Flexible Synthesis of Enantiomerically Pure 2,8-Dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-Dialkyl-1,6-dioxaspiro[4.5]decanes from Propargylic and Homopropargylic Alcohols

Abstract

A new approach to enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro[4.5]decanes is described and utilizes enantiomerically pure homopropargylic alcohols obtained from lithium acetylide opening of enantiomerically pure epoxides, which are, in turn, acquired by hydrolytic kinetic resolution of the corresponding racemic epoxides. Alkyne carboxylation and conversion to the Weinreb amide may be followed by triple-bond manipulation prior to reaction with a second alkynyllithium derived from a homo- or propargylic alcohol. In this way, the two ring components of the spiroacetal are individually constructed, with deprotection and cyclization affording the spiroacetal. The procedure is illustrated by acquisition of (2S,5R,7S) and (2R,5R,7S)-2-n-butyl-7-methyl-1,6-dioxaspiro[4.5]-decanes (1), (2S,6R,8S)-2-methyl-8-n-pentyl-1,7-dioxaspiro[5.5]undecane (2), and (2S,6R,8S)-2-methyl-8-n-propyl-1,7-dioxaspiro[5.5]undecane (3). The widely distributed insect component, (2S,6R,8S)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (4), was acquired by linking two identical alkyne precursors via ethyl formate. In addition, [(2)H(4)]-regioisomers, 10,10,11,11-[(2)H(4)] and 4,4,5,5-[(2)H(4)] of 3 and 4,4,5,5-[(2)H(4)]-4, were acquired by triple-bond deuteration, using deuterium gas and Wilkinson's catalyst. This alkyne-based approach is, in principle, applicable to more complex spiroacetal systems not only by use of more elaborate alkynes but also by triple-bond functionalization during the general sequence.

Biosynthesis of the Spiroacetal Suite in Bactrocera tryoni

“…[10] Addition of deprotonated alkyne 12 [12] to heptanal or octanal afforded propargylic alcohols 13 and 14, respectively, in good yields (Scheme 5). Introduction of the necessary deuterium labelling was achieved by palladium-catalysed reduction of the triple bond with deuterium gas.…”

“…A small 1:1:1 triplet was observed as part of the signal for both C3 carbons, clearly indicating deuterium incorporation at C3. This unavoidable scrambling of the deuterium label, which was observed in all palladium-catalysed reductions of triple bonds, [12] produces a mixture of selectively [13] deuterium-labelled compounds that can contain up to six deuterium atoms. Thus, in the interests of simplicity, mixtures of deuterium-labelled products are represented by the predominant product without positioning .…”

The Shortest (Four‐Step) Total Synthesis of the Eight‐Membered Cyclic Ether (rac)‐ and (–)‐cis‐Lauthisan

“…The synthesis of key unsaturated hydroxy ketone 8 began with ring opening9 of oxirane (±)‐ 13 with the lithium acetylide–ethylenediamine (EDA) complex ( 12 ) to provide carbinol (±)‐ 11 in 92 % yield (Scheme ). Conjugate addition of homopropargylic alcohol 11 to ethyl vinyl ketone ( 10 ) was accomplished by using Rh(acac)(CO) 2 (acac = acetylacetonate) as the catalyst and tri( o ‐methoxyphenyl)phosphane as the ligand10 (THF, 90 °C, 4 h) to give alkyne (±)‐ 9 containing the entire carbon skeleton of (±)‐ cis ‐lauthisan in 75 % yield.…”

Palladium(0)‐Catalyzed Suzuki—Miyaura Cross‐Coupling Reactions of Potassium Aryl‐ and Heteroaryltrifluoroborates with Alkenyl Bromides.

“…13 C NMR (CDCl 3 , 75 MHz) δ 80.2, 62.5, 37.7, 31.8, 25.9, 24.7, 19.5, 18.3, -5. 3 (Z)-(6-Bromo-hex-5-enyloxy)-tert-butyldimethylsilane (2a). This product was obtained as a colorless oil (9.06 g, 94% yield, 95% purity determined by GC and 96% with NMR using benzene as an internal standard) from the reaction of (6-bromo-hex-5-ynyloxy)-tert-butyldimethylsilane (33 mmol, 9.31 g) with dicyclohexylborane (36.3 mmol, formed in situ) 6 followed by protonolysis with acetic acid (17.4 M, 39.9 mmol, 2.29 mL).…”