Diastereoselective synthesis 3-alkoxy substituent

The threo stereoisomer was the major product obtained by the synthesis in Scheme 13.14. This stereochemistry was established by the conjugate addition in Step A, where a significant (4-6 1) diastereoselectivity was observed. The C(4)-C(7) stereochemical relationship was retained through the remainder of the synthesis. The other special features of this synthesis are in Steps B and C. The mercuric acetate-mediated cyclopropane ring opening was facilitated by the alkoxy substituent.19 The reduction by NaBH4 accomplished both demercuration and reduction of the aldehyde group. 

Changing the protecting group at O altered the ratio of products, particularly when a powerful Li-coordinating group (such as a carbamate) was introduced.121 Reasonable levels of diastereoselectivity could also be obtained from 141, with the alkoxy substituent in the 2-position.122 Diastereoselective bromine-lithium exchange of this sort has been employed in the synthesis of a segment of the bryostatins (section 9.7).123... 

Addition to imines. Effective synthesis of a-aminonitriles and of 3-amino acid derivatives from imines calls for the use of a Zr complex of 6,6 -dibromo-BINOL. Products containing an oxygen functionality at the a-position are similarly accessible, the diastereoselectivity of such a reaction can be controlled by choosing the proper a-alkoxy substituent in the nucleophiles. The TBSO substituent favors syn products whereas BnO derivatives give anti products selectively. 

A number of investigations have explored the reactions of ally lie stannanes containing a y-alkoxy substituent. A direct preparation of these substances utilizes the kinetic deprotonation of an allyl ether followed by alkylation with tri-n-butylstannyl chloride. In a typical experiment, the deprotonation of 101 with 5-butyllithium leads to internal coordination of lithium cation and provides formation of the Z-allylstannane 102. The behavior of y-alkoxyallylstannanes is similar to the corresponding Z-alkylstannanes, and as a result, the reaction provides a stereoselective route for the synthesis of complex diol derivatives. In the allylation of chiral aldehyde 80 with stannane 102, /l-chelation dictates face selectivity. The expected. yyn, anti-product 104 is obtained with high diastereoselection via the antiperi-planar 103, which accommodates the sterically demanding silyl (TBS) ether (Scheme 5.2.23).23... 

Similarly photocycloaddition of ethylene with chiral 5-alkoxyfuranones 181 proceeds with facial diastereoselection [153], Although selectivity remains low, the reaction has been used for the enantiospecihc synthesis of grandisol because it is easy to separate the initial diastereoisomers [154]. Selectivity is greatly influenced by temperature and by substituents on the ethylenic bond of the furanone ring. It was concluded that steric hindrance of the alkoxy group and stereoelectronic effects of substituents on the conjugated system are responsible for the selectivity observed. It was also proposed that the diastereoselection of the photocycloaddition of ethylene with 181 was dominated by the approach of ethylene to the vibrationally relaxed (71,71 ) excited furanone rather than by the selectivity of the reactions of biradicals. 

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