Double trisubstituted

Cyclopentene derivatives with carboxylic acid side-chains can be stereoselectively hydroxy-lated by the iodolactonization procedure (E.J. Corey, 1969, 1970). To the trisubstituted cyclopentene described on p. 210 a large iodine cation is added stereoselectively to the less hindered -side of the 9,10 double bond. Lactone formation occurs on the intermediate iod-onium ion specifically at C-9ot. Later the iodine is reductively removed with tri-n-butyltin hydride. The cyclopentane ring now bears all oxygen and carbon substituents in the right stereochemistry, and the carbon chains can be built starting from the C-8 and C-12 substit""" ... 

Triethylammonium formate is another reducing agent for q, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

Trisubstituted alkene (Section 5 6) Alkene of the type R2C=CHR in which there are three carbons directly bonded to the carbons of the double bond (The R groups may be the same or different)... 

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. 

Tetrasubstituted and some hindered trisubstituted alkenes react rapidly only to the monoalkylborane stage. Rarely, when the tetrasubstituted double bond is incorporated in a cycHc stmcture, does hydroboration under normal conditions fail (25—27). However, such double bonds may react under conditions of greater force (25,28—31). Generally, trialkylboranes are stable at normal temperatures, undergoing thermal dissociation at temperatures above 100°C (32—34). In the presence of B—H bonds, trialkylboranes undergo a redistribution reaction (35—38). 

Since the olefmic CC double bond is trisubstituted, the relative configuration cannot be determined on the basis of the cis and trans couplings of vicinal alkene protons in the H NMR spectrum. What is the relative configuration given the C NMR spectra 19 ... 

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... 

Degree of substitution. We classify double bonds as monosubstituted, disubstituted, trisubstituted, or tetrasubstituted according to the number of carbon atoms directly attached to the C=C stnactural unit. 

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.)... 

Danishafsky and Feldman (21) have shown that the cyclization of the aminoketone (28) led to the internal enamine (29), which lacks the steric interaction of the type existent in the enamines of 2-alkycyclohexanones. In this case, the tetrasubstituted isomer was favored over the trisubstituted one by a factor of 4 1, which may be ascribed to the double bond being in the exo position in the latter case. 

Reaction of the pyrrolidine enamine of cyclohexanone with phenyl vinyl sulfone afforded a 9 1 mixture of the tri- and tetrasubstituted isomers (2(5). The preference of the less substituted isomer in this case is in keeping with the greater overlap requirement between the n electrons of the double bond and the electron pair on the nitrogen atom, since the double bond exo to the five-membered ring is much more favored than the double bond exo to the six-membered ring. It is, however, hard to explain the formation of largely the trisubstituted isomer with the piperidine enamine of cyclohexanone, where both of the rings involved are six-membered. 

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. °... 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

The cis-trans naming system used in the previous section works only with disub-stituted alkenes—compounds that have two substituents other than hydrogen on the double bond. With trisubstituted and tetrasubstituted double bonds, a more general method is needed for describing double-bond geometry. (Tiisub-stitnted means three substituents other than hydrogen on the double bond tetrasubstituted means four substituents other than hydrogen.)... 

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... 

The successful implementation of this strategy is shown in Scheme 4. In the central double cyclization step, the combined action of palladium(n) acetate (10 mol %), triphenylphosphine (20 mol %), and silver carbonate (2 equiv.) on trienyl iodide 16 in refluxing THF results in the formation of tricycle 20 (ca. 83 % yield). Compound 20 is the only product formed in this spectacular transformation. It is noteworthy that the stereochemical course of the initial insertion (see 17—>18) is guided by an equatorially disposed /-butyldimethylsilyl ether at C-6 in a transition state having a preferred eclipsed orientation of the C-Pd a bond and the exocyclic double bond (see 17). Insertion of the trisubstituted cycloheptene double bond into the C-Pd bond in 18 then gives a new organopal-... 

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]. 

---