Acyclic diastereoselection

Few examples exist in the literature concerning the stereoselective addition of acyl radicals to a radical acceptor in an acyclic manner. Equation (13.1) shows the efficient 1,2-asymmetric induction in the addition of aliphatic or aromatic acyl radicals to chiral acyclic alkenes 1 [7]. The corresponding a-hydroxy ketones 3 were produced with high syn selectivity (Table 13-1). This acyl radical addition is very exothermic, and it is hypothesized that Hammond s postulate can be invoked to predict a transition state that is very close in energy to the starting alkene 1. The X-ray structure of 1 was then used to rationalize the stereochemical outcome of this radical addition by determination of the least sterically hindered path for the approaching radical. 

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In contrast to the 2-butenylboranes, 2-butcnylboronates have found widespread application in acyclic diastereoselective synthesis owing to their ease of preparation (Section 1.3.3.3.3.1.1.), configurational stability and highly stereoselective reactions with aldehydes3 4. The results of reactions of substituted allylboronates and representative achiral aldehydes are summarized in Table 1. 

The reactions of allylboronates 1 (R = H or CH3) may proceed either by way of transition state 3, in which the a-substituent X adopts an axial position, or 4 in which X occupies an equatorial position. These two pathways are easily distinguished since 3 provides 7 with a Z-olefin, whereas 4 provides 8 with an E-olefinic linkage. There is also a second fundamental stereochemical difference between these two transition states 7 and 8 are heterochirally related from reactions in which 1 is not racemic. That is, 7 and 8 arc enantiomers once the stereochemistry-associated with the double bond is destroyed. Thus, the selectivity for reaction by way of 3 in preference to 4, or via 6 in preference to 5 in reactions of a-subsliluted (Z)-2-butenylboronate 2, is an important factor that determines the suitability of these reagents for applications in enantioselective or acyclic diastereoselective synthesis. 

Temporary bridges and auxiliary rings as control elements in acyclic diastereoselection... 

Particularly useful is the introduction of a sulphur atom as bridging element. One of the most classical examples, in which the sulphur atom introduces the necessary "rigidity" in order to ensure a complete acyclic diastereoselection of polyolefins, is the synthesis of the Cig-juvenile hormone [1] (Scheme 9.1). 

The synthesis of aldehyde 48 proceeds in 16 steps from (S)-39 in 15% yield and 75% stereoselectivity. The brevity, efficiency, and selectivity of this synthesis rivals alternative acyclic diastereoselective approaches to the rifamycin ansa chain, (see footnote 4 in reference 3i), thereby providing a clear testimony to the potential of the tartrate allylboronates as reagents for complex synthetic problems. 

For a general review of acyclic diastereoselective synthesis, see Bartlett, P. A. Tetrahedron - 960, 36, 2. 

Thiazole-aldehyde synthesis Preparation of aldehydes from C-2 substituted thiazoles by thiazolyl-to-formyl conversion, see A. Dondoni, Carbohydrate synthesis via thiazoles, in Modem Synthetic Methods, R. Scheffold, ed., Verlag Helvetica Chimica Acta, Basel, 1992, p. 377 A. Dondoni, Acyclic diastereoselective synthesis using functionalized thiazoles. Routes to carbohydrates and related natural products, in New Aspects of Organic Chemistry, Z. Yoshida and Y. Ohshiro, eds., Kodansha, Tokyo, and VCH, Weinhcim, 1992, p. 105. 

Acyclic diastereoselective hydroboration,J Hydroboration-oxidation of terminal alkenes substituted at C4 by a large and a medium alkyl group can proceed asymmetrically with BH3 S(CH,)2 or, even more selectively, with thexylborane. Example ... 

A special class of acyclic diastereoselective reactions involves the use of chiral auxiliaries to control the absolute stereochemistry of nucleophilic additions at carbonyl centers. This process takes advantage of steric and/or electronic factors within the chiral adjuvant to promote nucleophilic addition from one face of the molecule, and thereby generate one predictable diastereomer. Removal of the auxiliary, in the best cases, generates enantiomerically pure products, as well as the recyclable chiral adjuvant. The end result of this process is the synthesis of enantiomerically pure products via diastereoselective reactions. 

For lithium enolate anions, the tendency is for the enolate to occupy the concave face of the transition structure cf. Figure 6.4d and 6.5c) and therefore to prefer transition structures such as those illustrated in Figure 6.6b and c. Table 6.2 lists several examples of simple acyclic diastereoselection, which show a tendency for E -> syn and Z —> anti selectivity, in contrast to the tendency observed for hydrocarbon substituted carbanions (Table 6.1). Entries 1 and 2 involve dianions of crotyloxy acetates, and show E -> syn and Z —> anti selectivity. A more complex example involving extension of a steroid side chain (similar to Scheme 6.6a), is 100% anti selective from an -alkene, however [53]. 

Selectivity during epoxidation reactions is of paramount importance in synthesis. Consequently, comparison of the Ti -Bu OOH method with m-chloro-perbenzoic acid for alkoxy-olefins shows that high acyclic diastereoselection is... 

Burke, S. D., W. F. Fobare, and G. J. Pacofsky Chelation control of enolate geometry. Acyclic diastereoselection via the enolate Claisen rearrangement. J. Organ. Chem. (USA) 48, 5221 (1983). 

Six-membered Rings Five-membered Rings Stereocontrol in Cyclic Systems Acyclic Diastereoselection Biomimetic Synthesis... 

Five-membered Rings Olefin Synthesis Acyclic Diastereoselection... 

The erythromycins are examples of polypropionates , natural products biosynthetically derived largely from propionic acid units via a series of condensation reactions. Many natural products, broadly called polyketides, share this biosynthetic origin. These compounds are decorated with multiple stere-ogenic centers, and acyclic diastereoselection problems that are much more complex than the terpenoid sidechain stereochemistry problem will surface with erythromycin, including the problem of asymmetric synthesis. 

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