Secondary homoallylic

Ether was a better solvent in cases where the propargylic position was unsubstituted (methylene group) since, in THF, a competitive [1,2] -Wittig rearrangement took place and led to diminished yields. When applied to the secondary homoallylic propargyl ethers 388, the zinc-ene-allene cyclization afforded the c -2,3,5-trisubstituted tetrahydrofurans 389 with moderate to satisfactory levels of diastereoselectivity, which could be rationalized by the preferential pseudo-equatorial positioning of the homoallylic substituent in the cyclic... 

The combined catalyst of Sc(OTf)3 and distannoxane gives the one-treatment process. Namely, in the reaction of ro-hydroxy alkanal, one-pot aldehyde allylation and acetylation of a primary alcohol are achieved without protection/ deprotection procedures. The unwanted acetylation of a secondary homoallyl alcohol by Sc(OTf)3 is suppressed by hybridization with distannoxane (Equation (46)).151... 

Asymmetric hydroboration 2171 of prochiral alkenes with monoisopinocampheyl-borane in the molar ratio of 1 1, followed by a second hydroboration of non-prochiral alkenes with the intermediate dialkylboranes, provides the chiral mixed trialkylbo-ranes. Treatment of these trialkylboranes with acetaldehyde results in the selective, facile elimination of the 3-pinanyl group, providing the corresponding chiral borinic acid esters with high enantiomeric purities. The reaction of these intermediates with base and dichloromethyl methyl ether provides the chiral ketones (Eq. 130)2l8>. A simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities via B-allyldiisopinocampheylborane has been also reported 219),... 

Chiral homoallylic alcohols. The borane 1 reacts with aldehydes in ether at - 78° to furnish, after oxidation, chiral secondary homoallylic alcohols (2) with enantiomeric excesses of 83-96%. The addition occurs in all six cases examined in the same stereochemical sense. 

Hydroformylation of a secondary homoallylic alcohol such as 1 followed by PCC oxidation provides a useful route to the 8-lactone 2. The product was converted by known reactions into the Prelog-Djerassi lactone (3). ... 

Good stereoselectivity was observed in the cyclization of secondary homoallylic imidates. High 1,3-asymmetric induction was effective and the ri.v-4,6-disubstituted 5,6-dihydro-4//-l,3-ox-azine 5 predominates142. 

The mercury-induced cyclization of amidals derived from secondary homoallylic alcohols afforded only six-membered ring products 7 via a 6-exo mode. For short periods (under kinetic control) the fa-isomer was the major product, while for longer periods (under thermodynamic control) the trans-isomer was formed with very high stereoselectivity161,162. 

Tietze et al. emphasized the usefulness of chiral trimethylsilyl ethers of readily accessible amino alcohol derivatives in allylation of aldehydes and ketones [43]. As a consequence, careful design of the norpseudoephedrine derivatives and proper choice of silicon Lewis acids have led to the convergent preparation of enantiomerically enriched secondary and tertiary homoallylic alcohols in high yields (Sch. 12) [43a], It should be noted that the configuration of the newly formed stereogenic center of the secondary homoallylic alcohols is the opposite of that in the allylation of ketones [43c], They also described in detail mechanistic studies of the above allylation reaction by use of and NMR. 

The formation of chiral secondary homoallylic alcohols via the enantioselective addition of allylic nucleophiles to aldehydes is an important tool in organic synthesis. An efficient way to achieve this transformation is to use allylic organometallic reagents in the presence of chiral Lewis acid catalysts. The most widely studied catalysts in the area... 

The complex polyene hydroxyl-substituted tetrahydrofuran metabolite ( )-citreoviral was synthesized by G. Pattenden and co-workers." All four carbons on the tetrahydrofuran ring are chiral, and in the final stages of the synthetic effort the stereochemistry of the C3 secondary homoallylic alcohol had to be inverted. This step was best achieved by a Moffatt ox/daf/on/NaBH4 reduction sequence. 

Brown, H. C., Jadhav, P. K. Asymmetric carbon-carbon bond formation via 3-allyldiisopinocampheylborane. Simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities. J. Am. Chem. Soc. 1983, 105, 2092-2093. 

Carbanions derived from a-sulfonyl ethers 5 undergo [2.3] sigmatropic rearrangement the resulting a-hydroxy sulfoties are subject to a further fragmentation, yielding an aryl sulfinic acid and an aldehyde which reacts further with excess alkyllithium Lo afford a secondary homoallylic alcohol61 66. 

Not surprisingly, Martin s sulfurane mediates the production of acyclic dienes from allylic and homoallylic alcohols. In Heathcock s synthesis of altohyrtin C, secondary homoallylic alcohol 55 reacted with sulfurane 1 to yield the desired ( T)-alkene 56 in greater than 84% yield.26 Interestingly, Tse generated diene 58 from tertiary allylic alcohol 57 in 95% yield with only 5% of the undesired trisubstituted diene isomer.27... 

Scheme 1 Iridium-catalyzed coupling of primary alcohols with allyl acetate to form secondary homoallylic alcohols...

The Overman pyrrolidine synthesis is a tandem reaction, or cascade, used to generate acylpyrrolidine derivatives. This process begins with condensation of an allylic alcohol/ether-containing secondary homoallylic amine with an aldehyde, followed by an aza-Cope rearrangement and subsequent Mannich reaction. Commonly, this reaction is run in refluxing benzene with an acidic additive, such as c/-10-camphorsulfonic acid (CSA). 

Remarkably, while the primary alcohol reactants readily dehydrogenate, the secondary homoallylic alcohol products resist further oxidation due to chelation of homoallylic olefin to ruthenium to generate a coordinatively saturated complex. 

Although several classes of carbonyl compounds or their derivatives react with allylboronates (see below), the most common use of allylboronates in synthetic chemistry is their nucleophilic addition to aldehydes to produce secondary homoallylic alcohols (Figure 6.5) [1-6], a process first discovered in 1974 [lOj. 

Similar to rhodium, copper mediates retro-allylation when it is complexed with an N-heterocyclic carbene ligand [31]. The allyl transfer takes place not only to aromatic aldehydes but also to aromatic imines (Scheme 5.43). Notably, secondary homoallylic alcohols transfer their allyl groups, retro-allylation dominating over P-hydride elimination from the copper alkoxide intermediates. 

The Lewis-acid-catalyzed carbonyl-ene reaction represents an important alternative method for the addition of an allyl group to a carbonyl group (Equation 23). The resulting secondary homoallylic alcohols are amenable to a number of structural modifications and constitute useful synthetic building blocks. Because the olefin of the products can be a surrogate for a carbonyl functionality, these homoallylic alcohol are formally the synthetic equivalent of aldol addition products. Powerful asymmetric versions of the carbonyl-ene reaction [196, 197] provide an important alternative to the more traditional allylation methods, which primarily employ silanes, boranes, or stannanes (see Chapter 5). 

Nokami reported a study that documents the asymmetric rearrangement of chiral oxonium ions (Scheme 16.19) [97]. These reactive intermediates are generated upon condensation of optically active alcohols and aldehydes. The requisite alcohol 158 was prepared by diastereoselective addition of cro-tylmagnesium chloride 156 to menthone 157. Subsequent treatment of the alcohol with an aldehyde such as PhSCH2CH2CHO under acidic conditions induced formation of 159. The ensuing [3,3]-rearrangement gave 160, and in situ hydrolysis of the chiral auxiliary afforded the secondary homoallylic alcohol with excellent optical purity (99% ee). 

---