Vien V. Khau

Selective monosulfonylation of internal 1,2-diols catalyzed by di-n-butyltin oxide†

The reaction of internal 1,2-diols with catalytic n-Bu2SnO, p-TsCl (1.05 equiv.) and Et3N (1.1 equiv.) led to selective monotosylation. In the case of cyclic substrates, the cis-1,2-diol moiety appeared best suited for optimal results, supporting the intermediacy of a five-membered chelate.

1,3-Dipolar cycloreversion of a 1,3,4-oxadiazolidine as a controlled azomethine imine surrogate for pyrazolidine synthesis

Abstract Azomethine imines were generated in a controlled manner through a thermally allowed 1,3-dipolar cycloreversion of 1,3,4-oxadiazolidines and subsequently trapped with dipolarophiles. This method results in the construction of the pyrazolidine heterocycles. A new method for the selective formation of the key semicarbazide substrate, from benzylidene hydrazone, is also disclosed.

A novel approach for total synthesis of cryptophycins via asymmetric crotylboration protocol

Abstract Acyclic and a highly efficient stereoselective C C bond formation of aldehyde 3 with the crotylboron reagent 4 , derived from (−)-α-pinene, provided a homoallylic alcohol 6 in ≥99% enantio-(ee) and diastereomeric excess (de). The alcohol 6 was linearly converted into the desired Fragment A 10 of cryptophycins in seven steps. This enantiomerically pure Fragment A was conveniently and efficiently coupled with the other three fragments, namely B, C and D, and provided the desired cryptophycin A derivative ( LY404291 ). The terminal double bond in LY404291 was further elaborated to provide a terminal epoxide LY404292 , and cryptophycins 51 and 52 .

Synthesis of enantioenriched 4-thiazolidinone (−)-LY213829 by chemoselective benzylamide cleavage in the presence of a C-S bond

Abstract ( R )-2-Methylbenzylamine has been used to covalently “resolve” thiol acid 7 and assemble 4-thiazolidinone 8a in one step. Selective deprotection of the 2-methylbenzylamide using lithium in ammonia/THF has been achieved in the presence of a readily hydrogenolyzed C-S bond. Enantioenriched (−)-LY213829 ( 1 ) of 98% ee has been prepared by this five step route in 25% yield from aldehyde 2 .

A novel, stereoselective synthesis of cis-4a (S), 8a(R)-decahydro-6(2H)-isoquinolones from meroquinene esters

Abstract Intramolecular cyclization of N-acylated meroquinene t-butyl esters in cold H2SO4 cleanly afforded cis-4a(S), 8a(R)-decahydro-6(2H)-isoquinolones with cmnplete stereocontrol in ⪢95% yield. Formation of the meroquinene esters from cinchona alkaloid autoxidation using an improved Doering protocol was accomplished in three steps with 85% overall yield.

Reaction of cryptophycin 52 with thiols

The chemical reactivity of cryptophycin 52 towards sulfur and phosporous nucleophiles under different conditions was explored to reveal the differential reactivity of the epoxide and olefinic centers. Under basic conditions 1,4-addition to the enone is favored, while under acidic conditions the epoxide is more reactive.

Diastereoselectivity in the heterogeneous hydrogenation reactions of phosphorous substituted olefins

Phosphorous substituted methylenecyclohexane olefins show enhanced diasteroselectivity in heterogeneous hydrogenation reactions using Pd/C. A model system, derived from 4-t-butylcyclohexanone was used to explore the effects of solvent polarity and catalyst on the reduction reaction. It was found that olefins hydrogenated with catalytic Pd/C in polar solvents afford the highest diastereoselectivities (>15:1).