Alkyl conjugates, development

Friedel-Craft Alkylation Conjugated Additions. In the last decade, several methodologies have been developed to enantios-electively alkylate the Al-methylindole via a conjugated addition. One of them uses an a./S-unsaturated acylphosphonate as electrophile and a scandium(III) PyBox as chiral catalyst. After the Michael addition, the phosphonate moiety is directly converted into an ester by adding the corresponding alcohol in the presence of DBU. The desired product is isolated in 88% yield and 98% ee (eq... 

Regarding the chemical bond, we must turn the clock back to 1850 in order to give credit where credit is due. In that year, Edward Frankland (1825-1899), a British chemist best known for his work on water quality and analysis, developed a theory of valence following his research into the properties of Zn(CH3)2, zinc methyl in Frankland s terminology, a new reactive organometallic compound, and a series of alkyl-conjugated metals that had different combining powers than the metals alone. Colin Russell remarks [17] ... 

A noteworthy development is the use of KH for complexing alkylboranes and alkoxyboranes to form various boron hydrides used as reducing agents in the pharmaceutical industry. Potassium tri-j -butylborohydride [54575-50-7] KB(CH(CH2)C2H )2H, and potassium trisiamylborohydride [67966-25-0] KB(CH(CH2)CH(CH2)2)3H, are usefiil for the stereoselective reduction of ketones (66) and for the conjugate reduction and alkylation of a,P-unsaturated ketones (67). 

Helquist and coworkers60 have developed a six-membered ring annulation via a conjugate addition of aryllithium generated by metal-halogen exchange and subsequent intramolecular alkylation. This is illustrated in equation 71. 

The availability of sequence-specific DNA binding molecules led to the development of bifunctional polyamides that covalently react with the minor groove of DNA. Two classes of alkylating agents were conjugated to the hairpin turn unit and bound proximal to their alkylation sites by a DNA-binding polyamide [58, 59]. 

Fluoran compounds having an 7V-alkyl-/V-arylamino group at 3 -position such as 2 -chloro-6 -(7V-ethyl-4-methylanilino)fluoran (26 R1 = CH3, R2 = H, R3 = Cl),22 6 -((V-ethyl-4-methylanilino)-2 -methoxyfluoran (26 R1 = CH3, R2 = H, R3 = CH30),22 and 6 -(4-chloro-(V-ethylanilino)-2, 3 -dimethylfluoran (26 R1 = Cl, R2, R3 = CH3)22 also develop vermilion color, but these color tones are more bathochromic because of longer conjugated double bond system. 

Finally, the major structural features in the substrate promoting E2 elimination are those that serve to stabilise the resultant alkene or, more particularly, the T.S. that precedes it. Such features include increasing alkyl substitution at both a- and //-carbon atoms (leading to alkenes of increasing thermodynamic stability), or introduction of a phenyl group that can become conjugated with the developing double bond. 

Several modifications have been made to organoaluminum-based catalysts. Methylaluminum bis(2,6-di-tert-butyl-4-alkylphenoxide) (MAD) shows high diastereofacial selectivity in carbonyl alkylation (Scheme 72).31 11 Aluminum tris(2,6-diphenylphenoxide) (ATPH) has been developed as a catalyst for conjugate addition reactions. Since a carbonyl group is stabilized by steric effect of ATPH, the 1,4-adduct is obtained selectively.312... 

In a preliminary study, in situ generated B-alkylcatecholboranes were allowed to react with PTOC-OMe under irradiation with a standard 150 W lamp. The S-pyridyl products coming from primary, secondary and tertiary alkyl radicals were isolated in moderate to good yields [88]. Based on these initial results, a procedure for conjugate addition to various activated alkenes was developed. A one-pot procedure involving hydroboration of an alkene with catecholborane followed by irradiation in the presence of five equivalents of an activated alkene and three equivalents of the chain transfer reagent PTOC-OMe was developed (Scheme 36) [88]. 

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