Stereoselective Synthesis of a Family of Alternating Polyols from Six-Carbon Epoxyalkynol Modules

Abstract

Our new synthetic strategy for assembling polyacetate structures features efficient cross-couplings of six-carbon modules derived from any stereoisomer of the epoxyalkynol derivative (1). Hydration of the internal alkyne in the coupled products and stereoselective reduction of the resulting ketone intermediate provides a general approach to a library of stereoisomeric 1, 3, 5, ... alternating polyols (2). The strategy is demonstrated in a stereoselective synthesis of the C11-C28 polyol substructure of the natural product RK-397.

A Gold‐Catalyzed Entry into the Sesquisabinene and Sesquithujene Families of Terpenoids and Formal Total Syntheses of Cedrene and Cedrol

“…The absolute stereochemistry was assigned by comparison of the optical rotation. [ α ]${{{20\hfill \atop {\rm D}\hfill}}}$ =−22.1 ( c =1.3 in CHCl 3 ), Lit:47 [ α ]${{{{\rm RT}\hfill \atop {\rm D}\hfill}}}$ =−29 ( c =0.85 in CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ =5.93–5.83 (m, 1 H), 5.21–5.19 (m, 1 H), 5.17 (br s, 1 H), 4.41 (t, J =6.1 Hz, 1 H), 2.47 (t, J =7.0 Hz, 2 H), 1.79 (br s, 1 H), 0.17 ppm (s, 9 H); 13 C NMR (100 MHz, CDCl 3 ): δ =132.9, 119.0, 105.9, 89.8, 62.0, 42.1, −0.2 ppm; IR (film): $\tilde \nu $ = 3351, 3073, 2960, 2901, 2175, 1643, 1250, 1027, 837, 759 cm −1 ; MS (70 eV): m / z (%): 168 (0.1) [ M + ], 127 (98), 99 (100), 75 (33), 59 (11), 45 (16); HRMS (CI): m / z : calcd for C 9 H 20 NOSi [ M + +NH 4 ]: 186.1314, found: 186.1316.…”

Highly enantioselective addition of terminal alkynes to aldehydes catalyzed by a new chiral β‐sulfonamide alcohol/Ti(OiPr)4/Et2Zn/R3N catalyst system

“…46 However, that research focused solely on methyl propiolate. 3,4,32,33 Other functional alkynes such as trimethylsilylacetylene and ethynylcyclohexene are particularly desirable alkynes due to the possible use of the desilylated product for alkylation or the Sonogashira coupling [47][48][49][50][51] and the possible further tranformation of the alkene group such as epoxidation, hydroxylation, ozonolysis, and addition of carbenes, 52 respectively. However, to our knowledge, the enantioselective trimethylsilylacetylene addition of hetroaromatic, a,b-unsaturated aldehydes has attracted less attention yet.…”

Epoxides in Complex Molecule Synthesis

“…A recent new synthetic strategy for assembling polyol substructures is based on cross-couplings of six-carbon modules [62]. In this way, each of the four stereoisomers of epoxide 133 and diol 132a is produced, with very high diastereoselectivity, from either enantiomer of unsaturated alcohol 131 (Scheme 8.34) by epoxidation followed by hydrolytic kinetic resolution (HKR) [63].…”

“…Reduction of 135 can be performed with either 1,3-anti or syn stereoinduction from the C 8 -OH group, demonstrating the potential of this strategy for the stereoselective preparation of all 32 stereoisomers of polyol 136. This strategy was successfully tested in the stereoselective synthesis of the alternating polyol segment corresponding to the C 11 -C 28 substructure of the polyene macrolide RK-397, in a process requiring only two carbon-carbon bond formation steps [62].…”