Allyltitanates in Stereospecific Additions to Chiral δ-Lactol:  Efficient Enantioselective Route to a Potential Precursor of the C1−C9 Portion of Tylonolide

Abstract

The Hoppe reaction, which is an allylation reaction of aldehydes using an optically active titanated crotyl carbamate intermediate generated from the corresponding N,N-diisopropyl crotyl carbamate with n-BuLi/(-)-sparteine, was in most cases applied to achiral aldehydes. In this work an extension of this reaction is reported using a racemic γ-alkoxy allyltitanate ( 17) and an optically active aldehyde ( 16) to deliver in good yield the anti adduct 18 as the major isomer. When the corresponding δ-lactol 24 was used in place of aldehyde 16, the anti adduct 25 was obtained in 94% yield as the only product. Structural modifications effected on 25 delivered aldehyde 28 which was in turn submitted to a second allylation reaction in the presence of the optically active titanated crotyl carbamate 2, prepared as described by Hoppe from crotyl carbamate 1, to conduct to compound 29 in 80% yield. This derivative corresponds to a potential precursor of the C1-C9 portion of Tylonolide, aglycon of Tylosin (4).Allylation of aldehydes have been largely described in the literature for many years. 1 In most cases the diastereoselectivities obtained were fair to excellent, in an S E ′ Lewis-acid-catalyzed reaction 2,3 via an open transition state or via a Zimmerman-Traxler transition state in others cases. 4 The enantioselectivity in these reactions arise either from the allylmetal or the aldehyde, or from both enantiopure partners.

Alkynyliodonium Salts in Organic Synthesis. Dihydrofuran Formation via a Formal Stevens Shift of a Carbon Substituent within a Disubstituted-Carbon Oxonium Ylide

“…The substrates 1a − h examined in this study were all derived from 4-butynol ( 18 ), eq 3. Ethers 19a − e have been described, as have the alkynylstannanes 20a and 20c . The remaining ethers 19f − h were prepared by TsOH-catalyzed exchange between 18 and cis / trans 1-hydroxy-2-methyltetrahydropyran or 2-methoxy-1,3-dioxane, respectively.…”

Enantioselective Synthesis of a C1-C9 Moiety of Tylonolide, Tylosin Aglycon

“…For this observed and surprising increasing selectivity (7a/8a = 70:30 to 94: 6), it clearly appears that the yield of major compound 7a did not Downloaded by: NYU. Copyrighted material.…”

“…Final synthesis of the eastern C1-C9 part of tylonolide was achieved using the methodology developed in another approach. 6 The tertbutyldimethylsilyl ether 14b, prepared from 14a, was ozonolyzed into aldehyde 15 in 90% yield. Reaction of 15 with optically active titanated crotyl carbamate under the Hoppe's conditions 7,8 led to the expected C1-C9 fragment 16 9 in 80% yield.…”

ChemInform Abstract: Organometallic Chemistry. Part 2. Transition Metals in Organic Synthesis: Stoichiometric Applications

“…The resulting silazirconacyclopropanes react with acetylenes to give allyl or vinyl silanes, depending on the nature of the acetylene. For example, silazirconacyclopropane 13 (generated from Me 2 PhSiLi and Cp 2 ZrCl 2 ) reacts with diphenylacetylene (14) to give vinyl silane 16 but with hex-3-yne (17) to give allyl silane 19. The structures of the postulated intermediates (15 and 18 respectively) are supported by isolation of d 2 -16 and d 2 -19 on quenching with D 2 O, Scheme 5.…”

“…16 Reaction of racemic allyltitanates with enantiomerically enriched aldehydes allows a novel switch of chiral information in the Hoppe reaction. 17 TMS tri£ate promotes the addition of crotyltitanates to acetals. In some cases good diastereoselectivity is observed.…”