1.3- Dienes alcohols, synthesis

Most asymmetric syntheses require rather more than one or two steps from chiral pool constituents. Male bark beetles of the genus Ips produce a pheromone that is a mixture of several enantiomerically pure compounds. One is a simple diene alcohol (S)-(-)-ipsenol. Japanese chemists in the 1970s noted the similarity of part of the structure of ipsenol (in black) to the widely available amino acid (S)-leucine and decided to exploit this in a chiral pool synthesis, using the stereogenic centre (green ring) of leucine to provide the stereogenic centre of ipsenol. 

The diene alcohol derivative 68 is used to prepare the starting material 69 for an intramolecular hetero-Diels-Alder reaction to give a new heterocyclic ring 70 that can be cleaved with phenyl Grignard to release a sulfoxide 71 for the preparation of a new allylic alcohol 72. Notice that the stereochemistry of the sulfoxide is shown and that there is complete control over 2D and 3D stereochemistry. The allylic alcohol 72 was used in Weinreb s synthesis of toxins10 produced by fresh water blue-green algae. 

The diene monomer required to make polyolefins with precisely placed ether groups is synthesized in one step from a symmetric secondary diene alcohol (the synthesis of which is discussed in Section 10.4.1) using the classic Williamson ether synthesis. Polymerization followed by hydrogenation results in a defect-free, linear-sequenced copolymer of ethylene and either methyl vinyl ether or ethyl vinyl ether, as confirmed by careful NMR characterization. 

The last example is an interesting application of the diene synthesis, for the adduct upon dehydrogenation (most simply by the action of oxygen upon its solution in alcoholic potash) yields 2 3-dimethylantbraquinone. 

Fig. 5. Synthesis ofisophytol (14) pseudoionone [141-10-6] (20), hexahydropseudoionone [1604-34-8] (21), C -acetylenic alcohol [1604-35-9] (22), C g-aUenic ketone [16647-10-2] (23), C g-diene ketone [1604-32-6] (24), C g-saturated ketone [16825-16-4] (25), and C2Q-acetylenic alcohol [29171-23-1] (26).

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

The nitro-dldolredcdon between nitrodlkdnes and carbonyl compounds to yieldfi-nitro alcohols was discovered in 1895 by Henry. Since dien, diis reaction has been used extensively in many important syndieses. In view of its significance, diere are several reviews on die Henry reaction." These reviews cover syndiesis of fi-nitro alcohols and dieir applications in organic synthesis. The most comprehensive review is Ref 3, which summarizes the literature before 1970. More recent reviews are Refs. 4 and 5, which summarize literatures on the Henry reaction published until 1990. 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

Enyne metathesis starting either from acetylenic boronates and homoallylic alcohols [104a,c] or from propargyl alcohols and allylboronates [104b] has recently been described. The resulting boronated dienes can be converted to allenes or cycloaddition products. The cross metathesis of vinylcyclopropyl-boronates directed toward the total synthesis of natural products has very recently been investigated by Pietruszka et al. [104d]. 

Intramolecular versions of the Diels-Alder reaction are well known, and this is a powerful method for the synthesis of mono- and polycyclic compounds.There are many examples and variations. One interesting internal Diels-Alder reaction links the diene and dienophile by a C—O—SiR2—or a C—O—SiR2—O—C linkage. Internal cyclization to give a bicyclic product is followed by cleavage of the O-Si unit to give a monocyclic alcohol. 

Zanarotti, A. Preparation and reactivity of 2,6-dimethoxy-4-allylidene-2,5-cyclohexa-dien-l-one (vinyl quinone methide). A novel synthesis of sinapyl alcohol. Tetrahedron Lett, 1982, 23, 3815-3818. 

Generally, trialkylboranes are useful intermediates in the field of organic synthesis with versatile reactivity. The polymers prepared by polyaddition between diene monomers and thexylborane are polymer homologues of trialkylboranes, which can be converted to poly(alcohol)s, poly(ketone)s, and other polymers having some functional groups (scheme 4).8-12... 

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