Trisubstituted double bonds

When aiomatics aie present, they can capture the intermediate vinyl cation to give P-aryl-a,P-unsatutated ketones (182). Thus acylation of alkyl or aryl acetylenes with acyhum salts in the presence of aromatics gives a,P-unsaturated ketones with a trisubstituted double bond. The mild reaction conditions employed do not cause direct acylation of aromatics. 

Isolated tetrasubstituted double bonds do not react under these conditions and the saturation of trisubstituted double bonds is extremely slow, thus limiting the general utility of the method. This difference in reactivity is used to advantage for the selective deuteration of the -double bond in androsta-l,4-diene-3,17-dione (138). In homogeneous solution, saturation usually occurs from the a-side and consequently the deuterium labels are in... 

Homogeneous catalytic deuteration of various unsaturated 5a-spirostane derivatives is an excellent method for the preparation of side chain labeled analogs. Thus, saturation of the double bonds at positions 20(21), 23 and 24 provided the corresponding deuterated compounds (144), (145) and (146) in high isotopic purity. The preparation of (146) is a rare example of the saturation of an isolated trisubstituted double bond in the steroid field. 

The hydroboration step, being very sensitive to steric effects, yields only secondary alkylboranes from trisubstituted double bonds, whereas the less hindered alkylborane is formed predominantly from disubstituted steroidal double bonds. The diborane attack occurs usually towards the a-side and hence results in overall a-hydration of double bonds after alkaline hydrogen peroxide oxidation. ... 

For steroids bearing two trisubstituted double bonds, such as A - and 11 -dienes, e.g. (35), the 5,6-oxirane is formed preferentially. The 9(ll)-double bond in -dienes, e.g. (38), is usually attacked first by... 

Write structural formulas or build molecular models and give the lUPAC names for all the alkenes of molecular formula C6H12 that contain a trisubstituted double bond. (Don t forget to include stereoisomers.)... 

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

Methyl-2-hexcne has a disubstituted double bond, RCH=CHR, and would probably give a mixture of two alcohols with either hydration method since Markovnikov s rule does not apply to symmetrically substituted alkenes. 3-MethyI-3-hexene, however, has a trisubstituted double bond, and would give only the desired product on non-Markovnikov hydration using the hydroboration/oxidation method. 

Low -molecular-weight ozonides are explosive and are theretore not isolated. Instead, the ozonide is immediately treated with a reducing agent such as zinc metal in acetic acid to convert it to carbonyl compounds. The net result of the ozonolysis/reduction sequence is that the C=C bond is cleaved and oxygen becomes doubly bonded to each of the original alkene carbons. If an alkene with a letrasubstituted double bond is ozonized, two ketone fragments result if an alkene with a trisubstituted double bond is ozonized, one ketone and one aldehyde result and so on. 

Acid-catalyzed dehydrations usually follow Zaitsev s rule (Section 11.7) and yield the more stable alkene as the major product. Thus, 2-methyl-2-butanol gives primarily 2-methyl-2-butene (trisubstituted double bond) rather than 2-methyl-l-butene (disubstitulecl double bond). 

A prominent structural feature of 21 and its precursor 22 is the trans C16-C17 trisubstituted double bond. The particular relationship between the ethoxycarbonyl function and the A16 17 double bond in 22 is significant because it satisfies the structural prerequisite for the Johnson ortho ester Claisen rearrangement transform.2130 Mixed ketene acetal 23 thus emerges as the immediate... 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

In the synthesis of the squalenoid glabrescol (72 originally attributed structure), containing five adjacent (all cis) THF rings, the necessary precursor of the polyepoxide cascade, the pentaepoxide 71, was achieved by epoxidation of each of the trisubstituted double bonds of the known (R)-2,3-dihydroxy-2,3-dihydrosqualene (70) by the Shi epoxidation approach (Scheme 8.18) [34]. Treatment of 71 with CSA at 0 °C and subsequent purification by column chromatography provided the pure polycyclic ether 72 by a cascade process reasonably initiated by the free secondary alcohol functionality [35a]. 

Hydrogenations in most cases are carried out at room temperature and just above atmospheric pressure, but some double bonds are more resistant and require higher temperatures and pressures. The resistance is usually a function of increasing substitution and is presumably caused by steric factors. Trisubstituted double bonds require, say, 25°C and 100 atm, while tetrasubstituted double bonds may require 275°C and 1000 atm. Among the double bonds most difficult to hydrogenate... 

