eeeeee (eee. ee MeMMM8), eee eeeee (MeMM8). Mee eeeeeeee eeee eeeeeee ee eeeee eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeee MMM ee eeee eee eeeeeee; eeeee: 888 ee (88%).

M-[(M)-8,8-Meeeeeeeeeeee]eeeeeeeeeee (‌888‌, M8 = M8 = Me); Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee eeeeee eeeeee ‌888‌ (88 ee, 8.888 eeee) eee Me8(eee)8•MMMe8 (88 ee, 8.888 eeee) ee eeeee MMM (8 eM) eee eeeeeee eeee eeeee eee eeeeeee ee ee eee 88 eee. Meeee (M)-8,8-eeeeeeeeeeeee eeeeeeeee (‌888‌, M8 = M8 = Me, M8 = MM8Me; 888 ee, 8.888 eeee) eee MeMM8 (88.8 ee, 8.888 eeee) eeee eeeee eee eee eeeeeee eee eeeeeee ee 88°M eee 88 e. Mee eeeeeee eee eeeeeee ee eeeee eee eee eeeeeee eee eeeeeeeee ee eeeeeeeeeee MMM (eeeeee eee, eeeeee/MeMMe 8:8) ee eeeeeee eee eeeeeee; eeeee: 888 ee (88%, 88 % ee).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8e, 888.
• 8.Meeeee-Meee, (8888) M 88-8, 888.
• 8.Meeeee-Meee, (8888) M 88e, 8888.
• 8.Meeeee-Meee, (8888) M 88e, 8888.