Imines allylations

Secondary allylic amines 184 have been prepared from aldehydes 181 (R1 = H, Me or Ph R2 = Me, Et or H) by the following sequence treatment with an amine R3NH2 (R3 = i-Pr, t-Bu, cyclohexyl or PhCH2) yields an imine 182, which is chlorinated by N-chlorosuccinimide. Dehydrochlorination of the resulting chloro compound with potassium t-butoxide gives an allylic imine 183, which is reduced to the product by means of methanolic sodium borohydride191. 

In previous work, Corey used the free base form of 34 as an effective chiral ligand in the Os04-promoted dihydroxylation of olefins [90]. He later found that ammonium salt 34 catalyzed the addition of HCN to aromatic N-allyl imines (Scheme 5.50) [91]. The U-shaped pocket of the catalyst is essential in fixing the orientation of the hydrogen-bonded activated aldimine via n-n interactions. 

In the presence of 42 (2mol% loading), aliphahc and aromafic N-allyl as well as N-benzyl aldimines were efficiently converted after 20 h at -70 °C in toluene to the respective Strecker adducts and subsequently trifluoroacetylated to obtain the products 1-10 in good to excellent yields (65-99%) and ee values J7-97%) (Scheme 6.41). It turned out that N-benzyl imines could be used as substrates without significant difference in comparison to analogous N-allyl imines (e.g., N-benzyl adduct 8 85% yield, 87% ee N-allyl adduct 9 88% yield, 86% ee Scheme 6.41). 

In addition, acyclic aliphatic N-allyl imines and cycloalkylimines were acceptable starting materials for the asymmetric hydrocyanation and enantioselectivity of up to 95% ee was obtained by use of 10a as catalyst [10]. Representative examples of the range of substrates are summarized in Scheme 5.6. It should be added that as an alternative to the N-allyl imines the analogous N-benzyl imines can be efficiently used as starting material [10]. An optimized procedure for preparation of the catalyst 10a has recently been reported by the Jacobsen group [11]. 

All the investigations that have been performed so far suffer from the fact that the deprotonation of the imines by strong bases gives metalation—after which an electrophilic reaction takes place on the less substituted a-carbon. Lithiation that does not depend on the degree of substitution on the a-carbon was developed by Wender and co workers3 9,40 using a,/ - unsaturated ketones 23 via 24, 25 and the lithium salt 26 (equation 7) or primary allyl imines via 29, 30 and the lithium salt 31 (equation 8). The products 27 and 32 are obtained after alkylation and hydrolysis. 

The metal-alcohol reduction of imines usually produces the reduced amine in good yield however, the reduction of some allylic imines (81, R = Pr",Bu") with Na-alcohol proceeds with hydrogenolysis to give alkene (82). ... 

Electro-deficient substrates afforded superior yields and rates as opposed to their electron-rich counterparts. In order to expand the diversity of allyl-imine substrates for this reaction, the olefin... 

The formal amine-mediated 4-i-4-cyclodimerization of benzyl or allyl imines (132) produced 2,6,9-triazabicyclo[3.3. l]nonanes (133) in good to excellent yields under mild conditions (Scheme 41). ... 

In 1998, Jacobsen reported an asymmetric metal-catalyzed Strecker reaction that employs aluminium salen complex 145 (Equation 20) [105], Interestingly, the salen(aluminum) complex 145 proved superior to a wide range of other salen(metal) complexes both in terms of conversion and of enantioselectivity. This constituted the first example of successful use of a main group salen(metal) catalyst for asymmetric synthesis. The N-allylated imine 144 was thus converted into the trifluoroacetyl derivative 146 in 91 % yield and 95 % ee. 

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Allylic phosphates are used for carbonylation in the presence of amines under pressure. Carbonylation of diethyl neryl phosphate (389) affords ethyl homonerate (390), maintaining the geometric integrity of the double bond[244]. The carbonylation of allyl phosphate in the presence of the imine 392 affords the /3-lactam 393. The reaction may be explained by the formation of the ketene 391 from the acyl phosphate, and its stereoselective (2 + 2] cycloaddition to the imine 392 to give the /3-lactam 393(247],... 

Trifluoromethyl-substituted 1,3-dipoles of the allyl type. Trifluoromethyl-substituted azomethine imines ate readily available on reaction of hexafluo-... 

Addition of Allylic Ylides and Related Reagents to Imines... 

The synthesis of vinylaziridines through reactions between allylic carbenoid reagents and imines (i.e., Darzen-type reactions) was first reported by Mauze in 1980 [13]. Treatment of aldimines or ketimines 16 with gem-chloro(methyl)allyllithium (17) afforded N-substituted vinylaziridines 18 (Scheme 2.6). Similarly, 2,3-trans-N-diphenylphosphinyl-2-vinylaziridines 21 were prepared with good stereoselectivities (trans cis= 10 1 Scheme 2.7) by treatment of a-bromoallyllithium (20) with N-diphenylphosphinyl aldimines 19 in the presence of zinc chloride [14]. 

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

The Stockman group has also studied reactions between the same imines and allyl sulfonium ylides (first reported by Hou and Dai [45]) [46], N-Sulfinyl vinylazir-... 

In contrast to ordinary chiral aldehydes (having no ability to be chelated), the reaction of 9-allyl-9-borabicyclo[3.3.1]nonane(allyl-9-BBN) with the corresponding chiral imines 4 produces the isomer syn-6 either exclusively or predominantly (Cram selectivity Table 8)5,6. The very high 1,2-asymmetric induction is explained by a six-membered. chair-like transition state, in which the inline R group occupies an axial position due to the stereoelectronic effect of imines (R CH = NR). 

The combination of metal tuning and double stereodifferentiation helps to prepare chelation and nonchelation products in the imine series7. In the case of an alkoxy substituent adjacent to the aldimino, the chelation product 10 is predominantly obtained with allylmagnesium chloride, chloromagnesium allyltriethylaluminate or allylzinc bromide, while the use of allyl-boronates or allyltitanium triisopropoxide, which lack the requisite Lewis acidity for chelation, gives 11 with good Cram selectivity. 

The reaction of allyl-9-BBN with the chiral imine 1 gives the Cram isomer 2 predominantly5,6. The 1,3-asymmetric induction is developed by a transition state 3, in which the 1,2-axial-equa-torial interaction between R and the ligand (L) plays an important role in the high chiral induction. 

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

Allylic silanes also add to imines, in the presence of TiCU, to give amines. ... 

Allylic phosphonate esters react with imines, in the presence of a palladium catalyst, to give P-lactams. " Alkynyl reagents such as BuC=CO Li react with imines to form P-lactams. 

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