Dimethylindene derivatives were hydroaluminated with BujAlH using Ni(acac)2 as the nickel(O) precursor (Scheme 2-13) [9]. Hydroalumination of the trisubstituted double bond in 9 was also achieved, although more forcing conditions... 

These results suggest that the transition states leading to the formation of the cyclo-adducts (33) and (34) are product-like and that the greater than statistical formation of adducts (34) is due to the increased thermodynamic stability of a trisubstituted double bond. In agreement with this explanation is the fact that in reactions with for example p-xylene and durene (1,2,4,5-tetramethylbenzene) only the adducts (35) and (36) were obtained 54-59). Also as expected, two adducts were obtained with tetralin but only the compound (37) was obtained using 5,8-dimethyltetralin, which we may regard as a 1,2,3,4-tetra-alkylben-zene 54>. 

In molecules containing a 1,3-diene unit and an isolated double bond, the diene is cyelopropanated preferentially (Scheme 7) 72,82). What has been said about the influence of steric and electronic factors as well as the nature of the catalyst (see above), can also be applied to explain the product distribution in these cases. The inertness of a trisubstituted double bond and the low reactivity of an E-disubstituted olefinic bond are quite obvious in these intramolecular competitions. 

Only a few results are available concerning competitive cyclopropanation of non-conjugated dienes. The case of 1,4-hexadiene72 (mixture of Z and E isomers) illustrates the reactivity difference between a monosubstituted and a 1,2-disubstituted double bond, whereas in limonene (24)47, a 1,1-disubstituted and a trisubstituted double bond compete for the carbenoid derived from ethyl diazoacetate. In both cases, the less substituted double bond reacts preferentially (Scheme 8). 

Exclusive O/H insertion takes place in the Rh2(OAc)4-catalyzed reaction of diethyl diazomalonate with a,(J-unsaturated y-hydroxyesters 167 a-c163). This is not surprising in view of the reluctance of electrophilic metal carbenes to add to electron-poor double bonds (see Sect. 2.3.2). However, the more electron-rich double bond of p-methoxybenzyl clavulanate 168 also cannot compete with the O—H function for the same carbenoid 164). The steric situation at the trisubstituted double bonds of 167 and 168 may be reason enough to render an attack there highly unfavorable as compared to the easily accessible O—H function, no matter how nucleophilic the double bond is. 

In the above mentioned reaction, platinum oxide and palladium on barium sulfate showed no perceptible change in the rate of hydrogen uptake. On the other hand, platinum oxide was selective in the hydrogenation of cyclohexa-2,4-diene-l,2-dicarboxylic acid to 1,4,5,6-tetrahydrophthalic acid140. A similar result may be the favored reduction of a symmetrical disubstituted double bond over a more hindered trisubstituted bond. The retarding effect of additional substitution is demonstrated in the hydrogenation of a trisubstituted double bond in the presence of a tetrasubstituted double bond (equation 53)141. 

Recently, a series of substituted dihydrothiazines such as (93) was reported by workers at Merrell Dow to display potent inhibition of partially purified rat neutrophil 5-LO (0.2-2.0 //M) [243], Substitution on the phenyl group or variation of the benzyl to other alkaryl had little effect on activity, but replacement of the benzyl by alkyl or hydroxyalkyl reduced potency about 10-fold. Replacement of the phenyl substituent by benzoyl reduced potency, while reduction of the trisubstituted double bond completely destroyed activity. No anti-inflammatory activity was reported for this series. 

The route for the cytotoxic ipomoeassin resin glycosides relied on the use of compound 256 as a new cinnamic acid surrogate with its trisubstituted double bond and meets the requirement of being hydrogenation resistant in the presence... 

The stereospecific construction of the trisubstituted double bond of the side chain at C-1 of carbazomadurins A (253) and B (254) was achieved using Negishi s zirconium-catalyzed carboalumination of alkynes 758 and 763, respectively. Reaction of 5-methyl-l-hexyne (758) with trimethylalane in the presence of zirconocene dichloride, followed by the addition of iodine, afforded the vinyl iodide 759 with the desired E-configuration of the double bond. Halogen-metal exchange with ferf-butyllithium, and reaction of the intermediate vinyllithium compound with tributyltin chloride, provided the vinylstannane 751a (603) (Scheme 5.79). 

---