Alkynylation of imines

Although the CuBr/QUINAP system is an effective chiral catalyst in alkynylation of imines or iminiums, one drawback is that enantiopure QUINAP is quite expensive. An analog of QUINAP, PINAP (Figure 5.2), was readily synthesized and found as a very effective chiral ligand in the direct addition of alkynes to iminiums generated from aldehydes and secondary amines in situ (Scheme 5.8). ... 

Other Systems In contrast to the highly successful alkynylation of imines, copper catalysts failed in the asymmetric alkynylation of aldehydes. On the other hand, the combination of various Uewis acids and chiral amines were studied extensively to... 

Copper complexes of chiral Pybox (pyridine-2,6-bis(oxazoline))-type ligands have been found to catalyze the enantioselective alkynylation of imines [26]. Moreover, the resultant optically active propargylamines are important intermediates for the synthesis of a variety of nitrogen compounds [27], as well as being a common structural feature of many biologically active compounds and natural products. Portnoy prepared PS-supported chiral Pybox-copper complex 35 via a five-step solid-phase synthetic sequence [28]. Cu(l) complexes of the polymeric Pybox ligands were then used as catalysts for the asymmetric addition of phenylacetylene to imine 36, as shown in Scheme 3.11. tBu-Pybox gave the best enantioselectivity of 83% ee in the synthesis of 37. 

Although the Lewis basicity of the nitrogen atom of imines is weak, the bis-alkynyl complex Os(C2Ph)2(CO)(P Pr3)2 also coordinates benzophenone imine to give the six-coordinate bis-alkynyl complex Os(C2Ph)2(CO)(NH=CPh2)(PI Pr3)2,... 

Iwasawa and co-workers developed a facile method for the construction of polycyclic indole derivatives 190a and 190b by the tungsten(0)-catalyzed reaction of A-(2-(l-alkynyl)phenyl)imine 188 with the electron-rich alkenes 189a and 189b (Scheme 32).42b Photoirradiation of a mixture of imine 188 and ketene silyl acetal 189a with 10mol% of... 

Alkynyl azomethine ylides containing an aryl bridge have been shown to undergo cyclization. Thus, tautomerization of imine (137) afforded an azomethine ylide which cyclized to give two diastereomeric dihydropyrroles and traces of aromatized product (Scheme 42).56 The activated cyclic ylide (138), generated via the desilylation route, underwent cyclization to afford dihydropyrrole (139) in 42% yield.67b The structure of (139) is closely related to erythramine. The structurally related non-stabilized azomethine ylide (140) did not cyclize, tautomerizing to the corresponding enamine instead. 

Numerous alkynyl nitrile imines have been shown to undergo cyclization. Typical examples are the preparation of pyrazoles (177) and (178 Scheme 56).90-94... 

Intermolecular carbon-carbon bond formation of alkenylsilanes by electrophilic substitution is rather limited except for the reaction with acyl chlorides.1. The alkenylations of imines and epoxides are achieved with electronically activated alkenylsilanes (Equation (3)).2 a Alkynylsilanes have frequently been used for intermolecular alkynylation of carbon electrophiles activated by a Lewis acid.30 30a-30d... 

The chemistry of iron vinylidene complexes is dominated by the electrophilicity of the carbon atom adjacent to the iron organometallic unit. While addition of water leads to an acyl complex (i.e., the reverse of the dehydration shown in equation 10), addition of an alcohol leads to a vinyl ether complex. Similarly, other iron vinyl complexes can be prepared by the addition of thiolate, hydride, or an organocuprate (Scheme 33). " The nucleophilic addition of imines gave enaminoiron intermediates that could be further elaborated into cyclic aminocarbenes. This methodology has been used to provide access to /3-lactams and ultimately penicillin analogs, and good diastereoselectivities were observed (6 1-15 1) (Scheme 34). 04 Iso, vinylidene complexes are intermediates in cyclizations of alkynyl irons with substituted ketenes, acid chlorides, and related electrophiles an example is shown (equation 11). These cyclizations led to the formation of a series of isolable and characterizable cyclic vinyl iron complexes. 

Cycloaddition Reactions of Imines with Alkynyl Sulfides... 

Table 1.19 Copper catalyzed alkynylation of N aryl imines.

Reactions of imines. Silyl alkynyl ethers and aldimines undergo catalyzed condensation, the strained heterocycles that ensue open to afford conjugated amides. YbfOTfjj is also a useful catalyst for the reaction of organocuprates with N-sulfonylimines. ... 

Imines combine with electron-poor alkynes to form di and tri-substituted quinolines in good yields (Scheme 56). The reaction is catalyzed by iron trichloride but not by other metal hahde catalysts. A variety of imines were prepared and all of them reacted well with methyl propionate. The aryl groups on the imines can be electron-rich or electron-poor with no noticeable effect. While other alkynyl esters will react luider these conditions, only DMAD and ethyl propionate reacted with the similar yields to the methyl propionate (14T8971). 

C,A-Cyclic azomethine imines undergo an inverse-electron-demand 1,3-cycloaddition with electron-rich alkenes using a BINOL-derived diacid catalyst, excellent chemo- and enantio-selectivities have been reported. " Asynometric alkynylation of cyclic azomethine imines has been carried out using copper(I) and a chiral Brpnsted acid as catalysts. ... 

The N-tert-butyl imine cyclization strategy can also be applied to the synthesis of isoquinolines via non-oxidative addition/reductive ehmination processes. For example, it has been found that the ortho-alkynyl substituted imine 28 can undergo palladium-catalyzed cyclization in an analogous fashion to the ortho-alkynylanilines noted in Section 6.2.1. In this case, the extra carbon unit provides a synthesis of 2-substituted isoquinolines (Scheme 6.52) [71]. This cyclization can be coupled with the formation of 28 from imines and either TMS-substituted or terminal alkynes, providing access to a diverse range of substituted products with perfect regiocontrol. 

Treatment of imines and alkynyl selenides in the presence of Sc(OTf)3 caused the formation of a,P-unsaturated selenylimidates (Scheme 12.18) [34]. This reaction was assumed to proceed via [2 + 2] cycloaddition of the imines to the alkynyl selenides to form the corresponding azetine intermediates, which were unstable and immediately fragmented to the corresponding a,P-unsaturated selenylimidates. 

Ishitani H, Nagayama S, Kobayashi S. A new reaction of imines with alkynyl sulfides affording a,p-unsaturated thioi-midates./. Org. Chem. 1996 61 1902-1903. 

Ma Y, Qian C. [2+2] Cycloaddition reactions of imines with alkynyl selenides catalyzed by scandium triflate. Tetrahedron Lett. 2000 41 945-947. 

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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