Synthesis of Enantiopure Homoallylic Alcohols and Ethers by Diastereoselective Allylation of Aldehydes

Abstract

A highly selective asymmetric domino allylation of aliphatic ketones is described. When methyl ketones 1 a ± g, the chiral trimethylsilyl ether 2, and allylsilane 3 react in the presence of catalytic amounts of trifluoromethanesulfonic acid, the homoallylic ethers 4 a ± g are produced with up to 24:1 diastereoselectivity and 89 % yield. Cleavage of the obtained tertiary homoallylic ethers 4 using lithium or sodium in liquid ammonia gives the homoallylic alcohols 5 in 75 to 95 % yield and up to 92 % ee. Even ethyl methyl ketone 1 a, the most difficult example, showed a stereoselectivity of 9:1 at À 78 8C and 24:1 at À 109 8C. In addition, the allylation of protected hydroxyalkyl methyl ketones 7 a ± j was investigated to give the corresponding homoallylic ethers 8 a ± j with a diastereoselectivity of up to b 24:1 and 98 % yield. In contrast, ethyl alkyl ketones 1 h ± j have a low selectivity.

Preparation and odour properties of the four stereoisomers of 2‐hexyl‐4‐acetoxytetrahydrofuran

“…The absolute configuration of the products obtained by resolution was assigned by comparing the specific rotation values of ( R )‐ 2 , ( S )‐ 2 and the acetate ( S )‐ 3 with the literature data. The specific rotation value of the acetate 3 we obtained is opposite to that of ( R )‐dec‐1‐en‐4‐yl acetate in the literature . Most of the literature data regarding the specific rotations of ( R )‐ 2 and ( S )‐ 2 are consistent, i.e.…”

“…The only exception is that Fürstner et al . reported a negative value for ( R )‐ 2 , which could be a mistake due to the authors’ misreading the literature data . In contrast to lipase CAL‐B, Amano PS showed much poorer enantioselectivity and the two enantiomers of (±)‐ 2 were converted to the corresponding acetates almost at an equal rate.…”

“…Optically active 1‐decen‐4‐ols were prepared through several different methods, such as by the reaction of heptanal with allylsilane using a norpseudoephedrine derivative as a chiral auxiliary, the asymmetric catalytic reaction of heptanal with allyltributylstannane using the complex of Ti(O i ‐Pr) 4 and enantiomerically pure 1,1′‐bi‐2‐naphthol as a catalyst, the reaction of heptanal with allyltrichlorosilane mediated by ( S , S )‐ N , N ‐bis( α ‐methylbenzyl)formanide, the reaction of enantiomerically enriched 1,2‐epoxyoctane produced by kinetic resolution with vinylmagnesium bromide, the Cr‐mediated catalytic asymmetric allylation of heptanal, the treatment of heptanal with allyl isoborneol in the presence of catalytic amounts of camphorsulfonic acid . Although almost all of these methods could produce 1‐decen‐4‐ol with high stereoselectivity, some disadvantages exist, such as demanding reaction procedures required for both the use of metal catalyst and for the preparation of reagents.…”

Total Syntheses of Squamocin A and Squamocin D, Bi-tetrahydrofuran Acetogenins from Annonaceae

“…on a 30-mmol scale, it was necessary to reflux the catalyst with molecular sieves for 90 min before adding further reagents. The (S) configuration of the new chiral center was proven by conversion of the alcohol 23 into the acetate 24 followed by comparison of the chiroptical data for 24 and ent-24 [27] {found: [α] D 20 ϭ Ϫ23.5 (c ϭ 0.23, CHCl 3 ), ref. [27] : [α] D 20 ϭ ϩ 23.7 for ent-24 (c ϭ 1.0, CHCl 3 )}.…”

“…The (S) configuration of the new chiral center was proven by conversion of the alcohol 23 into the acetate 24 followed by comparison of the chiroptical data for 24 and ent-24 [27] {found: [α] D 20 ϭ Ϫ23.5 (c ϭ 0.23, CHCl 3 ), ref. [27] : [α] D 20 ϭ ϩ 23.7 for ent-24 (c ϭ 1.0, CHCl 3 )}. A TBDMS protection of 23 and a subsequent hydroboration with 9-BBN gave the primary alcohol 25, which was then converted via its tosylate into bromide 26.…”