Imines diastereoselective additions

For diastereoselective addition of pcrfluoroalkyl lithium generated in situ to imines and %-alkoxy imines in the presence of BF, OEt2. see refs 13 and 14. 

For diastereoselective addition of organometallic agents to imines attached to arene tricar-bonylchromium or ferrocenyl moieties, see refs 26 28 and Section 1.4.1.1.2.2. 

Scheme 13 Diastereoselective addition of a-nitrocarbanions to chiral imines...

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

The diastereoselective addition to imines proceeds well with aromatic enolsi-lanes (249). Propiophenone- and tetralone-derived enolsilanes provide good levels of diastereoselectivity (>95 5) and excellent enantioselectivity (>98% ee) with selective formation of the anti diastereomer. Nonaromatic enolsilanes are somewhat less selective although cyclohexanone enolsilane still provides useful levels of diastereoselectivity and enantioselectivity (92 8 anti/syn and 88% ee at -78°C). A one-pot procedure using glyoxylate, sulfonamide, and enolsilane as coupling partners was developed subsequently, leading to the product in comparable yields and selectivities (250, 251). 

Although the diastereoselective addition of nucleophiles to imines offers an attractive route to chiral amine derivatives, most chiral nonracemic imines suffer from low reactivity (electrophilicity), resulting in no reaction or competitive reduction with organometallic reagents. Other problems include enolization of aliphatic imines, poor... 

Imines with an adjacent chiral auxiliary undergo diastereoselective addition of organometallic reagents in a similar fashion, as discussed above (equation 122)487. The products are readily converted into enantiomeric /J-amino alcohols, which are useful in further synthetic sequences or the target moiety in some natural products. Other such syntheses have been performed via additions to both imines488-490 and the related hydrazone moiety491-493. 

Scandium triflate catalyses a highly diastereoselective addition of imines to 1,1-cyclopropane diesters to give multi-substituted pyrrolidines.77... 

The use of stoichiometric amounts of sulfur ylides in the diastereoselective addition to imines has been recognized for a long time as a means of efficient synthesis... 

Aldimines can be trifluoromethylated at the imine carbon using Me3SiCF3 in dimethyl formamide at —20 °C, using a lithium carboxylate as catalyst.71 It is proposed that the carbon-silicon bond of the reagent is activated via formation of a lithium silicate bearing carboxylate and DMF ligands on silicon. A similar process has been used for diastereoselective addition to sulftnylimims.12... 

Herein, we describe highly enantioselective and diastereoselective additions of diorganozincs to aldehydes, imines, and enones. Enantioselective cyclo-propanation of allylic alcohols will also be mentioned. 

Table 1.2 Diastereoselective addition to N tert butanesulfinyl imines derived from aldehydes.

For diastereoselective addition reactions of trialkoxysilylalkynes to N tert butanesulfinyl imines, see Lettan, R.B. 

Diastereoselective Additions of Chiral Silyl Ketene Acetals to Imines... 

Diastereoselective Additions to Chiral Imines, Nitrones and 4-Acetoxyazetidin-2-ones... 

In the Held of chiral electrophiles, diastereoselective additions of enolsilanes to chiral a-fluoro-a-methyl-P-alkoxy aldehydes, a-methyl aldehydes, a-alkoxy aldehydes, a,p-dialkoxy aldehydes and a-methyl-P-alkoxy aldehydes were reported to proceed with good stereocontrol following Felkin-Anh or chelation models (c/. Section 2.4.4.1). Very good selectivities were reported in the addition of enolsilanes to chiral imines, particularly those derived from carbohydrates (Scheme 17 and 18).i. 6... 

Danishefsky prepared the furanophane 184 and converted it to hydropyrone 185 through a directed epoxidation with DMDO. Diastereoselective addition of methyllithium was followed by an acid catalyzed isomerization to the furanoside 186. Vinylogous aldol addition of a silyloxy furan to an imine gave 189 that was easily isomerized to the azacycle 190. Another general strategy to prepare pyran derivatives is a cycloaddition/fragmentation route involving an oxabicyclo[3.2.1]octane intermediate (Scheme 24). 

Silvani and coworkers have converted isatin to the chiral imines 94 and 97 that were employed as electrophiles for the diastereoselective addition of Grignard reagents [60]. As illustrated in Scheme 26, addition of allyl Grignard to 94 or 97 afforded the amino-substituted quaternary oxindoles 95 or 98 with good diastereos-electivity (80 20 and 89 11 dr, respectively). Grignard adducts 95 and 98 were further manipulated to afford the enantiomeric pair of 3-amino-3-allyloxindoles (5)-96 and (R)-99, respectively. 

Diastereoselective addition of organolithium reagents to imines which contain chiral auxiliaries gives chiral amines after the removal of the auxiliaries. Taka-... 

Kaboudin and Yokomatsu reported the diastereoselective addition of a-substituted a-amino-//-phosphinates 304 to imines catalyzed by Lewis acids. Among Lewis acids, Yb(OTf)3 was found to be the best catalyst. With this catalyst the a,a -diaminophosphinic derivatives 305 were obtained with des ranging from 10% to 95%. The structure of product 305 was determined by X-ray analysis as shown in Scheme 102. The reaction proceeded with retention of configuration at the phosphorus atom [200, 201]. 

Kaboudin B, Hamki T, Yamagishi T, Yokomatsu T (2007) Diastereoselective addition of a-substituted a-amino-H-phosphinates to imines using Yb(OTf)3 as an efficient Lewis acid catalyst. Tetrahedron 63 8199-8205... 

The first synthesis of an optically active a-aminophosphonic acid was reported by Gilmore and McBride [25], Diastereoselective addition of diethyl H-phosphonate to imine, derived from enantiomerically pure a-methylbenzylamine, furnished a-aminobenzylphos-phonic acid enantiomers. 

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