Enantioselective condensation

Scheme 118 shows enantioselective condensation of alkanals and ni-tromethane promoted by a binaphthol-modified rare earth alkoxide in wet THF. Reaction of the initially formed metal /3-nitro alkoxide and acidic nitromethane, leading to the j8-nitro alcohol product and chiral metal nitronate, makes the C—C bond formation catalytic (284). 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

Aldol-type reactions comprise one of the most important classes of synthetic reactions. Although direct enantioselective condensation of aldehydes and unmodified ketones is not easy (280), it is highly desirable. A partly successful example is given in Scheme 115 (281). 

SCHEME 129. Enantioselective condensation of phenylacetic acid lithium enolate with benzalde-hyde and the proposed transition state model603... 

SCHEME 130. Enantioselective condensation of /-butyl propionate lithium enolate with various... 

SCHEME 131. Enantioselective condensation of a protected glycine lithium enolate on various aldehydes in presence of sparteine (Ref. 609)... 

SCHEME 134. Enantioselective condensation of a lithium ester enolate on an imine in the presence of a chiral diether618... 

Irradiation of the M-crystals caused solid-state photodecarboxylation, and then enantioselective condensation occurred, to give the optically active condensation product (S)-( —)-151 as the main product with [a] = —30 in 35% ee and in 37% chemical yield (Scheme 35). Conversely, irradiation of the P-crystals resulted in formation of the opposite handed condensation product (/ )-(+ )-151 with [a]r = +30 in 33% ee and in 38% chemical yield. For a comparison, solution phase photolysis of acridine 150 and diphenylacetic acid DPA in acetonitrile did not produce chiral product 151 but rather gave the achiral condensation product 153 in 74% as the major product at complete conversion of DPA. 

L-Serine by enantioselective condensation of glycine and formaldehyde Klebsiella aerogenes... 

Lewis add complexes formed by the reactions of various aminoalcohols with Et2AlG [778, 824] or by the reaction of Et2Zn with a chiral sulfamide [806] have displayed a low efficiency in the asymmetric condensations of ketene and thioketene silyiacetals derived from acetic acid with aldehydes. Disappointing se-lectivities have also been observed with some binaphtol-titanium complexes [778]. However, Mikami and Matsukawa [1296] recently performed the enantioselective condensation of various aldehydes with acetic acid derivatives in the presence of a chiral binaphtol-titanium complex. Good selectivities were observed when the reaction was performed at 0°C in toluene (Figure 6.95). Quaternary ammonium fluorides derived from cinchona alkaloids have been proposed as catalysts to perform additions of enoxysilanes derived from ketones to PhCHO, but the observed selectivities are modest [1303],... 

Early studies on KRP focused on the enantioselective condensation polymerization of an activated chiral diacyl donor (21) with achiral diols such as 22 (Scheme 11.6a) [29]. Lipases of different origin were tested and the formation of optically active trimers and pentamers was demonstrated for the dibromo monomer. The isolated oligomers were end capped with free hydroxy groups and showed small optical rotation values ([a]D25 +4.5 and +4.3 for the trimer and pentamer, respectively). Similarly, the condensation polymerization of achiral diacyl donors 23 with diastereomeric mixtures of chiral diols (24) was shown as well, affording optically active oligomers (Scheme 11.6b) [29]. 

Chiral triazines 292a-d have been found to be very efficient enantioselective condensing reagents (Scheme 56). Their application enables the synthesis of optically active products from racemic substrates with ee s exceeding 98% <2001ABP1143>. 

Scheme 7.39 Enantioselective condensation of thioester-derived ketene silyl acetals with aldehydes.

Among protic species, water is the most problematic for Cu(I)-conjugated Brpnsted base catalysts due to the instability of Cu(I)OH. Cu(I)OH is considered to decompose into insoluble and polymeric CU2O by dehydration [53]. In 2012, our group developed an enantioselective condensation between ketones and cyclic... 

Fig. 8 Copper(I)-catalyzed enantioselective condensation of ketones and cyclic hemiaminals...

Enantioselective condensation between the cycHc hemiaminal 1373 and 3,4-dimethoxybenzalacetone (1374) in the presence of a catalyst... 

---