Garner’s aldehyde

Boland applied this methodology to Garner s aldehyde, and found the addition to be substrate-controlled rather than reagent-controlled (Scheme 9.13b) [68]. Viny-lepoxide 15 could thus also be obtained with high diastereoselectivity with achiral 9-MeO-9-BBN. 

Enantiopure a-amino aldehydes are valuable synthons in natural product synthesis [57]. However, problems are often encountered with their configurational instability [58]. Aziridine-2-carboxaldehydes are also a-amino aldehydes and accordingly have a potential synthetic value. We found that M-tritylaziridine-2-carboxaldehyde 56 is a perfectly stable compound and therefore comparable to Garner s aldehyde (ferf-butyl 2,2-dimethyl-4-(S)-formyl-oxazolidine-3-car-boxylate). Aldehyde 56 can readily be prepared from aziridine-2-carboxylic ester 12 by the sequence shown in Scheme 42 [59]. 

It should be noted that Baylis-Hillman reaction of Garner s aldehyde with methyl acrylate and DABCO results in racemization of the stereocenter of the amino aldehyde [61]. In the case of substrate 56 such racemization is seriously hampered due to the large inversion barrier in three-membered ring compounds [62]. 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

EDCI), the nitrogen and hydroxy] groups were protected as the N,0-acetal 123.3 by reaction of 1232 with 2 2-dimethoxylpropane in acetone in the presence of trifluoroborane e the rate. Finally, reduction of the N me thoxy amide with lithium aluminium hydride afforded Garner s aldehyde in 88% overall yield for the 4-step sequence. Epimerisation of the stereogenic centre is negligible under these conditions. 

A five-step chemical modification of 51 gives A,0-protected a-amino-a -hydroxy-ketone 54. Difluorination of the ketone 54 at the carbonyl carbon with morpho-DAST followed by conventional chemical modification results in the synthesis of P-amino-a,a-difluorocarboxylic acid 55 (see Scheme 9.13) [31]. Enantiomerically pure 5,5,5,5, 5, 5 -hexafluoroleucine 57 is efficiently synthesized from Garner s aldehyde 52 as shown in Scheme 9.14 [32]. Triphenylphosphine-induced reductive coupling of 52 with hexafluo-rothioacetone produces 56 in an excellent yield, which is conventionally transformed to... 

The addition of the 2-butenylchromium reagents to the a-amino aldehydes give predominantly the iyn isomer 245 independently of the nature of the group bonded to the nitrogen (Table 10-27) [146b]. Ohta has recently examined the addition of allyl chromium reagents to Garner s aldehyde [147]. Poor to moderate diastereoselectivity is observed in these reactions. 

Figures 5.7-5.9 were synthesized. Pen III (129) is a metabolite of Penicillium funiculosum isolated as a fruiting inducer against Schizophyllum commune. Its synthesis was carried out, as shown in Figure 5.7, employing Garner s aldehyde (D) as a starting material.13 The aldehyde D is not so unstable, and does not racemize easily. For the preparation of (-R)-hydroxy acid C, ( )-C was subjected to asymmetric acetylation with vinyl acetate in the presence of lipase PS.13...

Pen II (130) is another metabolite of P. fumiculosum, and also induces fruiting-body formation of S. commune. For the synthesis of the sphingadienine part C of 130, a new and simpler route was adopted, as shown in Figure 5.8.14 Garner s aldehyde I was employed in this case, too. 

Ceramide B (163) can be synthesized by connecting the sphingosine part A with the acyl part B. Preparation of B can be achieved as shown in Figure 6.25. It was an intermediate for the synthesis of type I epidermoside (162). The sphingosine part A is to be synthesized from Garner s aldehyde C and acetylene D. The problem was how to prepare both the enantiomers of l-alkyn-3-ol like D. 

The acetate CR)-F was then converted to D, which was coupled with Garner s aldehyde C to give G. The building block A was prepared from G, and coupled with acid B to furnish H. Global desilylation of H afforded ceramide B (163) with 6R-configuration. Similarly, by employing (S )- as an intermediate, (2S,3R,4E,6S)-16y was synthesized. 

A contribution to the synthesis of oxoindoles equipped with quaternary stereocenters of high stereochemical purity was made by Smith et al. [15] in 2009. Nitrones 31 derived from Garner s aldehyde cycloadd readily to ketenes 32, a process that intensifies its asymmetric induction with increasing size of the protecting group (PG). An initially proposed ionic addition to the quaternary carbon of the ketene was subsequently mled out through computational methods [16]. The weak N-O... 

Garner s aldehyde is a key building block in the synthesis of chiral natural products [66]. It can be converted, for example, into a chiral 2-amino-l,3-dihydroxypropyl substructure (Scheme 4.94). This motif can be found in numerous natural products, such as in some imino sugars, the antifungal antibiotic polyoxin J, sphingosine, or the cytotoxic sphingosine derivative pachastrissamine. 

Scheme 4.94 Conversion of Garner s aldehyde into biologically active compounds.

Garner s aldehyde (81) has been diastereoselectively hydrocyanated solvent and temperature effects and the use of Lewis acid or enzyme catalysts are described. 

Sudhakar, N., Ravi Kumar, A., Prabhakar, A., Jagadeesh, B., and Venkateswara Rao, B. (2005) The first synthesis of the anhydrophy-tosphingosine pachastrissamine (jaspine B) from Garner s aldehyde. Tetrahedron Lett., 46, 325-327. 

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