Applications of NHCs and isothioureas as Lewis base organocatalysts

Enols--Synthesis;Anions;Chirality

Leckie, Stuart M. ; Smith, Andrew David ; Smith, Andrew David

University:University of St Andrews

Department:Chemistry (School of)

关键词: Enols--Synthesis;    Anions;    Chirality;   

Others  :  https://research-repository.st-andrews.ac.uk/bitstream/handle/10023/3622/Thefulltextofthisdocumentisnotavailable.pdf?sequence=1&isAllowed=y

来源: DR-NTU

【 摘 要 】

This thesis details investigations into two modes of organocatalytic enolate generationand reactivity. The first is the addition of chiral NHCs to a ketene to form an azoliumenolate. Investigations into three different electrophiles within this system will bediscussed. The second catalytic system investigated is the formation of aC1-ammonium enolate through the addition of chiral isothioureas to activated carboxylic acids. Studies on one electrophile within this system will be discussed.Chapter 2 investigates the use of bespoke C₂-symmetric NHCs in the asymmetricStaudinger reaction: the formal [2+2] cycloaddition between ketenes and imines. Achiral relay mechanism was proposed and experimentally validated with β-lactamsprepared in good yields (up to 85%) and moderate enantioselectivity (up to 61% ee).Chapter 3 describes the asymmetric formal [4+2] cycloaddition betweenalkylarylketenes and γ-substituted-β,γ-unsaturated α-ketocarboxylates. A substrate dependant switch in diastereoselectivity was observed with γ-aryl α-ketocarboxylates giving preferentially the syn-dihydropyranones (up to 70:30 dr syn:anti, up to 98% eesyn) and γ-alkyl α-ketocarboxylates giving preferentially the anti-dihydropyranones(up to 18:82 dr syn:anti, up to 75% ee anti, 97% ee syn).Chapter 4 illustrates the extension of the methodology described in Chapter 3 toinclude γ-substituted-β,γ-unsaturated α-ketophosphonates. Once more, a substratedependant switch in diastereoselectivity was observed with γ-aryl α-ketophosphonates giving preferentially the syn-dihydropyranone-phosphonates (up to72:28 dr syn:anti, up to 98% ee syn) and γ-methyl α-ketophosphonate givingpreferentially the anti-dihydropyranone-phosphonates (20:80 dr syn:anti, 71% ee anti,90% ee syn). Within this system it is also possible to generate the alkylarylketenes insitu with no loss in stereoselectivity but with typically improved yield when comparedwith the corresponding two-step procedure.Chapter 5 describes the activation of arylacetic acids via the formation of a mixedanhydride followed by C1-ammonium enolate generation with a chiral isothiourea.Asymmetric Michael addition and lactonisation with γ-substituted-β,γ-unsaturated α-ketophosphonates gave the corresponding anti-dihydropyranone-phosphonates (up to 89:11 dr anti:syn, up to 97% ee anti). More conveniently however, in situ ring opening with MeOH gave di-esters with excellent stereocontrol (up to >98:<2 dranti:syn, up to 99% ee anti) and which can be readily derivatised.