Alkenyl alcohols, - disubstituted

Alkenyl alcohols, (E) disubstituted, 55, 66 ALKYL HALIDES, alkenes from, 55, 103 C-ALKYLATION, phase transfer catalysis... 

Alkenes, chain elongation, 56, 32 Alkenyl alcohols, (E J-disubstituted, 55, 66 A -Alkenylhydroxylamines, 58, 108... 

Sequential Rh-catalysed etherification of the allylic carbonate using the Cu(I) alkoxide derived from the enantiomers of the alkenyl alcohols followed by a RCM occur with excellent regio- and enantiospecificity and lead to cis- and traws-disubstituted dihydropyrans <04AG(E)4788>. 

This procedure illustrates a general method for the stereoselective synthesis of (B)-disubstituted alkenyl alcohols. The reductive elimination of cyclic j8-halo-ethers with metals was first introduced by Paul and one example, the conversion of tetrahydrofurfuryl chloride [2-(chloromethyl)tetrahydrofuran] to 4-penten-l-ol, is described in an earlier volume of this series.In 1947 Paul and Riobe prepared 4-nonen-l-ol by this method, and the general method has subsequently been applied to obtain alkenyl alcohols with other substitution patterns. " (B)-4-Hexen-l-ol has been prepared by this method and in lower yield by an analogous reaction with 3-bromo-2-methyltetra-hydropyran. ... 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

B-Alkenyl-9-borabicyclo(3,3,l)nonane (B-alkenyl-9-BBN) adds across the carbonyl group of a simple aldehyde to afford in good yields, the corresponding allylic alcohol S2). The reaction proceeds with complete retention of vinylic borane stereochemistry resulting in the /raw-disubstituted olefin linkage in the final product. The reac-... 

Disubstituted A-alkoxypyrrolidines were obtained by iodocyclization of 1-substituted 4-alkenyl-jV-alkoxyamines by the addition of iodine in acetonitrile in the presence of sodium hydrogen carbonate. Moderate 1,3-asymmetric induction was observed with little dependence on the bulk of the R1 substituent. The 2,5-/rc n.v-pyrrolidine trans-3 was the predominant product, unless the disubstituted double bond had E configuration77. The iodides were transformed to alcohols with net retention of configuration. 

In addition to Ni and Pd catalysts, Li2CuCU is also an effective catalyst for the coupling of alkenyl iodides with Grignard reagents. Since the stereochemistry of alkenyl iodides is also retained, the coupling reactions are useful for the stereoselective synthesis of disubstituted alkenes, - trisubstituted al-kenes, allylsilanes, allyl alcohols and tetrasubstituted alkenes (equations 25-29). ... 

Eliminations. Homopropargylic alcohols are formed from 3,3-disubstituted 2-methyleneoxetanes. Alkenyl triflates give alkynes. ... 

In contrast to the reaction with diisobutylaluminium hydride, hydroalumination of disubstituted alkynes with lithium hydridodiisobutylmethylaluminate, obtained from diisobutylaluminium hydride and methyllithium, results in anti addition across the triple bond. Subsequent reaction with aldehydes gives allylic alcohols, with CO2 gives a,p-unsaturated acids and with iodine gives alkenyl iodides, isomeric with the products obtained in the reaction sequences using diisobutylalvmiinium hydride. ... 

Kozmin has reported the formation of polyqrclic ethers via the gold(I) or gold(III)-catalyzed tandem enyne cydization/alkoxylation of 1,5-enynes that contained a tethered hydroxy group [126]. As an example, treatment of homopropargyUc alcohol 86 with a catalytic 1 1 mixture of (PPhs) AuCl and AgC104 at 20 °C led to isolation of 6-oxabicyclo[3.2.1]octene 87 in 89% yield (Scheme 12.15). Conversion of 86 to 87 presumably occurs via attack of the pendant alkene on a goldhydroxy group at the disubstituted alkenyl carbon atom. Protodeauration then releases heterocycle 87 (Scheme 12.15). 

In the intermolecular process, cross-metathesis offers a usefid and versatile alternative to alkyne hydroboration for the synthesis of functionalized alkenyl pinacol boronates with a moderate to high -selectivity. Styrenes, allylsilanes, protected alcohols and amines are good partners as 1,1-disubstituted olefins [105-107]. This reaction has been exploited recently as part of a macrocyclization strategy in the epothilone series (Scheme 9.52) [108]. 

The Zr-Zn transmetalation, aldehyde addition strategy has also been used in the total syntheses of (-)-ratjadone [85] and fostriecin. In the latter example, the substrate was a chiral epoxyketone, which was converted to a tertiary alcohol in excellent diastereoselectivity by chelation control [86]. More recently, the reaction scope has been extended to the addition to C=N electrophiles to form allylic amides [87] as well as allyl hydroxylamines [88], and to the preparation of frans-1,2-disubstituted cyclopropanes [87, 89]. Powell and Rych-novsky found that the BF3-mediated addition to in situ formed oxacarbenium ions led to a mixture of alkyl and alkenyl ligand transfers [90] (Scheme 18). 

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