Silicon-mediated Synthesis Of Chiral Alcohols By Catalytic Asymmetric Silylations

Chiral alcohols are prevalent in a broad range of biologically active compounds,pharmaceutical agents and natural products.Therefore,organic chemists have been paying close attention to form chiral alcohol compounds in an efficient,and highly enantioselective manner.For the construction of chiral alcohol compounds,the most classic method is the asymmetric addition of carbonyl compounds is accompanied by organometallic reagents such as Grignard reagents,lithium reagents and organoboron reagents.However,these organometallic reagents have some shortcomings such as problematic preparation,harsh reaction conditions,and low safety factor,which largely limit the wide application of such methods.Therefore,the development of simple and efficient methods to construct chiral alcohols with diverse structures is still highly desirable.In the past decades,owing to the unique properties in stability,solubility and toxicity,a wide range of diverse and functional organosilicon reagents have been developed and applied in organic synthesis.Specifically,the organic silicon reagent-mediated synthesis and transformation strategies using transition metal catalyst received increasing attention.In this thesis,we developed two new strategies for the synthesis of chiral alcohols mediated by silicon in the presence of transition metal catalysts.The specific research content is as follows:(1)Novel Ni(cod)₂/phosphinamide-catalyzed ring expansion and desiliconization reaction of silacyclobutane and benzaldehyde derivatives have been developed.A series of functionalized bisarylmethanol derivatives(up to 98%yield,97%ee)with potential applications in the field of pharmaceutical molecules have been synthesized in a straightforward,efficient,and highly enantioselective manner.This strategy featured easy-to-obtain substrates,mild reaction conditions,wide substrate compatibility,high yields and stereoselectivities,which provide a new way for the construction of biaryl chiral alcohols containing tertiary carbon stereocenters.(2)The copper/pyridine bisoxazoline(Pybox)catalytic system was employed for the first time to carry out the desymmetric monoesterification reaction of prochiral2-silyl-1,3-propanediol.A series of chiral methanol derivatives containing silicon stereocenters were assembled with moderate to good enantioselectivity(up to 83%yield,78%ee).However,owing to the background reaction of esterification under non-catalytic reaction conditions,the enantioselectivity is difficult to control by adjusting chiral ligands.Based on the desymmetric esterification of prochiral silicon-based diols,12 new chiral silyl substituted methanol derivatives were synthesized,which provided a new method for the synthesis of optically active silicon-based methanol derivatives.In summary,we have synthesized a series of bisarylmethanol derivatives with tertiary carbon stereochiral centers using the ring expansion/desiliconization reaction between the prochiral carbonyl compound and the high ring tension silacyclobutane compound.On the other hand,based on the copper-catalyzed desymmetric monoesterification of silicon bridged prochiral diols,we have constructed a variety of methanol derivatives containing silicon stereocenters.The use of asymmetric strategy offers a new scheme for the synthesis of chiral alcohol compounds.