Transition metal promoted alkylations of unsaturated alcohols: the selective methylation of homopropargyl alcohols via titanium tetrachloride-trimethylaluminum

Abstract

The reactions of homopropargyl alcohols with titanium tetrachloride-trimethylaluminum in methylene chloride under mild conditions selectively yield after hydrolysis alkenols of the type HOCH(R)CH2CH=C(R')CH3, R = H, Me, and Et and R' = H, Me, Et, n-Pr, i-Pr, n-C4H9, n-C5Hn, and Ph.Ziegler-Natta polymerization catalysts are remarkably facile and repetitive carbometalating reagents toward alkene and alkyne functionalities. While Z-N reagents have been widely successful in the synthesis of stereoregular polyolefins since the 1950's, relatively little attention has been given to controlling their carbometalating properties in a manner that would extend their usefulness to nonmacromolecular synthetic organic chemistry. As part of our continuing interest in synthetic applications of Z-N reagents,1"4 we recently reported the reaction of 3-hexynl-ol with trimethylaluminum-titanium tetrachloride to give in good yield the single carbometalation derived product, (Z)-4-methyl-3-hexen-l-ol,5 an alkenol used by Corey et al. in the synthesis of d,Z-Cls Cecropia juvenile hormone6 and by Baker et al. in the synthesis of the trial pheromone of the Pharaoh's ant.7,8 In this paper we wish to report further studies on the selective methylation of homopropargyl alcohols with the titanium tetrachloridetrimethylaluminum reagent system. Experimental SectionMaterials. The alkynols were purchased from Parchan and used without further purification except for storage over 3-Á molecular sieves. Titanium tetrachloride and neat trimethylaluminum were obtained from Aldrich and the Ethyl Corp., respectively, and used without purification. Trimethylaluminum and titanium tetrachloride solutions were prepared in a nitrogen-filled Vacuum Atmospheres Dri-Lab. Methylene chloride was redistilled over P2Os under nitrogen before use. All chemistry was performed under nitrogen or argon atmospheres by using syringe techniques to transfer reagents.Procedure for Alkynol Methylations. In a typical reaction, 40 mmol of A1(CH3)3 was transferred by syringe into 75 mL of CH2C12 contained in a 250-mL three-necked round-bottom flask equipped with a gas inlet, rubber septa, and a magnetic stirring bar. Titanium tetrachloride (18 mmol) was transferred by syringe into 50 mL of CH2C12 contained in a 120-mL "pop-bottle", which

Scandium-Catalyzed Regio- and Stereospecific Methylalumination of Silyloxy/Alkoxy-Substituted Alkynes and Alkenes

“…Some representative results are summarized in Table . Generally, in the reactions of phenyl- or alkyl-substituted alkynes such as 1c − g , the methyl group was introduced to the CC carbon atom distal from the ether group in a syn fashion to give exclusively the corresponding Z alkenes in high yields after hydrolysis (Table , entries 1−5). , In contrast, methylalumination of trimethylsilyl (TMS)-substituted alkynes such as 1h − l took place in an anti-selective manner with introduction of the methyl group to the carbon atom proximal to the tethered ether group (Table , entries 6−10). , Under similar conditions, the Zr-catalyzed reactions were found to show much lower activity and lower selectivity. In a comparison experiment, the methylalumination of 1g catalyzed by Cp 2 ZrCl 2 (a representative Zr catalyst) yielded a mixture of the two regioisomers in a much lower yield (<10%).…”

Total Synthesis of Borrelidin

“…Next we turned to regioselective methylation of homopropargyl alcohol 12 to construct ( Z )-homoallylic alcohol 13 (Table ). Our first attempt under the conditions reported by Schiavelli et al gave the desired product 13 in poor yield (16%) and recovered 12 (77%) (entry 1). Although it seemed likely that a rise in the reaction temperature would lead to side reactions such as oligomerization, we were pleased to find that this reaction could be effected in a much improved, 80%, yield and with a short reaction time if the reaction temperature was set at −5 °C and excess Me 3 Al−TiCl 4 was used (entry 4).…”

Achieving Site-Selectivity for C–H Activation Processes Based on Distance and Geometry: A Carpenter’s Approach

“…The use of native functionalities as directing groups has enabled the development of valuable variants of canonical transforms, allowing reactions such as regio­selective hydrogenation, carbometalation, and various oxidation and reduction processes to become established in the chemical vernacular. Beyond the conventional modes of chemical reactivity, the directing group strategy has been particularly pivotal for the advancement of the relatively nascent field of transition metal-catalyzed C–H functionalization (i.e., the conversion of a C–H bond to a C–X bond) .…”