Protonation of double bonds

Carbenium ions can be generated not only by ionization of alkyl halides with Lewis acids, but also by protonation of double bonds. Unfortunately, addition of excess triflic acid to a vinyl ether leads to polymer rather than to the monomeric cation [Eq. (6)]. 

The biosynthetic cyclization reactions leading to the various diterpene skeleta are summarized in Figure 3.16 (for a review see MacMillan and Beale (1999)). In addition to the well-established mode of cyclization driven by pyrophosphate ionization (sometimes referred to as Type T), a second mode ( Type IT), driven by protonation of double bonds. 

The second strategy to achieve the asymmetric protonation of double bonds through a conjugate addition is based on the use of a chiral proton source. This last strategy mainly focuses on the use of organocatalysts. This concept introduced by Pracejus et al. in 1977 in the course of thia-Michael addition to acceptor 98, mainly uses protic nucleophiles with low pKa such as thiol, a-ketoester, a-cyanoester, or secondary phosphine oxyde. ... 

We can gam a general understanding of the mechanism of hydrogen halide addi tion to alkenes by extending some of the principles of reaction mechanisms introduced earlier In Section 5 12 we pointed out that carbocations are the conjugate acids of alkenes Therefore strong acids such as HCI HBr and HI can protonate the double bond of an alkene to form a carbocation... 

Proton chemical shift data from nuclear magnetic resonance has historically not been very informative because the methylene groups in the hydrocarbon chain are not easily differentiated. However, this can be turned to advantage if a polar group is present on the side chain causing the shift of adjacent hydrogens downfteld. High resolution C-nmr has been able to determine position and stereochemistry of double bonds in the fatty acid chain (62). Broad band nmr has also been shown useful for determination of soHd fat content. 

At first glance, the product is not what we might have expected. Once again, we turn to the mechanism for an explanation. The first step of the mechanism is identical to what we have seen so far—we protonate the double bond to produce the more stable carbocation (secondary, rather than primary) ... 

Using the data from Table 1 and plotting 1/A vs 1/[TBSM], the value of Kc for the formation of the TBSM. .. MA complex was determined (involving 7i-electrons of double bonds due to the shift of anhydride protons) ... 

Although the monoterpene camphor occurs naturally, substantial amounts are produced semi-synthetically from a-pinene, a component in turpentine. Treatment of a-pinene with aqueous HCl protonates the double bond by an... 

As in the case of double bond isomerization of butenes, the double bond isomerization of VBH is considered to be initiated by abstraction of an allylic proton from a tertiary carbon atom to give an allylic anion that may be stabilized by metal ions, yielding the E- and Z-EBH isomers. 

The presence of fluorine strongly destabihzes a carbocation centered on the jS carbon because only the inductive effect takes place. " The effect on solvolysis or protonation reaction of double bonds can be very important. The destabilization of carbenium and alkoxycarbenium ions plays an importantrole in the design of enzyme inhibitors (cf Chapter 7) and in the hydrolytic metabolism of active molecules (cf. Chapter 3). 

In more esoteric compounds like (50) (78JA4326) and (51) (78CB1330) there is no reported tendency for cycloadditions to occur. A doubly protonated cation of undetermined structure reportedly forms on protonation of (50), however. Benzo[6 ]thiophenes can be annelated in a similar manner as occurs with (52) (79JOC2491). The question of the localization of double bonds in benzo[c] fused heterocycles continues to attract theoretical interest (77JA8248). 

A second important feature worth emphasizing is that the proton leak is affected by the lipid composition of the inner mitochondrial membrane. In general, the fatty acyl chains of phospholipid components of membranes can vary in their degree of unsaturation. The proton leak increases with the incorporation of polyunsaturated fatty acids (FAs) the greater the number of double bonds, the greater the proton leak (Hulbert and Else, 2000). As we shall note in the chapter on temperature relations, fatty acyl composition of membranes, including the inner mitochondrial membranes, changes in various... 

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