Catalytic asymmetric addition

Dai X, Nikkei T, Romero JAC, Fu GC (2007) Enantioselective synthesis of protected amines by the catalytic asymmetric addition of hydrologic acid to ketenes. Angew Chem Int Ed 46 4367 369... 

In 1999, Shi el al. showed that a diphenylthiophosphoramide derived from (li ,2i )-l,2-diaminocyclohexane could be used as a ligand in the catalytic asymmetric addition of ZnEt2 to aldehydes in the presence of Ti(Oi-Pr)4, providing the corresponding alcohols in enantioselectivities of 40-50% ee (Scheme 3.20). Another class of new ligands such as the phenylthio-phosphoramide of (7 )-1,1 -binaphthyl-2,2 -diamine was developed by the same group, and further tested as a ligand in the same conditions (Scheme 3.20). ... 

Yamakoshi, K., Harwood, S.J., Kanai, M., and Shibasaki, M., Catalytic asymmetric addition of diphenylphosphine oxide to cyclic imines, Tetrahedron Lett., 40, 2565, 1999. 

Vinylsilane to copper transmetallation has entered the literature,93 93a,93b and a system suitable for catalytic asymmetric addition of vinylsilanes to aldehydes was developed (Scheme 24).94 A copper(l) fluoride or alkoxide is necessary to initiate transmetallation, and the work employs a copper(ll) fluoride salt as a pre-catalyst, presumably reduced in situ by excess phosphine ligand. The use of a bis-phosphine was found crucial for reactivity of the vinylcopper species, which ordinarily would not be regarded as good nucleophiles for addition to aldehydes. The highly tailored 5,5 -bis(di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino-4,4 -bis(benzodioxolyl) (DTBM-SEGPHOS) (see Scheme 24) was found to provide the best results, and the use of alkoxysilanes is required. Functional group tolerance has not been adequately addressed, but the method does appear encouraging as a way to activate vinylsilanes for use as nucleophiles. 

CATALYTIC ASYMMETRIC ADDITIONS OF DIALKYLZINC TO KETONES ENANTIOSELECTIVE FORMATION OF TERTIARY ALCOHOLS... 

The catalytic asymmetric preparation of a-chiral amines, by addition of organo-metallic reagents to C=N bonds, is one of the most important reactions in homogeneous catalysis [26]. However, the catalytic asymmetric addition of simple alkylmetals has been achieved only in recent years. 

Use of proline as a catalyst has become an important methodology in the catalytic asymmetric addition of stabilized carbanions to conjugated carbonyl compounds. Hannessian employed L-proline (S)-l in the addition of nitroalkanes to enones (Scheme 1) [5]. In the presence of 3-7 mol % of (S)-l and an excess of trans-2,5-dimethylpiperazine in chloroform, comparable or higher enantiose-lectivities were attained compared to the Yamaguchi s method using L-proline... 

The bifunctional mechanism proposed for the Ti-catalyzed Strecker suggests that electrophiles other than amines can be induced to undergo catalytic asymmetric additions with cyanide. The details of the optimal conditions (exactly what ligand structure, metal salt, solvent, and any needed additives) would however have to be identified through screening of parallel libraries as mentioned above. In this fashion, we have been able to develop an Al-catalyzed asymmetric... 

The addition of hydrogen cyanide to a carbonyl group results in the formation of an a-hydroxy nitrile, a so-called cyanohydrin (A, Scheme 6.1) [1]. Compounds of this type have in many instances served as intermediates in the synthesis of, e.g., a-hydroxy acids B, a-hydroxy aldehydes C, fS-amino alcohols D, or a-hydroxy ketones E (Scheme 6.1) [1], In all these secondary transformations of the cyanohydrins A, the stereocenter originally introduced by HCN addition is preserved. Consequently, the catalytic asymmetric addition of HCN to aldehydes and ketones is a synthetically very valuable transformation. Besides addition of HCN, this chapter also covers the addition of trimethylsilyl cyanide and cyanoformate to car-... 

High reactivity was observed for 21b, and 21a was found to be the most selective. In the presence of 10 mol% 21a selectivity factors as high as 6.5 were observed with racemic 1-(1-naphthyl)ethanol as substrate (Scheme 12.6) [18]. The TBS analog of 21a was found to be good catalyst for asymmetric addition of methanol to a variety of prochiral aryl alkyl ketenes [18]. The catalytic asymmetric addition of achiral alcohols to prochiral ketenes is discussed in Section 13.2. 

The alkaloid-catalyzed addition of alcohols to prochiral ketenes is one of the very first examples of catalytic asymmetric synthesis. In pioneering work by Pracejus in the 1960s quite remarkable 76% ee was achieved and it was not until 1999 that substantial improvement of enantioselectivity in catalytic asymmetric addition of O- and N-nucleophiles to prochiral ketenes was reported. In particular, the chiral... 

Recent advances in catalytic asymmetric addition to imines and other C=N systems have been reviewed.68... 

Catalytic asymmetric addition of functionalized alkylzincs to ketones and enones has been reported.238 Functional groups include esters, silyl ethers, alkyl chlorides, and alkyl bromides, with ees >99% in some cases. 

The first catalytic asymmetric addition of functionalized organozinc reagents to ketones has been reported.107 These investigations indicated that catalyst (40) is tol- erant to a variety of functionalized zinc reagents and enantioselectivities generally exceed 90%. 

Reagents of this type are suitable for performing catalytic asymmetric additions to aldehydes. For example, an enantiomerically pure Lewis acid is generated in situ from Ti(OiPr)4 and the enantiomerically pure bis(sulfonamide) C. It catalyzes the enantioselective addition of functionalized (or unfunctionalized) dialkylzinc compounds to widely variable aldehydes. There is no detailed, substantiated rationalization of the underlying addition mechanism in this case. 

Fig. 10.40. Catalytic asymmetric addition of Et2Zn to Ph— C(=0)H. Chiral amplification through a mutual kinetic resolution of the (auxiliary/ZnEt)2 complex which is produced from two molecules of chiral aminoalcohol and diethylzinc each.

A different method for the catalytic asymmetric addition of a dialkylzinc compound—Et2Zn and aromatic aldehydes have almost always been used—is shown in Figure 8.31. With regard to stereoselective synthesis, this method has an importance... 

Table 1 Catalytic asymmetric addition of diethylzinc to cyclohexenone in the presence of 1-23...

Habermas KL, Denmark SE, Jones TK (1994) Qrg React 45 1-158 Hagiwara E, Fujii A, Sodeoka M (1998) J Am Chem Soc 120 2474 Hamashima Y, Sasamoto N, Hotta D, Somei H, Umebayashi N, Sodeoka M (2005) Catalytic asymmetric addition of beta-ketoesters to various imines by using chiral palladium complexes. Angew Chem Int Ed Engl 44 1525-1529... 

Allylation of Aldehydes. Synthesis of enantiomerically pure allyl alcohols can be accomplished by catalytic asymmetric addition of divinylzinc to aldehydes using a camphorsulfonic acid-derived catalyst (eq 22). ... 

Scheme 1.17 Initial reports of the catalytic asymmetric addition of organometallic reagents to achiral aldimines.

Table 1.4 Catalytic asymmetric addition to N tosyl imines R sZn...

Table 1.6 Selected examples of catalytic asymmetric addition of diorganozinc reagents to N phosphinoyl imines.

---