Carbamate-protected imines

Scheme 7.51. Decomposition of silaaziridines derived from o ,/3-unsaturated imines or carbamate-protected imines.

Another pioneering study [16] by the Dixon group, published in 2006, involved the addition of malonates to carbamate-protected imines (Scheme 6.6). Using the cinchonine-derived thiourea catalyst 32, the Mannich-type products were obtained in good to excellent enantioselectivity and good yields. 

A new copper-catalyzed reaction involving imines, acid chlorides, and alkynes has been applied to the synthesis of propargyl amides 160 in a single operation by Arndtsen and co-workers. The same method allows the synthesis of N-carbamate-protected propargylamines [149]. a-Substituted amides 161 may also be prepared under palladium catalysis by substituting alkynes for vinyltin (Scheme 8.71) [150]. 

In 2005, Schaus and coworkers found that the natural cinchona alkaloids such as cinchonine (CN) or cinchonidine (CD) themselves can serve as highly enantioselective catalysts (10mol%) for the Mannich reaction of P-keto esters 57 with the various carbamate-protected aryl imines 58 [25]. Using either CN or CD, both enantiomers of the resulting secondary amine products 59 were obtained in excellent yields (up to 99%) and ee values (up to 96% ee) (Scheme 8.19). The extension of this protocol to encompass the use of the 2-substituted-l,3-dicarbonyl nucleophiles 60... 

DABCO, the reaction afforded the desired BH adducts in excellent enantioselectiv-ities and with good ElZ ratios [122]. A-carbamate protected a-amidosulfones was then used to generate imines in situ in the presence of KF, and efficient reactivity and excellent enantioselectivity were observed in this case [123]. 

Mannich Reaction Carbamate-protected alkyl imines are important building blocks in the synthesis of chiral alkyl amines. However, they are usually unstable, and most of them cannot be prepared in pure form. As the optimal substitutes, a-amido sulfones 142 were first used in the PTC-catalyzed enantioselective aza-Henry reaction in 2005 [57]. Subsequently, Song et al. reported a chiral Cinchona alkaloid thiourea (130b)-catalyzed Mannich reaction with in situ generation of... 

The only asymmetric synthesis of the Nuphar indolizidine to date is due to Barluenga and co-workers (615). Their route to the (5S,8 ,8aS)-( -) enantiomer of 944 commenced with cycloaddition between the proline-derived 2-amino-butadiene 957 and imine 958 (Scheme 125). Hydrolysis of the adduct 959 gave piperidinone 960 in 51% yield and an ee of better than 99%. Once the alcohol and amine groups had been mutually protected as the cyclic carbamate 961, defimctionalization of the ketone was accomplished via an enol triflate. Chain-extension of the deprotected piperidine 962 at the hydroxymethyl substituent afforded 963, which was cyclized to the bicyclic lactam 964 simply by heating in toluene. Reduction with lithium aluminum hydride completed the synthesis of ( - )-944 ([a]n -99°, c 1.3, CH2CI2). 

In one approach, an imine moiety was generated in situ by reaction of a methoxy carbamate with lithium diisopropylamide. This imine was then condensed with an ester enolate to give the amino-ester, protected as a carbamate. Reaction of 4,70 with lithium diisopropylamide gave imine 4.71, for example. Subsequent reaction with... 

Liu and coworkers reported in the same year a three-component allylation of in situ generated imines [100,101]. In this case, 5mol% of copper(II) triflate (Cu(OTf)2) was used as a catalyst furnishing the corresponding Cbz-protected homoallylic amines in good to excellent yields (75-95%) from an aldehyde, a carbamate, and an allyltrimethyl silane. 

---